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Biomedical subjects

K Fält

Publications and source records attributed to K Fält.

At least 37 records · Page 2Linked to original sources
PubMed1990

Detection of antibodies to islet cell and splenic lymphocytes in diabetes-prone BB and adjuvant-streptozotocin treated Lewis rats by ELISA and immunoblot analysis.

An enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against surface components of rat islet and spleen lymphocytes. Live islet tumor RIN5 AH cells expressing characteristic ganglioside target antigens or rat spleen cells were immobilized onto wells of microtiter polystyrene plates precoated with poly-l-lysine and then incubated with test or normal rat sera. Cell surface-bound antibodies were quantitated after reaction with horseradish peroxidase-conjugated rabbit anti-rat Ig. With this assay, 46% (6/13) of sera from diabetes-prone BB rats and 100% (8/8) of sera from rats treated with complete Freund's adjuvant/streptozotocin (CFA/STZ) prior to immunization with RIN cells had islet cell surface antibodies: 54% (7/13) and 75% (6/8), respectively, were positive for lymphocyte antibodies (defined as the HRP anti-rat Ig binding exceeding the mean + 2SD of control group values). SDS polyacrylamide gel electrophoresis followed by immunoblotting analysis suggested that the islet cell antibodies in sera from the BB and CFA/STZ rats recognized RIN-cell components that were different in their molecular weights. These antigens were not detectable on spleen cells indicating that the ELISA described can be used to quantitate levels of islet cell specific antibodies which possibly reflect beta cell damage with progression to islet degeneration in the rat.

Animals↗
PubMed1990

Feline E. coli bacteremia--effects of misoprostol/scavengers or methylprednisolone on hemodynamic reactions and gastrointestinal mucosal injury.

Live E. coli were infused i.v. in cats to induce gastrointestinal mucosal injury and the gastric mucosa was exposed to bile and a luminal pH of 1. A gastric lesion index was calculated and intestinal injury was graded. The effects of i.v. methylprednisolone before and after induction of bacteremia were compared with those of intragastric misoprostol combined with i.v. superoxide dismutase (SOD) and catalase and with a control group. Methylprednisolone, but not misoprostol/SOD/catalase, significantly reduced the gastric lesion index (p less than 0.05). The duodenum/small intestine was significantly injured in 4/6, 2/6 and 4/6 cats in the misoprostol/SOD/catalase, methylprednisolone and control groups, respectively (NS). End gastric luminal pH was 3.9, 2.7 and 4.5 in the respective groups (p less than 0.05), with systemic arterial pH 7.15, 7.15 and 7.32 (NS). Mean arterial pressure and cardiac output were improved with methylprednisolone. Misoprostol/SOD/catalase reduced late hypotension. Pulmonary arterial pressure rose to c. 200% of basal in all groups. Methylprednisolone, but not misoprostol/SOD/catalase, thus protected the gastric mucosa from sepsis-induced gastric injury concomitant with reduced disappearance of protons from the gastric lumen, but did not significantly affect small-bowel damage. Hemodynamic responses were significantly improved in methylprednisolone-pretreated cats.

Acid-Base Equilibrium↗
PubMed1990

The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion.

Tissue injury at reperfusion has been reported after partial ischemia. However, previous attempts to demonstrate a component of injury caused by reperfusion after total ischemia have failed. This study was performed to evaluate the hypothesis that in such situations the extent of the tissue injury caused by ischemia itself prevented detection of a reperfusion component. Rats were subjected to near-total intestinal ischemia by means of a hydrostatic pressure clamp that produced preferential venous occlusion (strangulation) for periods from 1 to 90 minutes. Tissue injury was evaluated microscopically by a blinded examiner. Ischemic periods of 20 minutes or less did not induce detectable tissue injury. Longer durations of ischemia caused villous injury: the longer the period of ischemia, the more extensive the tissue injury. However, there was no exacerbation of injury seen after reperfusion, regardless of the duration of ischemia. In a separate series of rats, total arterial occlusion was employed without concomitant venous congestion. Such isolation arterial occlusion of 40 to 60 minutes' duration was followed by a statistically significant exacerbation of tissue injury at reperfusion. Thus total intestinal ischemia may be followed by reperfusion injury if there is no concomitant congestion and if ischemic injury is not too extensive.

Animals↗
PubMed1990

Immunocytes in the human fetal pancreas--a contribution to developmental immunoendocrinology concerning diabetes mellitus and organ cultivation.

The studies were performed on 103 samples of human fetal pancreas tissue (10th to 26th week of gestation). Of the mothers, 14 had insulin dependent type I diabetes mellitus (IDDM), and 33 of the samples were examined before and after cultivation for 14 days. 3 samples taken from fetuses in the 14th week of development (mothers without metabolic disorders) were examined in the electron microscope. Lymphocytes are generally irregularly distributed within the tissue. Groups of 3 to 5 lymphocytes are found in addition in the 12th week of development, and larger clusters (10 to 15 lymphocytes) appear from the 14th week onward. Relating these quantitative results to the 3 phases of early fetal islet organ development, it can be seen that lymphocyte numbers increase from the 10th to the 26th week of development. The significance of this is discussed in connection with the development of the immune system. In view of the contemplated transplantation of fetal pancreas tissue as treatment for IDDM, it means that a relatively low immunogenicity can be expected up to the 14th week of development. Thymic differentiation is not complete before the 17th week, and differentiation of the lymph nodes and spleen continues until weeks 20 to 23. Although IgG antibodies are transferred across the placental barrier already in about the 8th week, this flux does not reach its maximum until the 32nd week. Endogenous antibody synthesis in the fetus does not start until the 18th week. IDDM of the mother during fetal development (10th to 26th week) does not increase the lymphocyte number in the pancreas. This also applies to tissue that has been cultivated for 14 days after reaching the same stage of development.

Culture Techniques↗
PubMed1989

Augmentation of streptozotocin-induced hyperglycemia in mice by prior treatment with complete Freund's adjuvant.

The effect of complete Freund's adjuvant (CFA), in combination with streptozotocin (STZ), on pancreatic insulin content, plasma glucose, and pancreatic histopathology were studied in male Balb/c mice. One injection of CFA, followed 24 h later by a single dose of 100 mg/kg of STZ (group I), produced a 92% (p less than 0.01) reduction in pancreatic insulin, a 54% (p less than 0.01) increase in glucagon content, and severe hyperglycemia. The depletion of pancreatic insulin was associated with degranulation, necrosis of beta cells, and reduction of the apparent islet size. Focal pancreatitis, without apparent islet inflammation, occurred in all animals in this group. After treatment with STZ alone (group II), pancreatic insulin content decreased 73% (p less than 0.01), whereas plasma glucose levels, even though being in the hyperglycemic range, were significantly lower (p less than 0.02) than the mice in group I. Although pyknotic and hypertrophic cell nuclei could be observed in several islets of mice from group II, major histopathological changes, such as pancreatitis and extensive beta cell necrosis seen in group I, were absent. The results show that in the Balb/c mouse strain, a nonspecific insult by CFA prior to a cell-specific cytotoxic insult markedly enhanced destruction of beta cells and the development of hyperglycemia.

Animals↗
PubMed1989

Immunohistochemical investigations of beta-endorphin in human pancreatic islets.

The PAP technique was used to examine adult human pancreata (corpus) immunohistochemically for the presence of beta-endorphin containing cells. These cells were found to account for 4.8% of the islet cells. They are irregularly distributed within the islets, where they occur singly or in groups of 3 to 5 cells between the acini (0.4% of the parenchyma). Investigations designed to detect the simultaneous presence of beta-endorphin and somatostatin or glucagon revealed that beta-endorphin occurs in somatostatin cells (1.0% of the islet parenchyma). This is the 1st proof that these 2 hormones appear together. The simultaneous presence of beta-endorphin and glucagon in the same cell was also observed in 0.9% of the islet parenchyma. Earlier studies undertaken by us have shown that beta-endorphin is synthetized in the islets of Langerhans. Possible functions of beta-endorphin in the islets are discussed.

Aged↗
PubMed1989

Neuron-specific enolase (NSE) as a neuroendocrine cell marker in the human fetal pancreas.

Using the PAP technique, we investigated the presence of neuron-specific enolase in the human fetal pancreas of 10, 12, and 14 weeks of gestational age. Neuron-specific enolase is present in the islet cells in the 10th week. Positive cells are situated mainly in duct epithelium. The number of cells with a positive reaction increases from the 12th to the 14th week. In the 14th week, they are clustered either near the ducts or between the acini. The numbers and localizations of the cells correspond to those obtained in previous studies with 4 basic islet cell types in the same material. The present results are a further proof that islet cells are biologically active during early fetal development.

Biomarkers↗
PubMed1989

The course of neuroendocrine differentiation in prostatic carcinomas. An immunohistochemical study testing chromogranin A as an "endocrine marker".

To gain further insight into the pathogenetic aspects of neuroendocrine (NE) differentiation in prostatic carcinoma, the incidence of NE manifestations was studied during tumour progression in the course of the disease. This follow-up took the form of semiquantitative assessment of the NE cells in carcinomas by means of repeat biopsies at intervals of a few years, correlating the findings with those of conventional histopathological grading of the prostatic tumours. Immunoreactivity to chromogranin A (ChrA) and the Grimelius silver-staining technique were used to detect NE cells. A strong correlation was observed in all the 25 carcinomas studied between the results obtained with the Gimelius silver-staining and those obtained on the basis of immunoreactivity to ChrA. In addition, cells immunoreactive to an antiserum against ChrA found in virtually all sections from 24 cases of hyperplastic prostatic glands were found to be almost invariably argyrophil. Most of the 25 carcinomas underwent marked tumour progression, while the number of NE cells concomitantly increased. An unequivocal relationship can be stated between the degree of NE differentiation and tumour progression in our series of prostatic carcinomas treated with steroids-i.e., the more anaplastic the prostatic carcinoma, the more numerous are its NE cells. ChrA may be considered to be a sensitive marker for NE cells both in hyperplasia and in prostatic carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Pancreatic enzymes in serum and urine as indicators of pancreatic allograft rejection in the pig.

We have studied the reliability of serum and urinary immunoreactive anionic trypsin (irAT), immunoreactive cationic trypsin (irCT), and amylase activity as rejection indicators in a porcine whole-organ pancreaticoduodenal transplantation model with exocrine drainage to the urinary bladder. No immunosuppressive therapy was administered. Exocrine tissue integrity and function were studied by measuring these enzymes in serum and urine. Urine analyses were performed before and after an intravenous secretin-cholecystokinin stimulation. Of 16 transplanted pigs, 10 became diabetic during a 2-week observation period while six remained normoglycemic. Serum irAT was found to predict rejection while serum amylase and serum irCT did not. An increase in irAT was seen in rejecting pigs preceding the onset of hyperglycemia by a median of 2 days (range 1-9). Secretion of irAT into the urine remained high during the observation period in nondiabetic pigs while the output declined in diabetic pigs. This decline was seen after the increase in serum irAT. When urine was sampled after a secretin-CCK stimulation, these findings were clearly evident, but less unequivocal results were obtained without stimulation. IrAT measurements were superior to measurements of amylase, irCT, or bicarbonate. Thus rejection of a pancreatic allograft was first indicated by a temporary rise in serum immunoreactive anionic trypsin, probably due to the onset of tissue damage. Thereafter, stimulated urinary enzyme output levels gradually declined and finally, hyperglycemia developed.

Amylases↗
PubMed1989

Influence of prostanoids on gastrointestinal mucosal injury in experimental septic shock.

Capillary stasis and mucosal injury in the stomach and small intestine were studied in septic shocked pigs. Septicemia was induced by live E. coli i.v. in 28 animals. Additionally, five animals were infused with Ringer's solution and served as sham controls. The 28 E. coli-infused animals were pretreated with either a cyclooxygenase inhibitor--indomethacin, n = 6, a thromboxane (TxA2)-synthetase inhibitor--UK 38,485 alone, n = 6, or combined with a serotonin-antagonist--ketanserin, n = 9. Seven E. coli-infused animals were left untreated and served as septic controls. The sham controls were hemodynamically stable and had normal histological findings. All bacteria-infused animals exhibited signs of septic shock with pronounced hemodynamic reactions. Attenuation of the bacteria-induced increase in pulmonary arterial blood pressure was found in all pretreated animals but most pronounced in the indomethacin-pretreated group which also showed protection against gastric mucosal injury and capillary stasis. TxA2-inhibited animals had aggravated capillary stasis and mucosal injuries. It is concluded that gastric mucosal damage could be modified by drugs influencing the prostanoid system. The "cytoprotective" effect of prostaglandins seem to be of minor importance for the prevention of the gastro-intestinal mucosal injury seen in some series.

Animals↗
PubMed1989

Immunohistochemical, morphometric, and ultrastructural investigations of the early development of insulin, somatostatin, glucagon, and PP cells in foetal human pancreas.

Fresh autopsy specimens of pancreas, taken from 18 human foetuses at the 10th (n = 4), 12th (n = 7), and 14th (n = 7) weeks of gestation, were analyzed immunohistochemically for the presence of islet parenchymal cells, immunoreactive with antisera raised against insulin (B cells), somatostatin (D cells), glucagon (A cells), and pancreatic polypeptide (PP cells). All four islet cell types were found sporadically within or near the epithelium of the small excretory ducts at the 10th week of development. At the 12th week, their presence appeared to be no longer restricted to the duct epithelium, as some B cells were found also in small clusters outside the ducts. At the 14th week of development, the B cells formed large clusters in the neighborhood of the excretory ducts. It is at this stage that the first parenchymal cells with Grimelius argyrophilia could be found. They were supposed to represent A cells. The B cells were found to be the predominating type of islet cells (about 50%) at the 10th week of gestation. The relative volume density was about 25% for the D cells, about 15% for the A cells, and about 10% for the PP cells. At the 12th and 14th weeks of development, the relative numbers of B and PP cells decreased somewhat (to 36 and 6%, respectively), whereas those of the D and A cells were found to increase (to 30 and 27%, respectively). The relative volume density of the total islet parenchyma was about 2, 6, and 21% at the 10th, 12th, and 14th weeks of development, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryonic and Fetal Development↗
PubMed1988

Effects of a calcium antagonist (nifedipine) on cats in live E. coli bacteriemic shock.

The effects of a calcium antagonist, nifedipine, on cardiovascular reactions and on gastrointestinal mucosal integrity was studied in a standardized feline bacteriemic model. Nifedipine pretreatment delayed the development of cardiovascular derangement and reduced the severity of the intestinal but not the gastric mucosal injury. The effect on the intestinal mucosa could be due to the delayed development of hypotensive shock but also to a protective effect on the superficial mucosal cells.

Animals↗
PubMed1988

Identification of monoclonal antibodies to pancreatic islet cells by immunoperoxidase staining.

Immunoperoxidase staining and enzyme-linked immunosorbent assay (ELISA) were used to identify monoclonal antibodies that reacted with pancreatic islet cells. All monoclonal antibodies produced against isolated human or rat pancreatic islets including one mouse autoantibody reacted with pancreatic islets in formalin-fixed pancreas sections, but not with rat kidney or thyroid. Reactivity was also found with suspensions of normal rat islet cells and rat insulinoma cells using a 3-stage immunoperoxidase procedure and an ELISA technique. Differences were observed in staining intensity between the various antigenic substrates tested suggesting variable cross-reactivity and/or number of epitopes. The sensitivity of the immunoperoxidase technique proved to be favourable for identification of monoclonal antibodies that recognize cellular constituents such as islet cell antigens present in low concentrations.

Animals↗
PubMed1988

Production of pro-insulin, C-peptide, and insulin in nesidioblastosis, focal islet-cell adenomatosis, and genuine insulomas. A correlated radioimmunochemical, immunohistochemical, and ultrastructural investigation with particular regard to the occurrence of argyrophil and pro-insulin immunoreactive cells.

Subtotal pancreatectomy specimens from one case of nesidioblastosis, one case of focal adenomatosis, and two cases of insulin-producing islet-cell tumours were studied with special reference to their production of pro-insulin, C-peptide and insulin, and their contents of argyrophil parenchymal cells. Specific immunostaining revealed the presence of abundant cells reacting with pro-insulin, C-peptide, and insulin antiserum; at least the great majority of them were obviously non-argyrophil cells. The content of extractable immunoreactive insulin (IRI) was higher in the cases of nesidioblastosis and focal adenomatosis than in the two insulomas. Molar ratios of IRI to C-peptide immunoreactivity (CPR) varied between 7 and 100. Gel filtration analysis of the extracts revealed two peaks of CPR, corresponding to 3,000 and 10,000 daltons, respectively. Ultrastructurally, the insulin cells in cases of nesidioblastosis and focal adenomatosis contained numerous typical beta granules. In the islet-cell neoplasms some "polycrine" islet cells were also found, containing typical as well as atypical granules with electron dense or pale cores. Some cells even showed a mixture of apparent beta and alpha granules. Despite structural differences and variable contents of IRI and CPR, the predominance of cells reactive with antibodies to pro-insulin, C-peptide, and insulin, and the absence of argyrophil pro-insulin cells in adenomatosis and insulomas indicates that the hormonal products of these parenchymal cells are not any chemically modified insulin or any other member of the insulin family.

Adenoma↗
PubMed1988

[Immunocytochemical studies of the development of basal cell types of human islet organs].

The investigations are carried out in 19 human fetal pancreases. The detection of the 4 islet hormones insulin, glucagon, somatostatin and PP ist carried out in PAP-technique. The parts of these 4 types of islet cells are estimated quantitatively. In the 10th to 15th week of development insulin-producing B-cells are present. Moreover glucagon-, somatostatin- and PP-cells in the islet organ are present. In the group of 16th to 20th week of gestation insulin-, glucagon- and somatostatin-cells are increased compared to the first group. PP-cells are not altered. The increase of 3 types of islet cells is a result of fetal development.

Glucagon↗