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T J Nevalainen

Publications and source records attributed to T J Nevalainen.

At least 109 records · Page 6Linked to original sources
PubMed1990

Pancreatic acinar cell necrosis with intact storage of digestive enzymes in selenomethionine treated rats.

Morphological and biochemical changes were observed in the pancreas and serum of rats after the intraperitoneal administration of selenomethionine, sodium selenite and methionine. Selenomethionine caused rapidly developing acinar cell necrosis. The first pathological changes were mitochondrial swelling and flocculent densities, and dilatation of cisternae of the endoplasmic reticulum. Zymogen granules appeared disrupted only in disintegrated acinar cells. Signs of autodigestive pancreatic inflammation with fat necrosis, elevation of pancreatic phospholipase A2 and serum amylase activities, as well as pulmonary oedema were present. Sodium selenite caused similar histologic changes to those produced by selenomethionine, but no changes were seen after methionine administration. Destruction of pancreatic acinar cells by an intraductal oleic acid injection that resulted in exocrine atrophy did not prevent systemic selenomethionine toxicity. Our results show that selenomethionine causes pancreatic acinar cell necrosis and that intracellular transport and storage of digestive enzymes is not primarily altered by this chemical.

Animals↗
PubMed1990

[Possible involvement of phospholipase A2 in the pathogenesis of schizophrenia].

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. PLA2 is enriched in neuronal membranes and plays an essential role in the functioning of membrane structures in the brain. Because a disordered phospholipid metabolism has been postulated in schizophrenia we started in 1985 a series of exploratory studies in an attempt to clarify the role of PLA2 in schizophrenic disorders. Our results can presently be summed up as follows: 1. Drug-free schizophrenics showed significantly higher PLA2 activity in serum and in plasma as compared with healthy controls as well as with nonschizophrenic psychiatric patients; the latter did not differ from the control group with regard to PLA2 activity. These findings suggest that increased PLA2 activity might be specific for schizophrenia. 2. The possibility that increased PLA2 activity is an artifact due to prior neuroleptic treatment could be ruled out as improbable by the findings that a) neuroleptic treatment significantly reduced PLA2 activity, and b) increased PLA2 activity was also found in first-onset, never-treated schizophrenic patients. 3. Increased PLA2 activity in schizophrenic patients was not caused by the entry of pancreatic enzyme into circulation. Our findings in serum rather suggest that the increment reflects increased intracellular enzyme activity. We speculate that our results might reflect an increment of the intraneuronal PLA2 activity in the brain. The activation of PLA2 in the brain was found to result in changes in neuronal function due to alterations in receptor sensitivity as well as in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathology of schizophrenia should be investigated in further experiments.

Adult↗
PubMed1990

DNA ploidy in pancreatic neuroendocrine tumors.

The nuclear DNA content of 17 pancreatic neuroendocrine tumors was measured from paraffin-embedded tissue with flow cytometry. The tumors were classified by immunostaining with antisera for synaptophysin, insulin, gastrin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal polypeptide. Eight (47%) of the 17 tumors were aneuploid, and two (12%) were multiploid (had two aneuploid stemlines of cells). Seven of the eight insulinomas, one of the four gastrinomas, and two of the four nonspecified neuroendocrine tumors had an abnormal nuclear DNA content. The DNA indices of the aneuploid and multiploid cases ranged from 1.13 to 1.93, and three cases had a DNA index greater than 1.50. During the follow-up for up to 16 years (mean, 7 years), one patient with diploid nonspecified tumor died of the disease, another patient with a multiploid gastrinoma had metastatic disease develop, and a third patient with a multiploid nonspecified tumor was alive with the disease. The authors conclude that many neuroendocrine tumors of the pancreas have an abnormal nuclear DNA content as measured by DNA flow cytometry. DNA multiploid pancreatic neuroendocrine tumors may be associated with a less favorable clinical course, but this needs to be confirmed in additional studies.

Adult↗
PubMed1990

Serum phospholipase A2 in patients with multiple injuries.

Catalytic phospholipase A2 activity (CA-PLA2) and the concentration of immunoreactive pancreatic PLA2 (IR-PLA2) were measured in serum samples from 12 patients with multiple injuries (median Injury Severity Score: 41). CA-PLA2 was increased in all patients and positive correlations were found between the extent of the increase of CA-PLA2, mortality, and impairment of pulmonary function. IR-PLA2 values were slightly increased in the serum of nine patients with multiple injuries. Of these nine patients, eight had an additional blunt abdominal trauma. On the other hand, no relationship was found between IR-PLA2 and CA-PLA2 values. This finding was confirmed by immunoadsorption experiments with an antiserum to human pancreatic PLA2, which demonstrated that the increased serum levels of IR-PLA2 were not responsible for the increased CA-PLA2 values. The results suggest the existence of at least two immunologically different phospholipase A2 enzymes in sera of patients with multiple injuries.

Adolescent↗
PubMed1990

Mumps, enteroviruses, and human acute pancreatitis.

The presence of mumps virus and enterovirus RNA was studied by in situ hybridization in 15 surgical biopsy specimens from patients with acute pancreatitis. 35S-Labeled cRNA probes, detecting the 5' end of the poliovirus type 3, a 1.1-kb fragment of the polymerase gene region of coxsackievirus B3, and mumps virus mRNA, encoding the nucleocapsid protein, were used. The controls consisted of mumps virus-infected and uninfected cultured cells, normal human and mouse pancreatic tissue, and mouse tissue from experimental coxsackievirus B3-induced pancreatitis. No specific hybridization signal was observed in any of the acute pancreatitis cases. It is concluded that neither mumps virus nor enteroviruses tested were present in pancreatic tissue of advanced human acute pancreatitis.

Acute Disease↗
PubMed1989

Time-resolved fluoroimmunoassay of pancreatic phospholipase A2.

We have developed an immunoassay for human pancreatic secretory phospholipase A2 based on time-resolved fluorescence. The labeled antibody technique in combination with the time-resolved fluorometric detection of the Europium label, which essentially eliminates all background fluorescence, resulted in a high sensitivity and a wide linear range. Our assay is a one-incubation, multi-site, solid-phase assay on polystyrene microtiter strips, even though a polyclonal antibody was used. Increased levels of immunoreactive phospholipase A2 are found by this assay in sera of patients suffering from acute pancreatitis.

Acute Disease↗
PubMed1989

The role of phospholipase A2 in human acute pancreatitis.

Several studies suggest that the activation of pancreatic phospholipase A2 (PLA2) and its release from injured acinar cells play an important role in the pathogenesis of acute pancreatitis. Elevated catalytic activity of PLA2 in serum is associated especially with severe forms of the disease. PLA2 has been purified from human cadaver pancreas and an antiserum raised against the enzyme in rabbits. Immuno-histochemical localization of PLA2 in pancreatic tissue was abnormal in acute pancreatitis. A time-resolved fluoroimmunoassay for human pancreatic PLA2 has been developed. Increased serum concentrations of immunoreactive PLA2 were found in acute pancreatitis during the first week after hospital admission. The values returned to normal somewhat more slowly than corresponding serum amylase values. The immunochemical determination of PLA2 in serum provides a fast and specific detection of injury to pancreatic acinar cells. The pancreas is not the only source of PLA2 in acute pancreatitis. The nonpancreatic PLA2 may originate from various inflammatory cells, but this hypothesis remains to be proven.

Acute Disease↗
PubMed1989

Carboxyl ester lipase in human tissues and in acute pancreatitis.

Carboxyl ester lipase was purified from human pancreatic juice. Antisera were raised in rabbits and the monospecificity of the antibody was verified by immunoblotting. The enzyme was present in zymogen granules of acinar cells, in occasional duct cells, and in secretory material in normal pancreas in immunohistochemistry. Also, occasional cells in the epithelium of small intestinal villi but not the granules of Paneth cells, were stained. Decreased and evenly dispersed staining was observed in necrotic acinar cells in acute pancreatitis, whereas the reaction was intensive in plugs in acinar lumina. Interstitial staining was seen around necrotic pancreatic lobules and in areas of fat necrosis. This staining pattern is similar to that obtained with antisera against other lipolytic pancreatic proteins, but differed from that with antisera against trypsin and pancreatic secretory trypsin inhibitor. We conclude that carboxyl ester lipase behaves similarly to the other lipolytic enzymes during acute pancreatitis and that interstitial localization of secretory lipolytic enzymes is characteristic of the necrotizing inflammatory process in pancreas.

Acute Disease↗
PubMed1989

Role of phospholipase A2 in human acute pancreatitis.

In a prospective clinical trial, 85 patients with acute pancreatitis, including 50 with acute interstitial-edematous pancreatitis and 35 with necrotizing pancreatitis, were recruited. Serum pancreatic immunoreactive phospholipase A2 (IR-PLA2), serum phospholipase A catalytic activity (CA-PLA), and serum phospholipase A2 catalytic activity (CA-PLA2) were determined daily between day 1 and day 10 after the onset of the disease. The serum course of IR-PLA2 values for patients with acute interstitial-edematous pancreatitis was comparable to that for patients with necrotizing pancreatitis. In contrast, the determination of CA-PLA and of CA-PLA2 specific activity in the serum revealed a high differentiation between patients with interstitial edematous and those with necrotizing pancreatitis. The overall accuracy for differentiating patients with necrotizing pancreatitis from those with the interstitial-edematous type was 79% for CA-PLA and 77% for CA-PLA2 (cut-off level: CA-PLA, 15 U/L, day 1-5; CA-PLA2, 3.5 U/L, day 1-5). Patients with pancreatitis-associated pulmonary complications showed significantly higher CA-PLA and CA-PLA2 values in the serum. This study demonstrates the role of serum catalytic phospholipase A2 in human acute pancreatitis where the development of pancreatic necrosis and pulmonary failure is concerned.

Acute Disease↗
PubMed1989

Effects of chronic alcohol intake and secretory stimulation on sodium taurocholate-induced pancreatic necrosis in the rat.

The effects of long-term alcohol intake and pancreatic secretory stimulation on pancreatic necrosis were studied in rats with acute pancreatitis induced by an intraductal injection of sodium taurocholate. Neither alcohol nor pancreozymin alone influenced the extent of pancreatic tissue damage in this experimental model. However, when animals were exposed to both alcohol and pancreozymin, the tissue lesions induced by the bile salt were wider than those in the presence of either alcohol or secretory stimulation alone. The results indicate that secretory stimulation with pancreozymin superimposed on chronic alcohol intake sensitizes the pancreas to the injury caused by intraductal bile salt administration.

Acute Disease↗
PubMed1989

Decrease in the number of muscarinic receptors in rat pancreas after chronic alcohol intake.

The effect of eight months of alcohol intake on the number and affinity of muscarinic receptor sites in the rat pancreatic tissue were measured by using N-3H-methylscopolamine (NMS) as a radioligand. There were no differences in the receptor affinities for NMS between the alcohol-exposed and age-matched control animals, but the number of muscarinic receptor sites was 60 percent lower in the alcoholic animals. The present experimental model is consistent with altered food and water intake as consequences of chronic alcoholism and thus changes in food and water consumption may participate in mediating the effects of chronic alcohol intake on NMS binding sites. We suggest that the previously reported marked alcohol-induced increase in pancreatic acetylcholine levels, which has been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis, may be a secondary phenomenon induced by increased resistance at the muscarinic receptor level.

Animals↗
PubMed1989

The role of phospholipase A2 in acute pancreatitis.

Several studies suggest that phospholipase A2 (PLA2) plays an important role in the pathology of acute pancreatitis. PLA2 is activated within the pancreas in experimental and human acute pancreatitis. Elevated catalytic activity of PLA2 in serum is associated especially with the severe forms of the disease. The pancreas seems not to be the only source of the enzyme entering the circulation in acute pancreatitis. The source of the non-pancreatic PLA2 may be various inflammatory cells, but this hypothesis remains to be proven. The results of the treatment of experimental acute pancreatitis with PLA2 inhibitors have been promising, but adequate human trials have not been conducted.

Acute Disease↗
PubMed1988

Changes in zymogen granule membrane and pancreatic juice after supramaximal stimulation with caerulein in the rat.

Pancreatic exocrine secretion was stimulated supramaximally with an intravenous infusion of 10 micrograms/kg of body weight of caerulein for 10 min in four rats. Two animals were killed immediately, and two animals 120 min after the cessation of the caerulein infusion. In specimens fixed immediately after the caerulein infusion, there were irregular electron lucent structures that resembled zymogen granules and were associated with bristle-coated membranes, coated pits and coated vesicles. Two hours after the caerulein infusion there were large vacuoles that contained amorphous or membranous material and cell organelles in acinar cells. The HPLC-analysis of pancreatic juice revealed two new peaks after caerulein injection. It was concluded that supramaximal caerulein stimulation prevents normal maturation and discharge of zymogen granules leading to altered membrane recycling of secretory granules in acinar cells and to the appearance of abnormal secretory products in pancreatic juice. The novel ultrastructural findings of this study, the bristle-coated membranes and the coated pits in the membrane of dilated zymogen granules, may be related to the exceedingly high dose of caerulein administered.

Animals↗
PubMed1988

Pancreatic digestive enzymes and ultrastructure after chronic alcohol intake in the rat.

The effects of chronic ethanol intake on the digestive enzyme content of rat pancreas, pancreatic juice and serum were studied by means of reversed-phase high performance liquid chromatography (HPLC), gel electrophoresis, isoelectric focusing and traditional enzymatic methods. The biochemical changes were further correlated to ultrastructural lesions caused by chronic alcohol consumption. 55 animals were given ethanol in their drinking water as 15% (w/v) solution up to 16 months. 49 control animals received water. The protein composition of the pancreatic juice was qualitatively similar in the alcoholic and control animals. Alcohol had a biphasic effect on pancreatic enzyme secretion. The protein and especially the trypsinogen concentrations of the pancreatic juice were increased after 8 months alcohol intake and diminished after 16 months. The changes in the acinar cell ultrastructure were marked only during the 2nd year of alcohol consumption. The amylase, lipase and especially the trypsinogen concentrations of pancreatic tissue were increased in the alcoholic animals. The results suggest that chronic ethanol consumption profoundly interferes with the pancreatic protein metabolism, especially that of trypsinogen and that the decrease in the enzyme secretion after 16 months alcohol intake may be due to acinar cell injury.

Amylases↗
PubMed1988

The intestinal and diffuse types of gastric carcinoma in Maori and non-Maori patients in Auckland.

Histologic specimens of gastric carcinoma from 128 Maori, Pacific Island Polynesian, and European patients in Auckland, New Zealand, were classified into intestinal or diffuse type. The ratio of intestinal to diffuse type (ID) was lowest (0.3) in the female Maori patients and highest (1.4) in the male Maori. The higher ID ratio reflects the increased risk of gastric carcinoma in the Maori men as compared with the other groups studied.

Adult↗
PubMed1988

Immunoreactive pancreatic phospholipase A2 and catalytically active phospholipases A2 in serum from patients with acute pancreatitis.

Measuring the content of immunoreactive pancreatic phospholipase A2 (PLA2; EC 3.1.1.4) and the catalytic activity of PLA2 in serum samples from five patients with acute pancreatitis, we found no correlation between these two measurements overall. To test the specificity of the method for catalytic PLA2, we measured PLA2 activity in serum samples before and after immunoadsorption with an antiserum to human pancreatic PLA2. The results suggest the presence of at least two immunologically distinct PLA2 enzyme proteins in sera from these patients. One of the enzymes is pancreatic in origin and may exist in active, inactive, or inhibited form. The activity profile of the second PLA2 enzyme in serum during acute pancreatitis differs from that for other common pancreatic enzymes. In the present experiment, the catalytic activity was not removed by treatment with the anti-human pancreatic PLA2 antiserum. The source of this second PLA2 activity is unknown. Some samples contained increased activities of both PLA2 forms.

Acute Disease↗
PubMed1986

Effects of ischaemia on vasculature.

The effects of ischaemia on the structure and function of coronary vessels have been evaluated most thoroughly in the open-chest anaesthetised dog. In the beating heart the flow into the capillary bed is controlled by precapillary sphincters in the terminal arterioles. Short periods (up to 20 min) of ischaemia result during reperfusion in vasodilatation which is mediated through increased tissue adenosine levels. Longer periods of ischaemia (60 or more min) result in degenerative vascular changes and no-reflow during reperfusion. Endothelial cells swell, lose their pinocytotic vesicles and form spherical cytoplasmic protrusions into the capillary lumina. Prolonged ischaemia (over 3 hours) causes ruptures in microvascular walls. Such vessels become permeable to large tracers, e.g. carbon particles, and reperfusion results in haemorrhage. Capillaries in ischaemic myocardium are collapsed by compression resulting from intra- and extracellular oedema and contracture of myocytes. Erythrocytes plug collapsed microvessels. However, in vitro observations have shown that no-reflow may result from ischaemia even without erythrocyte plugging. Capillary compression is the main determinant of no-reflow after ischaemia. Degenerative ischaemic changes in vascular walls further contribute to vascular incompetence in vivo.

Animals↗