PubMed Health⌕ Search

Biomedical subjects

T J Nevalainen

Publications and source records attributed to T J Nevalainen.

At least 127 records · Page 7Linked to original sources
PubMed1986

Fat necrosis in human acute pancreatitis. An immunohistological study.

Localization of phospholipase A2, lipase and colipase immunoreactivity were studied in paraffin embedded tissue sections. The samples were taken from the pancreas of 12 patients suffering from acute haemorrhagic necrotizing pancreatitis, and from diseased adipose tissue of 7 patients suffering from traumatic mammary fat necrosis. Peroxidase-antiperoxidase immunohistology revealed consistent positive reaction against phospholipase A2, lipase and colipase at the border of fat necrosis in pancreatic interlobular adipose tissue and in peripancreatic, mesenterial and retroperitoneal fat. The fat necroses of the breast were devoid of reaction. The results support the idea that in addition to lipase colipase and phospholipase A2 participate in the development of fat necrosis in acute pancreatitis. Pancreatic lipolytic enzymes are not present in the adipose tissue in mammary fat necrosis.

Adipose Tissue↗
PubMed1985

Ischaemic contracture in isolated rat heart: reversible or irreversible myocardial injury?

An isolated rat heart preparation was reperfused at 37 degrees C for 10 min after 10, 20, 30 and 40 min of ischaemia. The left ventricular tension was measured by means of a balloon catheter filled with water and connected to a pressure recorder. The left ventricular resting tension began to increase at 9 +/- 1 min (mean +/- SEM) and was maximally developed (myocardial contracture) at 18 +/- 1 min of ischaemia. There was a striking and constant exacerbation of the resting tension during reperfusion after 30 and 40 min (but not after 10 or 20 min) of ischaemia with simultaneous acceleration of creatine phosphokinase (CK) release into the coronary effluent and with the loss of the recovery of contractile activity. Myocardial adenosine triphosphate (ATP)-content decreased during 20 min of ischaemia more in the endocardial (ENDO) (from 17.7 +/- 1.9 mumol/g to 0.7 +/- 0.1 mumol/g) than in epicardial (EPI) (from 15.5 +/- 0.9 mumol/g to 3.2 +/- 0.6 mumol/g) parts of myocardium. Reperfusion after 10 min of ischaemia resulted in a slight increase of myocardial ATP-content both in EPI (from 7.5 +/- 0.6 to 10.4 +/- 0.8 mumol/g, p less than 0.05) and ENDO (from 5.0 +/- 0.8 to 8.9 +/- 2.5 mumol/g, n.s.). Reperfusion after the completion of contracture (after 20 min) had no effect on myocardial ATP-content. The results indicate that there is a transmural ATP gradient in ischaemic isolated rat heart and that myocardial ATP net production during reperfusion (10 min) is prevented after the development of ischaemic contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Immunoreactive phospholipase A2 in serum in acute pancreatitis and pancreatic cancer.

Immunoreactive phospholipase A2 (EC 3.1.1.4) was measured by a new sensitive time-resolved fluoroimmunoassay in the serum of 58 healthy subjects and 103 patients with acute pancreatitis. Patients with acute pancreatitis were grouped according to the etiology and clinical severity of the disease. The mean phospholipase A2 concentration in the reference (healthy) group was 5.5 (SD 1.9) micrograms/L. In acute pancreatitis the mean phospholipase A2 concentration was increased on the first day after hospital admission in all groups, and returned to normal somewhat more slowly than did serum amylase, especially in the patients with severe alcoholic pancreatitis. In this latter group the mean concentration of serum phospholipase A2 on the first day was 42.6 (SD 29.5) micrograms/L. In patients with pancreatic cancer, serum phospholipase A2 was 29.2 (SD 21.3) micrograms/L. The phospholipase A2 and amylase values were closely associated in all groups. The clinical sensitivities were 90.9% for severe alcoholic pancreatitis and 87.5% for pancreatic cancer. Immunochemical determination of phospholipase A2 in serum provides fast and specific detection of injury to pancreatic acinar cells. In addition to the early diagnosis of acute pancreatitis, follow-up determinations of phospholipase A2 seem to be useful in differentiating between mild and severe forms of pancreatitis.

Acute Disease↗
PubMed1984

Experimental pancreatitis in the rat. Ductal factors in sodium taurocholate-induced acute pancreatitis.

Spreading of injected material and ductal resistance were studied in the rat pancreas after intraductal injection of Indian ink, human serum or sodium taurocholate. Indian ink filled the main pancreatic duct and small ductules revealing the lobular structure in macroscopic preparation. Escape into the interstitium was observed both in the macroscopic preparations and in histologic sections. Human IgG was demonstrated immunohistochemically in single acinar cells and around acinar cells after intraductal injection of human serum. The changes were most pronounced at 15 min and at 6 h after the injection but were almost resolved at 24 h. The intraductal pressure was registered during sodium taurocholate infusion. The pancreatic duct ruptured at the pressure of 82 mm Hg in average. It was concluded that in the ductal model of experimental acute pancreatitis the infusion causes ruptures in pancreatic ducts and the infusate escapes into the interstitium where it remains for several hours.

Acute Disease↗
PubMed1984

Effect of verapamil on reperfusion damage and calcium paradox in isolated rat heart.

The effect of verapamil on ischaemic contracture, reperfusion injury after global ischaemia, and calcium paradox was studied in isolated rat heart. The development of ischaemic contracture was measured by a balloon catheter inserted into the left ventricle, filled with water, and connected to a pressure recorder. Myocardial perfusability was tested by infusing sodium fluorescein solution into the cannulated aortic root. Creatine kinase (CK) activity and protein leakage from myocardium into the effluent were measured during reperfusion (30 min) after ischaemia (50 min) and during calcium repletion (30 min) after calcium depletion (5 min). Ischaemic contracture developed later in the verapamil-treated group (31.7 +/- 0.7 min) than in the control group (23.6 +/- 2.2 min). There was less CK (29.16 +/- 3.26 U/g) and protein leakage (4.81 +/- 0.41 mg/g) in the verapamil-treated group than in the control group (38.81 +/- 3.30 U/g and 6.14 +/- 0.49 mg/g, respectively) during reperfusion. Verapamil had no effect on the myocardial perfusability or on the strength of the ischaemic contracture. Verapamil did not reduce the CK or protein leakage in calcium paradox. It was concluded that verapamil has some protective effect against cell injury on myocardium during post-ischaemic reperfusion but none in calcium paradox.

Animals↗
PubMed1984

Anaerobic glycolysis and the development of ischaemic contracture in isolated rat heart.

The relationship between myocardial ATP content and the increase in left ventricular resting tension during ischaemia (ischaemic contracture) was studied in isolated rat hearts perfused for 15 min either with aerobic buffer (pO2 greater than 500 mmHg) containing non-glycolytic substrate, acetate (5 mmol X litre-1), or with hypoxic buffer (pO2 less than 10 mmHg) with glucose (10 mmol X litre-1) before making them totally ischaemic for 10 min. ATP was determined spectrophotometrically from extracts of frozen whole hearts. Left ventricular tension was recorded by intraventricular balloon catheter. Myocardial ATP content was 15.4 +/- 1.0 mumol X g-1 dry weight (mumol X g-1) after 10 min stabilising period, 14.1 +/- 0.9 mumol X g-1 after 15 min aerobic perfusion (plus acetate) and 9.0 +/- 1.3 mumol X g-1 after 15 min hypoxic perfusion (plus glucose). During 10 min of ischaemia ATP decreased in aerobic hearts to 5.4 +/- 1.1 mumol X g-1 and to 7.9 +/- 1.0 mumol X g-1 in hypoxic hearts. The left ventricular resting tension increased during ischaemia in hypoxic hearts to 9 +/- 5% of control systolic pressure (0 = diastolic pressure, 100 = systolic pressure during stabilising period), whereas in aerobic hearts the tension began to increase immediately and was 84 +/- 22% of systolic pressure at the end of the ischaemic period. In parallel control experiments, hearts were also perfused either with glucose-containing aerobic buffer or acetate-containing hypoxic buffer. ATP was well preserved during aerobic perfusion (plus glucose) but decreased markedly during hypoxic perfusion (plus acetate). There was no increase in resting tension in the aerobic hearts (plus glucose) whereas the resting tension increased considerably during hypoxic perfusion (plus acetate). The results indicate that the initiation of ischaemic contracture occurs at much higher myocardial ATP level when ATP comes from mitochondrial sources than when ATP is generated by anaerobic glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1984

Presence of a phospholipase A2 inhibitor in porcine serum.

Porcine pancreatic phospholipase A2 (PLA2) was immobilized to Sepharose 4B and porcine serum was passed through this affinity column. Bound substances were eluted by an EDTA-containing buffer and fractionated in a Sepharose 6B column. A single protein peak of the eluate from the latter column was found to inhibit PLA2 activity in a dose-dependent manner in an assay system using radioactive lecithin as a substrate and porcine pancreatic PLA2 as the enzyme source. The serum fraction containing the PLA2 inhibitory protein(s) (PIP) appeared inhomogeneous on SDS-polyacrylamide gel electrophoresis with two major bands close to each other, corresponding to a molecular weight of approximately 60,000. It was concluded that PIP might act as a protective principle against autodigestion in acute pancreatitis and other inflammatory diseases as well as playing a regulatory role in prostaglandin metabolism.

Animals↗
PubMed1983

Experimental pancreatitis in the rat. Changes in pulmonary phospholipids during sodium taurocholate-induced acute pancreatitis.

Acute haemorrhagic pancreatitis was induced in rats by injecting aqueous solution of sodium taurocholate into the common biliopancreatic duct. Lecithin and lysolecithin were separated from pulmonary homogenate by thin layer chromatography and quantified by phosphorus determination. The ratio of lysolecithin to lecithin increased after the sodium taurocholate injection as well as after i.v. administration of porcine pancreatic phospholipase A2. It was concluded that phospholipase A2, released from pancreatic acinar cells into blood, may convert pulmonary lecithin into lysolecithin during acute pancreatitis. Destruction of pulmonary surfactant may contribute to the development of the adult respiratory distress syndrome as seen in patients suffering from severe acute pancreatitis.

Acute Disease↗
PubMed1983

Immunohistochemical localization of phospholipase A2 in human pancreas in acute and chronic pancreatitis.

Phospholipase A2 was localized with peroxidase anti-peroxidase (PAP)-technique in pancreatic tissue resected from normal portions of tumor-bearing glands of 4 patients and from pancreases of 16 patients suffering from either acute or chronic pancreatitis. In acute pancreatitis the enzyme immunoreactivity was detected in the apical zymogen granule portion of acinar cells and in ductal secretory material similarly as in normal tissue. At the border of necrotic and non-necrotic exocrine parenchyma the staining reaction was evenly dispersed throughout the cytoplasm or localized in small cell fragments. There was no reaction in necrotic acinar cell remnants. Some dilated acinar lumina contained intensively stained plugs. Fat necroses were stained but surrounding neutrophil leukocytes were unstained. Thrombosed small vessels were also unstained. In chronic pancreatitis, diminished staining characterized small acinar cells at the border of lobules. Some macrophages stained positively. It was concluded that during acute inflammation in pancreas, localization of phospholipase A2 in pancreatic tissue is abnormal, and that phospholipases A2 of neutrophil leukocytes and platelets are not crossreactive with the secretory enzyme.

Acute Disease↗
PubMed1983

Experimental pancreatitis in the rat. Development of pancreatic necrosis, ischemia and edema after intraductal sodium taurocholate injection.

Acute hemorrhagic pancreatitis was induced in rats by injecting sodium taurocholate into the common biliopancreatic duct. The extent of pancreatic necrosis was quantified in histological sections during the course of the disease. The proportion of necrotic acini was low, although the amount of necrosis increased from 3.3% of pancreatic parenchyma at 15 min to 10.5% at 12 h. The degree of ischemia in the inflamed pancreas was estimated by extracting intravenously injected toluidine blue from the gland. The amount of the dye in the gland decreased progressively during 12 h to 58.8% of the amount in normal pancreas. The development of pancreatic edema was studied by recording the water content of the gland. The edema was maximal at 3 h and resolved partly in 12 h after the induction of the disease. Necrosis and ischemia become progressively more pronounced in the edematous pancreas during sodium taurocholate-induced acute hemorrhagic pancreatitis. This kind of pathophysiologic course is also thought to characterize human pancreatitis. The present simple model of acute hemorrhagic pancreatitis in the rat is suitable for quantitative observations on the development of pancreatic damage under various experimental conditions.

Animals↗
PubMed1983

Immunohistochemical localization of trypsinogen and trypsin in acute and chronic pancreatitis.

Immunoreactive trypsin was localized with the peroxidase-antiperoxidase technique in normal human pancreatic tissue and in the glands of patients suffering from acute or chronic pancreatitis. In the normal pancreas and in the histologically normal areas of the inflamed pancreas, trypsin was detected in the zymogen granules of acinar cells and in ductal secretory material. During acute pancreatitis, three characteristic changes were observed: (1) separate acinar cell fragments in early lesions; (2) decreased and evenly dispersed staining in necrotic acinar cells, and (3) intensive reaction in plugs in acinar lumina in advanced lesions. In chronic pancreatitis, the localization of trypsin in acinar cells was similar to that in normal pancreas. Some proteinaceous plugs in dilated pancreatic ducts were weakly immunoreactive. The results show that the tissue distribution of immunoreactive trypsin is altered in acute pancreatitis.

Acute Disease↗
PubMed1983

Time-resolved fluoroimmunoassay of human pancreatic phospholipase A2.

We describe an immunofluorometric assay for human pancreatic phospholipase A2 based on time-resolved fluorescence. The labeled antibody technique in combination with the time-resolved 1-s fluorometric detection of the europium label, which essentially eliminates all background fluorescence, resulted in a high sensitivity (20 ng/L) and a wide (5000-fold) linear range. Nonspecific binding was minimized by treating the solid-phase antibody with NaSCN before coating, to remove endogenous antigen, and by immunosorbent purification of the antibody before labeling with europium. This is a one-incubation, multi-site, solid-phase assay on polystyrene microtiter strips, even though a polyclonal antibody was used. As measured by this assay, activity of immunoreactive phospholipase A2 was found to be above normal in sera of patients suffering from acute pancreatitis.

Adult↗
PubMed1983

Purification and characterization of human pancreatic phospholipase A2.

We purified human pancreatic phospholipase A2 from postmortem pancreatic tissue by elution of the semi-purified enzyme on CM-Sephadex C-25 with a linear NaCl gradient at pH 6.0. The enzyme appeared as a single polypeptide chain with an isoelectric point of 9.2 +/- 0.1. The relative molecular mass of the enzyme was estimated to be 15 800 +/- 1000 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme is resistant to heating and to a 25 g/L concentration of sodium dodecyl sulfate. It is inhibited by Ca2+ ions in the presence of ovolecithin and deoxycholate. By immunohistochemical methods we showed the enzyme to be localized in the apical zymogen granule portion of pancreatic acinar cells.

Cadaver↗
PubMed1982

Experimental pancreatitis in the rat. Light and electron microscopical observations on early pancreatic lesions induced by intraductal injection of trypsin, phospholipase A2, lysolecithin and non-ionic detergent.

Trypsin, phospholipase A2, lysolecithin or non-ionic detergent polyoxyethylene p-t-octyl phenol solutions were injected into the rat biliopancreatic duct. Histological and ultrastructural changes in the gland were studied 15 min and 3 h after the injections. The rough surfaced endoplasmic reticulum disintegrated in two ways: (1) the endoplasmic reticulum in the cell periphery was vesiculated but ribosomes were well preserved at 15 min, and (2) large, round membranous structures appeared in apical cytoplasm at 3 h. Zymogen granules disintegrated in the second type, which possibly represents autodigestion. Both types of injury lead ultimately to structureless necrosis. Lesions induced by phospholipase A2 and lysolecithin were identical. Trypsin-induced damage developed slowly and the two phases of endoplasmic reticulum disintegration were not sharply separable. Lesions caused by polyoxyethylene p-t-octyl phenol were variable at 15 min, but at 3 h the type 2 injury described above was observed. It was concluded that although the initial damage in pancreatic acinar cells may vary, necrotic changes are similar despite the injected material at the later time interval. During acute pancreatitis, the acinar cell necrosis is most probably due to the action of lysolecithin produced by the activation of phospholipase A2.

Animals↗
PubMed1982

Human acute pancreatitis: a light and electron microscopic study.

The histology and ultrastructure of resected pancreas from seven patients suffering from acute haemorrhagic pancreatitis were studied. Special attention was paid to necrotic acini and zymogen granules. Acinar cells in the border of necrotic and non-necrotic parenchyma contained lipid droplets, autophagic vacuoles, bundles of intermediate filaments and degenerated cell organelles, including zymogen granules, PAS-positive material derived from secretory proteins was situated in dilated acinar lumina and in the interstitium, and proved to be fibrillar in fine structure. There were thrombosed vessels and extravasated erythrocytes at the border of the parenchymal necrosis. Bundles of intermediate filaments were often the only identifiable structures in the severely necrotic acinar cells. The amount of lipid was decreased in damaged fat cells. Older fat necroses were surrounded by myofibroblasts. It was concluded that acinar and fat cells undergo concomitant necrosis in the inflamed pancreas, zymogen granules degenerate in the acinar cells at the border of necrotic and non-necrotic areas, and secretory proteins may be displaced in the interstitium outside acinar lumina. Myofibroblasts participate in the healing of autodigestive injuries.

Adipose Tissue↗
PubMed1981

Effect of hypoxia on the microvascular function in isolated rat hearts.

The effect of hypoxia on the microvascular function in continuously perfused isolated rat hearts was studied. The development of hypoxic contracture was determined by measuring the left ventricular pressure or the decrease of the left ventricular volume. The myocardial perfusability was tested by infusing 0.1 percent sodium fluorescein in isotonic saline into the cannulated aortic root at 0, 15, 30, 60 and 90 minutes of hypoxic glucose-free buffer perfusion. The percentage perfused with the fluorescent tracer in horizontal frozen myocardial sections was estimated by point counting from colour photographs taken under ultraviolet light. The coronary flow was estimated by measuring the flow of the perfusate through the vasculature under constant perfusion pressure. The hypoxic contracture was completed in 25 minutes in which time the coronary flow decreased gradually by 50 percent and thereafter the flow remained constant. The myocardium was fully perfused in controls and at 0 minutes of hypoxic glucose-free perfusion. There was an abrupt decrease in the perfusability between 15 and 30 minutes from 99 percent to 58 percent, respectively. At 60 and 90 minutes 65 percent of the myocardium were still perfused. It was concluded that the myocardial perfusability decreases when the left ventricular contracture develops during hypoxic perfusion.

Animals↗
PubMed1980

Ischaemic contracture and myocardial perfusion in isolated rat heart.

The development of left ventricular contracture and myocardial perfusion defect was studied in isolated rat hearts during global ischaemia of 90 min duration. The left ventricular pressure was measured by a balloon catheter inserted into the ventricle and filled with water. The pressure reached the maximum at 16 min of ischaemia. The left ventricular volume and compliance (passive distensibility) were measured by the same balloon, the former by connecting the balloon to an open catheter and the latter by applying a constant additional volume (0.020 ml) into the balloon. the left ventricular volume and compliance both decreased progressively for 20 min of ischaemia after which they remained low for the rest of the observation period (90 min). The myocardial perfusability was tested by infusing 0.1 per cent sodium fluorescein in isotonic saline into the cannulated aortic root of the isolated heart preparation. The percentage perfused with the fluorescent tracer in horizontal frozen myocardial sections was estimated by point counting from colour photogragraphs taken under ultraviolet light. The proportion of the perfused area decreased gradually from 100% at 0 min of ischaemia to 93, 67, 43 and 37% at 15, 30, 60 and 90 min of ischaemia, respectively. It was concluded that ischaemic contracture of the left ventricle is followed by the development of a myocardial perfusion defect in isolated ischaemic rat heart.

Animals↗