Biomedical subjects

T J Nevalainen

Publications and source records attributed to T J Nevalainen.

At least 73 records · Page 4Linked to original sources

PubMed1995

Phospholipase A2 in sodium taurocholate-induced experimental hemorrhagic pancreatitis in the rat.

We investigated the concentration of immunoreactive pancreatic phospholipase A2 (pan-PLA2) and the catalytic activity of phospholipase A2 (CA-PLA2) in plasma, peritoneal fluid, and pancreas of rats in which acute hemorrhagic pancreatitis was induced by an intraductal injection of sodium taurocholate. The contribution of pancreas to the CA-PLA2 in plasma was studied by removing pancreatic PLA2 by absorbing plasma samples with a polyclonal antibody raised in a rabbit against rat pancreatic PLA2. Sodium taurocholate injected into the pancreatic duct produced hemorrhagic pancreatitis with necrosis and inflammatory cell invasion within 8 hr. Saline injection caused edematous pancreatitis, but sham operation did not alter pancreatic morphology from normal. The concentration of pan-PLA2 increased rapidly in plasma in all animals, but significantly more in sodium taurocholate-injected animals than in saline-injected or sham-operated animals. The level of CA-PLA2 in plasma increased in sodium taurocholate-injected animals only. There was no correlation between pan-PLA2 and CA-PLA2 values in plasma in sodium taurocholate-injected animals. The CA-PLA2 was marginally increased in pancreatic tissue of sodium taurocholate-injected animals compared to that of saline-injected and sham-operated animals at 8 hr. Treatment by the anti-pan-PLA2 antibody effectively removed pan-PLA2 from plasma and peritoneal fluid samples in sodium taurocholate-injected animals. The level of CA-PLA2 in plasma was similar before and after antibody treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Phospholipase A2 content of aqueous humour in cataract patients.

In order to determine the content of group II phospholipase A2 in the aqueous humour we studied 41 cataract patients including 8 men and 33 women with age ranging between 65 and 92 (mean +/- SD being 77.0 +/- 6.7) years. In all patients preoperative biomicroscopy showed neither aqueous flare nor cells. Eleven patients (26.8%) had pseudoexfoliation syndrome. Aqueous humour tap was done at the beginning of cataract surgery before perforating the corneoscleral wound. We used time-resolved fluoroimmunoassay for the detection of group II phospholipase A2 in the aqueous humour. The group II phospholipase A2 content in the aqueous humor varied between less than measurable (in 23 patients) and 3.3 ng/ml, with an interquartile range from less than measurable to 1.4 ng/ml. There was no significant difference in the group II phospholipase A2 content of the aqueous humour whether or not the patient had pseudoexfoliation syndrome. The results show that the aqueous humour of cataract patients contains only minute amounts of group II phospholipase A2.

Aged↗

PubMed1995

Acinar cell carcinoma of the pancreas. Report of three cases.

Pancreatic acinar cell carcinoma is a rare neoplasm (comprising about 1% of pancreatic tumours). We studied three cases (61-year-old female; 42-year-old male; 57-year-old male), whose survival after diagnosis ranged from 1 year 2 months to 6 years 8 months. There were widespread metastases in each case. The tumours had acinar, trabecular and solid growth patterns. By immunohistochemistry, pancreatic acinar cell markers including carboxyl ester lipase, pancreatic secretory trypsin inhibitor and pancreatic phospholipase A2 (group I PLA2) gave a strong positive reaction in all three cases. By electron microscopy, zymogen granules were seen in the cytoplasm of the tumour cells. Immunostaining for prostate-specific antigen was positive in all three cases. Above-normal concentrations of pancreatic PLA2 were measured in the serum of one patient and the values decreased during chemotherapy concomitantly with the reduction in the size of the tumour mass. In conclusion, immunohistochemical demonstration of the secretory products of acinar cells including the new marker pancreatic PLA2 is useful in the differential diagnosis of pancreatic acinar cell carcinoma. Determination of the concentration of pancreatic group I PLA2 in serum may be helpful in the evaluation of therapy.

Adult↗

PubMed1995

Serum phospholipases A2 after aortobifemoral reconstruction.

Phospholipase A2 has been implicated in the pathogenesis of local and distant tissue injury after ischaemia and reperfusion. A common operation inducing ischaemia and reperfusion is aortobifemoral reconstruction, during which the aorta is clamped and the blood supply via the inferior mesenteric artery and iliac arteries is interrupted. The purpose of the present work was to study the catalytic activity concentration of phospholipase A2 and the mass concentrations of group I and group II phospholipases A2 in the sera of patients undergoing aortobifemoral reconstruction. Both the catalytic activity concentration of phospholipase A2 and the mass concentrations of group I and group II phospholipases A2 increased in serum samples after the operation. The catalytic activity concentration of phospholipase A2 correlated well with group II phospholipase A2 mass values (r = 0.81, p < 0.001), whereas no correlation was found between the catalytic activity concentration of phospholipase A2 and group I phospholipase A2 mass values (r = 0.12, p = 0.54). The results emphasize the role of group II phospholipase A2 in tissue injury after ischaemia and reperfusion.

Aged↗

PubMed1995

Expression of group II phospholipase A2 in the human gastrointestinal tract.

BACKGROUND: It has been suggested that group II phospholipase A2 (PLA2-II) plays an essential role in inflammation, but the cellular source(s) of the enzyme is (are) largely unknown. EXPERIMENTAL DESIGN: Expression of PLA2-II was analyzed in human gastrointestinal tract at both protein and mRNA levels. Both normal tissues and specimen from patients with a few different common gastrointestinal disorders were analyzed. RESULTS: Expression of PLA2-II mRNA was seen in the Paneth cells but not in any other cell type of the intestinal tract. Blood vessel walls showed PLA2-II immunoreactivity but were negative in in situ hybridization for PLA2-II mRNA. CONCLUSIONS: It was concluded that nonpancreatic group II PLA2 is synthesized and stored by Paneth cells, whereas other cell types of the gastrointestinal tract seem incapable of synthesis of this enzyme. The positive immunoreaction in vascular structures may reflect the entry of circulating PLA2-II into vessel walls rather than local production of the enzyme.

Blotting, Northern↗

PubMed1994

Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat.

Alcohol-induced changes in cholinergic and pancreozymin pathways regulating exocrine pancreatic secretion have been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis. In the present study we investigated the role of chronic alcohol intake in an experimental acute pancreatitis induced in rats by cholinergic hyperstimulation. Chronic alcohol intake interfered with the function of rat pancreatic muscarinic receptors in carbachol-induced acute pancreatitis. However, chronic alcohol intake did not sensitize the experimental animals to cholinergic hyperstimulation. Whether this increased resistance at the level of pancreatic muscarinic receptors contributes to acute alcoholic pancreatitis is discussed in the present article.

Acute Disease↗

PubMed1994

Group II phospholipase A2 in serum in critically ill surgical patients.

OBJECTIVE: To study the association of increased serum group II phospholipase A2 concentrations to C-reactive protein concentrations in the sera of critically ill surgical patients. DESIGN: Prospective study. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: Sixty-seven consecutive patients admitted to the surgical ICU. INTERVENTIONS: The catalytic activity of phospholipase A2 and the serum concentrations of group II phospholipase A2 and C-reactive protein were measured daily during each patient's stay in the ICU. A total of 205 blood samples were taken. In addition, the preoperative serum levels of group II phospholipase A2 were determined in patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum group II phospholipase A2 values correlated statistically significantly with the catalytic activity of phospholipase A2 and serum C-reactive protein values. In particular, severe infections, diseases involving tissue destruction, and elective operations per se, caused considerable increases in serum group II phospholipase A2 concentrations. CONCLUSION: Our results support the earlier presented idea that group II phospholipase A2 is an acute-phase reactant.

Acute-Phase Proteins↗

PubMed1994

Group II phospholipase A2 in synovial fluid and serum in acute arthritis.

Increased catalytic activity of synovial-type (group II) phospholipase A2 (syn-PLA2), has been associated with cartilage erosions in rheumatoid arthritis and osteoarthritis. The catalytic activity of phospholipase A2 and the concentration of syn-PLA2 were measured in a prospective study in synovial fluid (SF) samples from 66 patients with acute knee joint effusion. The median (range) of the concentration of syn-PLA2 in SF was 210 micrograms/l (80-1480 micrograms/l) in culture-positive septic arthritis, 460 micrograms/l (270-1040 micrograms/l) in reactive arthritis, 780 micrograms/l (120-2710 micrograms/l) in osteoarthritis and 230 micrograms/l (80-1400 micrograms/l) in traumatic joint effusions. High concentrations of syn-PLA2 are found also in SF of patients with arthritides not expected to lead to permanent destruction of cartilage.

Acute Disease↗

PubMed1994

Phospholipase A2, C-reactive protein, and white blood cell count in the diagnosis of acute appendicitis.

We compared the predictive value of determining group II phospholipase A2 (PLA2) in serum for diagnosing acute appendicitis with the predictive values of white blood cell count (WBC) and measurement of C-reactive protein (CRP). In this prospective study, we included 186 patients who were undergoing appendectomy after clinical diagnoses of acute appendicitis. The performance of each test was measured by receiver-operating characteristic curves. WBC was the test of choice in diagnosing uncomplicated acute appendicitis. However, in contrast to CRP and PLA2, which increased in patients with protracted inflammation, there was not a concomitant increase in WBC. Therefore, especially CRP, but also PLA2, were better indicators of appendiceal perforation or abscess formation than was WBC. Increased WBC, CRP, and PLA2 values did not unequivocally corroborate the clinical suspicion of appendicitis, but if all three values were within normal limits, acute appendicitis could be excluded with a 100% predictive value. PLA2 values showed a highly significant correlation with CRP but not with WBC values, which supports the view that PLA2 represents an acute-phase reactant.

Acute Disease↗

PubMed1994

Secretion of group 2 phospholipase A2 by lacrimal glands.

PURPOSE: Tears are known to have antimicrobial properties. The authors investigated the presence of the antibacterial enzyme phospholipase A2 (PLA2) in tears and lacrimal glands. METHODS: The catalytic activity of PLA2 and the amount of pancreatic group 1 PLA2 and nonpancreatic group 2 PLA2 were measured in homogenates of eight human lacrimal glands from autopsied subjects and in tears from four healthy volunteers. The localization of PLA2s in lacrimal gland sections was studied by immunohistochemistry. Skeletal muscle was used as a control. RESULTS: The catalytic activity of PLA2 was significantly higher in lacrimal glands than in skeletal muscle. Immunochemical analysis showed significantly higher amounts of group 2 PLA2 in lacrimal gland than in skeletal muscle homogenates. Group 1 PLA2 was present in trace amounts only. The concentration of group 2 PLA2 in tears was high (1451.3 micrograms/l) compared to that in the serum of healthy individuals (3.7 micrograms/l). By immunohistochemistry, a granular reaction of group 2 PLA2 was localized in the glandular cells of lacrimal glands. The apical cytoplasm of many duct cells also was labeled. CONCLUSIONS: The lacrimal glands secreted nonpancreatic group 2 PLA2, which most likely acts as an antiinfectious factor in tears.

Adult↗

PubMed1993

Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas.

The incidence of gastric cancer has declined markedly in Finland during the last 4 decades. To document the changes caused by that in the ratio of the intestinal type (IT) to the diffuse type (DT) of gastric carcinoma we compared the 367 cases diagnosed from southwestern Finland at the Department of Pathology, Turku University, from 1950-1959 and 1076 cases from 1980-1989. IT virtually disappeared in the male and female populations younger than 50 years, and in patients younger than 60 years, DT became more common than IT (P < 0.001). The transitional age, the time at which IT exceeds DT in frequency, shifted by 20 years to older age groups. In patients older than 60 years, IT remained the dominant type, but the ratio of IT to DT (IT:DT) decreased in men from 3.8 to 2.1 (P < 0.05) and in women from 4.4 to 2.1 (P < 0.001). No decrease in the frequency of DT could be demonstrated in the material studied. The disappearance of the male-dominant IT in the younger male population changed the male-to-female ratio of patients reported to the Finnish Cancer Registry. When the ratio IT:DT in Finland was compared with the ratios reported by the authors in data from other continents and by other investigators, regional variations in basal level of IT:DT emerged. This phenomenon seems to be based on the differing genetic susceptibility to DT of various races. The decrease of IT, seen in reports from regions with declining incidence of gastric carcinoma, seems to be connected to a diminished rate of severe chronic gastritis.

Adult↗

PubMed1993

Distribution of pancreatic (group I) and synovial-type (group II) phospholipases A2 in human tissues.

The catalytic activity of phospholipase A2 (cat-PLA2) and the concentration of pancreatic (group I) phospholipase A2 (pan-PLA2) and synovial-type (group II) phospholipase A2 (syn-PLA2) were studied in 19 human tissues in order to find potential sources of circulating phospholipase A2. Five specimens of each tissue were collected at autopsies or from normal deliveries (placentas and amnionic membranes). The concentrations of pan-PLA2 and syn-PLA2 were measured by specific time-resolved fluoroimmunoassays. The cat-PLA2 was measured by radioactive dipalmitoyl phosphatidylcholine as substrate. The concentration of pan-PLA2 was negligible in all tissue homogenates except the pancreas. Immunoreactive syn-PLA2 was found in the homogenates of the digestive tract, cartilage, and prostatic and parotid glands. By immunohistochemistry, syn-PLA2 was localized in Paneth cell secretory granules, chondrocytes, cartilage matrix, and glandular cells of prostate.

Aged↗

PubMed1993

Pancreatic phospholipase A2 in cerulein-induced acute pancreatitis in the rat.

We investigated the concentration of immunoreactive pancreatic phospholipase A2 (pan-PLA2) and the catalytic activity of phospholipase A2 (CA-PLA2) in plasma and pancreases of rats with cerulein-induced acute pancreatitis. Edematous pancreatitis with ascites and fat necroses in the abdominal cavity developed after 8 h infusion of cerulein (5 micrograms/kg/h). Large vacuoles were found in acinar cells and there were small areas of acinar cell necrosis. No pathological changes were seen in saline-infused control animals. Pancreatic PLA2 was localized by immunohistochemistry in pancreatic acinar cells in both groups of animals and in the proximal tubular cells of the kidney in cerulein-infused animals. The lungs and kidneys appeared normal by light microscopy in all animals. The pan-PLA2 values increased markedly, whereas the CA-PLA2 values did not change during the cerulein-infusion. The CA-PLA2 values in the homogenates of pancreatic tissue of cerulein-infused animals did not differ significantly from those of saline-infused controls. The results indicate that the CA-PLA2 in plasma is independent from the concentration of pan-PLA2 in cerulein-induced acute pancreatitis in rat.

Acute Disease↗

PubMed1993

Rat pancreatic phospholipase A2. Purification, localization, and development of an enzyme immunoassay.

Phospholipase A2 (PLA2, E.C. 3.1.1.4) was purified from rat pancreatic tissue by heat treatment of the homogenate and use of cation-exchange chromatography on a CM-Sepharose column. The enzyme was apparently homogenous on SDS polyacrylamide gel electrophoresis, and its mol wt was estimated to be 14,400. An antiserum raised against rat pancreatic PLA2 in a rabbit was used in a solid-phase enzyme immunoassay employing inorganic pyrophosphatase (E.C. 3.6.1.1) as the enzyme label. As measured by this assay, the concentration of pancreatic PLA2 in plasma was found to be above normal in rats with hemorrhagic pancreatitis induced by an intraductal injection of sodium taurocholate. PLA2 was localized in pancreatic acinar cells and in the chief cells in the mucosa of the glandular stomach by immunohistochemistry. By immunoelectron microscopy, the immunogold conjugates were mainly located on profiles of zymogen granules in acinar cells.

Acute Disease↗

PubMed1993

Toxic effects of human pancreatic and snake and bee venom phospholipases A2 on MCF-7 cells in culture.

The toxicity of phospholipase A2 (PLA2) has been suggested to be involved in the pathology of a number of severe diseases including septic shock and acute pancreatitis. However, testing the toxicity of these substances is difficult in vivo. In the present study we compared the toxicity of PLA2s from three snake venoms, bee venom and human pancreas on MCF-7 cells grown in culture. Tetrazolium microculture assays were developed to test the cytostatic and cytotoxic effects of PLA2 on MCF-7 cells. These tests are based on the ability of viable cells to reduce a tetrazolium-based compound MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to a blue formazan product. Leakage of lactate dehydrogenase (LD) from the cells into the culture medium was also measured. There were marked differences in the toxicity of the PLA2s tested. Cobra (Naja mosambique mosambique) venom PLA2 was toxic to the cells at a concentration of 4.5 U/ml. Light microscopic changes were seen in the injured cells after 3 hr treatment. Sixty-seven per cent of cells were dead after 24 hr treatment. Treatment for 4 hr caused irreversible changes in the cells. Leakage of LD was noted from 4 hr onwards. Other snake (Crotalus adamanteus and Laticauda semifasciata) venom PLA2s, even after continuous exposure to 4.5 U/ml caused only slight decreases in values obtained in the MTT test. No morphologic changes suggesting a cytotoxic effect were seen. PLA2 from bee (Apis mellifera) venom had no toxic effect, either. Continuous exposure of cells to human pancreatic PLA2 caused a 15% decrease in the MTT-test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Group II phospholipase A2 in sera of febrile patients with microbiologically or clinically documented infections.

Group II phospholipase A2 (PLA2-II) is an inflammatory enzyme, which has been shown to be an acute-phase protein and to correlate with the severity of sepsis. In a prospective study, the concentration of PLA2-II in the sera of 46 patients with sepsis and nonseptic bacterial and viral infections was measured by a fluoroimmunoassay. The serum concentration of PLA2-II in patients with infections (median, 164.5 micrograms/L; range, 5.07-1,740 micrograms/L) was elevated 46-fold above normal concentrations (median, 3.61 micrograms/L; range, 1.32-25.25 micrograms/L). The concentration of PLA2-II was higher in patients with sepsis (median, 284.5 micrograms/L; range, 12.95-1,574 micrograms/L) and nonseptic bacterial infections (median, 210.6 micrograms/L; range, 5.07-1,740 micrograms/L) than in those with viral infections (median, 46.78 micrograms/L; range 11.46-275.9 micrograms/L) (P = .0042). The concentration of PLA2-II correlated well with the concentration of C-reactive protein (CRP) (r = .613, P = .0001) but not with the concentration of pancreatic PLA2 (r = .089, P = .365). Measuring the serum concentration of PLA2-II is useful as an adjunct to the determination of CRP concentrations for differentiating bacterial from viral infection.

Adolescent↗

PubMed1993

Synovial-type (group II) phospholipase A2 in serum of febrile patients with haematological malignancy.

Elevated concentrations of synovial-type (group II) phospholipase A2 (PLA2-II) in serum are associated with septic bacterial infections. We measured the concentrations of PLA2-II in serum in 24 fever episodes involving patients suffering from haematological malignancies and having fever after cytotoxic treatment. We applied a novel time-resolved fluoroimmunoassay using a polyclonal antibody raised against recombinant human synovial-type PLA2. The concentrations of PLA2-II in serum were 194.7 +/- 204.4 micrograms/l (mean +/- SD, median 141.9, range 4.6-931.5 micrograms/l). The concentrations of PLA2-II correlated well to the concentrations of C-reactive protein (CRP) in serum (r = 0.688, p < 0.001). The PLA2-II concentrations increased faster than the corresponding CRP values and began to decrease 12 hours after the beginning of antimicrobial treatment. Inverse correlations were found between the concentrations of PLA2-II and blood neutrophil and platelet counts. No correlation was found between the concentrations of PLA2-II and the duration of the time interval from the onset of preceding cytotoxic and corticosteroid treatment to the first blood sample. The concentration of pancreatic PLA2 was within the reference interval in all samples. The present results indicate that PLA2-II resembles an acute-phase protein and is not of blood cell or pancreatic origin.

Adult↗

PubMed1993

Pancreatic and synovial type phospholipases A2 in serum samples from patients with severe acute pancreatitis.

Phospholipase A2 (PLA2) is the rate limiting enzyme in the formation of prostaglandins and probably plays a key part in the pathology of various inflammatory diseases. In acute pancreatitis, the catalytic activity of PLA2 in serum correlates with the severity of the disease. The cellular source of the catalytically active PLA2 in serum of patients suffering from acute pancreatitis and other diseases is unknown. Immunoassays for the measurement of pancreatic group I PLA2 and nonpancreatic synovial type group II PLA2 have recently been developed and the present study investigated the presence of group I and group II PLA2s in serum samples from 36 patients with severe acute pancreatitis. The catalytic activity of PLA2 showed a highly significant correlation with the concentration of synovial type PLA2 (r = 0.939, p = 0.001) but not with the concentration of pancreatic PLA2 (r = 0.067, p = 0.698). The results suggest that pancreatic PLA2 circulates mostly as inactive enzyme in patients with acute pancreatitis whereas synovial type PLA2 is responsible for the increased catalytic activity of the enzyme and thus might be associated with the pathophysiology of the disease.

Acute Disease↗