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Biomedical subjects

S Nordling

Publications and source records attributed to S Nordling.

At least 127 records · Page 7Linked to original sources

Tumour-associated trypsin inhibitor, TATI, in patients with pancreatic cancer, pancreatitis and benign biliary diseases.

The serum and urine concentrations of a tumour-associated trypsin inhibitor, TATI, were determined by radioimmunoassay in patients with pancreatic cancer and with benign pancreatic and biliary diseases. Elevated serum levels (greater than 20 micrograms l-1) were found in 85% of the patients with pancreatic cancer, and elevated urine levels (greater than 50 micrograms g-1 creatinine) in 96% of the patients. Thus low TATI level, especially in urine, makes the possibility of pancreatic cancer less likely. Serial assay of TATI in serum from three patients with surgically removed pancreatic cancer showed elevation of the TATI level at the time of detection of recurrence. However, high serum and urine levels were also seen in pancreatitis and in benign extrahepatic cholestasis. Thus TATI is a sensitive, although not specific, indicator of pancreatic and biliary disease, but the use of TATI as a tumour marker in the primary diagnosis of pancreatic cancer is limited. Immunohistochemical staining of pancreatic lesions showed that half of the pancreatic tumours expressed TATI, but the pancreatic tissue adjacent to a carcinoma always stained stronger than the carcinoma. It therefore seems that the main source of TATI in serum and urine of patients with pancreatic cancer are the normal acini and not the tumour tissue. In pancreatitis the staining was intense and clearly stronger than in normal pancreas.

Acute Disease↗

Gastrointestinal cancer-associated antigen CA 19-9 in histological specimens of pancreatic tumours and pancreatitis.

The expression of the gastrointestinal cancer associated antigen CA 19-9, defined by the monoclonal antibody 1116 NS 19-9, was studied by immunoperoxidase staining in routine formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The formalin-fixed specimens were treated with pepsin, which enhanced the staining intensity. Eighty-five per cent of well to moderately differentiated adenocarcinomas were positive. The staining was most intense in the apical border of cells lining the lumina of malignant glands, and in mucus inside the lumina, but cytoplasmic staining was also seen. In poorly differentiated adenocarcinomas the number of positive cells was smaller and in anaplastic carcinomas only occasional cells were stained. All mucinous cystadenomas and cystadenocarcinomas stained intensely, whereas serous cystadenomas, and all benign and malignant islet cell tumours were negative. Ducts in chronic pancreatitis and in normal pancreata were positive in 96% and 79%, respectively, but the staining was focal and usually weaker than in carcinomas. In acute pancreatitis (92% positive) the staining was more intense, and the CA 19-9 expression was seen predominantly in small terminal ducts and in centroacinar cells. There was an apparent correlation between the degree of differentiation of the ductal adenocarcinomas and the expression of CA 19-9, whereas the correlation between tissue expression and serum levels of CA 19-9 was poor.

Adenocarcinoma↗

The effect of peritoneal exudate on peritoneal morphology in experimental acute pancreatitis. A histologic and scanning electron microscopic study.

Changes in peritoneal morphology were examined histologically and by scanning electron microscopy during porcine acute hemorrhagic (n = 8) and edematous (n = 9) pancreatitis and after intraperitoneal installation of hemorrhagic pancreatitis-associated peritoneal exudate in healthy piglets (n = 3). In all experimental groups peritoneal inflammatory changes with mesothelial damage were evident already 1 h after the induction of the disease, and increased with time. Hemorrhagic pancreatitis caused desquamation of mesothelial cells and denudation of the basal membrane. Intraperitoneal installation of hemorrhagic pancreatitis-associated peritoneal exudate in healthy piglets caused similar changes, whereas the changes in edematous pancreatitis were much less extensive. Peritoneal exudate accumulating in the peritoneal cavity during hemorrhagic pancreatitis caused early chemical peritonitis characterized by severe inflammation of the peritoneum with destruction of the mesothelial cell layer, leading to denudation of the underlying connective tissue. The significance of these changes in the pathophysiology of acute fulminant pancreatitis remains to be further studied.

Acute Disease↗

Flow cytometric determination of DNA content in malignant and benign bone tumours.

The nuclear DNA content of 38 malignant and 25 benign bone tumours was measured by flow cytometry. The specimens were taken either from biopsies or from surgical specimens. Seventeen of 26 primary malignant bone tumours were aneuploid, 15 had a single aneuploid DNA content, and 2 had a biclonal abnormality. Thirteen of 15 osteosarcomas were aneuploid, but only 2 of 6 chondrosarcomas showed an aneuploid DNA content. Six of 12 metastatic malignant bone tumours were also aneuploid. All 25 benign tumours had a diploid DNA content. Cell cycle analysis showed that the proportion of cells in S- and G2M-phases was higher in the malignant compared to benign tumours, indicating a higher proliferative activity. The increase was statistically significant (p less than 0.05) both in diploid and in aneuploid tumours. Among five tumours studied after chemotherapy, four displayed a marked hyperdiploid abnormality. Aneuploidy and high proliferative activity both were highly associated with malignant bone tumours, suggesting that DNA flow cytometry may be an adjunct in the assessment of malignancy of bone tumours.

Adolescent↗

Surgery in mandibular condylar hyperplasia.

The experience with 35 patients with unilateral condylar hyperplasia is described. Possibilities of distinction between active and non-active cases are discussed as well as the histological findings. Different surgical procedures were used for treatment. Pain in the joint area is a prominent feature in this group. The treatment was effective in this regard in all patients.

Adolescent↗

Glomerular sialic acid in Heymann nephritis and diacetylbenzidine induced nephropathy in rats.

Glomerular sialic acid was chemically measured in rats with experimental proteinuria induced by N,N'-diacetylbenzidine (DAB) or with autoimmune Heymann nephritis. In DAB nephrosis and in Heymann nephritis the relative amount of glomerular protein was increased. In DAB nephrosis the quantity of sialic acid expressed per amount of protein was decreased, but expressed per amount of DNA, which reflects the number of cells, there was no significant change. In Heymann nephritis the amount of sialic acid was not significantly altered when expressed per amount of protein or per amount of DNA. In individual animals, the amount of glomerular sialic acid expressed per amount of protein or per amount of DNA did not correlate with the severity of proteinuria. An increase in the total number of glomerular cells was found only in Heymann nephritis. The results suggest that proteinuria in the reported models is not the result of changes in glomerular sialic acid.

Animals↗

Expression of laminin in pancreatic neoplasms and in chronic pancreatitis.

The distribution of laminin, a basement membrane glycoprotein, was studied by immunohistological techniques in 10 samples of normal pancreatic tissue, in 15 samples of chronic pancreatitis, and in 33 pancreatic neoplasms. Sections of formalin-fixed, paraffin-embedded specimens were pretreated with pepsin and immunostained for laminin. As judged by the expression of laminin, normal pancreatic glands were surrounded by a continuous, intact basement membrane. In chronic pancreatitis the basement membrane was also mainly continuous, but focally weaker and thinner than around normal glands. In pancreatic adenocarcinomas laminin was irregularly distributed and in large areas totally absent. In anaplastic carcinomas no extracellular laminin was seen, but two cases showed some intracellular laminin in a punctate pattern. The findings suggest that these cancers have defects in the deposition of a basement membrane or that it is degraded. Our data suggest that the integrity of the basement membrane correlates with the degree of malignancy in ductal adenocarcinomas, but this is not the case for mucinous cystic neoplasms or for islet cell tumors. In these neoplasms a nearly intact basement membrane was seen both in malignant tumors and in their benign counterparts.

Adenocarcinoma↗

Distribution of Ia-positive cells in the pig and human pancreas.

With monoclonal antibody reacting with both human and porcine Ia antigens, we demonstrate with immunoperoxidase staining that Ia expressing endothelial cells are found in Langerhans' islets as well as in exocrine tissue of the pig and human pancreas. However, neither endocrine cells in Langerhans' islets nor acinar or ductal cells do express the Ia antigen.

Animals↗

DNA synthesis and cell generation cycle during determination and differentiation of the metanephric mesenchyme.

Isolated metanephrogenic mesenchyme can be induced for epithelial differentiation and tubule formation by an embryonic spinal cord that is cultivated in a transfilter position to the target cells. Under such conditions, determination of the cells starts at 12 hr and is completed around 24 hr. To correlate this event to DNA synthesis, thymidine incorporation was followed in such cultures from 2 to 96 hr after setting up the transfilter explants. Controls were cultured under conditions which did not result in induction. Incorporation into both induced and noninduced mesenchymes dropped rapidly during the first 12 hr when the tissues were transferred to the in vitro conditions. During the subsequent critical 12- to 24-hr period, mesenchymes continuously exposed to an inductor showed a marked increase in their incorporation of thymidine. If induction was interrupted during the first 10 hr there was no stimulation of incorporation when measured at 24 hr. Similarly, isolated mesenchymes and those exposed to a tissue devoid of inducing capacity did not show stimulation, and their incorporation remained at a low level when measured at 24 hr. Parallel DNA measurements were made by flow cytometry of individual nuclei from mesenchymes exposed to the inductor from 0 to 46 hr. No major changes in the distribution of the various phases of cell generation cycle were detected nor could any synchronization be shown. Hence the changes in the incorporation rate of thymidine seem to be due to variations in the total length of the cell cycle. We conclude that induction of differentiation of the metanephric mesenchyme is accompanied by a contact-mediated stimulation of DNA synthesis. The stimulation may represent a permissive effect on a predetermined cell population in the metanephrogenic mesenchyme.

Animals↗

Changes in the electrophoretic mobility of cells from chick blastoderms during early development.

A change in cell surface charge density during early avian development is shown with a free-flow electrophoresis apparatus. The blastoderms of freshly laid eggs consist of two electrophoretically distinct cell populations. After the onset of gastrulation a third cell population with an intermediate electrophoretic mobility appears. With increasing time of incubation there is a shift in the proportion of these populations and an increase in the mobility of the fastest fraction.

Animals↗

Chlorpromazine treatment of experimental acute fulminant pancreatitis in pigs.

Acute pancreatitis was induced in 20 piglets. In the controls (10 piglets) no specific treatment was given, while in the experimental group the animals were treated with chlorpromazine, a potent phospholipase A2 inhibitor in vitro. Blood samples were taken from all animals for the assay of amylase, lipase, phospholipase A2, calcium, blood glucose and arterial blood gases both before the experiment and at various time intervals after its commencement. At autopsy, tissue specimens were taken from the pancreas, liver, lungs, heart and kidneys for histological studies. In the untreated animals there was a continuous rise in the phospholipase A2 levels, while the level decreased to zero on the second day in the treated animals (p less than 0.01, Student's t test). Moreover, in the untreated animals there was a sharp drop in the arterial pO2, while this remained unchanged in the treated animals (p less than 0.1, Student's t test). The mortality was significantly less (p less than 0.01, chi-square test) in the chlorpromazine-treated animals than in the controls. Serum phospholipase A2 levels correlated with the changes in pulmonary function and mortality. The results support the view that phospholipase A2 is of importance in the pathophysiology of acute pancreatitis.

Acute Disease↗

An improved colloidal iron stain for glomerular sialoproteins.

The thick sialoglycoprotein coat of the glomerular epithelial cells is a part of the glomerular filtration barrier. It can be demonstrated in paraffin histoslogy by means of the colloidal iron procedure. We have studied the special requirements of tissue processing to obtain reproducible results by this staining method. The requirements include proper fixation, avoiding heat during sectioning and ample rehydration. We have further tested a colloidal iron-PAS procedure for simultaneous demonstration of the glomerular epithelial coat and the basement membrane.

Animals↗

Characterization of storage material in cultured fibroblasts by specific lectin binding in lysosomal storage diseases.

The lysosomal storage material in cultured fibroblasts from patients with various lysosomal storage diseases was characterized by fluorescence microscopy using lectins specific for different saccharide moieties. In normal fibroblasts and cultured amniotic fluid cells lectins specific for mannosyl and glucosyl moieties, Con A and LcA gave a bright perinuclear cytoplasmic staining corresponding to the localization of endoplasmic reticulum in the cells. All other lectins stained the Golgi apparatus as a juxtanuclear reticular structure. In fucosidosis fibroblasts, only lectins specific for fucosyl groups LTA and UEA, distinctly stained the lysosomal inclusions. The lysosomes in mannosidosis fibroblasts did not react with Con A and LcA, both specific for mannosyl moieties of glycoconjugates, but were brightly labeled with WGA, a lectin specific for N-acetyl glucosaminyl moieties. In I-cell fibroblasts, the numerous perinuclear phase-dense granules, representing abnormal lysosomes, were labeled with every lectin used. In fibroblasts from patients with Salla disease, a newly discovered lysosomal storage disorder, the lysosomes were brightly stained only with LPA, indicating the presence of increased amounts of sialic acid residues in the lysosomal inclusions.

Carbohydrate Metabolism, Inborn Errors↗

Carcinoembryonic antigen in endoscopic brush specimens from benign and malignant gastric lesions.

The measurement of carcinoembryonic antigen (CEA) in serum and endoscopic brush specimens was evaluated for the differential diagnosis of malignant and nonmalignant gastric disease. Brush specimens were studied from 33 patients with gastric cancer and 36 patients with benign gastric lesions or apparently normal gastric mucosa. Demonstrable CEA immunoreactivity was found by radioimmunoassay in brush specimens from 24/33 cancer patients (73%) and from 23/36 patients with benign lesions (64%). Patients with CEA+ tissue in the immunoperoxidase test had somewhat higher CEA concentrations in the brush specimens than cases with CEA- biopsy tissue, although overlap was considerable. Thirty-five per cent of cancer patients had both a positive tissue CEA reaction and a CEA/DNA ratio greater than 10 ng/micrograms, whilst patients with benign lesions had only 15% of positives by these criteria (0.01 greater than P greater than 0.001). The serum CEA concentration was above the upper normal level of 5 ng/ml in 2/39 patients, both of whom had gastric cancer. The CEA immunoreactive material from benign and malignant lesions eluted in gel filtration on Sephadex G-200 in the same volume as CEA purified from liver metastases of cancer of the colon, showing that a glycoprotein sharing immunological and physicochemical properties with CEA is present both in malignant and nonmalignant lesions of the gastric mucosa, and that there is considerable overlapping in the amount of CEA. The estimation of CEA in gastric-brush specimens is therefore of limited value in the differential diagnosis of benign and malignant gastric lesions.

Adult↗