Search PubMed⌕ Search

Biomedical subjects

M Klockars

Publications and source records attributed to M Klockars.

At least 91 records · Page 5Linked to original sources

The induction of angiotensin converting enzyme by its inhibitors.

The inhibitors of angiotensin converting enzyme (ACE), captopril and enalapril, were found to increase ACE concentration in cultured human endothelial cells from cord artery as measured with a novel ACE assay employing MK 351A, an inhibitor of ACE, and with immunofluorescense labeling using anti-human lung ACE antibody. Dexamethasone (10 nM) also increased ACE and potentiated the increase of cellular ACE caused by captopril. Similar effects of ACE inhibitors were seen in cultured human macrophages, particularly after prestimulation with E. coli lipopolysaccharide. In Wistar Kyoto rats, captopril caused a 3-fold increase of serum ACE, while dexamethasone (40 ug/day, 14 days) did not increase serum ACE. Combined treatment with captopril and dexamethasone caused a 5-fold increase of ACE in purified lung plasma membranes. ACE inhibitors induce increased ACE biosynthesis in endothelial cells, and in macrophages. The rise of cellular ACE with ACE inhibitors is potentiated by glucocorticoid.

Angiotensin-Converting Enzyme Inhibitors↗

Fibronectin in exudative pleural effusions.

Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in pleural effusion was found to be immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis. Fibronectin isolated from pleural fluid by affinity chromatography on gelatin-Sepharose had a polypeptide pattern similar to that of plasma fibronectin in SDS-polyacrylamide gel electrophoresis. In 28 patients with infectious or non-specific pleural effusion fibronectin concentrations in pleural fluid were 335 +/- 104 micrograms/ml (mean +/- SD), in 15 patients with malignant disease the concentrations were 369 +/- 173 micrograms/ml and in 26 patients with tuberculosis 441 +/- 103 micrograms/ml. The highest concentrations, 605 +/- 252 micrograms/ml, of fibronectin in pleural fluid were detected in 14 patients with connective tissue diseases. The results suggest that increased fibronectin concentrations reflect the presence of a pleurisy due to connective tissue disease or tuberculosis rather than other infectious or malignant disease.

Bacterial Infections↗

Chemical and immunological features of pleural effusions: comparison between rheumatoid arthritis and other diseases.

The value of determination of pleural fluid glucose, pH, lactic dehydrogenase, IgG, IgA, IgM, C3, C4, anti-IgG antibody, and hydroxyproline in distinguishing between pleural effusions caused by rheumatoid arthritis (RA) and those resulting from other diseases was studied. The series comprised seven patients with RA and 115 patients with other diseases including systemic lupus erythematosus, tuberculosis, malignant disease, empyema, pneumonia, congestive heart failure, and nonspecific pleural effusion. The low glucose concentration, the low pH and the low C4 level in rheumatoid pleural effusion were the most valuable diagnostic findings. The presence of anti-IgG antibody in pleural fluid was not specific for RA. The concentration of hydroxyproline in pleural fluid and the pleural fluid-to-plasma hydroxyproline ratio were significantly higher in RA than in tuberculosis and malignant disease. The results support the view that local metabolic and immunological phenomena as well as a high turnover of collagen occur in the pleural cavity in RA.

Adolescent↗

Beta 2 microglobulin in pleural effusions.

Beta 2 microglobulin (beta 2m) concentrations in serum and pleural fluid from 64 patients with pleural effusion were studied. The level of beta 2m in pleural fluid was generally twice that in serum. The ratio of pleural fluid beta 2m to serum beta 2m in patients groups defined according to the final diagnosis showed an interestingly high value in tuberculous pleuritis and in patients with rheumatoid arthritis with pleural effusion. There was a positive correlation between the beta 2m and lysozyme contents in pleural fluid, suggesting local and simultaneous activation of different cell lines when the pleura is involved. We suggest that pleural fluid and concomitant serum beta 2m measurements should be taken into consideration when pleural effusion of tuberculous origin is suspected. Furthermore, beta 2m determination might help to differentiate between rheumatoid pleural fluid and pleural involvement due to the other systemic diseases.

Adolescent↗

Blood monocytes and serum and bone marrow lysozyme in sarcoidosis.

Serum lysozyme (LZM) concentrations were correlated to the number of neutrophils and monocytes in patients with sarcoidosis and nongranulomatous diseases. In sarcoidosis patients with an increased activity of serum angiotensin converting enzyme (ACE), a positive correlation was noted between LZM and blood monocytes. In sarcoidosis patients with normal ACE activity, as well as in patients with non-granulomatous diseases, a correlation was found between blood neutrophils and LZM, but not between blood monocytes and LZM. LZM was found in bone marrow plasma and in serum in a ratio of 1.5 to 1. Sarcoidosis patients had 30% higher LZM levels than healthy controls. The concentration of LZM in bone marrow plasma did not correlate to detectable granulomas in bone marrow specimens. The positive correlation between blood monocytes and LZM in patients with clinically active sarcoidosis is possibly due to recruitment of bone marrow monocytes for the granuloma formation.

Bone Marrow↗

PHA and PPD reactivity of lymphocytes in pleural effusions.

The functional properties of lymphocytes in pleural fluid were studied in 23 patients admitted to the hospital for the diagnostic evaluation of a unilateral or bilateral pleural effusion. The in vitro reactivities of the patients' pleural fluid lymphocytes and peripheral blood lymphocytes to phytohemagglutinin (PHA) and to purified protein derivative (PPD) were compared. In most patients with pleural effusion, the function of pleural fluid lymphocytes was intact and comparable to that of lymphocytes from peripheral blood. The PHA- and PPD-stimulated 3H-thymidine incorporation by peripheral blood lymphocytes did not differ significantly from that by pleural fluid lymphocytes in any of the patient groups. Similarly, the comparison of PHA- and PPD-stimulated 3H-thymidine uptake by peripheral blood or pleural fluid lymphocytes from patients with pleural effusions of various causes revealed no significant differences. In vitro reactivity to PPD by peripheral blood and pleural fluid lymphocytes correlated positively with the in vivo intradermal reactivity to PPD.

Adult↗

Hyperreninemia, lysozymuria, and erythrocytosis in Fanconi syndrome with medullary cystic kidney.

Adult onset Fanconi syndrome with medullary cystic kidney was diagnosed in a 30-year-old male with muscular weakness, hypokalemia, normal BP, hyperreninemia, and secondary aldosteronism. He also had non-specific aminoaciduria, lysozymuria, and beta 2-microglobulinuria. Urinary concentrating and acidifying capacity was impaired, and both sodium and potassium were lost into the urine. I.v. pyelography revealed medullary cystic kidney. Renal biopsy showed juxtaglomerular hyperplasia, heavy subintimal deposits and C3 and IgG in preglomerular arteriolar walls, and degenerative changes in the tubules, including loss of brush border and "macula densa-like" lesions. Polycythemia with elevated serum erythropoietin levels, and raised blood ACTH values with features of cortisolism were also present. Indomethacin therapy decreased plasma renin activity (PRA), plasma aldosterone, and urinary loss of potassium and sodium, while serum potassium approached normal levels. Metoprolol, a beta-adrenergic blocking agent, caused similar effects. Insensitivity to the pressor effect of angiotensin II was reversed by indomethacin treatment. Somatostatin infusion lowered PRA and aldosterone without affecting BP. Several biochemical aberrations of this patient resemble Bartter's syndrome, including the effect of indomethacin.

Adult↗

Circulating immune complexes in sarcoidosis.

Circulating immune complexes (CIC) were detected in 100 out of 112 sera from 33 sarcoidosis patients. Five tests were used representing three different basic principles. All patients had detectable CIC at some stage of their disease. The three platelet tests detecting IgG complexes exhibited the highest positive titres in the acute cases. The ClqB-ELISA test, which detects complement fixing IgG complexes, was the test most frequently positive in the chronic cases. The presence of extra-pulmonary lesions or corticosteroid therapy did not influence the appearance or disappearance of CIC. No positive correlation was found between CIC and elevated levels of serum angiotensin-converting enzyme (ACE) and/or serum lysozyme (LZM). The evaluation of CIC in sarcoidosis requires a battery of different tests carried out at regular intervals during the follow up.

Antigen-Antibody Complex↗

Immunohistochemical identification of renal lysozyme during allograft rejection in man.

An immunoperoxidase staining method was used to identify lysozyme in biopsy or transplantectomy specimens of human renal allografts during reversible and irreversible rejection of the grafts. Proximal tubules in apparently functioning nephrons showed lysozyme staining. In irreversibly rejected grafts, infiltrating mononuclear phagocytes in and near peritubular and glomerular capillaries also stained intensely for lysozyme. In acute necrotizing arteritis, lysozyme-positive cells (mononuclear phagocytes) infiltrated the blood vessel wall. The presence of infiltrating lysozyme-positive cells in the transplant was consistent with poor graft survival. The variation in lysozyme staining of proximal tubular cells apparently was a reflection of the differences in the reabsorption capacity of the tubular cells, attributable to the tubular dysfunction of renal allografts. The infiltrating lysozyme-positive cells probably contribute to the increased urinary excretion of lysozyme during acute rejection.

Adolescent↗

Pleural fluid lysozyme in human disease.

Lysozyme content was measured in the plasma and pleural fluid of 110 patients with pleural effusions of various causes. The concentration of pleural fluid lysozyme was significantly higher (P less than .001) in patients with tuberculous pleurisy than in those with primary pulmonary carcinoma, metastatic carcinoma of the lung, connective tissue disease, nonspecific pleurisy, or congestive heart failure. Tuberculous patients also had a significantly higher (P less than .001) pleural fluid-to-plasma lysozyme ratio than did the other patients. Plasma lysozyme activity did not differ significantly among the various patient groups. Lysozyme was identified immunohistochemically in epithelioid cell granulomas in tuberculosis, in activated macrophages in lymph nodes adjacent to tuberculous lesions, and in granulocytes in pleural empyema. No lysozyme was detected in neoplastic cells in pulmonary carcinoma. The results show that the determination of pleural fluid lysozyme is a simple, fast method for obtaining corroborative information in the differential diagnosis of tuberculous pleurisy.

Adolescent↗

Cerebrospinal fluid lysozyme in bacterial and viral meningitis.

The concentration of lysozyme (LZM) in cerebrospinal fluid was determined in 25 patients with bacterial meningitis, in 18 patients with viral meningitis and in 25 control patients who had other fibrile illnesses. The concentration of LZM was less than 1.5 microgram/ml in all control patients, and slightly to markedly raised in 10 patients with viral meningitis and in 11 out of 13 patients with untreated bacterial meningitis. The concentration of LZM was significantly different in the viral and bacterial meningitis patients (p less than 0.001). Most raised concentrations of cerebrospinal fluid LZM persisted for at least one week after the start of antibiotic treatment. The concentrations of LZM correlated well with concentrations of lactic dehydrogenase. These results show that the determination of cerebrospinal fluid LZM is a useful tool in the differential diagnosis of meningitis, particularly when the prehospital treatment with antibiotics may be responsible for a diagnostically misleading negative bacterial culture of the cerebrospinal fluid and altered cerebrospinal fluid cytology.

Diagnosis, Differential↗

IgA in blood and thoracic duct lymph: concentration and degree of polymerization.

Lymph fluid and serum samples from four mammalian species were studied forthe concentration and degree of polymerization of IgA. The results suggest that in the mouse, in the rat and in the dog circulating IgA represents only a small fraction of all IgA entering the blood stream from the lymph vessels. A majority of the input IgA of oligomeric type (13S, 11S and 9S) in these species is cleared rapidly. Monomeric IgA, and in the mouse and the dog the dimeric (9S) variety, dwell much longer in the blood; and because of this they form the majority of the circulating IgA. Blood concentration of IgA is high in man, a species whose blood seems to receive mostly monomeric IgA. It is much lower in the rat, mouse and dog, and in these species most of IgA entering the blood is probably oligomeric.

Animals↗

Revision of light-microscopic kidney biopsy diagnosis in glomerular disease.

Paraffin-embedded kidney biopsies sent to our laboratory in 1967 were re-embedded in Epon and studied with electron and light microscopy (1-micrometer thick sections). Of 28 biopsies with enough material 18 were cases with clinical suspicion and symptoms of glomerular disease. In electron microscopy all of these were shown to be of glomerular origin by demonstrating either dark deposits in or at the basement membrane, or amyloid fibrils, or areas with retraction of the foot processes of the epithelial cells. Original light microscopy in 1967 had given proof of glomerular origin in 9 of these 18 cases. Light microscopy of plastic sections of these originally paraffin-embedded biopsies was also helpful in diagnosis and showed deposits in 9 out of 14 cases with ultrastructural deposits. The study shows that considerable benefits can be gained through re-embedding biopsies in plastic, especially in cases with minor alterations.

Adult↗

Effect of furosemide on the urinary excretion of some plasma proteins.

In 30 patients with a variety of glomerular renal disorders, intravenously administered furosemide was associated with a significant increase of the urinary excretion of the protein fraction with a molecular weight higher than 50,000. The excretion of protein with a molecular weight less than 50,000 was not altered. In relation to endogenous clearance of creatinine the clearance of transferrin, IgG and alpha2-macroglobulin increased significantly. In relation to transferrin clearance, the clearance values of albumin and IgG remained unchanged, whereas that of alpha2-macroglobulin increased significantly. These results support the view that furosemide increases the permeability of the glomerular capillary for serum proteins.

Adolescent↗

T and B lymphocytes in pleural effusions.

To determine the diagnostic significance of the determination of T and B lymphocytes in pleural fluid, we studied these cells in peripheral blood and in pleural fluid by means of surface markers. Our study comprised 30 patients suffering from pulmonary tuberculosis, pulmonary malignancy, connective tissue disease, nonspecific pleurisy or congestive cardiac failure. In pulmonary tuberculosis, both the percentage and absolute numbers of T lymphocytes in pleural fluid were significantly higher than in peripheral blood. In patients with pulmonary tuberculosis, pulmonary malignancy or nonspecific pleuritis, the percentages and absolute numbers of B lymphocytes were significantly lower in pleural fluid than in peripheral blood. Considered together with other clinical and laboratory indices, these determinations may aid in the differential diagnosis of pleurisy of various etiology.

Adult↗