Treatment of myocarditis and polymyositic heart disease guided by endomyocardial biopsy.
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Biomedical subjects
Publications and source records attributed to V Andersen.
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The in vivo release of a microvillar enzyme, aminopeptidase N (EC 3.4.11.2), and a cytosolic enzyme, lactate dehydrogenase (EC 1.1.1.27), into the intestinal lumen was measured to gain information on the fraction of desquamated cell protein in intestinal juice and on the mechanism of release of intestinal microvillar enzymes. 1.6% and 2.9% of the mucosal activities of aminopeptidase N and lactate dehydrogenase were released to the intestinal lumen per hour, respectively. The ratios between aminopeptidase N and lactate dehydrogenase in intestinal perfusates and mucosal homogenates were similar. This result is compatible with the view that aminopeptidase N in the rat small intestine is predominantly released into the intestinal lumen by desquamation of enterocytes. This conclusion was supported by the failure to demonstrate microvesiculation of the microvilli by electron microscopy. 30-40% of the aminopeptidase N in the intestinal lumen is membrane-bound indicating that partial solubilization occurs during desquamation. The addition of calcium ions did not augment the release of aminopeptidase N or the membrane-bound fraction in the lumen. 10-20% of the protein content in the intestinal lumen is due to extruded cell protein. This includes aminopeptidase N which constitutes 1% of the luminal protein.
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The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.
The levels of purine enzyme activities were studied in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS related complex (ARC) and in 6 healthy individuals with antibodies against human immunodeficiency virus (HIV). All AIDS/ARC patients studied had ecto-5'nucleotidase (ecto-5'NUC) activity in B lymphocytes below the normal range and 4 out of 6 clinically healthy HIV-positive likewise had reduced activity. Increased numbers of activated B lymphocytes were found both in the group of healthy HIV positive individuals and in AIDS/ARC patients. Further studies are needed to define whether the decrease in ecto-5'NUC activity on the B lymphocytes is a result of increased activation of the cells or of a B cell defect. No significant changes were found in ecto-5'NUC levels in T lymphocytes or mononuclear cells (MNC), neither in the group of AIDS/ARC patients nor in the healthy HIV-positive group. Both AIDS/ARC patients and healthy individuals with antibodies against HIV had increased levels of adenosine deaminase (ADA) activity in mononuclear cells, but only in the group of AIDS/ARC patients was the increase significant. No changes were found in purine nucleoside phosphorylase (PNP) activity in the two groups tested. From these investigations of purine enzyme levels and other markers of immune function in both sick and healthy HIV infected individuals we conclude that the observed changes in ecto-5'NUC and ADA activities in HIV infected patients are not a direct result of the HIV infection but develop early in the course of the disease.
A hemolytic assay was developed with the primary aim of being able to identify human lymphocytes producing anti-dsDNA antibodies found in patients with systemic lupus erythematosus (SLE). The coating of sheep red-blood cells with DNA was performed after precoating the cells with poly-L-lysine. The DNA-SRBC were lysed by anti-DNA antibodies from SLE sera, and the percent hemolysis was found to correlate with the anti-DNA activity demonstrated by the Farr assay (r = 0.87). Single-stranded DNA at the surface of the coated cells could be removed after digestion with nuclease S1. The effect of the digestion was verified by SLE serum specific for single-stranded DNA. With slight modifications, the target cells may be used to determine not only the titer of anti-DNA antibodies but also the complement-consumption and immunoglobulin classes of the anti-DNA antibodies.
A murine hybridoma cell line (aDNA35I9) secreting anti-DNA antibodies was used as a model for haemolytic plaque forming cells in an assay where DNA-conjugated sheep red blood cells (DNA-SRBC) were used as target cells. DEAE-dextran, employed to abolish the anti-complementary activity of agar gel, completely inhibited anti-DNA plaques. This problem was solved by using agarose instead of agar. Since the occurrence of small plaques may make reading of the test difficult, it was established that plaque size could be increased by decreasing the antigen density on the target cells. Free DNA in the gel inhibited plaque formation, indicating the specificity of the assay. Spleen cells from mice of the strains MRL/MP and NZB/W which are known to develop a stage of autoimmunity, produced plaques in numbers which were correlated to the age of the mice and to the anti-DNA antibody level in serum.
DNA was conjugated to sheep red blood cells (SRBC) by chemical methods using CrCl3, poly-L-lysine or methylated bovine serum albumin as conjugation agents and by a physical method where conjugation was accomplished by incubation at 45 degrees C. The degree of conjugation was estimated using 32P-DNA (mean size 1 kbase pairs). Employing the CrCl3 method 5.8 +/- 3.6 micrograms DNA were conjugated per 10(8) SRBC at a concentration of 70 micrograms DNA/10(8) cells. At the same DNA concentration in the incubation medium 3.0 +/- 0.6 microgram DNA/10(8) cells were conjugated by poly-L-lysine, 4.1 +/- 0.8 microgram DNA/10(8) cells by methylated bovine serum albumin and approximately 4 micrograms DNA/10(8) cells when the cells were incubated at 45 degrees C. Cells conjugated with DNA by CrCl3 showed linearly increasing conjugation with increasing concentration of DNA. Cells conjugated by poly-L-lysine (pLL) or methylated bovine serum albumin seemed to be saturated by DNA at 30 micrograms DNA per 10(8) cells. At 45 degrees C the spontaneous adhesion of DNA to SRBC increased in the concentration range investigated. The degree of conjugation of DNA to SRBC was influenced by pH, and Ca2+.pLL-conjugated DNA-SRBC, but none of the other preparations were lysed in a hemolytic assay using anti-DNA antiserum from a patient with systemic lupus erythematosus.
The proposal that the beta-alanine carrier of the rabbit ileum is a high affinity carrier of the neutral amino acids was examined by means of measurements of influx across the brush border membrane of the intact epithelium using L-alanine as a representative of the neutral amino acids. Confirming the proposal, evidence was provided for mutual competitive inhibition between beta-alanine and L-alanine; and it was also demonstrated that a process contributes to the influx of L-alanine, which is characterized by a maximum rate of transport equal to that of beta-alanine and a Kt, which is equal to the Ki of L-alanine against the influx of beta-alanine. In the concentration range 0.01 to 0.125 mM the influx of L-alanine was found to be linearly related to the concentration indicating a significant unstirred layer influence on present and previous estimates of the Kt values for influx of amino acids across the brush-border membrane of intact intestinal epithelia.
The binding of monoclonal antibodies against CD4 was specifically inhibited by treatment of human CD4+ cells with either alkaline protease (AP) or elastase (Ela), purified from Pseudomonas aeruginosa. Binding of antibodies against CD3 (pan T), CD5 (pan T), CD8 (T suppressor/cytotoxic), HLA-ABC, HLA-DR, HLA-DQ, HLA-DP/DR, and beta 2 microglobulin was not inhibited by AP or Ela. Heat-inactivation of the proteases at 65 degrees C for 20 min or treatment with the metal chelator EDTA abolished the inhibitory activity of both proteases. These findings may serve to develop novel immunological methods for the isolation and study of the lymphocyte CD4 structure, which plays an important part in the immune response.
The CEJ on radiographs is often used as a reference point in the assessment of alveolar bone loss. The aim of the present study was to test the stability of the radiographic CEJ ("RCEJ") in relation to the alveolar crest under varying angulations of the central X-ray beam. In an experimental model four types of extracted teeth were radiographed at 0 degree and 20 degrees vertical angulation and at 15 horizontal angulations varying from a 17.5 degrees mesial view to a 17.5 degrees distal view. The buccal alveolar bone margin was simulated by a steel needle. RCEJ-"crest" distances were read at a X 10 magnification. Changing the vertical angulation from 0 degree to 20 degrees reduced the RCEJ-"crest" distances for all tooth types (range of average reduction 2.2-4.1 mm). Horizontal angulations without concomitant vertical angulation had a significant effect but were without clinical significance. Horizontal angulations in combination with a 20 degrees vertical angulation had a considerable influence; in a mesial view, mesial RCEJ-"crest" distances decreased and distal ones increased, and vice versa in a distal view. The deviations from the true CEJ-crest distance demonstrated may be of clinical significance, and a critical attitude to alveolar bone loss measures on radiographs using the RCEJ as reference point is recommended.
Fifty-four patients with systemic lupus erythematosus (SLE) were examined for (1) CR1 (C3b/C4b receptor) levels on erythrocytes by an enzyme-linked immunosorbent assay, (2) levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and (3) concentrations of C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. A preponderance of low CR1 levels was found among patients with SLE (mean 40%, range 13-106) as compared with normal controls (mean 70%, range 24-130) (p less than 0.001). The concentrations of circulating IC were elevated in 38% of 58 samples. The concentrations of C3d were elevated in 72%, and were positively correlated with the levels of IC (tau = 0.28; p less than 0.005) and with disease activity as assessed by a modification of the UCH/Middlesex criteria. Negative correlations were seen between the CR1 numbers and disease activity (p = 0.01), concentrations of circulating IC (tau = -0.14; p less than 0.005), and C3d (tau = -0.21; p less than 0.005). The changes found in CR1 levels on repeated study were, however, relatively small (less than or equal to 27%; median 5), even during periods of changing disease activity.
Natural killer (NK) cell activity against K562 target cells was measured in patients within 24 h of acute myocardial infarction (AMI) and regularly thereafter for 6 weeks. NK cell activity was suppressed on days 1, 3, and 7 (P less than 0.01), day 14 (P less than 0.05) and at 6 weeks (P = 0.05) when compared to controls. Interferon, interleukin 2 and indomethacin enhanced NK cell activity on all days measured, but did not completely restore the defective NK cell activity. Serum from the patients did not suppress the NK cell activity of healthy mononuclear cells. The number of NK cells, identified as large granular lymphocytes (LGL), measured on days 1, 3, and 14 and at 6 weeks was not reduced in comparison to that of controls. Thus, the defective NK cell activity can be characterized as functional.
In 5 consecutive patients with rheumatoid arthritis who received intravenous high-dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high-dose MP is recommended. High-dose MP may be contraindicated in patients with known heart disease.
As it has been shown that the natural killer (NK) cell activity is depressed and the prostaglandin (PG) metabolism is disturbed in patients with primary Sjögren's syndrome (primary SS), we examined the in vitro effect of indomethacin on the NK cell activity. The NK cell activity against K 562 target cells was measured in 20 female patients with primary SS and in 18 female normal controls matched for age. Blood mononuclear cells were incubated with indomethacin (1 microgram/ml). Median baseline NK cell activity in primary SS was 15.4% (range 5.8-50.4) versus 24.7% (range 6.2-47.4) in the controls (p less than 0.05). After in vitro exposure to indomethacin median NK cell activity in the patients was 21.2% versus 34.9% in the controls (p less than 0.02). Indomethacin-enhanced NK cell activity was significantly higher than baseline NK cell activity in both patients (p less than 0.05) and controls (p less than 0.01), but the NK cell activity of the patients was significantly less enhanced than that of the controls (p less than 0.02). We conclude that the impaired indomethacin-boosting of NK cell activity in patients with primary SS probably reflects a decreased capacity of blood mononuclear cells to produce PG in vitro.
The four most frequently used criteria for definition of Sjögren's syndrome--the Copenhagen, the Japanese, the Greek and the Californian criteria--are critically evaluated. The article focuses on the similarities and the dissimilarities as well as the advantages and the disadvantages between the various sets of criteria.