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Biomedical subjects

V Andersen

Publications and source records attributed to V Andersen.

At least 73 records · Page 4Linked to original sources

In vitro studies of theophylline-induced changes in Na, K and Cl transport in hen (Gallus domesticus) colon suggesting bidirectional, basolateral NaK2Cl cotransport.

1. In isolated mucosa from a NaCl-loaded hen theophylline stimulates both unidirectional chloride fluxes (JmsCl and JsmCl). Conductive and electroneutral exchange processes, besides a bumetanide-sensitive, rheogenic process contribute. 2. The bumetanide-sensitive fraction of the theophylline-induced delta JcmCl is sodium-dependent. 3. Incubation in nominally K(+)-free solutions reduces the bumetanide-sensitive fraction delta JsmCl more than treatment with ouabain. 4. With respect to chloride the bumetanide-sensitive fraction of delta JsmCl has a Hill coefficient of 1.93 +/- 0.03, a Jmax of 12.9 +/- 0.2 mumol/cm2.hr and a K 1/2 of 73 +/- 1 mmol/l. 5. After ouabain treatment delta JmsCl and delta JsmCl are equally sensitive to bumetanide, while delta JmsCl is bumetanide insensitive without ouabain treatment.

Animals↗

Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine.

The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide-specific antibody-secreting cells (AbSC) of the isotypes IgM, IgG, and IgA. The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated. AbSC were detected from post-vaccination day 5 to day 14. IgA was the predominant isotype among these cells. IgM AbSC peaked slightly earlier (median day 7) than IgG and IgA AbSC (both day 8). On post-vaccination day 8 the numbers of AbSC were: IgA, 1217/10(6) mononuclear cells (median); IgG, 211; and IgM, 30 (n = 11). Similar isotype distribution has earlier been found after vaccination with pure capsular polysaccharides from Hib and pneumococci. The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide or cross-reacting antigens.

Adult↗

Nephrotoxicity of cyclosporin A in patients with newly diagnosed type 1 diabetes mellitus.

Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian-European randomized placebo-controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12 to 18 months, cyclosporin A caused significant reductions in the glomerular filtration rate (before drug withdrawal, cyclosporin 97 +/- 18 vs placebo 125 +/- 16 ml min-1 1.73-m-2, p less than 0.05), renal plasma flow (454 +/- 83 vs 536 +/- 70 ml min-1 1.73-m-2, p less than 0.05), and lithium clearance (17 +/- 3 vs 28 +/- 5 ml min-1 1.73-m-2, p less than 0.05). The fractional proximal reabsorption was increased (0.82 +/- 0.03 vs 0.78 +/- 0.03, p less than 0.05), and the fractional distal sodium reabsorption reduced (0.88 +/- 0.03 vs 0.94 +/- 0.02, p less than 0.05). These results are in accordance with the hypothesis that the nephrotoxic effect of cyclosporin A results from a preferential constriction of afferent glomerular vessels. One year after withdrawal of the drug, all variables were similar in the two groups, except for blood glucose control which was worse in the cyclosporin A treated group. When corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side-effects of cyclosporin A treatment for 1 year are reversible. There are, however, signs of minor and perhaps chronic renal injury.

Adult↗

Identification and quantification of serum proteins secreted into the normal human jejunum.

The in vivo transfer of serum proteins to the human intestinal lumen was characterized by crossed immunoelectrophoretic analyses of intestinal perfusates from four healthy volunteers. Serum proteins with molecular masses below 100 kDa and the immunoglobulins were found in human jejunal perfusates. Larger serum proteins were either absent (alpha and beta lipoproteins) or present in small amounts (alpha 2-macroglobulin, haptoglobulin and ceruloplasmin). These results demonstrate the existence of a selective transfer of serum proteins to the intestinal lumen under physiological conditions. The intestinal clearance rate was 0.1 ml serum per hour per 10 cm jejunum for albumin, prealbumin, alpha 1-antitrypsin, orosomucoid, transferrin and haemopexin. The rate of secretion of total protein to the jejunal lumen was 100 mg protein per hour per 10 cm jejunum. About 45% was due to immunoglobulins and further 10-15% due to the remaining serum proteins. It is suggested that the serum proteins pass through the epithelium by a transcellular mechanism.

Biological Transport↗

[Herpes zoster in immunosuppressed patients with immuno-inflammatory disease].

We analysed 19 episodes of herpes zoster in 16 patients, who received cytotoxic drugs or cyclosporin for immuno-inflammatory disease. Reactivation of varicella-zoster virus was not associated with increased activity of the rheumatic disease nor with increased intensity of immunosuppressive therapy. Six of the patients who had received the largest cumulative doses of cytotoxic drugs had fever and/or vesicles outside the primarily affected dermatome. Two of these patients developed post-herpetic neuralgia. Although not encountered in this material, immunocompromised patients may develop severe complications of herpes zoster, and therefore prompt treatment with acyclovir is recommended in all cases. It is suggested that oral acyclovir therapy is sufficient in uncomplicated cases but this question has not been elucidated in controlled studies.

Adult↗

NcoI restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNF alpha) region in four autoimmune diseases.

The two-allele NcoI Restriction Fragment Length Polymorphism (RFLP) of the TNF alpha region yielding bands of 5.5 and 10.5 kb was investigated in patients with systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In all four disease, we found a decreased frequency of the 10.5 kb allele which, however, was significant only in the SLE group. In all conditions except RA, the frequency of the 5.5 kb fragment was increased. In pSS and SLE, the frequency of HLA-B8 was increased in 5.5 kb fragment positive patients compared with corresponding controls and thus, the increase of this band and the decrease of the 10.5 kb band may be secondary to HLA-B8 associations owing to strong positive linkage disequilibrium between HLA-B8 and the 5.5 kb band.

Arthritis, Juvenile↗

IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes.

The restriction enzymes MspI and BglII identify two different two-allele restriction fragment length polymorphisms (RFLP) in the human IL-6 genes of healthy Danes. Co-dominant segregation was demonstrated for both marker-systems and the test for Hardy-Weinberg equilibrium showed no significant deviation from expectations. There is a strong correlation between the two marker systems. The two IL-6 RFLP's were studied in Danish patients with rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, and systemic lupus erythematosus. The frequencies of the MspI and BglII marker phenotypes did not differ between healthy controls and the three disease groups. No extra or missing DNA fragments were observed in the disease groups when compared with controls.

Arthritis, Juvenile↗

The occurrence of aminopeptidase N and desquamated cell proteins in intestinal perfusate of the rat.

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.

Aminopeptidases↗

Modulation of natural killer cell activity in peripheral blood by physical exercise.

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.

Adult↗

Decreased B lymphocyte ecto-5'nucleotidase and increased adenosine deaminase in mononuclear cells from patients infected with human immunodeficiency virus.

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.

5'-Nucleotidase↗

Immune hemolytic assay for identification of human anti-dsDNA antibodies with DNA-coated red blood cells as target cells.

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.

Antigen-Antibody Reactions↗