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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 307 records · Page 17Linked to original sources
PubMed1986

Complement C3b receptors on erythrocytes, circulating immune complexes, and complement C3 split products in patients with primary Sjögren's syndrome.

Twenty-one patients with primary Sjögren's syndrome (SS) and 22 age- and sex-matched healthy controls were examined for levels of C3b receptors (CR1) on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation complement consumption method), and C3 split products, C3d and C3c (by intermediate gel rocket immunoelectrophoresis). CR1 varied within a wide range (20-124%), and a preponderance of low numbers was found among patients with primary SS (P less than 0.05). The levels of circulating IC and C3d were elevated in primary SS patients (P less than 0.01) and were mutually correlated (P less than 0.01; tau = 0.5), but levels of circulating IC and C3d did not correlate with CR1 values. C3c concentrations were the same in patients and controls. It is possible that the CR1 level serves as a predictor for the development of IC-induced manifestations, and the C3d concentration serves as an objective parameter for disease activity in primary SS.

Adult↗
PubMed1986

An intron in a ribosomal protein gene from Tetrahymena.

We have cloned and sequenced a single copy gene encoding a ribosomal protein from the ciliate Tetrahymena thermophila. The gene product was identified as ribosomal protein S25 by comparison of the migration in two-dimensional polyacrylamide gels of the protein synthesized by translation in vitro of hybrid-selected mRNA and authentic ribosomal proteins. The proteins show strong homology to ribosomal protein S12 from Escherichia coli. The coding region of the gene is interrupted by a 979-bp intron 68 bp downstream of the translation start. This is the first intron in a protein encoding gene of a ciliate to be described at the nucleotide sequence level. The intron obeys the GT/AG rule for splice junctions of nuclear mRNA introns from higher eukaryotes but lacks the pyrimidine stretch usually found in the immediate vicinity of the 3' splice junction. The structure of the intron and the fact that it is found together with the well described self-splicing rRNA intron is discussed in relation to the evolution of RNA splicing.

Journal Article↗
PubMed1986

Enhancement of defective monocyte function during immunotherapy with recombinant interferon.

The influence of immunotherapy with high dose (50 X 10(6) units/m2) recombinant leukocyte A interferon on blood monocyte functions was studied in eight patients with bronchogenic carcinoma. Monocyte chemotactic responsiveness (MCR) was initially depressed (9.8 +/- 1.6 cells/field) compared to healthy controls (17.6 +/- 5.1 cells/field), P less than 0.01. Recombinant interferon was administered three times weekly, and after 7 days a significant improvement in chemotaxis was observed (16.6 +/- 3.0 cells/field), P less than 0.05. The MCR remained normal until cessation of interferon therapy (greater than 1 month). Phagocytic and candidacidal activities were normal in the patients and were not influenced by treatment with interferon. In conclusion, high dose recombinant interferon given to cancer patients caused a normalization of defective blood monocyte chemotaxis, which persisted for greater than 1 month.

Adjuvants, Immunologic↗
PubMed1986

Acute and long-term nephrotoxicity of cis-platinum in man.

To detect whether the nephrotoxicity of cis-diamminedichloroplatinum (DDP) is acute and can be demonstrated at an early stage in man, a method for estimating the function of the kidneys during intensive hydration was devised. The method includes a calculation of the clearance of 125I-orthoiodohippurate and an estimation of the glomerular filtration rate (GFR) from fast changes of the extracellular volume (ECV) and the mean transit time of 99mTc-DTPA in this volume. We examined nine patients with testicular cancer on 2 consecutive days for acute nephrotoxicity while they were undergoing treatment with cis-platinum. Placebo was given on day 1, cis-platinum on day 2. On both days the patients were hydrated with 4 l saline, glucose, and mannitol (0.51) over a period of 4 h, which resulted in an increase of 125I-orthoiodohippurate clearance on both days (P less than 0.01). The increase was, however, lower on the day of treatment with cis-platinum than on the day with placebo (P less than 0.05). There were no acute changes in the GFR. This indicates that treatment with DDP inhibits the active transport of 125I-orthoiodohippurate in the tubules; that is to say there is an acute effect on the kidney function. There were no acute changes in the GFR, but in the long-term followup study we found that the GFR had decreased significantly (P less than 0.05) after 2 months of treatment. During the first year after the initiation of treatment the GFR changes were found to progress. A significant increase in se-creatinine was not observed until 6 months after the initiation of treatment (P less than 0.05). The degree of chronic nephrotoxicity did not correlate in individual patients with the acute changes in kidney function.

Acute Disease↗
PubMed1986

Augmentation of human blood monocyte microbicidal activity by RU 41740, a glycoprotein extract from Klebsiella pneumoniae.

Non-specific activation of host defences may have a significant impact on the outcome of infections in the immunocompromized patient. RU 41740, a glycoprotein extract from Klebsiella pneumoniae, effective in increasing resistance to experimental infections in animals, has been examined in vitro for its effect on human blood monocyte locomotion, phagocytosis, killing of Candida albicans, and release of superoxide anion. RU 41740 had no chemo-attractant activity nor any effect on monocyte chemotactic and phagocytic function. Candidacidal capacity and superoxide anion production by monocytes were significantly enhanced after preincubation with RU 41740 greater than 1.0 microgram/ml. The effect was dose- and time-dependent and was not influenced by the presence of lymphocytes or their culture supernatants. This suggests a direct interaction with monocytes as the mechanism of action of the extract.

Adjuvants, Immunologic↗
PubMed1986

In vitro effect of fansimef on human neutrophil and monocyte function.

The effect of Fansimef, a recently registered triple combination of mefloquine, sulfadoxine and pyrimethamine (10:25:1) on human peripheral blood polymorphonuclear and mononuclear leucocyte function was studied. At clinically obtainable concentrations Fansimef had no effect on leucocyte viability, it did inhibit neutrophil chemiluminescence and it had no effect on other major functions, such as chemotaxis, NBT reduction, superoxide production, phagocytosis and the bactericidal activity of phagocytic cells.

Blood Bactericidal Activity↗
PubMed1986

Antiemetic effect and pharmacokinetics of high dose metoclopramide in cancer patients treated with cisplatin-containing chemotherapy regimens.

Fifteen cancer patients receiving cisplatin-containing chemotherapy participated in two antiemetic studies. In Study 1 they received standard antiemetics in low doses on demand, and in Study 2 the same patients participated in an open randomized cross-over study between metoclopramide 1 and 2 mg/kg i.v. X 5. Serum metoclopramide was determined by HPLC. Self-reporting of nausea using a visual analogue scale (VAS) was compared with observer rated scores. Tolerability and volume vomited were assessed by nurse observers. The biological half-life of metoclopramide was 9.9 h, the volume of distribution was 9.9 l/kg and the clearance was 0.68 l/h/kg. The pharmacokinetics of high dose metoclopramide was linear in the range 0.15-2 mg/kg X 5, with very little accumulation. Compared to standard antiemetics, both high dose regimens of metoclopramide had a significant effect on nausea, but no effect on the volume vomited. Self reports of nausea were significantly correlated with observer rated values. Tolerance of high dose metoclopramide was good except in 3 patients who left the study because of restlessness and trismus. It is concluded that high dose metoclopramide probably can be administered for several consecutive days without appreciable accumulation of the drug. Self-reporting of nausea by patients on VAS is a simple and feasible method of evaluation. The finding that metoclopramide affects nausea but not vomiting supports the hypothesis that nausea and vomiting should be evaluated separately in assessing antiemetic efficacy.

Adult↗
PubMed1986

Immunostimulation of blood monocyte function by RU 41.740 (Biostim) in patients with chronic bronchitis.

RU 41.740 (Biostim), a glycoprotein extract from Klebsiella pneumoniae, which is effective in heightening resistance to experimental infections in animals, was examined with regard to influence on human blood monocyte function in vitro after administration to patients with chronic bronchitis in a randomized, double-blind clinical trial. Twelve patients were given Biostim orally (seven patients received 8 mg daily and five patients received 2 mg daily) while eight patients received placebo. In the Biostim group monocyte phagocytosis increased from 1.4 yeast cells per monocyte before therapy to 3.1 yeast cells per monocyte after 1 month (P less than 0.05) with no further increase after 3 months. Monocyte candidacidal activity increased in the Biostim group from 51% before therapy to 69% after 1 month (P less than 0.05) with a decrease to 57% after 3 months. As expected, placebo had no significant effect on monocyte functions. There was no difference between the improvement in the high dose vs the low dose group. These results suggest that Biostim exerts part of its immunostimulatory property by stimulating blood monocyte antimicrobial function.

Adjuvants, Immunologic↗
PubMed1986

A new transhepatic endoprosthesis to prevent dislodgement.

A new transhepatic endoprosthesis, a so-called screw endoprosthesis with a spiral-shaped elevation to prevent dislodgement, is presented. The elevation is created by a silver wire wound around the endoprosthesis. Further, the wire may be used as a marker for radiotherapy or for taking biopsies, and it makes it easier to control the position of the endoprosthesis. The screw endoprosthesis was used in 22 patients, including 9 patients with high strictures in which dislodgement is known to be frequent, and 2 patients in whom previously inserted ordinary endoprostheses had been dislodged. The insertion of the screw endoprosthesis was easy. The complication rate was similar to that of ordinary transhepatic endoprosthesis. No cases of dislodgement were observed.

Adult↗
PubMed1986

Defective monocyte function in Legionnaires' disease complicating hairy cell leukaemia.

We describe a case of Legionnaires' disease in a 64-year-old man, in which hairy cell leukaemia was diagnosed after the onset of the infection. Immunological studies revealed a complete suppression of blood monocyte chemotactic and oxidative burst activities. We suggest that in hairy cell leukaemia both monocytopenia and defective functions of monocytes underlie the increased susceptibility to intracellular infections including Legionnaires' disease.

Diabetes Mellitus, Type 2↗
PubMed1986

Monocyte chemotactic properties in hereditary hemochromatosis.

Several observations indicate that the innate metabolic defect in hereditary hemochromatosis (HH) leads to a defective function of the monocyte-macrophage system. The present study was performed to investigate the possibility that a defect in migration of cells of the monocyte-macrophage system can explain the abnormal location of the submucosal macrophages in HH. Monocytes isolated from 14 patients with HH were investigated with regard to chemotactic responsiveness (MCR). Two different methods were used at two different laboratories. Casein and zymosan-activated serum were used as attractants. No difference in MCR was found between the control group and the group of HH patients. The conclusion can therefore be drawn that the abnormal location of the macrophages of the gut wall in HH cannot be explained by an inborn abnormality of the function of receptors responsible for the chemotactic activity of the monocyte-macrophage system. It is, however, still possible that local factors responsible for the macrophage migration (gut hormones?) may have defective activity in HH patients.

Adult↗
PubMed1986

Effects of Legionella pneumophila sonicate on human neutrophil granulocyte and monocyte chemotaxis.

The interaction of L. pneumophila serogroup 1 sonic extract with human polymorphonuclear neutrophils and monocytes was studied in an in vitro chemotaxis assay. The sonicate showed heat-stable chemotactic activity towards neutrophils and monocytes. It also exhibited cytotoxicity for neutrophils but not for monocytes. Incubation and pretreatment with the sonicate at apparently non-toxic concentration resulted in inhibition of the chemotactic response of neutrophils to various chemoattractants while monocyte chemotaxis was unaffected. The inhibitory activity was reduced to one half by heat treatment of the sonicate. High endotoxic activity was demonstrated in both heated and non-heated extract. Only two antigens (nos 1 and 61) were identified in the sonicate exposed to 121 degrees C for 1 h. It is therefore suggested that the lipopolysaccharide (no. 61) of L. pneumophila could contribute to the chemotactic activity. The adverse effects exerted by L. pneumophila on neutrophils may be one of the mechanisms by which Legionella bacteria resist the normal phagocytic host defenses.

Antigens, Bacterial↗
PubMed1986

Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria.

The host response to Plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivation in vivo or a direct suppressive effect of plasmodia induced products.

Antimalarials↗
PubMed1986

Blood monocyte and neutrophil functions in the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is characterized by infections with microorganisms against which phagocytes (especially monocytes/macrophages) play an important role. Therefore, various functions of blood monocytes and neutrophils were tested in 16 patients with AIDS. Neutrophil chemotactic responses towards casein and N-formyl-methionyl-L-leucyl-L-phenylalanine were depressed in patients with a short duration of disease (n = 9), whereas they were normal in those with a longer duration (n = 5), P less than 0.05. Neutrophil superoxide anion release was normal. In contrast, we found no evidence of an altered monocyte activity in the patients, since chemotactic responsiveness, phagocytosis of opsonized Candida albicans, and superoxide anion release were all normal. These findings suggest that the depressed neutrophil chemotaxis may play an important role in the high incidence of opportunistic infections in AIDS. Furthermore, it appears that in AIDS the immune deficiency does not extend to peripheral blood monocytes, but it does not exclude the possibility that the function of tissue macrophages is abnormal.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Erythrocyte CR1 determination using monoclonal antibody in a microtiter plate ELISA; receptors are not masked by immune complexes.

The microtiter plate ELISA using monoclonal antibody is a specific, sensitive and quantitative technique for measuring CR1 on human erythrocytes. The present investigations established that receptor occupancy by immune complexes did not affect the measurements. The monoclonal anti-CR1 antibody To5 bound unimpeded to receptors that had reacted with an excess of complement-opsonized tetanus toxoid anti-tetanus toxoid complexes prepared at antigen:antibody ratios between 32:1 and 1:8. The CR1 levels on erythrocytes from 11 patients with systemic lupus erythematosus (SLE) were not increased (P greater than 0.30) after release of CR1-bound immune complexes by incubation with factor I. Neither did the serum from these patients contain blocking anti-CR1 activity (P greater than 0.10). Additionally, the number of antigenic CR1 sites in 10 normals and in the 11 patients with SLE was well correlated with the number of functional receptor sites as assessed by binding of soluble complexes (P less than 0.001). These data establish that the true CR1 levels are determined using the microtiter plate ELISA for quantitation of CR1 in patients with diseases involving immune complexes and/or autoantibodies.

Antibodies, Monoclonal↗
PubMed1986

Release of immune complexes bound to CR1 on erythrocytes; suramin inhibits factor I in the presence of EDTA.

An experimental model was established in order to study the release of immune complexes (IC) bound by complement C3b receptors (CR1) on human erythrocytes (RBC). Soluble tetanus toxoid anti-tetanus toxoid complexes were incubated with RBC in the presence of autologous serum at optimal conditions for binding. The RBC carrying complement-opsonized complexes were incubated with appropriate serum reagents, and it was shown that factor I was required for release of the complexes, which occurred without loss of CR1. Suramin was, irrespective of factor I, found to induce release of CR1-bound IC in the absence of EDTA, whereas factor I-mediated release was inhibited by suramin in the presence of EDTA. EDTA probably interfered through a charge-dependent interaction. These observations are decisive for the interpretation of in vitro experiments involving these reagents. The combination of EDTA and suramin was found inappropriate for use in quantitative determination of in vivo CR1-bound IC.

Antigen-Antibody Complex↗