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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 325 records · Page 18Linked to original sources

Inhibition of natural killer cell activity by antigen-antibody complexes.

The natural killer (NK) cell activity of human peripheral blood mononuclear cells was found to be inhibited by precipitated tetanus toxoid anti-tetanus toxoid complexes (Te/aTe) as well as soluble Te/aTe. Preincubation of the immune complexes with protein A decreased the inhibition of NK cell activity. When mononuclear cells were preincubated with interferon (IF) or interleukin 2 (Il-2) before incubation with Te/aTe, the immune complex-induced inhibition was decreased, while IF or Il-2 added after incubation with the immune complexes had no effect. Using NK cell-enriched suspensions in a single cell agarose assay, the immune complexes were shown to inhibit NK cell activity by inhibiting the formation of effector/target cell conjugates.

Antigen-Antibody Complex↗

Reversible ischemic neurological deficit and minor strokes before and after EC/IC bypass surgery. A neuropsychological study.

Thirty-three patients with reversible ischemic deficits or completed minor strokes had their cerebral function measured neuropsychologically a few days before and 3 months after extra-intra cranial bypass surgery. Three months post-operatively bypass patency was demonstrated by angiography. Ten patients were operated on the right side and 23 on the left side. The right hemisphere patients were found to be neuropsychologically intact or only slightly impaired before, as well as after, the operation whereas the left hemisphere patients pre-operatively had impaired verbal sequential thinking, reduced capacity for repetition, verbal learning, and mental arithmetic. Post-operatively they improved significantly on 5 of 15 tests and performed no worse on any test than the control group. Consequently, they, too, had post operatively no or only slight neuropsychological impairment.

Adult↗

Thalidomide enhances superoxide anion release from human polymorphonuclear and mononuclear leukocytes.

The effect of thalidomide on the function of human polymorphonuclear leukocytes (PMNs) and blood monocytes was tested in vitro. The chemotactic and spontaneous migration was not affected by thalidomide between 0.001 and 0.1 mg/ml. PMN oxygen consumption was not changed after pre-incubation with thalidomide. However, superoxide anion release upon stimulation of the cells with phorbol-myristate-acetate or the chemotactic tripeptide N-f-Methionyl-Leucyl-Phenylalanine was enhanced in a dose-dependent manner after pre-incubation with thalidomide. Both PMNs and monocytes were influenced. Leukocytes from two patients with chronic granulomatous disease (defective in oxidative burst response) remained unable to produce superoxide anion after pre-incubation with thalidomide. Thus, we suggest that thalidomide primes the phagocytes to respond with an enhanced superoxide anion release upon stimulation. These findings do not explain the anti-inflammatory effect of thalidomide but could have relevance in conditions with quantitative defects in phagocyte oxidative responsiveness.

Chemotaxis↗

Normal distribution of complement C3b receptor (CR1) numbers on erythrocytes in blood donors: low levels are associated with HLA-B27.

Blood donors were examined for C3b receptor (CR1) levels on erythrocytes by a microtiter plate enzyme-linked immunosorbent assay and for HLA-A, -B, and -C antigens, C3 phenotypes and blood groups. The CR1 levels among 150 donors varied in the range from 24 to 130% (mean +/- 1 SD = 69.9 +/- 22.9) of an erythrocyte standard, and in accordance with a polygenic model of inheritance the distribution of CR1 was well approximated by a normal curve (chi-square goodness-of-fit test nonsignificant, p = 0.66). Low CR1 levels were associated with HLA-B27 (n = 11, p = 0.05), which was confirmed by investigation of further 20 HLA-B27-positive donors (p = 0.05). The CR1 levels were not associated with a certain C3 phenotype. Possibly, the blood group phenotype M-M + S-s+ is associated with high and the S antigen with low CR1 numbers. The relation between low CR1 numbers and HLA-B27 might be important for the understanding of the association between HLA-B27 and certain inflammatory rheumatological diseases.

Blood Donors↗

Late-onset rubella syndrome: coexistence of immune complex disease and defective cytotoxic effector cell function.

We studied a classical case of late-onset rubella syndrome characterized by multi-organ disease and persistence of live rubella virus in spite of high titres of specific antirubella antibodies and presence of large amounts of circulating immune complexes. When first studied at the age of 5 months there was a low proportion of T8+ lymphocytes. Functional studies revealed decreased activity of K and NK cells as well as alloreactive direct cytotoxic cells (CTL). Removal of cell-bound immunoglobulin and immune complexes tended to improve K and NK cell function in vitro. Plasma exchange transfusions carried out at 9 months of age resulted in clinical improvement. Normalization of cytotoxic effector cell functions and cessation of viremia accompanied recovery from active disease. The results indicate that defective cytotoxic effector cell function is the primary cause for the defective virus elimination in this syndrome.

Antibodies, Viral↗

Erythrocyte complement C3b receptor (CR1) levels and immune complex-induced manifestations in patients with primary Sjögren's syndrome.

To assess the importance of low C3b receptor (CR1) numbers on erythrocytes for the development of clinical features in patients with primary Sjögren's syndrome (SS), two groups of patients were selected for investigation--one without (n = 13), and one with (n = 21) extraglandular, possibly immune complex-induced, clinical manifestations during the disease course. A preponderance (p less than 0.01) of low CR1 levels was found in patients with primary SS (mean 57%) as compared with normal controls (mean 70%), but the CR1 levels did not differ between the two groups of patients. The CR1 values did not correlate with the levels of circulating immune complexes and C3d. Although the preponderance of low CR1 levels is pathogenetically intriguing, it appears to be of little help in the clinical assessment of patients with primary SS.

Antigen-Antibody Complex↗

Complete heart block in Reiter's syndrome.

Complete heart block with Stokes-Adams attacks was diagnosed in a 30 year old male, who had suffered from a Reiter's syndrome for only 3 1/2 years. The heart block was unaffected by treatment with high dose corticosteroids, and a permanent pacemaker was implanted. There were no signs of concomitant aortic insufficiency or spondylitis/sacroiliitis.

Adams-Stokes Syndrome↗

Association of defective monocyte chemotaxis with recurrent acute exacerbations in chronic obstructive lung disease.

Since mononuclear phagocytes are crucial in resisting microbial challenge in the lung, selected functions of blood monocytes were studied in 27 patients with chronic bronchitis (19 with hypersecretory symptoms and many acute infectious exacerbations and eight with obstructive symptoms without recurrent infections), and compared with 82 healthy controls. While monocytes from patients with solely obstructive symptoms had a normal migratory function, both spontaneous and chemotactic migration were depressed in the patients with hypersecretory symptoms. Phagocytic activity of the blood monocytes was equally depressed in both subgroups. Intracellular killing of Candida albicans was normal in all patients when compared with smoking control subjects. Chemotactic responsiveness was thus decreased only in patients with hypersecretory symptoms, suggesting that a defect in monocyte migration in these patients might contribute to the high incidence of acute bronchial exacerbations.

Aged↗

Sequence comparison of the rDNA introns from six different species of Tetrahymena.

We have studied the sequence variation of the rDNA intron among six species of Tetrahymena. From these data, the intron appears to be relatively well conserved in evolution. We have evaluated the sequence variations among the most distant of these species in relation to the secondary structure model for the intron RNA of Cech et al. (Proc. Natl. Acad. Sci. U.S.A. 80, 3903 (83)). Most of the sequence variation in the four new sequences reported here is found in single stranded loops in the model. However, in four cases we found nucleotide substitutions in duplex stem regions, two of them involving compensating base pair changes. Interestingly, one of these is found in a region that is known to be dispensable in the in vitro splicing reaction suggesting differences between the in vivo and in vitro reactions. One of the single nucleotide deletions is found in the so-called "internal guide sequence" which has been implicated in the alignment process during splicing. In conclusion, none of the observed natural sequence variations are in disfavor of the proposed secondary structure model.

Base Sequence↗

A microtiter plate enzyme-linked immunosorbent assay for measuring C3b receptors on human erythrocytes.

An enzyme-linked immunosorbent assay was developed for quantitation of complement C3b receptors (C3bR) on human erythrocytes fixed in monolayer to microtiter plates. The disadvantages of macro test tube systems (large consumption of sample material and reagents, tedious washing procedures, cell loss and hemolysis) were avoided, and the fixed cells could be stored. In return a modest reduction in antigenicity induced by glutaraldehyde was inevitable. The calibration curve expressed a detection limit of about 10% and discrimination between levels of C3bR in the interval of about 10-120% of a standard erythrocyte with a high uptake of anti-C3b-receptor antibodies. The determinations of C3bR in normals as well as in patients varied within these limits, and showed a preponderance of low levels in the patients. The between-day coefficient of variation was 10.3%; the within-assay interplate and intraplate determinations respectively gave coefficients of variation of 9.7% and 6.2%. The method is suitable for further development and use for investigation of erythrocyte-bound immune complexes.

Antibodies, Monoclonal↗

Functional intron+ and intron- rDNA in the same macronucleus of the ciliate Tetrahymena pigmentosa.

Diallelic clones of Tetrahymena pigmentosa containing equal amounts of intron+ and intron- rDNA in the macronucleus were constructed. The macronucleus of the resulting strains divides amitotically during vegetative growth and the diallelic genotype is therefore unstable. The coexistence of the two alleles was followed in the total culture and in single cells during their vegetative segregation and it was observed that replication was non-preferential with respect to the two alleles. The diallelic clones were also used to demonstrate that intron-containing rDNA was transcribed and the transcript processed in the presence of corresponding intron- rDNA. The results are discussed in the light of the 'non-function' idea for ribosomal RNA introns.

Alleles↗

Monocyte chemotaxis in patients with nonseminomatous testicular carcinoma. Effect of chemotherapy.

The chemotactic responsiveness of blood monocytes was tested in 16 patients with nonseminomatous testicular carcinoma before, during, and after chemotherapy. All the patients initially had monocyte chemotaxis within the normal range. No correlation with the histology of the tumor, the clinical stage, or the presence in serum of alpha-fetoprotein and human chorionic gonadotropin was observed. Plasma from the patients did not inhibit the chemotaxis of normal monocytes, and serum from the patients contained no chemotactic factor inhibitor. During intensive chemotherapy with cis-platinum, bleomycin, and vinblastine a reversible defect in chemotaxis occurred without correlation to the development of fever. Two months after the completion of chemotherapy the chemotactic responsiveness was unchanged compared with pretreatment values. In conclusion, this study shows normal monocyte chemotaxis in patients with testicular carcinoma, which is in contrast to reports on a variety of other solid tumors.

Adolescent↗

Plasmapheresis in hyperviscosity syndrome.

Three patients with Waldenström's macroglobulinaemia developed circulatory complications due to increased plasma viscosity, i.e. relative viscosity value above 4. Plasmapheresis was performed either in a Haemonetics 30 S cell separator, by plasma filtration through a CPS 10 TM filter or by a double-double pack Fenwal system. All three methods reduced the plasma viscosity and abolished the clinical symptoms. In cases of acute hyperviscosity syndrome, apheresis of small amounts of plasma by the double-double pack system may serve as an alternative to the more advanced techniques.

Adult↗

Demonstration of circulating immune complexes by the indirect leucocyte phagocytosis test in chronic inflammatory bowel disease. Relation to results of a standard complement consumption assay.

Circulating immune complexes were studied in untreated Crohn's disease (CD) and ulcerative colitis (UC) by leucocyte phagocytosis. Neutrophils from normal donors took up large immunoglobulin-containing inclusions from 14 of 15 CD sera, 3 of 15 UC sera (p less than 0.002) and from none of 15 reference sera from healthy volunteers (p less than 0.002). In contrast, inclusions could not be demonstrated on direct microscopic investigation. Our study confirms the presence of circulating immune complexes in Crohn's disease. Predominance of IgG-containing complexes in this condition is consistent with a mucosal origin. Discrepant results obtained by direct examination and by incubation of sera from patients with normal test neutrophils suggest a defective immune complex phagocytosis in CD. In consistency with this possibility, control experiments revealed a markedly decreased complex uptake by neutrophils of CD patients in vitro.

Antigen-Antibody Complex↗

Effect of cyclosporin A on human neutrophil and monocyte function.

The effect of various concentrations of cyclosporin A (CyA), ranging from below peak blood levels to 20 times higher than blood levels of human peripheral blood polymorphonuclear and mononuclear leukocytes, was examined. CyA was found to bind to neutrophils with Kd values in the range of 20-50 nM. CyA at clinically obtainable blood level concentrations had no effect on neutrophil and monocyte chemotaxis, neutrophil oxidative burst, monocyte phagocytosis, or neutrophil bactericidal activity. The data on the release of lactoferrin, a secondary granule substance, from activated neutrophils showed that the calcium ionophore A 23187-induced lactoferrin release was inhibited by treatment of cells with 4 microM CyA, whereas release of lactoferrin from zymosan- or phorbol myristate acetate-activated neutrophils was not affected by the same concentration of CyA. This effect could either be due to differences in the degree of cell membrane perturbation by the various activators or to calcium dependence of neutrophil activation. A third possibility may be that CyA acts at some subsequent steps in the release process of neutrophils. It is concluded that CyA does not interfere with important functions of human phagocytes, the cells that play a major role in the defence against invading microorganisms.

Binding Sites↗

Humoral autoimmune manifestation in subacute thyroiditis.

To study the autoimmune manifestations in subacute thyroiditis (SAT), the patterns of thyroid antibodies, thyroglobulin and circulating immune complexes were investigated in 10 patients during the course of the disease. Eight patients were thyrotoxic at diagnosis, and became euthyroid during recovery with a median observation of 8 months (4-30 months). Thyroid stimulating immunoglobulins were measured as TSH binding inhibiting immunoglobulins (TBII) and as thyroid stimulating antibodies (TSAb). TBII were present in all patients at least once during the observation period and remained detectable in six patients after recovery. TSAb were detected in three patients without relation to the hyperthyroid state. Thyroglobulin antibodies (TgAb) were present in four patients and persisted in three, while microsomal antibodies (MAb) were negative. Thyroglobulin (Tg) in the TgAb negative patients (n = 6) was high at diagnosis (median 229 micrograms/l, range 55-375) and fell rapidly during the course of SAT. Circulating immune complexes (CIC), which were found in all patients, reached maximal levels shortly after the onset of the disease and persisted after recovery. No correlation could be demonstrated between the different thyroid antibodies, and there was no clear relation between the levels of CIC and presence of the autoantibodies. However, the changes in CIC paralleled the changes in TBII, and it is suggested that immune complex formation is a major feature of the regulatory mechanisms controlling the immune responses in SAT.

Adult↗