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Biomedical subjects

H M Jansen

Publications and source records attributed to H M Jansen.

At least 109 records · Page 6Linked to original sources
PubMed1994

Variability of IgE-dependent histamine-releasing activity in supernatants of human mononuclear cells.

Histamine-releasing factors (HRF) that release mediators from human basophils by interacting with IgE have been identified from different cell sources, including lymphocytes, monocytes, thrombocytes and endothelial cells. These factors are studied in view of their potential importance as a stimulus in chronic inflammation. In this report we investigated the qualitative variability of the histamine-releasing activity in the supernatants of activated mononuclear cells. Purified human mononuclear cells of 8 donors were activated with streptokinase/streptodornase (SK/SD) and the supernatants (HRF-MN) were tested for histamine-releasing activity (HRA) in both allergic (RAST positive for inhalant allergens) and nonallergic individuals. Four of the eight HRF-MN supernatants were discriminating, i.e. showing no histamine-release response with nonallergic individuals, whereas four supernatants were not. Two of the HRF-MN supernatants that exhibited discriminating properties were studied in more detail. The response to HRF-MN was tested (1) in a direct bioassay on basophils of allergic (RAST positive for inhalant allergens) and nonallergic individuals and (2) in an indirect bioassay with 70% pure basophils of RAST-negative donors after passive sensitization with sera of allergic donors. An association was found between the response to HRF-MN and the RAST for inhalant allergens: none (0/12) of the RAST-negative but 15/22 of the RAST-positive individuals were HRF-MN responders. The IgE dependency of HRF-MN was shown e.g. by inhibition of passive sensitization by preincubating a responder serum with monoclonal antibody (moAb) anti-IgE MH25-1. Our results are in contrast with findings of other investigators who use pooled supernatants and demonstrated HRF-MN responsiveness with both allergic and nonallergic donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Basophils↗
PubMed1994

Analysis of plasma-protein leakage and local secretion in sputum from patients with asthma and chronic obstructive pulmonary disease.

In order to assess the usefulness of sputum analysis in studying plasma-protein exudation and local secretion of proteins in the airways, we measured specific proteins in the sputum sol phase (SSP) and sputum gel phase (SGP) from patients with stable asthma or chronic obstructive pulmonary disease (COPD). Protein levels in SSP showed relatively small variations between two subsequent visits of each patient (n = 22), as also reflected by intraclass correlation coefficients above 0.79. Protein levels differed between SSP and SGP, but inclusion of the SGP data did not affect the variation of protein levels in sputum. The degree of plasma-protein leakage was estimated from the relative coefficients of excretion (RCE) of alpha 2-macroglobulin and albumin (QA2M/QALB), and of alpha 2-macroglobulin and ceruloplasmin (QA2M/QCP), which do not depend on variable dilution of sputum. Despite the heterogeneity of the study group of 26 patients with asthma (atopic [13] smokers [13], including five patients using inhaled steroids), QA2M/QALB and QA2M/QCP correlated both with bronchial hyperreactivity (Spearman rank: r = -0.45 and r = -0.36, p < 0.05) and with blood eosinophil counts (r = 0.37 and 0.56, p < 0.05). We conclude that protein levels in SSP are relatively constant in patients with stable asthma or COPD; in patients with asthma, the plasma-protein leakage, as measured with the RCE in SSP, appears to correlate with indirect indices of airway inflammation.

Adult↗
PubMed1994

Peptide specificity and HLA restriction do not dictate lymphokine production by allergen-specific T-lymphocyte clones.

Human and murine CD4+ T lymphocytes can be subdivided into distinct subsets [T-helper type 0 (Th0), Th1 or Th2], based on their lymphokine production profiles. Not much is known about the factors that determine these restricted lymphokine secretion profiles. Peptide specificity and human leucocyte antigen (HLA) restriction may be such factors. As it is well established that allergen-specific T lymphocytes from atopic individuals and non-atopic controls differ in their lymphokine secretion profile, we studied two allergen-specific T-lymphocyte clones (TLC) with identical peptide specificity and HLA restriction that were generated from the peripheral blood of an atopic donor and a non-atopic control donor. The two CD4+ TLC recognize the same epitope (20-33) of the house dust mite Dermatophagoides pteronyssinus major allergen Der p II. Both TLC recognize the epitope in an HLA-DQB1*0602-restricted manner. However, the lymphokine production profiles of these TLC show clear differences after allergen-specific or polyclonal activation. As expected, TLC JBD4 from the atopic donor produced high levels of interleukin-4 (IL-4) without detectable interferon-gamma (IFN-gamma), whereas TLC PBA1 from the non-atopic donor produced both IFN-gamma and IL-4 upon allergen-specific or polyclonal activation. Inasmuch as both TLC recognized the same epitope of Der p II in association with the same HLA-DQ molecule, these data suggest that peptide specificity and HLA restriction of human allergen-specific TLC do not dictate their lymphokine secretion profile.

Allergens↗
PubMed1994

T-cell regulation in allergic reactions.

Atopy is characterized by an increased tendency to form antibodies to airborne and food proteins. Specific IgE is central to the induction of allergic diseases through its binding of the high-affinity receptor on mast cells and basophils. Cross-linking by allergens of the bound IgE leads to an immediate release of various inflammatory mediators at the local site in the shock organ. Repeated exposure to allergens may lead to the induction of a more chronic inflammatory process where the local influx of T-lymphocytes and eosinophils appears to be an important event. There has been increasing recognition that cytokines, produced by a variety of inflammatory cell subsets, including T-cells, induce this ongoing inflammatory state. Besides, CD4+ T-helper-2 (Th2) cell products like IL-4 play a crucial role in the regulation of the production of specific IgE by B-cells. IL-4 appears to be the immunoregulatory cytokine with a relatively restricted action on reactive cells in this specific immune reaction. The effects of IL-4 are antagonised by IFN-gamma, and vice versa. Proliferation and differentiation of Th2 subsets producing predominantly IL-4 and IL-5 and no IFN-gamma provide an essential signal for isotype switching to IgE in B-cells, on the one hand, and direct the activation and influx of inflammatory effector cells such as eosinophils, on the other hand. In this report the causal relationship between the induction and expression of Th2 cells the IgE production and eosinophilia in atopic allergies is briefly reviewed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen Presentation↗
PubMed1994

Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography.

UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+ in damaged brain tissue irrespective of blood-brain barrier integrity, as affirmed by CT and MRI. CONCLUSION: Our preliminary results indicate that 55CoCl2 may prove to be a useful and relatively inexpensive PET radiopharmaceutical for visualization of degenerative processes in brain tissue.

Aged↗
PubMed1993

T cell epitopes of house dust mite major allergen Der p II.

Recent work has indicated the significance of IL-4- and IL-5-secreting allergen-specific human Th2 lymphocytes in the control of immune responses to allergens in atopic individuals. The precise allergenic epitopes that activate these allergen-specific Th2 cells are, however, hardly known. We analyzed the epitope-specificity of T lymphocytes specific for Der p II, one of the major allergens of house dust mite Dermatophagoides pteronyssinus. Using a panel of overlapping synthetic peptides that span the entire Der p II molecule, we could demonstrate that polyclonal Der p II-specific T cell lines prepared from the peripheral blood of five atopic patients can react with at least 10 different epitopes of the molecule. Each donor showed a different pattern of reactivity with the synthetic peptides, suggesting that Der p II contains multiple T cell epitopes that may differ from individual to individual. We studied the specificity of the T cell response to Der p II in more detail in one atopic patient using a short term polyclonal T cell line that strongly reacted to one single peptide (116-129) of the allergen. From this patient we established a panel of 11 Der p II-specific TLC. Ten TLC were of the CD3+ CD4+ phenotype and showed a high IL-4/IFN-gamma production ratio, whereas another TLC expressed CD3 and CD8 and failed to secrete substantial IL-4 and IFN-gamma. The use of at least four different TCR V beta gene segments was shown within this panel TLC. All TLC tested recognized the allergen in an HLA-DR1-restricted manner. Although this patient reacted to only one peptide on the polyclonal level, two T cell epitopes were identified on the clonal level by using synthetic peptides and autologous APC to stimulate the TLC. Combining data of CD4/CD8 expression, TCR V beta usage, and epitope specificity, at least six different types of Der p II-specific TLC could be identified within this patient. Binding of IgE to all synthetic peptides of Der p II is low and of low affinity, which may be of particular importance with respect to possible desensitization protocols using such peptides.

Allergens↗
PubMed1993

Genetic analysis of the diversity in outer membrane protein P2 of non-encapsulated Haemophilus influenzae.

The molecular basis for the diversity of the major outer membrane protein (MOMP) P2 of non-encapsulated Haemophilus influenzae was analyzed by direct sequencing of fragments of the P2 genes, obtained by the polymerase chain reaction. Genetically divergent H. influenzae strains were isolated from patients with otitis media and from infected patients with chronic obstructive pulmonary disease (COPD). The nucleotide sequences of these P2 genes were determined and compared with P2 gene sequences of three non-encapsulated strains and with the P2 gene of encapsulated H. influenzae type b. Variation in the nucleotide sequence of the P2 genes of non-encapsulated H. influenzae was localized in eight distinct regions which were interchanged with relatively conserved regions. Regions 2, 4, 5 and 8 were found to be hypervariable, since they were characterized by multiple deletions or substitutions of nucleotides. According to the proposed structure of MOMP P2 the variable regions were localized in eight loop structures exposed at the outside of the outer membrane. Loops 2, 4, 5 and 8 were hypervariable in all isolates whereas loop 6 varied only in isolates from COPD patients with persistent infections.

Amino Acid Sequence↗
PubMed1993

Interpretation of skin tests to house dust mite and relationship to other allergy parameters in patients with asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group.

BACKGROUND: The relationships between allergic symptoms after exposure to house dust, allergy parameters (skin test to house dust mite [HDM], total IgE, HDM-specific IgE, and blood eosinophil counts), and several confounding variables (age, sex, smoking habits, and airway hyperresponsiveness) were evaluated in 235 patients with asthma and chronic obstructive pulmonary disease (COPD). RESULTS: Skin tests had higher diagnostic value (sensitivity plus specificity) for symptomatic allergy than specific IgE (1.45 versus 1.36) or total IgE (1.16). The other allergy parameters gave no additional information on symptoms once the skin test was known. Expressing the skin test relative to the histamine control proved slightly better than uncorrected wheal size, but this probably has limited clinical value. The best cutoff level for a positive skin test was 0.7 when the histamine wheal size was accounted for by division, -6 mm when subtraction was used, and 7 mm for absolute wheal size. These cutoff levels proved equally applicable in various subgroups of patients with asthma and COPD. Only the skin test and female sex were independent predictors of allergic symptoms. CONCLUSION: We conclude that skin tests to HDM are better predictors for clinical allergy than total or specific IgE levels and eosinophil count, and that they are applicable in most patients with asthma and with COPD.

Adolescent↗
PubMed1993

Evaluation of different tests for the serodiagnosis of tuberculosis and the use of likelihood ratios in serology.

A serologic test for the diagnosis of tuberculosis was evaluated in 91 newly diagnosed tuberculosis (TB) patients, of whom 15 were HIV positive, in 17 TB patients during treatment, and in 220 control subjects (including individuals from endemic areas and patients with sarcoidosis or Crohn's disease). Purified proteins of M. tuberculosis with molecular weights of 10,000, 16,000, 24,000, 30,000, 38,000, and 70,000 were tested by ELISA. In addition, monoclonal antibody TB72 was tested by competition ELISA. The cutoff values were set at the mean plus three standard deviations of the values obtained in 100 healthy Dutch army recruits. Only the ELISA with the 10,000, 16,000, and 24,000 antigens and the TB72 assay discriminated between patients with TB who were not HIV positive and control subjects. Specificity varied from 95 to 98% and sensitivity from 29 to 51% with the different antigens. Combination of the test results of the ELISA with the 16,000 antigen and the TB72 assay had a sensitivity of 65% (95% confidence interval, 53 to 75%) and a specificity of 96% (95% confidence interval, 92 to 98%). The assay was useful for the diagnosis of both pulmonary and extrapulmonary TB. Optimal use of the serologic assay could be obtained when likelihood ratios for each test value are calculated instead of using the test dichotomized (positive or negative). High posttest probabilities indicate the presence of TB; low posttest probabilities do not exclude the disease and should lead to additional investigations.

AIDS-Related Opportunistic Infections↗
PubMed1993

Soluble and cellular markers of T cell activation in patients with pulmonary sarcoidosis.

We have characterized the activation state of T cells in the bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) from patients with sarcoidosis, to obtain more information about their mechanisms of activation. We analyzed the expression of activation markers (CD25, HLA-DR, Leu-8, and two recently defined markers, CD69 and CD27) on T cells by two-color flow cytometry. We also measured the levels of soluble CD27 and soluble CD25 in nonconcentrated BALF and in serum by ELISA. We found that most T cells in BALF from patients, but not in the peripheral blood, expressed CD69, whereas they did not express CD27. The phenotype (CD69+CD27-) of most BALF T cells and the coexpression of CD69 with HLA-DR and/or VLA-1 indicates that they are in a state of recent and persistent activation. We confirmed previous findings of expression of CD25, HLA-DR, and Leu-8 by T lymphocytes in BALF from patients. We also confirmed increased levels of soluble CD25 in the serum from these patients. The levels of sCD27 and sCD25 in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. They were increased in the patients compared with control subjects. In both patients and control subjects, levels in ELF were higher than in the peripheral blood. This indicates shedding of sCD27 (and sCD25) in the lung compartment, which likely contributes to levels in the serum. It is known that in vitro CD27+ cells become CD27- after repeated stimulation and that CD27- cells, after restimulation, do not shed sCD27.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Heterogeneous effects of histamine on proliferation of lung- and blood-derived T-cell clones from healthy and asthmatic persons.

We have studied the effects of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment and from both groups of donors were heterogeneous in their response to histamine. In BALF-derived TLC, three types of responses were observed: histamine inhibited, stimulated, or did not modulate the anti-CD3-induced proliferation. Histamine directly and dose dependently inhibited the anti-CD3-induced proliferation of six (two asthmatic) of 12 CD4+ BALF TLC, stimulated two BALF TLC (both nonasthmatic), and did not modulate the proliferation of four BALF TLC. The maximal inhibition was 70%, the maximal stimulation 200%, both at 10(-3) M histamine. The stimulation of proliferation was associated with increased interleukin-2 (IL-2) production, whereas the inhibition of proliferation was associated with decreased IL-2 production and downregulation of IL-2 receptor expression. The inhibitory effects could be partly reversed by H2-receptor antagonists and could be mimicked by an H2-receptor agonist. In contrast, the stimulatory effect was not reversed or mimicked by H1 or H2 antagonists or agonists. The majority of CD4+ TLC responded to histamine with a rise in the intracellular cAMP levels. A rise in cAMP, however, was often but not always associated with an inhibition of proliferation. In addition, stimulation of proliferation occurred in the absence of a rise in cAMP. We compared cAMP rises in panels of TLC obtained with high cloning efficiencies from the PB from a healthy person and from an asthmatic person.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1993

Standardized quantitative 67Ga scintigraphy in relation to carbon monoxide diffusion capacity in pulmonary sarcoidosis.

67Ga lung uptake, obtained by a standardized computer-assisted quantitative method of 67Ga scintigraphy, was compared to carbon monoxide diffusion capacity (DLCO) in 45 patients with biopsy proven pulmonary sarcoidosis. Increased 67Ga lung uptake was found in 24 (53%) patients and DLCO was decreased in only 16 (36%) patients. An inverse relationship (r = -0.53; p < 0.001) was demonstrated between 67Ga lung uptake and DLCO. Eleven patients had an increased 67Ga lung uptake whereas the DLCO values were normal. There was no correlation between 67Ga lung uptake or DLCO and either chest radiographic stage or mode of clinical presentation. On the basis of the normal limits for 67Ga lung uptake and DLCO, 4 subgroups of patients could be identified. The use of the combined investigations may open an opportunity for an early identification of those patients who require therapy. An increased 67Ga accumulation within the lung seems to be considered as a factor indicating risk for pulmonary disability, which is supported by the follow-up of the 4 subgroups of patients.

Adult↗
PubMed1992

ELISA of complement C3a in bronchoalveolar lavage fluid.

Activated complement factors within the lung may induce several local biological effects. In order to investigate local complement activation we have developed non-competitive two-site ELISAs of C3a and total C3 in bronchoalveolar lavage fluid (BALF). For the assay of C3a, both C3 and C3(H2O) were removed from the samples by precipitation with polyethylene glycol. It was necessary to add carrier proteins to BALF to remove C3 and C3(H2O) fully. The ELISA of C3a has the lowest limit of detection reported thus far, namely 0.045 nM (= 0.405 ng/ml). In BALF from healthy persons (n = 9) the C3a concentration was 0.20 nM (0.12-0.31 nM) (median, range). C3a was higher in BALF from patients with asthma or with sarcoidosis; asthma (n = 10), 0.45 nM (0.20-5.79 nM); sarcoidosis (n = 19), 1.31 nM (0.095-5.65 nM) (Mann-Whitney U test, p less than 0.005). In BALF from patients with Pneumocystis carinii pneumonitis (n = 10) the C3a concentration was 0.18 nM (0.07-0.57 nM). C3a concentrations in BALF may reflect local complement activation in the lung and/or diffusion into the lumen. This was studied by normalizing C3a concentrations in BALF into values for epithelial lining fluid (ELF), and calculating serum-to-ELF quotients of C3a, and C3a/total C3 quotients.

Adolescent↗
PubMed1992

Role of type 1 and type 2 T helper cells in allergic diseases.

Various characteristics of atopic allergic disorders seem to be causally related with the activation of allergen-specific T helper lymphocytes with a type 2 cytokine secretion profile, including high levels of interleukin-4 and interleukin-5. These cytokines are responsible for the occurrence of elevated levels of serum allergen-specific IgE and eosinophilia and play an important role in local inflammatory reactions.

Humans↗
PubMed1992

Polycyclic aromatic hydrocarbon--DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung.

Smokers of cigarettes are exposed to a number of carcinogens, including polycyclic aromatic hydrocarbons (PAHs), and are at a high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation to reactive intermediates that can damage DNA through adduct formation. Measuring DNA adducts in peripheral white blood cells (WBC) could serve as a means of monitoring human exposure to genotoxic agents and subsequently risk assessment. In this study, DNA from WBC obtained from 39 lung cancer patients was examined for PAH-DNA adducts both in an ELISA using a polyclonal antibody against benzo[a]pyrene 7,8-diol-9,10-epoxide (BPDE)-DNA and the 32P-post-labeling technique. The ELISA results showed BPDE-DNA antigenicity in WBC DNA from 12/38 (32%) patients and adduct levels ranged from 1.5 to greater than 150 adducts in 10(8) nucleotides. The autoradiographs of chromatograms of 32P-post-labeled digests of WBC DNA from the 38 patients showed a variety of adduct spots; relative adduct labeling (RAL) values ranged from 0.3 to 407 adducts in 10(8) nucleotides. In 18 of the 38 (47%) persons an adduct spot was detected that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG); RAL values ranged from 0.03 to 382 adducts in 10(8) nucleotides. Correlations were not significant between the adduct levels in WBC and smoking habits, age or sex. From 20 patients of the same group lung tissue was collected at surgery and examined for PAH-DNA adducts by ELISA and 32P-post-labeling assay. No significant correlation was found between DNA adduct levels in blood and lung. This finding stresses the limitations of the use of WBC as a surrogate for adduct levels in the target organ.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Antibodies against secreted and non-secreted antigens in mice after infection with live Mycobacterium tuberculosis.

Mice from four different inbred strains were infected with live Mycobacterium tuberculosis and the immune response to M. tuberculosis was followed for 24 weeks, using Western blotting. Nearly all mice, irrespective of H-2 type, reacted with the 38-kDa protein band. Antibodies against this secreted 38-kDa protein were the first to appear, 4 weeks after infection. Thereafter the secreted 19-kDa protein and non-secreted antigens, such as the 65-kDa and 33-kDa proteins, were recognized. The immune response against the non-secreted antigens was influenced by the mouse strain. However, the 33-kDa protein band was recognized by all mouse strains after a second injection with live M. tuberculosis. The specificity of the antibodies was analysed in Western blot using sonicates of M. tuberculosis, M. kansasii, M. avium, M. terrae, M. gordonae and Escherichia coli. Antibodies against the 38-kDa and 33-kDa protein bands seemed to be specific for M. tuberculosis, while antibodies against the 19-kDa protein band showed limited cross-reactivity. Antibodies against the 65-kDa protein were strongly cross-reactive. These results suggest that the 38-kDa protein is secreted in vivo and, therefore, may be available to the humoral immune system at an early stage of infection. The non-secreted 33-kDa protein is only recognized by all mouse strains after prolonged contact with M. tuberculosis.

Animals↗