Three days after withdrawal of maintenance treatment, peak expiratory flow rate (PEFR) was measur... more Three days after withdrawal of maintenance treatment, peak expiratory flow rate (PEFR) was measured in 38 asthmatic children every four hours during 24 hours on three consecutive days. In all children a circadian rhythm, with a nocturnal fall in PEFR existed. The interindividual amplitude varied from 2 to Two groups of 9 patients each', were selected from the total study population based on a difference in PEFR values between 16.00 and 04.00 hours of more then 20% or less then 15% on three study days. The remaining children did not fit in both subgroups because the 16.00 and 04.00 hour difference in PEFR values was not persistent. The clinical data of this group, however, were comparable with both subgroups. In the group with a 16.00 -04.00 hours difference of more then 20% (mean + SD: 31.5 + 8.5) both the mean PEFR value and the PEFR value-measured at 04.00 hours on day 6 was significantly decreased as compared to the values obtained on day 4. Moreover the amplitude of the PEFR still increased significantly from day 4 to day 6. In the group with 16.00 -04.00 hours difference of less then 15% (mean + SD: 6.4 + 2.7) no increase in amplitude and decrease in mean PEFR values during day 4 and day 6 were observed. lIIith regard to FEV IFEV I predicted, PC 20 Histamine and skintests no significant aifferences were observed between both subgroups. In retrospect the group of children with the large amplitude seems to be more inhaled steroid dependent.
Interaction of the glycosyl phosphatidylinositol-linked differentiation Ag CD73 (ecto-5'-nucl... more Interaction of the glycosyl phosphatidylinositol-linked differentiation Ag CD73 (ecto-5'-nucleotidase) with the CD73-specific mAb 1E9 generates agonistic signals that strongly synergize with T cell activation induced by CD3 and CD2 mAb. This synergy is observed only when 1E9 is immobilized on plastic and occurs in the absence of accessory cells or exogenous lymphokines. 1E9 induces a rapid (though transient) increase in [Ca2+]i in a minor proportion (20 to 30%) of unfractionated T lymphocytes (presumably CD73+ cells). However, this [Ca2+]i mobilization is not sufficient to fully activate CD73+ T cells, as shown by the requirement of additional signals such as CD3 or CD2 stimulation to initiate T cell proliferation. These signals cannot be substituted by the exogenous lymphokines, rIL-1, rIL-2, or rIL-4, or PMA (when T cells are rigorously depleted of monocytes). These data indicate that CD73 may behave as an accessory molecule regulating interactions between T cells and antigens...
The effect of deoxyguanosine on mitogen- and antigen-induced proliferation of peripheral blood ly... more The effect of deoxyguanosine on mitogen- and antigen-induced proliferation of peripheral blood lymphocytes from healthy donors was studied. Deoxyguanosine was found to inhibit the proliferative response to mitogens and antigens. Concentrations of deoxyguanosine causing 50% inhibition of the proliferation proved to be dependent on the activity of catabolic enzymes, such as purine nucleoside phosphorylase (PNP), in sera used in the culture media. The inhibitory effect of deoxyguanosine on phytohemagglutinin (PHA)-induced cell proliferation was prevented by deoxycytidine as well as by hypoxanthine. These findings were analyzed further by determination of intracellular (deoxy)-nucleotide levels. Stimulation of lymphocytes by PHA in the presence of deoxyguanosine leads to intracellular accumulation of dGTP. The presence of hypoxanthine in addition to deoxyguanosine abolished the inhibitory effect but did not prevent dGTP accumulation. On the other hand, the addition of deoxycytidine in c...
To study the hypothesis that COPD patients who do not achieve seroprotective levels after influen... more To study the hypothesis that COPD patients who do not achieve seroprotective levels after influenza vaccination, are a less immune-competent group with a higher risk of morbidity and mortality. Methods: 578 patients included in the COMIC cohort had pre-and post-vaccination stable state blood samples in which influenza-vaccine specific antibodies were measured. Post-vaccination titers of ≥40 were considered protective and indicative of being immuno-competent. Primary outcome was all-cause mortality. Morbidity was defined as time till first severe acute exacerbation in COPD (severe AECOPD) and time till first community acquired pneumonia (CAP). Results: 42% of the patients achieved seroprotective levels to both H1N1 and H3N2 after vaccination. Seroprotective levels to H3N2 were markedly higher (96%) than to H1N1(43%). Having seroprotective levels to both H1N1 and H3N2 was not associated with less morbidity (severe AECOPD HR 0.91 (95% 0.66-1.25; p = 0.564) (CAP HR 1.23 (95% 0.75-2.00; p = 0.412)) or lower mortality (HR 1.10(95% 0.87-1.38; p = 0.433)). In a large well-characterized COPD cohort only the minority of patients achieved seroprotective titers to H1N1 and H3N1 after the yearly influenza vaccination. While achieving seroprotection after vaccination can be considered a surrogate marker of being immunocompetent, this was not associated with lower morbidity and mortality. Whether this means that the immune status is not a relevant pheno/endotype in COPD patients for the course of their disease or that seroprotection is not an adequate (surrogate) marker to define the immune status in COPD needs to be further studied.
Objectives. The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was found recently ... more Objectives. The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was found recently to be caused by a de®ciency of mevalonate kinase (MK). The aim of this study was to examine whether a relationship exists between the clinical expression of HIDS and the extent of MK de®ciency. Methods. The medical records of children diagnosed with HIDS were reviewed for clinical features and serum immunoglobulin values. The mevalonic acid excretion in urine and MK enzyme activity in patients' cells were measured and the cDNA of the MVK gene was sequenced. Results. Fifteen patients with recurrent fever and raised serum immunoglobulin (Ig) D were included. Their clinical features varied. Eleven patients had a de®ciency of MK, caused by mutations in the MVK gene. One mutation ( V377 I) was common to all 11 patients. Nine patients were compound heterozygotes for V377I and various other MVK mutations. There was no apparent relationship between the observed mutations and the clinical features. Surprisingly, four boys had normal MK activity and no MVK mutations. Conclusions. Most HIDS patients have mutations in the MVK gene. The clinical variability observed cannot be explained by genotypic differences. Periodic fever and elevated IgD can result from other, still unknown, causes. Hence, testing for MK de®ciency is necessary in patients with unexplained periodic fever.
Community-acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in... more Community-acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose-binding lectin (MBL) and l-ficolin (l-FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Ch...
Background: The acquisition and development of infant gut microbiota can be influenced by numerou... more Background: The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life. Methods/Design: 450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics. Discussion: Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre-or probiotics can restore the ecological balance of the microbiota and may mitigate potential negative effects on the developing immune system, when use of antibiotics cannot be avoided. Trial registration: ClinicalTrials.gov NCT02536560. Registered 28 August 2015.
Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an ea... more Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for contro...
Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms rel... more Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections. The objective of the study was to investigate the effect of the probiotic strain Lactobacillus paracasei subsp. paracasei, L. casei 431 (Chr. Hansen A/S) (hereafter, L. casei 431) on immune response to influenza vaccination and respiratory symptoms in healthy adults. A randomized double-blind, placebo-controlled trial was conducted in 1104 healthy subjects aged 18-60 y at 2 centers in Germany and Denmark. Subjects were randomly assigned to receive an acidified milk drink containing ≥10(9) colony-forming units of L. casei 431 (n = 553) or placebo (n = 551) for 42 d. After 21 d, subjects received the seasonal influenza vaccination. The primary outcome was seroprotection rate (anti-influenza antibody titers by hemagglutination inhibition) 21 d after vaccination. Other outcomes were seroconversion rate and mean titers, influenza A-specific antibodies and incid...
Influenza virus vaccination is recommended for patients treated with chemotherapy. Little is know... more Influenza virus vaccination is recommended for patients treated with chemotherapy. Little is known about vaccination coverage in these patients. Vaccination coverage in the Netherlands was analysed by questionnaires completed by general practitioners, within a catchment area of 1.3 million people, in the period 2010-2011. Of 433 eligible adult patients treated with chemotherapy for breast or colorectal cancer, 144 patients gave permission for us to approach their general practitioner with a questionnaire. General practitioners were asked about vaccination coverage, awareness of recommendations and their opinion about the responsibility for vaccination. We received 114 (79%) completed questionnaires. Sixty-seven out of 114 patients (59%) were vaccinated against influenza. Forty-four (66%) of these patients also had an indication for vaccination based on age (age ≥60 years). According to 48% of the general practitioners, the responsibility for vaccination belongs to the competence of ...
Objective: The objective was to define the term evidence based nutrition on the basis of expert d... more Objective: The objective was to define the term evidence based nutrition on the basis of expert discussions and scientific evidence. Methods and procedures: The method used is the established Hohenheim Consensus Conference. The term "Hohenheim Consensus Conference" defines conferences dealing with nutrition-related topics. The major aim of the conference is to review the state of the art of a given topic with experts from different areas (basic science, clinicians, epidemiologists, etc.). Based on eight to 12 questions, the experts discuss short answers and try to come to a consensus. A scientifically based text is formulated that justifies the consensus answer. To discuss the requirements for the scientific substantiation of claims, the 26th Hohenheim Consensus Conference gathered the views of many academic experts in the field of nutritional research and asked these experts to address the various aspects of a claims substantiation process and the possibilities and limitations of the different approaches. Results: The experts spent a day presenting and discussing their views and arrived at several consensus statements that can serve as guidance for bodies performing claims assessments in the framework of regulatory systems. Conclusion: The 26th Hohenheim Consensus Conference addresses some general aspects and describes the current scientific status from the point of view of six case studies to illustrate specific areas of scientific interest: carotenoids and vitamin A in relation to age-related macular degeneration, the quality of carbohydrates (as expressed by the glycemic index) in relation to health and well-being, probiotics in relation to intestinal and immune functions, micronutrient intake and maintenance of normal body functions, and food components with antioxidative properties and health benefits.
Plant Varieties and Seeds - PLANT VARIETIES SEEDS, 1980
This study deals with several aspects of the immune system of cyprinid fish.Some observations on ... more This study deals with several aspects of the immune system of cyprinid fish.Some observations on the development of cellular and humoral responsiveness in rosy barb (Barbus conchonius) are described in appendix I. A humoral anti-sheep red blood cell (SRBC) response was demonstrated in 3-4 months old animals, but the peak response was lower than in adult (9 months old)animals (90 and 700 plaque forming cells (PFC)/10 <sup><font size="-1">6</font></SUP>white cells respectively). The scale transplantation technique was used for studying cellular immunity. No significant difference in the median survival time (MST) of allografts was observed in 6 and 9 months old animals (8.0 and 8.3 days respectively). It is concluded that 3-4 months old animals have the competence to respond to SRBC, but the humeral immune system is not fullgrown till 5-6 months later. Cellular immunity has cone to complete maturation at 6 months or earlier.For several reasons carp (C...
Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Aller... more Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.
Proceedings of the National Academy of Sciences, 1990
We have examined the ability of membrane immunoglobulin-binding ligands to desensitize several hu... more We have examined the ability of membrane immunoglobulin-binding ligands to desensitize several human B-cell surface molecules that normally transduce signals leading to Ca2+ mobilization. Ligation of membrane IgM or IgD leads to heterologous desensitization of the reciprocal receptor in Epstein-Barr virus-transformed B-cell lines and peripheral blood B cells, as evidenced by a failure of cells to mobilize in response to receptor ligation. Under these conditions CD19, CD21, and B-cell gp95 ligation also did not lead to normal Ca2+ mobilization, indicating that these transducers are also desensitized. The desensitization does not reflect receptor modulation from the cell surface or reduced accessibility to ligand and is long lived, lasting greater than 16 hr. Finally, data that indicate that desensitized cells remain responsive to the G protein activating agent AIF4-, as measured by Ca2+ mobilization, suggest that desensitization reflects uncoupling of these receptors from G proteins ...
0.. M'. K.. B. J.hl.%.]. Univer.si/j* Ho.spi/ul.fi)r ('lrildrc~r~ and Yorrrlr "Ile/ W CIi'llrelrn... more 0.. M'. K.. B. J.hl.%.]. Univer.si/j* Ho.spi/ul.fi)r ('lrildrc~r~ and Yorrrlr "Ile/ W CIi'llrelrninu Kindc~rzic~kcnlrrri.s. " U/rc~c.lt/. Tlrc Nmlrc~rlunds and In.s/itrrtc~ ~/'lt!/i~~~tiorr.v Di.se~u,ses and Immrtnolog~~ /R. v.d. Z.. M: v. E.]. Facrrl~!~ (?I' l,'~>tc~rinorj~ hlc>dic.inc~. C'nivcr.sit!~ (!I' Lr/rc,c.lt/. Tlrc~ Nc~tltrr1und.v ABSTRACT. The 60-kD heat shock protein (hsp60) has been implicated in the etiology and pathogenesis of both experimental and naturally occurring autoimmune diseases such as juvenile chronic arthritis (JCA). Human hsp60 is expressed in inflamed synovial tissue, and T lymphocytes both from peripheral blood and synovial fluid show reactivity to human hsp60. Because the anti-hsp60 B lymphocyte response has been less well studied, we have determined the occurrence of IgG anti-human hsp60 antibodies in patients with JCA and various other autoimmune diseases of childhood. Serum IgG anti-human hsp60 antibodies in JCA patients were significantly higher compared with control children (358 and 163 UImL, respectively). Within the group of JCA patients, the highest antibody titers were found in the subgroup with a polyarticular onset of JCA. IgG anti-human hsp60 antibody levels in synovial fluid were 3-to 4-fold higher compared with paired serum samples. Because this difference was not found for total IgC or for irrelevant antibodies (anti-polyribosylribitol phosphate), this suggests local anti-hsp60 antibody production in the synovial compartment. The occurrence of anti-hsp60 antibodies is not specific for JCA but also is found in children with systemic lupus erythematosus and in cystic fibrosis, whereas mixed connective tissue disease and insulin-dependent diabetes are negative in this respect. Whether the anti-human hsp60 antibodies are directed toward species-specific sequences or to conserved sequences of the hsp60 molecule remains to be determined. (Pediatr Res 34: 424-428,1993) Abbreviations hsp60,60-kD heat shock protein IDDM, insulin-dependent diabetes mellitus JCA, juvenile chronic arthritis OA, oligoarticular onset PA, polyarticular onset SO, systemic onset PRP, polyribosylribitol phosphate hsp, heat shock protein RA, rheumatoid arthritis SF, synovial fluid NOD, nonobese diabetic mice CF, cystic fibrosis SLE, systemic lupus erythematosus MCTD, mixed connective tissue disease ANA, antinuclear antibody
Increased levels of serum IgD can be found in single patients with a variety of clinical syndrome... more Increased levels of serum IgD can be found in single patients with a variety of clinical syndromes and in the disease entity designated hyper-IgD syndrome which is associated with periodic fever and lymphadenopathy. We investigated 17 patients, both children and adults, with high serum IgD levels ranging from 220 to 5300 IU/ml. Eight patients had periodic fever and lymphadenopathy, four showed a humoral immunodeficiency, and the re mainder had a variety of clinical abnormalities. Serum IgA levels were consistently high in all patients except in those with an immunodeficiency. Serum IgD complexes were detectable in each serum, which indicates that the occurrence is not pathognomic for the syndrome of periodic fever. Antibody formation against the primary antigen Helix pomatia hemocyanine and the secondary antigen tetanus toxoid showed no abnormalities in the patients without an immunodeficiency. Bone marrow origin of serum IgD was strongly suggested by enumera tion of IgD-containing plasma cells. We conclude that no apparent relationship exists between the several clinical syndromes and increased serum IgD. K EY W ORDS: Serum IgD; periodic fever; im m unodeficiency; im m une status.
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Papers by Ger Rijkers