PubMed Health⌕ Search

Biomedical subjects

H van den Berg

Publications and source records attributed to H van den Berg.

At least 37 records · Page 2Linked to original sources

Nuclear factor-kappaB activation is higher in peripheral blood mononuclear cells of male smokers.

Nuclear factor-kappaB (NF-kappaB) is an oxidative stress sensitive transcription factor involved in the regulation of inflammatory genes. Activation of NF-kappaB results into increased expression of inflammatory genes such as for interleukins, endothelial cell leukocyte adhesion molecules and inducible NO synthase. Our study, with six smokers and 10 non-smokers, showed that NF-kappaB activity in peripheral blood mononuclear cells of smokers compared to non-smokers is significantly higher (P<0.05). This indicates that NF-kappaB is involved in cigarette smoke induced inflammatory responses and that NF-kappaB activation can be used as a functional marker of oxidative stress.

Journal Article↗

Certification of B-group vitamins (B1, B2, B6, and B12) in four food reference materials.

In 1989, the Community Bureau of Reference started a research program to improve the quality of vitamin analysis in food. To achieve this task, vitamin methodology was evaluated and tested by interlaboratory studies and the preparation of certified reference materials, which will be used for quality control of vitamin measurements. The main improvements in methodology were achieved by testing and standardizing the extraction condition and enzymatic hydrolysis procedures. Results for each individual material are derived from five replicate determinations using at least two independent methods: liquid chromatography (HPLC) and microbiological assay for vitamins B1, B2, and B6; and radioprotein binding and microbiological assays for vitamin B12. The certificate of analysis for four reference materials gives mass fraction values for water-soluble vitamins. These certified values were based on the acceptable statistical agreement of results from collaborating laboratories. Certified values with uncertainties (mg/kg dry matter) for each CRM are as follows: 4.63 (0.20) and 4.10 (0.51) for vitamins B1 and B6, respectively, in CRM 121 (wholemeal flour); 6.51 (0.24), 14.54 (0.3), 6.66 (0.43), and 0.034 (0.003) for vitamins B1, B2, B6, and B12, respectively, in CRM 421 (milk powder); 3.07 (0.17) and 4.80 (0.40) for vitamins B1 and B6, respectively, in CRM 485 (lyophilized mixed vegetables), and 8.58 (0.55), 106.8 (2.8), 19.3 1.5), and 1.12 (0.044) for vitamins B1. B2, B6, and B12, respectively, in CRM 487 (lyophilized pig liver).

Chromatography, High Pressure Liquid↗

Fruit and vegetables and cardiovascular risk profile: a diet controlled intervention study.

OBJECTIVE: To evaluate the effect of fruit and vegetables consumption on markers of risk for cardiovascular disease. DESIGN: Randomised, diet controlled, parallel study. SUBJECTS: Forty-eight apparently healthy (40--60 y) volunteers with a low usual consumption of fruit and vegetables. Forty-seven of them completed the study. INTERVENTIONS: During 4 weeks 24 volunteers consumed a standardised meal, consisting of 500 g/day fruit and vegetables and 200 ml/day fruit juice ('high' group) and 23 volunteers consumed 100 g/day fruit and vegetables ('low' group) with an energy and fat controlled diet. RESULTS: Final total cholesterol was 0.2 (95% CI -0.5--0.03) mmol/l lower in the high group than in the low group (P>0.05). Final fibrinogen and systolic blood pressure were 0.1 (-0.1--0.4) g/l and 2.8 (-2.6--8.1) mmHg higher in the high group than in the low group (P>0.05), respectively. Also, other final serum lipid concentrations, diastolic blood pressure and other haemostatic factors did not differ between both groups. CONCLUSIONS: This was a small randomised well-controlled dietary intervention trial of short duration with a considerable contrast in fruit and vegetable consumption. No effects on serum lipids, blood pressure and haemostatic variables were observed.

Adult↗

Quantification of minimal residual disease in children with oligoclonal B-precursor acute lymphoblastic leukemia indicates that the clones that grow out during relapse already have the slowest rate of reduction during induction therapy.

Antigen receptor gene rearrangements are applied for the PCR-based minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL). It is known that ongoing rearrangements result in subclone formation, and that the relapsing subclone(s) can contain antigen receptor rearrangement(s) that differ from the rearrangements found in the major clone(s) at diagnosis. However, the mechanism leading to this so-called clonal evolution is not known, particularly at which time point in the disease the relapsing subclone obtains its (relative) therapy resistance. To obtain insight in clonal evolution, we followed the kinetics of several subclones in three oligoclonal ALL patients during induction therapy. Clone-specific nested PCR for immunoglobulin heavy chain or T cell receptor delta gene rearrangements were performed in limiting dilution assays on bone marrow samples taken at diagnosis, at the end of induction therapy and at possible relapse in three children with oligoclonal B-precursor ALL. We demonstrated that in all three patients the subclones were behaving differently in response to therapy. Moreover, in the two patients who relapsed, the clones that grew out during relapse showed the slowest regression or even evoluated during induction therapy and the clones that were not present at relapse showed good response to induction therapy. These results support the hypothesis that at least in some patients already at diagnosis or in the very first weeks, subclones have important differences in respect to resistance. Hence, these data give experimental evidence for the need to develop, during the first months after diagnosis, quantitative PCR assays for at least two different Ig/TCR gene rearrangement targets for every ALL patient.

Antineoplastic Combined Chemotherapy Protocols↗

Transcription factor NF-kappaB as a potential biomarker for oxidative stress.

There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-kappaB (nuclear factor-kappaB), in the pathogenesis of various diseases. NF-kappaB is involved in the control of the transcription of a variety of cellular genes that regulate the inflammatory response by the production of cytokines, chemokines, cell adhesion molecules and acute phase proteins. The involvement of NF-kappaB is especially of interest as it is activated by oxidative stress and its activation can be modulated by antioxidant compounds. The activation of NF-kappaB can be determined by the electromobility shift assay (EMSA) with a NF-kappaB binding-site-specific probe. EMSA can also be used on human mononuclear cells isolated from peripheral blood, which could make the assay applicable for clinical trials. The critical steps of the EMSA are discussed, addressing some pitfalls of the assay. The procedure that can be used to express NF-kappaB activity in human subjects is evaluated. This offers the possibility to use NF-kappaB as a functional biomarker of oxidative stress as illustrated by several examples of in vitro and in vivo studies.

Biomarkers↗

Retinoic acid metabolites in plasma are higher after intake of liver paste compared with a vitamin A supplement in women.

The objectives of the present study were to compare the bioavailability of vitamin A from liver paste and from a vitamin A supplement at three nutritionally relevant levels of intake, and to estimate levels of "safe" intake based on concentrations of retinoic acid and its metabolites in plasma after a single dose of vitamin A from liver paste. Women (n = 35; 19-47 y of age) consumed 3.0, 7.5 or 15 mg vitamin A as liver paste or as a vitamin A supplement with a test meal in a randomized design, with a combined crossover (two sources) and parallel approach (three dosages). Retinyl esters and retinoic acid (RA) metabolites were quantified in blood samples at 2-24 h after dosing. The areas under the time-response curves (AUC) were calculated to evaluate responses in plasma vitamin A after intake of liver paste and the vitamin A supplements. For retinyl esters, the AUC was significantly affected by the dosage, but not by the source. The formation of 13-cis-RA, 13-cis-4-oxo-RA, and to a lesser extent all-trans-RA was significantly higher after consumption of liver paste compared with the supplement, especially at higher dosages. Long-term baseline concentrations of retinol were not affected by a single intake of vitamin A. In conclusion, the bioavailability of vitamin A from single doses of liver paste and a vitamin A supplement does not differ, but the plasma concentrations of RA metabolites are higher after intake of liver paste. Thus, pregnant women should indeed limit the intake of vitamin A from liver products.

Adult↗

A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers.

The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids, proteins and DNA and on (functional) markers of oxidative stress were evaluated. A randomized, free living, open placebo-controlled cross-over trial of 3 wk, with a 2-wk washout period between treatments, was performed in a group of 22 male smokers with a relatively low vegetable and fruit intake using a vegetable burger and fruit drink. The vegetable burger and fruit drink increased serum levels of vitamin C, alpha-carotene, beta-carotene, beta-cryptoxanthin and zeaxanthin and plasma total antioxidant capacity. However, no effects were demonstrated on any marker of oxidative damage to lipids (malondialdehyde F(2)-isoprostane) proteins (carbonyls) and DNA (Comet assay) and (functional) markers of oxidative stress (reduced/oxidized glutathione ratio, glutathione-S-transferase alpha, glutathione-S-transferase pi and nuclear transcription factor-kappaB). Apparently, these increased levels of antioxidants in serum were not sufficiently high to show beneficial changes with the selected biomarkers. Alternatively, oxidative stress in male smokers with a relatively low fruit and vegetable intake might have been still too low to demonstrate a beneficial effect of antioxidants.

Adult↗

NF-kappaB activation in sarcoidosis.

BACKGROUND AND AIM: Sarcoidosis is an inflammatory disorder of unknown origin. The nuclear regulatory factor-kappaB (NF-kappaB) appears to play a key role in immune and inflammatory processes such as asthma, rheumatoid arthritis and inflammatory bowel disease. We hypothesized that NF-kappaB activation might be involved in the pathological process of sarcoidosis. METHODS: Twelve sarcoidosis patients, biopsy proven, and five healthy control subjects, all nonsmokers, were studied. Blood samples were taken and routinely analysed for several parameters including the serum angiotensin converting enzyme (sACE) level. Mononuclear cells were isolated from these patients in order to quantify the NF-kappaB contents in the nuclear extract of the mononuclear cells. RESULTS: Mononuclear cells NF-kappaB expressed per mg protein were twice as high in both untreated (n = 5) and treated (n = 7) patients with sarcoidosis compared to the control subjects (p < 0.001). In contrast, the sACE level appeared to be low in the treated patients compared to the untreated patients (p < 0.01). CONCLUSIONS: These results indicate that the inflammation in sarcoidosis is associated with NF-kappaB activation. Moreover, the suppression of the activated NF-kappaB response by glucocorticoids seems less successful than the suppression of the sACE activity. Future studies should focus on the clinical relevance of this observation and establish the possible therapeutic consequences of the increased NF-kappaB activation in sarcoidosis.

Adult↗

Contribution of planar (0-1 ortho) and nonplanar (2-4 ortho) fractions of Aroclor 1260 to the induction of altered hepatic foci in female Sprague-Dawley rats.

The hepatic tumor promoting activity of the planar 0-1 ortho ( approximately 9.7% w/w) and the nonplanar 2-4 ortho ( approximately 90.3% w/w) fraction of the commercial PCB mixture Aroclor 1260 was studied using a medium-term two-stage initiation/promotion bioassay in female Sprague-Dawley rats. Fractionation was carried out on an activated charcoal column. The composition of the effluent from the column was tested by GC-ECD. The absence of planar compounds in the 2-4 ortho fraction was confirmed by GC-MS analysis. The dioxin-like toxic potency of the fractions was determined with the DR-CALUX assay. The animal experiment was started with the initiation procedure (diethylnitrosamine injection, 30 mg/kg body wt ip, 24 h after (2)/(3) hepatectomy), followed 6 weeks later by the promotion treatment, which consisted of a weekly subcutaneous injection during 20 weeks. Exposure groups (n = 10) received the following treatments (dose/kg body wt/week): Aroclor 1260 (10 mg), 0-1 ortho fraction (0.97 mg), 2-4 ortho fraction (1, 3, or 9 mg), a reconstituted 0-4 ortho fraction (9.97 mg), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153; 1 or 9 mg), 2,3,7,8-TCDD (1 microg; positive control) or corn oil (1 ml; vehicle control). One group did not receive a promotion treatment. All exposure groups exhibited a significantly increased volume fraction of the liver occupied by hepatic foci positive for the placental form of glutathione-S-transferase-p compared to the corn oil control, except for the groups treated with 0-1 ortho fraction and 1 mg PCB 153/kg body wt/week. Approximately 80% of the total tumor promoting capacity of the reconstituted 0-4 ortho fraction could be explained by the 2-4 ortho PCB fraction while the 0-1 ortho fraction had only a negligible contribution. These results suggest that the majority of the tumor promotion potential of PCB mixtures resides in the non-dioxin-like fraction, which is not taken into account in the toxic equivalency factor (TEF) approach for risk assessment of PCBs. This may result in an underestimation of the tumor promotion potential of environmental PCB mixtures.

Animals↗

Delayed craniospinal irradiation for a first isolated central nervous relapse of acute lymphoblastic leukemia: report on 14 cases.

BACKGROUND: Children developing an isolated central nervous system (CNS) relapse as first recurrence of their acute lymphoblastic leukemia (ALL) are considered to have a systemic relapse as well. They are mostly treated with intensive chemotherapy and craniospinal irradiation. In most treatment schedules, irradiation is given early after induction treatment. Because craniospinal irradiation affects a large portion of hematopoietic bone marrow systemically, treatment is often delayed owing to aplasias. Also, dose reductions are frequently needed. Children receiving simultaneously irradiation and chemotherapy are prone to (often severe) neurotoxicity. This study reports on children with a first isolated CNS relapse of their ALL receiving chemotherapy for 40 weeks. Treatment ends with the administration of irradiation given after cessation of chemotherapy. PROCEDURE: Fourteen children, with blasts and >5 cells/mm(3) in two consecutive samples of cerebrospinal fluid and a blast percentage <5% in their bone marrow were treated according to an intensive systemic and site-specific chemotherapy. Craniospinal irradiation was administered after cessation chemotherapy. RESULTS: Event-free-survival was 57% (confidence interval 35-89%), freedom from relapse was 61.5%; follow-up ranges from 2.0 to 15.1 years (median 11.7 years). One child died from septicemia during induction. Five children experienced a second relapse and died from their malignancy. Two children [with a t(9;22) or a rearranged MLL gene] relapsed prior to radiotherapy. Outcome was related to duration of first remission, age at relapse, and identification as a high-risk patient at initial diagnosis. No neurologic complications were noted during and after treatment. CONCLUSIONS: Delayed irradiation for isolated CNS relapse in children with ALL gives favorable survival rates, without significant toxicity. Neurotoxicity was absent.

Brain Neoplasms↗

Prenatal HLA-matching to determine suitability for allogeneic bone marrow transplantation.

For several haematological malignancies, allogeneic stem cell transplantation is the treatment of choice. In most cases an HLA-identical sibling is required. If the mother of a patient is pregnant, cord blood from a related donor, which can be used for stem cell transplantation, might be obtainable in the near future. For the patient, knowledge of the foetal HLA-type can be important since it might influence choice of treatment and timing of transplantation. If the foetus is HLA compatible, as would be the situation in 25% of cases, the delivery has to be arranged in such a way that cord stem cells can be collected. As a result, in the other 75% of cases (spontaneous) delivery can take place in the home/local setting. Here we report four cases in which amniocentesis was performed and HLA-typing influenced treatment of the patient and delivery of the sibling.

Amniocentesis↗

Moderate consumption of beer, red wine and spirits has counteracting effects on plasma antioxidants in middle-aged men.

OBJECTIVE: To evaluate the in vivo effects of moderate consumption of red wine, beer and spirits on antioxidants, antioxidant enzymes and antioxidant capacity. DESIGN: Randomized, diet-controlled, cross-over study. SUBJECTS: Twelve apparently healthy, non-smoking middle-aged men were included; 11 of them completed the study. INTERVENTIONS: Each subject consumed four glasses of red wine, beer, spirits and water (negative control) with evening dinner during four successive periods of 3 weeks, daily at the Institute. The total diet was supplied to the subjects and had essential the same composition during these 12 weeks. RESULTS: Neither the enzyme activities of serum glutathion peroxidase, erythrocyte glutathion reductase and superoxide dismutase nor the plasma concentrations of alpha- and gamma-tocopherol, lutein, zeaxantin, beta-cryptoxanthin, lycopene and alpha-carotene were affected. Plasma beta-carotene concentrations were decreased after 3 weeks' consumption of red wine, beer and spirits (40 g alcohol/day) as compared to consumption of water, by 15% (P=0.0005), 11% (P=0.010) and 13% (P=0.003), respectively. Also, plasma ascorbic acid was decreased after beer (15%, P=0.004) and spirits (12%, P=0.030), but not after wine consumption. Serum uric acid concentrations were increased after consumption of beer (15%, P<0.0001), spirits (8%, P=0.008) and red wine (9%, P=0.003). The overall serum antioxidant capacity, assessed as Trolox equivalent antioxidant capacity (TEAC), was similar for all treatments. CONCLUSIONS: Moderate consumption of red wine, beer and spirits has counteracting effects on plasma antioxidant components, resulting in no significant effect on overall antioxidant status. The effects on antioxidant parameters are largely independent of the type of alcoholic beverage, and probably irrelevant to chronic disease risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

Adult↗

Stroma-supported progenitor production as a prognostic tool for graft failure following autologous stem cell transplantation.

To analyse the involvement of a possible numerical or qualitative stem cell defect in the development of sustained graft failure after autologous transplantation, we have determined the graft content of CD34+ nucleated cells, colony-forming cells and cobblestone area-forming cell subsets, as well as transplant ability to produce progenitors using the long-term culture colony-forming cell (LTC-CFC) assay. We evaluated material from the graft reference ampoules of 13 graft failure patients after bone marrow transplantation (BMT), four graft failure patients and four isolated thrombocytopenia patients after peripheral blood stem cell transplantation (PBSCT). We compared these data with those from six successfully engrafted BMT patients and 20 engrafted PBSCT patients respectively. In the BMT setting, the LTC-CFC 6-week assay represented a highly significant graft failure predictor. In the PBSCT setting, the total number of 2-week and 6-week LTC-CFCs transplanted per kg bodyweight (BW) showed the highest significant difference between the engrafted and the graft failure patients, as well as between the engrafted patients and the patients suffering from isolated thrombocytopenia after transplantation. These data show that the ability of a graft to generate progenitors in vitro rather than the number of primitive progenitors transplanted can have prognostic value for post-transplant haematological reconstitution.

Antigens, CD34↗

Minimal residual disease studies are beneficial in the follow-up of TEL/AML1 patients with B-precursor acute lymphoblastic leukaemia.

The t(12;21)(p13;q22) translocation has been identified as the most common chromosomal abnormality in childhood acute lymphoblastic leukaemia (ALL). Initially, several investigators reported an excellent prognosis in paediatric leukaemias with this translocation, but other studies showed a 20% incidence in relapsed ALL. We performed an extensive analysis of 90 ALL patients. In 17 (19%) cases a TEL/AML1 fusion was found. However, this group was not representative as it included a high number of relapsed patients compared with the normal incidence in B-precursor ALL [54 in continuous complete remission (CCR) and 36 relapsed patients] and only a slightly better prognosis for TEL/AML1-positive patients was found (not significant) (four relapses in 17 TEL/AML1-positive patients vs. 32 relapses in 73 TEL/AML1-negative patients). Comparison of known prognostic factors (age, sex, ploidy, white blood cell count and immunophenotype) between relapsed TEL/AML1-positive and TEL/AML1-positive patients in CCR did not reveal differences, except that the white blood cell count was significantly higher in the relapsed group (P = 0.001). Time between diagnosis and relapse was not different for the relapsed TEL/AML1-positive group vs. the relapsed TEL/AML1-negative group. In 11 TEL/AML1-positive patients, the minimal residual disease (MRD) level at the end of induction therapy was quantified in a limiting dilution assay using IGH or TCRD junctional regions as polymerase chain reaction (PCR) targets. In all four relapsed patients, the level of MRD at the end of induction therapy was high (range 0.24-1.2%), whereas in all seven CCR patients, the MRD level was extremely low (0.02 to < 0.001%). In agreement with previous studies in which MRD levels at the end of induction therapy were found to be the strongest risk factor independent of other risk factors, in the present study we show that the MRD level remains a risk factor independent of the presence of a TEL/AML1 fusion gene.

Chromosomes, Human, Pair 12↗