PubMed Health⌕ Search

Biomedical subjects

J de Jong

Publications and source records attributed to J de Jong.

At least 19 recordsLinked to original sources
PubMed2006

Membranes and microfluidics: a review.

The integration of mass transport control by means of membrane functionality into microfluidic devices has shown substantial growth over the last 10 years. Many different examples of mass transport control have been reported, demonstrating the versatile use of membranes. This review provides an overview of the developments in this area of research. Furthermore, it aims to bridge the fields of microfabrication and membrane science from a membrane point-of-view. First the basic terminology of membrane science will be discussed. Then the integration of membrane characteristics on-chip will be categorized based on the used fabrication method. Subsequently, applications in various fields will be reviewed. Considerations for the use of membranes will be discussed and a checklist with selection criteria will be provided that can serve as a starting point for those researchers interested in applying membrane-technology on-chip. Finally, opportunities for microfluidics based on proven membrane technology will be outlined. A special focus in this review is made on the membrane properties of polydimethylsiloxane (PDMS), since this material is frequently used nowadays in master replication.

Journal Article↗
PubMed2006

Spontaneous bending of 2D molecular bottle-brush.

Using a scaling approach we consider a 2D comb copolymer brush under bending deformations. We show that the rectilinear brush is locally stable and can be characterized by a persistence length lambda increasing with the molecular weight of grafting side chains as lambda approximately M3. A bending instability due to redistribution of the side chains appears in the non-linear regime where bending is strong. Arguments are presented that the brush conformations consist of alternating rectilinear and bent sections corresponding to the different free-energy minima.

Computer Simulation↗
PubMed2005

New replication technique for the fabrication of thin polymeric microfluidic devices with tunable porosity.

In this article we present a new versatile replication method to produce thin polymeric microfluidic devices with tunable porosity. This method is based on phase separation of a polymer solution on a microstructured mold. Compared to existing microfabrication techniques, such as etching and hot embossing, our technique offers four advantages: (a) simple and cheap process that can be performed at room temperature outside clean room facilities; (b) very broad range of applicable materials (including materials that could not be processed before); (c) ability to make thin flexible chips; (d) ability to introduce and tune porosity in the chip. By introducing porosity, the channel walls can be used for selective transport of gasses, liquids and solutes. A proof-of-concept will be given, by showing fast CO2 transport through the channel walls of a porous polymer chip. Furthermore, it will be demonstrated that the gas permeation performance of chips can be enhanced dramatically by a decrease in chip thickness and incorporation of porosity. We expect that the development of porous chips can lead to the on-chip integration of multiple unit operations, such as reaction, separation, gas liquid contacting and membrane emulsification.

Carbon Dioxide↗
PubMed2004

The building blocks of planets within the 'terrestrial' region of protoplanetary disks.

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

Journal Article↗
PubMed2003

Development and validation of a liquid chromatographic-tandem mass spectrometric method for the determination of galantamine in human heparinised plasma.

Galantamine is an acetylcholinesterase inhibitor, recently approved for the treatment of mild-to-moderate Alzheimer's disease. To allow a higher throughput of samples, a new bioanalytical method for the determination of galantamine in human plasma was developed and validated. A stable isotope labelled internal standard was used. Sample preparation consisted of a simple one-step liquid-liquid extraction with toluene. The extracts were analysed with positive ion TurboIonspray tandem mass spectrometry (LC-MS-MS). The method was validated in the 1-500-ng/ml range. The accuracy, precision, selectivity, lower limit of quantification, upper limit of quantification, linearity and extraction recovery were evaluated, as well as the stability of the compound in plasma, blood, methanol and 2% BSA solutions under different conditions. The method proved very rugged during the analysis of large numbers of samples from clinical trials.

Chromatography, High Pressure Liquid↗
PubMed2003

Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography-tandem mass spectrometry.

Since the first entry of risperidone on to the market in the early 1990s, investigation of the pharmacokinetic behaviour of the compound for which the availability of a bioanalytical method was a condition sine qua non, has received considerable attention. Most of the published methods, however, did not reach the level of sensitivity and selectivity which can be obtained today since the evolution of liquid chromatography-tandem mass spectrometry (LC-MS-MS) towards a routine technique in the bioanalytical laboratory. Therefore, we developed and validated a new LC-MS-MS method for the determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. This paper describes in detail the bioanalytical procedure and summarizes the validation results obtained. In addition, it focuses on the pitfalls one might encounter when developing similar assays. Despite the particular physicochemical characteristics of risperidone and 9-hydroxyrisperidone, the LC-MS-MS method enabled the quantification of both compounds down to 0.1 ng/ml. The method uses a sample preparation step by solid-phase extraction at pH 6 using a mixed-mode phase. In a short chromatographic run, separation of 9-hydroxyrisperidone from the minor metabolite 7-hydroxyrisperidone is achieved. Detection takes place by (turbo)ionspray tandem mass spectrometry in the positive ion mode. The validated concentration range is from 0.100 to 250 ng/ml, using 500 microliter of sample, with accuracy (bias) and precision (coefficient of variation) being below 15%. Although new developments in equipment will allow us to further improve and speed up the method, the assay reported can be used as a routine method to support a wide range of pharmacokinetic studies.

Antipsychotic Agents↗
PubMed2003

The promoter-terminator of chrysanthemum rbcS1 directs very high expression levels in plants.

Transgenic plants are increasingly used as production platforms for various proteins, yet protein expression levels in the range of the most abundant plant protein, ribulose-1,5-bisphosphate carboxylase have not yet been achieved by nuclear transformation. Suitable gene regulatory 5' and 3' elements are crucial to obtain adequate expression. In this study an abundantly transcribed member (rbcS1) of the ribulose-1,5-bisphosphate carboxylase small-subunit gene family of chrysanthemum (Chrysanthemum morifolium Ramat.) was cloned. The promoter of rbcS1 was found to be homologous to promoters of highly expressed rbcS gene members of the plant families Asteraceae, Fabaceae and Solanaceae. The regulatory 5' and 3' non-translated regions of rbcS1 were engineered to drive heterologous expression of various genes. In chrysanthemum, the homologous rbcS1 cassette resulted in a beta-glucuronidase (gusA) accumulation of, at maximum, 0.88% of total soluble protein (population mean 0.17%). In tobacco (Nicotiana tabacum L.), the gusA expression reached 10% of total soluble protein. The population mean of 2.7% was found to be 7- to 8-fold higher than for the commonly used cauliflower mosaic virus (CaMV) 35S promoter (population mean 0.34%). RbcS1-driven expression of sea anemone equistatin in potato (Solanum tuberosum L.), and potato cystatin in tomato (Lycopersicon esculentum Mill.) yielded maximum levels of 3-7% of total soluble protein. The results demonstrate, that the compact 2-kb rbcS1 expression cassette provides a novel nuclear transformation vector that generates plants with expression levels of up to 10% of total protein.

Base Sequence↗
PubMed2001

Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors.

The concept for cellular immunotherapy of solid tumors relies heavily on the capacity of class I MHC-restricted cytotoxic T lymphocytes (CTLs) to eliminate tumor cells. However, tumors often have managed to escape from the cytolytic machinery of these effector cells. Therefore, it is very important to chart the mechanisms through which this escape can occur. Target-cell killing by CTLs involves the induction of apoptosis by two major mechanisms: through death receptors and the perforin/granzyme B (GrB) pathway. Whereas tumors previously were shown to exhibit mechanisms for blocking the death receptor pathway, we now demonstrate that they also can resist CTL-mediated killing through interference with the perforin/GrB pathway. This escape mechanism involves expression of the serine protease inhibitor PI-9/SPI-6, which inactivates the apoptotic effector molecule GrB. Expression of PI-9 was observed in a variety of human and murine tumors. Moreover, we show that, indeed, expression results in the resistance of tumor cells to CTL-mediated killing both in vitro and in vivo. Our data reveal that PI-9/SPI-6 is an important parameter determining the success of T cell-based immunotherapeutic modalities against cancer.

Animals↗
PubMed2001

Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: differential modulation by T helper type 1 and type 2 cells.

Dendritic cells (DCs) play a central role in the immune system as they drive activation of T lymphocytes by cognate interactions. However, as DCs express high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and thereby limit induction of immunity. We show here that immature DCs are indeed susceptible to CTL-induced killing, but become resistant upon maturation with anti-CD40 or lipopolysaccharide. Protection is achieved by expression of serine protease inhibitor (SPI)-6, a member of the serpin family that specifically inactivates granzyme B and thereby blocks CTL-induced apoptosis. Anti-CD40 and LPS-induced SPI-6 expression is sustained for long periods of time, suggesting a role for SPI-6 in the longevity of DCs. Importantly, T helper 1 cells, which mature DCs and boost CTL immunity, induce SPI-6 expression and subsequent DC resistance. In contrast, T helper 2 cells neither induce SPI-6 nor convey protection, despite the fact that they trigger DC maturation with comparable efficiency. Our data identify SPI-6 as a novel marker for DC function, which protects DCs against CTL-induced apoptosis.

Animals↗
PubMed2001

Natural T-helper immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: identification of 3 human leukocyte antigen class II-restricted epitopes.

Tumor-specific T-helper (Th) immunity was found to play a pivotal role in the natural and vaccine-induced immune defense against tumors. Since the majority of cervical cancers express human papillomavirus type 16 (HPV16) E7 oncoprotein, it is important to investigate the Th response against this target antigen in detail. By means of PBMC cultures from HLA-typed healthy donors, we identified the central part of HPV16 E7 (E7(41-72)) as the major immunogenic region within this antigen. Furthermore, we mapped 3 distinct Th epitopes within this region (DR15/E7(50-62), DR3/E7(43-77), DQ2/E7(35-50)). In a parallel approach, employing IFN-gamma ELISPOT analysis, we detected Th immunity against HPV16 E7 in subjects with HPV16+ lesions. Several of these responses matched with the 3 Th epitopes defined in our study. A number of other HPV16+ subjects did not display any E7-specific type 1 cytokine-producing T-cell immunity, indicating failure of the immune response. Our combined data argue for more extensive as well as longitudinal analysis of HPV16-specific T-cell immunity using the ELISPOT assay described, as well as for HPV-specific vaccination of individuals with HPV+ lesions.

Cancer Vaccines↗
PubMed2001

Genetic analysis of the organic cation transporter genes Orct2/Slc22a2 and Orct3/Slc22a3 reduces the critical region for the t haplotype mutant t(w73) to 200 kb.

Here we report an analysis of two candidate genes for the t(w73) implantation mutation. The t(w73) gene maps to a 20-cM region of mouse Chromosome (Chr) 17 known as the t-complex, which exists in a wild-type and t haplotype form in present-day mice. The t haplotype variants contain several mutant alleles affecting male fertility and embryonic viability and offer the opportunity to identify genes critical for these processes. t(w73) homozygous embryos are defective in trophoblast production and fail to implant adequately, with death occurring at approximately 7.5 days post coitum (pc). Two recently described organic cation transporter genes, Slc22a2 (Orct2) and Slc22a3 (Orct3), fulfill criteria predicted for t(w73) candidate genes, since both map to the previously defined 500-kb t(w73) minimal region and both are also expressed in 7.5 days pc post-implantation embryos. The genomic locus of the Orct2 gene appears similar in wild-type and t(w73) chromosomes. In contrast, the genomic locus of Orct3 is amplified and displays an altered expression profile in all t haplotype variant chromosomes tested. In addition, Orct3 shows a t(w73) specific polymorphism. To test whether either Orct2 or Orct3 is involved in the t(w73) phenotype, we have performed a genetic rescue experiment using YAC transgenes overexpressing Orct2, and genetic complementation with an allele in which the Orct3 gene was inactivated by homologous recombination. The results eliminate both Orct2 and Orct3 as candidates and further reduce the critical region containing the t(w73) mutant from 500 kb to 200 kb.

Animals↗
PubMed2001

Graded exposure in vivo in the treatment of pain-related fear: a replicated single-case experimental design in four patients with chronic low back pain.

The aim of this investigation was to examine the effectiveness of a graded exposure in vivo treatment with behavioural experiments as compared to usual graded activity in reducing pain-related fears, catastrophising and pain disability in chronic low back pain patients reporting substantial fear of movement/(re)injury. Included in the study were four consecutive CLBP patients who were referred for outpatient behavioural rehabilitation, and who reported substantial fear of movement/(re)injury (Tampa Scale for Kinesiophobia score>40). A replicated single-case cross-over design was used. After a no-treatment baseline measurement period, the patients were randomly assigned to one of two interventions. In intervention A, patients received the exposure first, followed by graded activity. In intervention B, the sequence of treatment modules was reversed. Sixty-three daily measures of pain-related cognitions and fears were recorded with visual analogue scales. Before and after the treatment, the following measures were taken: pain-related fear, pain catastrophising, pain control and pain disability. Using time series analysis on the daily measures of pain-related cognitions and fears, we found that improvements only occurred during the graded exposure in vivo, and not during the graded activity, irrespective of the treatment order. Analysis of the pre-post treatment differences also revealed that decreases in pain-related fear concurred with decreases in pain catastrophising and pain disability, and in half of the cases an increase in pain control. This study shows that the external validity of exposure in vivo also extends to the subgroup of chronic low back pain patients who report substantial fear of movement/(re)injury.

Accidents, Occupational↗
PubMed2001

External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.

PURPOSE: No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. MATERIALS AND METHODS: Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. RESULTS: Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). CONCLUSION: The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.

Aged↗
PubMed2001

Development and validation of a method for the determination of sub-additive levels of virginiamycin in compound animal feeds by liquid chromatography.

A method for the detection of virginiamycin M1 as a marker compound of virginiamycin at sub-additive level in pig, calf, piglet, sow, poultry, cattle and laying hen feeds was developed and validated. Both UV detection at 230 nm and MS detection were applied. Virginiamycin M1 was extracted from animal feeds with ethyl acetate after wetting of the feed with water followed by clean-up on Sep-Pak silica gel and OASIS HLB cartridges. Analysis of extracts was carried out on an Inertsil ODS-2 column with acetonitrile-water-formic acid as the mobile phase and UV detection at 230 nm. The limit of quantification (LOQ) of the method was 2.7 mg kg(-1). The proposed method was validated at a target species dependent minimum required performance limit (MRPL), at 2MRPL and at 5MRPL levels in pig, calf, piglet, sow, poultry, cattle and laying hen feeds. Recoveries at target species dependent MRPL levels ranged from 38 to 67%, within-day repeatabilities from 7 to 19% and within-laboratory reproducibilities from 13 to 27%. The proposed UV method is primarily suitable for screening purposes at subadditive levels, but semi-quantitative data can also be produced. Three MS detection modes (ion-source CID, full MS and MS2) were tested as an alternative and/or extension to UV detection. The selectivity and sensitivity of both LC-MS2 and LC-MS were much better than those of UV detection at 230 nm.

Animal Feed↗
PubMed2001

Scheie syndrome presenting as myopathy.

We investigated two brothers with Scheie syndrome whose only complaint was exercise intolerance. In the quadriceps muscle biopsy of both patients, between the normal muscle fibres an increased number of markedly swollen periodic acid-Schiff-positive fibroblasts were seen. Ultrastructurally, these cells showed an accumulation of enlarged lysosomes, partly filled with electro-dense material. We hypothesize that the accumulation of pathological fibroblasts may interfere with intramuscular force transmission resulting in exercise intolerance.

Adolescent↗
PubMed2001

The relevance of the revised version of the international lung cancer staging system for non-small-cell lung cancer treated with radiotherapy.

In 1997, the International Union Against Cancer (UICC) introduced a new version of staging for lung cancer. The purpose of this study was to determine the prognostic value of the new UICC staging (1997) among patients with inoperable non-small-cell lung cancer (NSCLC) treated with radiotherapy. The status of a total of 1354 inoperable patients postintrathoracic irradiation for NSCLC was retrospectively analyzed. Restaging was performed according to the staging system of the UICC 1997. The median survival (MS) among patients with stage I disease was 12.4 months. In the case of stage IA disease, the MS was 17.6 months, which was significantly better compared to the 11.2 months observed among patients with stage IB disease (P = 0.002). The MS among patients with clinical T2 N1 M0 disease (stage IIB) was 8.0 months. The MS among those with clinical T3 N0 M0 disease (stage IIB) was 8.6 months, which was not statistically different from the group of patients with stage IIIA disease, who had an MS of 7.6 months. The MS among patients with stage IIIB disease was 6.5 months, and among patients with stage IV disease, MS was 4.0 months. It was concluded that in patients with inoperable NSCLC treated with radiotherapy, the distinction between stages IA and IB disease in the new staging system is clinically relevant. There was no significant difference in survival between patients with stage IIB and IIIA disease. The results clearly show that the prognostic significance of a staging system mainly based on surgically treated patients should be analyzed separately before it can be used among patients treated with nonsurgical modalities.

Journal Article↗
PubMed2000

Histone-containing immune complexes are to a large extent responsible for anti-dsDNA reactivity in the Farr assay of active SLE patients.

Increased titres of anti-dsDNA antibodies, especially if of high avidity, are associated with renal exacerbations in patients with systemic lupus erythematosus (SLE). One of the most reliable assays to measure anti-dsDNA antibodies, the Farr assay, is believed to detect preferentially high avidity antibodies. Purified non-complexed monoclonal antibodies (mAbs) against nucleosomes, obtained from mice with SLE, are not reactive in the Farr assay, but can become so once complexed to nucleosomes. These Farr-positive, nucleosome containing, immune complexes were also able to bind in vivo to the glomerular basement membrane (GBM), predominantly via heparan sulphate (HS). To evaluate whether in SLE patients the same kind of immune complexes are responsible for Farr reactivity, IgG from serum or plasma was isolated under dissociating and physiological conditions. We observed that after purification under dissociating conditions, Farr reactivity was significantly decreased (P<0.0001) in contrast to reactivity with histones and two 'control' antigens: Epstein Barr Virus (EBV) and Ro/SS-A. Reactivity with nucleosomes also decreased after purification, although to a lesser extent. Plasma purified under physiological conditions showed no decrease in Farr reactivity. The importance of histones for the generation of immune complexes is supported by the two following observations. Firstly, the presence of histones could be demonstrated in serum and plasma of SLE patients but not in serum of healthy controls or in IgG preparations purified under dissociating conditions. Secondly, Farr reactivity of purified IgG preparations could be restored by addition of purified histones. From these studies we conclude that histones containing immune complexes are responsible for a large part of the Farr reactivity in active SLE, and are therefore indirectly implicated in the pathogenesis of lupus nephritis.

Animals↗