Biomedical subjects

A van den Berg

Publications and source records attributed to A van den Berg.

At least 19 recordsLinked to original sources

PubMed2006

Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma.

BIC is a primary microRNA (pri-miR-155) that can be processed to mature miR-155. In this study, we show the crucial involvement of protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) in the regulation of BIC expression upon B-cell receptor triggering. Surprisingly, Northern blot analysis did not reveal any miR-155 expression upon induction of BIC expression in the Burkitt lymphoma-derived Ramos cell line, whereas other microRNAs were clearly detectable. Ectopic expression of BIC in Ramos and HEK293 cells resulted in miR-155 expression in HEK293, but not in Ramos cells, suggesting a specific block of BIC to miR-155 processing in Ramos. In line with the results obtained with Ramos, lack of miR-155 expression after induction of BIC expression was also observed in other Burkitt lymphoma cell lines, indicating a generic and specific blockade in the processing of BIC in Burkitt lymphoma. In contrast, induction of BIC expression in normal tonsillar B cells resulted in very high levels of miR-155 expression and induction of BIC expression in Hodgkin's lymphoma cell lines. It also resulted in elevated levels of miR-155. Our data provide evidence for two levels of regulation for mature miR-155 expression: one at the transcriptional level involving PKC and NF-kappaB, and one at the processing level. Burkitt lymphoma cells not only express low levels of BIC, but also prevent processing of BIC via an, as yet, unknown mechanism.

Blotting, Northern↗

PubMed2006

The role of microRNAs in normal hematopoiesis and hematopoietic malignancies.

Over the past few years, it has become evident that microRNAs (miRNAs) play an important regulatory role in various biological processes. Much effort has been put into the elucidation of their biogenesis, and this has led to the general concept that a number of key regulators are shared with the processing machinery of small interfering RNAs. Despite the recognition that several miRNAs play crucial roles in normal development and in diseases, little is known about their exact molecular function and the identity of their target genes. In this review, we report on the biological relevance of miRNAs for the differentiation of normal hematopoietic cells and on the contribution of deregulated miRNA expression in their malignant counterparts.

Animals↗

PubMed2006

Directional flow induced by synchronized longitudinal and zeta-potential controlling AC-electrical fields.

Electroosmotic flow (EOF) in a microchannel can be controlled by electronic control of the surface charge using an electrode embedded in the wall of the channel. By setting a voltage to the electrode, the zeta-potential at the wall can be changed locally. Thus, the electrode acts as a "gate" for liquid flow, in analogy with a gate in a field-effect transistor. In this paper we will show three aspects of a Field Effect Flow Control (FEFC) structure. We demonstrate the induction of directional flow by the synchronized switching of the gate potential with the channel axial potential. The advantage of this procedure is that potential gas formation by electrolysis at the electrodes that provide the axial electric field is suppressed at sufficiently large switching frequencies, while the direction and magnitude of the EOF can be maintained. Furthermore we will give an analysis of the time constants involved in the charging of the insulator, and thus the switching of the zeta potential, in order to predict the maximum operating frequency. For this purpose an equivalent electrical circuit is presented and analyzed. It is shown that in order to accurately describe the charging dynamics and pH dependency the traditionally used three capacitor model should be expanded with an element describing the buffer capacitance of the silica wall surface.

Buffers↗

PubMed2006

Electroporation of cells in microfluidic devices: a review.

In recent years, several publications on microfluidic devices have focused on the process of electroporation, which results in the poration of the biological cell membrane. The devices involved are designed for cell analysis, transfection or pasteurization. The high electric field strengths needed are induced by placing the electrodes in close proximity or by creating a constriction between the electrodes, which focuses the electric field. Detection is usually achieved through fluorescent labeling or by measuring impedance. So far, most of these devices have only concerned themselves solely with the electroporation process, but integration with separation and detection processes is expected in the near future. In particular, single-cell content analysis is expected to add further value to the concept of the microfluidic chip. Furthermore, if advanced pulse schemes are employed, such microdevices can also enhance research into intracellular electroporation.

Animals↗

PubMed2006

Differential expression and distribution of epithelial adhesion molecules in non-small cell lung cancer and normal bronchus.

BACKGROUND: Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis. AIM: To screen for altered expression of epithelial adhesion genes in lung cancer development. METHODS: Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels. RESULTS: 43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion-that is, integrin alpha3 (ITGA3), integrin beta4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell-matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell-cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas. CONCLUSIONS: Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested.

Adenocarcinoma↗

PubMed2006

Gene expression analysis of dendritic/Langerhans cells and Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a neoplastic disorder that results in clonal proliferation of cells with a Langerhans cell (LC) phenotype. The pathogenesis of LCH is still poorly understood. In the present study, serial analysis of gene expression (SAGE) was applied to LCs generated from umbilical cord blood CD34+ progenitor cells to identify LC-specific genes and the expression of these genes in LCH was investigated. Besides the expression of several genes known to be highly expressed in LCs and LCH such as CD1a, LYZ, and CD207, high expression of genes not previously reported to be expressed in LCs, such as GSN, MMP12, CCL17, and CCL22, was also identified. Further analysis of these genes by quantitative RT-PCR revealed high expression of FSCN1 and GSN in all 12 LCH cases analysed; of CD207, MMP12, CCL22, and CD1a in the majority of these cases; and CCL17 in three of the 12 cases. Immunohistochemistry confirmed protein expression in the majority of cases. The expression of MMP12 was most abundant in multi-system LCH, which is the LCH type with the worst prognosis. This suggests that expression of MMP12 may play a role in the progression of LCH. These data reveal new insight into the pathology of LCH and provide new starting points for further investigation of this clonal proliferative disorder.

Antigens, CD↗

PubMed2006

Upregulation of ADAM19 in chronic allograft nephropathy.

ADAM19 (a disintegrin and metalloproteinase 19) is involved in cell-cell and cell-matrix interactions and tumor necrosis factor (TNF)-alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.002). Using RNA in situ hybridization (ISH), we detected moderate ADAM19 mRNA expression in vascular smooth muscle cells (SMCs) and distal tubuli of control kidneys. In CAN, massive ADAM19 expression was detected in SMCs, distal tubuli, glomerular sclerotic lesions and inflammatory CD4+ cells. To determine whether ADAM19 is specifically related to CAN, we studied transplant biopsies with and without CAN, acute rejection and non-transplant-related kidney diseases: interstitial fibrosis (IF), interstitial atrophy, glomerular fibrosis and interstitial inflammation. In various renal structures, ADAM19 mRNA was significantly higher in CAN when compared with renal allografts without CAN or acute rejection. ADAM19 expression in renal endothelium was significantly higher in acute rejection when compared with renal allografts without CAN. When compared to CAN, ADAM19 was expressed to a similar extent in non-transplant-related interstitial and glomerular fibrosis, interstitial atrophy and inflammation. Although these observational data do not establish a cause and effect relationship, ADAM19 may have a modulatory role in the dysfunctional renal allograft state.

ADAM Proteins↗

PubMed2005

Strongly accelerated and humidity-independent drying of nanochannels induced by sharp corners.

Measurements are shown indicating that the drying rate of nanochannels can be enhanced by up to 3 orders of magnitude relative to drying by vapor diffusion, and that the drying rate is independent of the relative humidity of the environment up to a relative humidity of more than 90%. Micromachined Pyrex glass nanochannels of 72 nm height and with sharp corners (corner angles 7 degrees) were used. Available theory shows that the sharp corners function as a low-resistance pathway for liquid water, siphoning (wicking) the water to a location close to the channel exit before it evaporates. The described phenomena are of importance for the understanding of drying processes in industry and agriculture. The introduction of sharp corners or grooves can furthermore be beneficial for the functioning of microheat pipes and capillary-pumped loops.

Journal Article↗

PubMed2005

Technologies for nanofluidic systems: top-down vs. bottom-up--a review.

This paper gives an overview of the most commonly used techniques for nanostructuring and nanochannel fabrication employed in nanofluidics. They are divided into two large categories: top-down and bottom-up methods. Top-down methods are based on patterning on large scale while reducing the lateral dimensions to the nanoscale. Bottom-up methods arrange atoms and molecules in nanostructures. Here, we review the advantages and disadvantages of those methods and give some future perspectives. It is concluded that technology in the region of 1-10 nm is lacking and potentially can be covered by using the pulsed-laser deposition method as a controlled way for thin film deposition (thickness of a few nanometers) and further structuring by the top-down method.

Equipment Design↗

PubMed2005

Fabrication and characterization of high-temperature microreactors with thin film heater and sensor patterns in silicon nitride tubes.

In this paper the fabrication and electrical characterization of a silicon microreactor for high-temperature catalytic gas phase reactions, like Rh-catalyzed catalytic partial oxidation of methane into synthesis gas, is presented. The microreactor, realized with micromachining technologies, contains silicon nitride tubes that are suspended in a flow channel. These tubes contain metal thin films that heat the gas mixture in the channel and sense its temperature. The metal patterns are defined by using the channel geometry as a shadow mask. Furthermore, a new method to obtain Pt thin films with good adhesive properties, also at elevated temperatures, without adhesion metal is implemented in the fabrication process. Based on different experiments, it is concluded that the electrical behaviour at high temperatures of Pt thin films without adhesion layer is better than that of Pt/Ta films. Furthermore, it is found that the temperature coefficient of resistance (TCR) and the resistivity of the thin films are stable for up to tens of hours when the temperature-range during operation of the microreactor is below the so-called "burn-in" temperature. Experiments showed that the presented suspended-tube microreactors with heaters and temperature sensors of Pt thin films can be operated safely and in a stable way at temperatures up to 700 degrees C for over 20 h. This type of microreactor solves the electrical breakdown problem that was previously reported by us in flat-membrane microreactors that were operated at temperatures above 600 degrees C.

Biosensing Techniques↗

PubMed2005

A miniaturized carbon dioxide gas sensor based on sensing of pH-sensitive hydrogel swelling with a pressure sensor.

A measurement concept has been realized for the detection of carbon dioxide, where the CO(2) induced pressure generation by an enclosed pH-sensitive hydrogel is measured with a micro pressure sensor. The application of the sensor is the quantification of the partial pressure of CO(2) (Pco(2)) in the stomach as diagnosis for gastrointestinal ischemia. The principle is put to the proof by examining the sensor response to changes in Pco(2). Furthermore, the response time, temperature-sensitivity and resolution are determined. The sensor responds well to changes in Pco(2) with a maximum pressure generation of 0.29 x 10(5) Pa at 20 kPa CO(2). The 90% response time varies between 1.5 and 4.5 minutes at 37( composite function)C. The sensor shows a linear temperature-sensitivity which can easily be compensated for, and enables detection of Pco(2) changes as small as 0.5 kPa CO(2).

Biological Assay↗

PubMed2005

[Prevalence of gastric lesions in the pars proventricularis in finishing pigs at slaughter in Switzerland].

A cross-sectional study was conducted at two large abattoirs in the winter 2003/04 to determine the prevalence of gastric lesions in Swiss finishing pigs. The stomachs of 1897 pigs from 107 slaughter groups were examined for macroscopic epithelial lesion of the pars proventricularis. Severe hyperceratosis, erosion, ulceration and constriction at the transition between oesophagus and stomach were described as gastric lesions. Lesions were observed in 36% of all animals, with slaughter group prevalence ranging from 0% to 94%. Ulceration or constriction was present in four percent of the examined pigs. Associations between gastric lesions, farm management data, and data obtained at ante and post mortem examinations conducted at the slaughterhouse were analysed. A significantly higher prevalence of gastric lesions was found in pigs originating from conventional housing systems compared to pigs raised on farms with 'animal-friendly' housing systems providing straw bedding and outdoor exercise to pigs. In addition, significantly higher prevalence was observed in pigs originating from herds with clinical signs of tail biting and peritarsitis.

Abattoirs↗

PubMed2005

Genetic susceptibility to Hodgkin's lymphoma associated with the human leukocyte antigen region.

Based on the presence of an abundant inflammatory infiltrate, expression of a broad spectrum of cytokines and the professional antigen presenting phenotype of Hodgkin Reed-Sternberg cells it can be anticipated that immunological mechanisms play a major role in the pathogenesis of Hodgkin's lymphoma (HL). Genetic susceptibility to HL probably relates to functionality of the immune system and the large number of associations with the human leukocyte antigen (HLA) region in family and population-based studies supports this relation. In Epstein-Barr virus (EBV) positive HL cases, which usually demonstrate HLA class I expression, HRS cells should be able to present EBV derived antigenic peptides and trigger the immune system. This process depends on the affinity of the HLA binding groove for binding immunogenic peptides and thus on the HLA alleles. It can be anticipated that certain combinations of alleles predispose to or protect from the development of EBV positive HL. In EBV negative HL cases other antigenic peptides, related to malignant transformation, in combination with other HLA alleles may be involved. In addition, differential attraction and activation of inflammatory cells may influence HL subtype. In this article, possible roles of HLA in HL pathogenesis are explored and genetic associations of HLA with HL are reviewed and commented on.

Chromosomes, Human, Pair 6↗

PubMed2005

High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma.

AIM: To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL). METHODS: Serial analysis of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue samples to confirm the SAGE data. RESULTS: High expression of Mcl-1 was seen in the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-X(L), were not detected in the SAGE library. Quantitative RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2 and Bcl-X(L) in Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-X(L), and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK- ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-X(L) were expressed infrequently in ALK+ ALCL cases, but were present in a higher proportion of ALK- ALCL cases. CONCLUSION: The consistent high expression of Mcl-1 in ALK+ and ALK- ALCL suggests that Mcl-1 is the main antiapoptotic protein in this disease. The high frequency of Mcl-1, Bcl-2, and Bcl-X(L) positive ALCL cases in the ALK- group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.

Anaplastic Lymphoma Kinase↗

PubMed2004

Monolayer-functionalized microfluidics devices for optical sensing of acidity.

This paper describes the integration of opto-chemosensors in microfluidics networks. Our technique exploits the internal surface of the network as a platform to build a sensing system by coating the surface with a self-assembled monolayer and subsequently binding a fluorescent sensing molecule to the monolayer. Fluorescent molecules were used that can switch between a fluorescent and a non-fluorescent state, depending on the acidity of the surrounding solution. Two systems were investigated. The first employs surface confinement of a Rhodamine B dye in a glass micro channel that serves as a molecular switch in organic solutions. Upon rinsing the micro channels with acidic or basic solutions it was possible to switch between the fluorescent and non-fluorescent forms reversibly. Moreover, this system could be used to monitor the mixing of two solutions of different acidity along the micro channel. To widen the scope of optical sensing in micro channels an Oregon Green dye derivative was immobilized, which functions as a sensing molecule for pH differences in aqueous solutions. In this case, a hybrid system was used consisting of a glass slide and PDMS channels. The fluorescence intensity was found to be directly correlated to the pH of the solution in contact, indicating the possibility of using such a system as a pH sensor. These systems allow real-time measurements and can be easily implemented in micro- and nanofluidics systems thus enabling analysis of extremely small sample volumes in a fast and reproducible manner.

Journal Article↗

PubMed2004

Study of chemically induced pressure generation of hydrogels under isochoric conditions using a microfabricated device.

A method is proposed to study the behavior of stimulus-sensitive hydrogels under isochoric conditions. Freedom of swell movement of such a hydrogel was restricted in all directions by enclosing the hydrogel between a micropressure sensor and a porous cover. Water and external stimuli can be applied to the hydrogel through the pores of the cover to provoke swelling, which results in pressure generation measured by the pressure sensor. The method was put to the proof by examining the response of a pH-sensitive hydrogel to changes in pH, ionic strength, and buffer concentrations of the surrounding solution. Both equilibrium and dynamic pressure generation were observed. The results show that higher pressures are obtained by incorporating more ionizable groups into the hydrogel network or by lowering the ionic strength of the external solution. Furthermore it was proven that pressures reach equilibrium faster when less titratable groups are incorporated or at the presence of higher buffer concentrations in the surrounding solution. By using microfabrication techniques the dimensions of the hydrogel could be kept small with the advantage that responses are fast. A DMAEMA-co-HEMA hydrogel with 2.5% protonable groups and a thickness of 15 microm generated a Delta pressure of 0.67 x 10(5) Pa in 12 min when a pH step from 9 to 6 was applied. The presented method is a simple and fast manner to characterize the static and dynamic stimulus-dependent behavior of hydrogels.

Chemistry, Physical↗

PubMed2004

Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation.

The aim of this study was to find factors that could explain the accumulation difference of mitoxantrone in the BCRP1-negative GLC4-MITO cell line compared to GLC4. Comparative genomic hybridisation (CGH) was applied to determine chromosomal differences between GLC4 and GLC4-MITO. Comparative genomic hybridisation analysis revealed gain of 2q, 6p, 9q, 13q, 14q, 15q, 19q and Xp and loss of 1p, 2q, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p and Xq. In the over-represented chromosomal areas, seven transporter genes were identified: ABCB6, ABCB2 (TAP1), ABCB3 (TAP2), ABCF1 (ABC50), ABCC10 (MRP7), ABCA2 (ABC2) and ABCC4 (MRP4). No RNA or protein upregulation was observed for ABCB6, ABCF1, ABCC10, ABCC4, ABCB2 and ABCB3, but an increased expression was detected for ABCA2 mRNA in GLC4-MITO. ABCA2 is known to be involved in resistance to estramustine. In the MTT assay, GLC4-MITO was two-fold resistant to estramustine compared to GLC4. Coincubation with estramustine and mitoxantrone increased mitoxantrone accumulation in GLC4-MITO, while this was not affected in GLC4. This suggests that estramustine is able to block mitoxantrone efflux in GLC4-MITO cells. These data reveal that cellular reduction of mitoxantrone in a mitoxantrone-resistant cell line is associated with overexpression of ABCA2.

ATP-Binding Cassette Transporters↗

PubMed2004

Porous silicon as a stationary phase for shear-driven chromatography.

We report on the possibility to strongly increase the mass loadability and retention capacity of shear-driven chromatography (SDC) channels by growing a thin porous silicon layer on the stationary wall part. The thickness of the produced porous silicon layers was found to increase linearly with the anodisation time, and could easily be varied between 50 and 300 nm. Combining these layers with sub-microm thin flow-through channels, we believe it is the first time a sub-microm on-chip LC system with a phase ratio similar to that in packed column HPLC (i.e., Vs/Vm approximately equal to 1.5) is obtained. The chromatographic performance of the produced channels has been tested by separating binary mixtures of coumarin dyes under RP-LC conditions. The plate height measurements, yielding Hmin, approximately equal to 0.5 microm (corresponding to more than 2 x 10(6) plates/m) for a retained component with k" = 3, showed good agreement with the theoretical expectations. Due to the presence of some macroscopic defects in the prepared layers, the quality of the separations could however only be maintained over a few millimeters of the channel length. This length was however more than sufficient to separate the coumarin mixture, given the extremely small plate heights of the system.

Chromatography, High Pressure Liquid↗