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Biomedical subjects

A van den Berg

Publications and source records attributed to A van den Berg.

At least 37 records · Page 2Linked to original sources

Lab-on-a-chip systems for biomedical and environmental monitoring.

During the last decade, pocket-sized analytical equipment based on the "lab-on-a-chip" approach has become available. These chips, in combination with portable electronic equipment, are applicable in, for example, "point-of-care" ion analysis of body fluids, forensics, identification of explosives, tracking of pollution in environmental or waste waters, monitoring nutrients in agricultural or horticultural water, controlling quality in food production, or process control in chemical industry. This paper discusses several demonstrator systems with applications in these fields.

Environmental Monitoring↗

Apoptosis induced kinetic changes in autofluorescence of cultured HL60 cells-possible application for single cell analysis on chip.

INTRODUCTION: This paper presents a new method using natural cellular fluorescence (autofluorescence, AF) to study apoptosis. Measurement of AF reduces sample preparation time and avoids cellular toxicity due to the fact that no labelling is required. METHODS: Human promyelocytic leukemic HL60 cells were incubated with camptothecin (CPT), tumour necrosis factor (TNF)-alpha in combination with cycloheximide (CHX), or irradiated with 6 or 10 Gray, during varying time periods, to initiate apoptosis. AF was measured at the flow cytometer. RESULTS: Induction of apoptosis results in the shrinkage of the cell and the fragmentation into apoptotic bodies. With flow cytometry, 4 subpopulations, viable, early apoptotic, late apoptotic and the necrotic cells, can be distinguished. Induction of apoptosis results in a decrease in AF intensity compared to untreated HL60 cells, especially seen in the late apoptotic subpopulation. The AF intensity is found to decrease significantly in time (between 2 h and 24 h) for all the four apoptotic inducers used. CONCLUSIONS: Our results show that it is possible to specifically measure the apoptotic-induced kinetic changes in AF in HL60 cells. A decrease in AF intensity is seen from 2 h till 24 h. These results open a door for future developments in single-cell analysis.

Apoptosis↗

Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation.

OBJECTIVE: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants. DESIGN: Randomised controlled trial. METHODS: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth. RESULTS: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance. CONCLUSIONS: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

Blood Flow Velocity↗

Nanofluidic bubble pump using surface tension directed gas injection.

A new concept for liquid manipulation has been developed and implemented in surface-micromachined fluid channels. It is based on the surface tension directed injection of a gas into the liquid flow through micrometer-sized holes in the microchannel wall. The injected gas is directed to an exhaust by a cross-sectional asymmetry of the microchannel and thereby moves minute liquid volumes. Successful pumping experiments were performed with single stroke volumes of tens of picoliters at frequencies around 1 Hz. The minimum actuation pressure is 0.6 bar for a 2-microm channel height, in accordance with theoretical predictions.

Journal Article↗

Chemokines, cytokines and their receptors in Hodgkin's lymphoma cell lines and tissues.

BACKGROUND: Hodgkin's lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells, and an admixture of reactive cells including lymphocytes, plasma cells, eosinophils and histiocytes. Cytokines produced in HL, either by RS or infiltrating cells, might explain the presence and maintenance of an impaired immune response. Chemokines (cytokines with chemoattractant properties) produced by RS cells play a major role in leukocyte trafficking. These molecules with specific receptor affinities contribute, for example by attracting TH2-like T cells, to the maintenance of a favorable environment for survival of RS cells. RESULTS AND DISCUSSION: Cross-talk between RS cells and reactive elements involves several cytokine/chemokines that process proliferative [interleukin (IL)-13 and IL-17], immunosuppressive (IL-10 and transforming growth factor-beta) and background formation (IL-5, TARC, MDC, IP-10, RANTES, Mig and others) messages. These autocrine and paracrine interactions lead to an environment where RS cells are able to proliferate, escape from apoptosis and survive host anti-tumor defense. CONCLUSIONS: The proper modulation of these complex pathways may allow the development of new strategies in HL therapy.

Chemokines↗

New approaches for fabrication of microfluidic capillary electrophoresis devices with on-chip conductivity detection.

In practice, microfluidic systems are based on the principles of capillary electrophoresis (CE), for a large part due to the simplicity of electroosmotic pumping. In this contribution, a universal conductivity detector is presented that allows detection of charged species down to the microM level. Additionally, powderblasting is presented as a novel technique for direct etching of microfluidic networks. This method allows creation of features down to 50 microm with a total processing time (design to device) of less than one day. The performance of powderblasted devices with integrated conductivity detection is illustrated by the separation of lithium, sodium, and potassium ions and that of fumaric, malic, and citric acid.

Acids↗

Neonatal respiratory morbidity following elective caesarean section in term infants. A 5-year retrospective study and a review of the literature.

Respiratory morbidity is an important complication of elective caesarean section. The presence of labour preceding caesarean section reduces the risk of neonatal respiratory morbidity. Recently, it has been shown that the incidence of respiratory morbidity is lower in infants with a gestational age of at least 39(+0) weeks at elective caesarean section compared to infants with a gestational age less than 39(+0) weeks.This article describes the results of a 5-year retrospective study on the incidence of respiratory distress in term neonates delivered by elective caesarean section in relation to gestational age and provides a literature review on neonatal respiratory morbidity following elective caesarean section.

Cesarean Section↗

Assembly of Saccharomyces cerevisiae ribosomal stalk: binding of P1 proteins is required for the interaction of P2 proteins.

The yeast ribosomal stalk is formed by a protein pentamer made of the 38 kDa P0 and four 12 kDa acidic P1/P2. The interaction of recombinant acidic proteins P1 alpha and P2 beta with ribosomes from Saccharomyces cerevisiae D4567, lacking all the 12 kDa stalk components, has been used to study the in vitro assembly of this important ribosomal structure. Stimulation of the ribosome activity was obtained by incubating simultaneously the particles with both proteins, which were nonphosphorylated initially and remained unmodified afterward. The N-terminus state, free or blocked, did not affect either the binding or reactivating activity of both proteins. Independent incubation with each protein did not affect the activity of the particles, however, protein P2 beta alone was unable to bind the ribosome whereas P1 alpha could. The binding of P1 alpha alone is a saturable process in acidic-protein-deficient ribosomes and does not take place in complete wild-type particles. Binding of P1 proteins in the absence of P2 proteins takes also place in vivo, when protein P1 beta is overexpressed in S. cerevisiae. In contrast, protein P2 beta is not detected in the ribosome in the P1-deficient D67 strain despite being accumulated in the cytoplasm. The results confirm that neither phosphorylation nor N-terminal blocking of the 12 kDa acidic proteins is required for the assembly and function of the yeast stalk. More importantly, and regardless of the involvement of other elements, they indicate that stalk assembling is a coordinated process, in which P1 proteins would provide a ribosomal anchorage to P2 proteins, and P2 components would confer functionality to the complex.

Escherichia coli↗

Membrane characterization of anion-selective CHEMFETs by impedance spectroscopy.

Impedance spectroscopy can be used to determine the influence of several membrane parameters on the membrane resistance of anion selective CHEMFETs. The concentration of the ammonium sites in the membrane, the anion-receptor complex stoichiometry, and the polarity of the membrane matrix are of particular importance. In general the resistance of polysiloxane membranes is higher than that of PVC membranes. However, in polysiloxane membranes the membrane polarity can be influenced by the type or concentration of polar substituents on the polysiloxane chain. Polysiloxane ion-exchange membranes with 25 mol% of polar sulfone substituents exhibit the same conductance as NPOE plasticized PVC membranes. Remarkably, the membrane resistance of cation-selective polysiloxane membranes is much lower and is much less dependent on the substituents.

Algorithms↗

Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas.

Recent studies provide evidence that Reed-Sternberg (R-S) cells produce factors that may explain the characteristic inflammatory infiltrate in the affected tissues of Hodgkin lymphoma. The various chemokines and cytokines that are produced lead to a preferential influx of Th2-type T cells and suppress Th1-type immune responses. Overall, the immunophenotype of the lymphocytes surrounding the R-S cells is consistent with anergic and/or Th2-type T cells. Therefore, these cells do not support a cytotoxic anti-tumor response. Since the R-S cells are neoplastic B cells, the cytokines produced by these T cells may in fact help their growth and/or survival. The production and induction of various other cytokines may also explain the influx of eosinophils (IL-5, eotaxin) and plasma cells (IL-6). Differences in chemokine and cytokine production may be responsible for the differences between the histological subtypes.

Cell Communication↗

Phyto-adaptogens protect against environmental stress-induced death of embryos from the freshwater snail Lymnaea stagnalis.

The main purpose of the studies presented in this paper is twofold: 1) to evaluate whether phyto-adaptogens (Acanthopanax senticosus and Rhodiola rosea) are able to exert a protective action against stress-induced death of embryos of the pond snail Lymnaea stagnalis; and 2) whether a possible protective action by phyto-adaptogens can be explained by the induction of heat shock proteins. Enhancement in resistance by phyto-adaptogens was studied by applying plant extracts for a period of 20 hours to 3-day old larvae of the pond snail Lymnaea stagnalis. Subsequently they were exposed to a high and toxic dose of different environmental stressors. The following stress conditions were selected: a physical stress condition (heat shock: 43 degrees C for 4 minutes), an oxidative stress condition (superoxide radicals induced by menadione (600 microM for 2 hours)) and heavy metal-induced stress (copper (150 microM for 1 hour) or cadmium (20 microM during 1 hour)). Both Acanthopanax and Rhodiola exert a strong protective action against a lethal heat shock. These adaptogens also significantly protect against the negative effect of superoxide radicals as induced by menadione. With respect to the protective action against exposure to heavy metals a small but significant protection was observed against intoxication with copper or cadmium by the phyto-adaptogens. In summary, there appears to be a difference in efficiency in enhancing resistance to the various stress conditions used (heat shock>menadione>copper>cadmium). Based on the results presented in this paper, we can conclude that phyto-adaptogens are able to enhance the resistance against the different stress conditions tested in developing individuals of Lymnaea. Although the degree to which resistance is enhanced appears to depend on the type of stressor applied, our results confirm the definition of phyto-adaptogens as being universal enhancers of non-specific resistance against different kinds of stress conditions. With respect to the mechanism of enhanced resistance, the question was asked whether this protective action is caused by an induction of heat shock proteins (hsps), which are known to be involved in tolerance and adaptation. The phyto-adaptogens did not induce the synthesis of any of the hsps, nor did they modulate the normal heat shock induced synthesis of these stress proteins. We conclude that it is unlikely that hsps play a major role in obtaining an enhanced state of resistance provided by phyto-adaptogens.

Animals↗

An evolutionary rearrangement of the Xp11.3-11.23 region in 3p21.3, a region frequently deleted in a variety of cancers.

In searching for a tumor suppressor gene in the 3p21.3 region, we isolated two genes, RBM5 and RBM6. Sequence analysis indicated that these genes share similarity. RBM5 and-to a lesser extent-RBM6 also have similarity to DXS8237E at Xp11.3-11.23, which maps less than 20 kb upstream of UBE1. A homologue of UBE1, UBE1L, is located at 3p21. 3. FISH analysis showed that the distance between UBE1L and RBM5 in 3p21.3 is about 265 kb. DXS8237E and UBE1 on the X chromosome have the same orientation, whereas on chromosome 3 the orientation of RBM5 and that of RBM6 are opposite to the orientation of UBE1L. Presumably, part of the Xp11.3-11.23 region has duplicated to chromosome 3. Part of this region on chromosome 3 may subsequently have duplicated again within the same chromosomal region. Inversion at some stage of the evolution of the human genome would explain the change in orientation of the genes on chromosome 3 compared with that of the genes on the X chromosome.

Animals↗

Serial analysis of gene expression: rapid RT-PCR analysis of unknown SAGE tags.

In a pilot study on SAGE on Reed-Sternberg cells we have sequenced 1055 tags representing 701 genes. Screening of the GenBank database resulted in the identification of a corresponding gene or EST for 490 of them. For 211 of the tags no homology could be detected. A major problem of the serial analysis of gene expression (SAGE) approach is how to further analyse the unknown tags. We have developed an RT-PCR-based method, rapid analysis of unknown SAGE tags (RAST-PCR), to analyse the expression of the corresponding genes. This approach can be used as a screening method to investigate whether or not the gene is differentially expressed between several cell types of interest.

Cell Line↗

High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma.

Hodgkin's lymphoma is characterized by the combination of Reed-Sternberg (R-S) cells and a prominent inflammatory cell infiltrate. One of the intriguing questions regarding this disease is what is causing the influx of T lymphocytes into the involved tissues. We applied the serial analysis of gene expression (SAGE) technique on the Hodgkin's lymphoma-derived cell line L428 and on an Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cell line. A frequently expressed tag in L428 corresponded to the T-cell-directed CC chemokine TARC. Reverse transcription polymerase chain reaction analyses demonstrated expression of TARC in nodular sclerosis (NS) and mixed cellularity (MC) classical Hodgkin's lymphomas but not in NLP Hodgkin's lymphoma, anaplastic large-cell lymphomas, and large-B-cell lymphomas with CD30 positivity. Two of five cases of T-cell-rich B-cell lymphoma (TCRBCL) were TARC positive. RNA in situ hybridization (ISH) showed a strong signal for TARC in the cytoplasm of R-S cells, and immunohistochemical staining confirmed the presence of the TARC protein in the R-S cells of NS and MC Hodgkin's lymphomas. The lymphocytic and histiocytic (L&H)-type cells of nodular lymphocyte predominance Hodgkin's lymphoma and the neoplastic cells of non-Hodgkin's lymphomas with the exception of two cases of TCRBCL did not stain for TARC. TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes. The immunophenotype of lymphocytes surrounding R-S cells is indeed Th2-like, and by RNA ISH these lymphocytes showed a positive signal for the chemokine receptor CCR4. The findings suggest that production of TARC by the R-S cells may explain the characteristic T-cell infiltrate in classical Hodgkin's lymphoma.

B-Lymphocytes↗

Pathogenesis and medical therapy of primary sclerosing cholangitis. Any news?

Primary sclerosing cholangitis is characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. Medical therapy has focused on anticholestatic, antiinflammatory and immunosuppressive drugs. Although inflammation, fibrosis and cholestasis may all occur at the same time, inflammation dominates the early phase and fibrosis and cholestasis the later stages. With inflammatory bowel disease and rheumatoid arthritis as stimulants, research on anti-inflammatory drugs is in a very active stage, with an emphasis on cytokines and cytokine antagonists. For patients with primary sclerosing cholestasis to fully benefit from these developments, it is necessary to define the early disease stage that constitutes a potential therapeutic window for these agents.

Anti-Inflammatory Agents↗

Immune reactions in classical Hodgkin's lymphoma.

The immune reaction in classical Hodgkin's lymphoma (HL) can be separated into an inflammatory response in the involved tissues and a generalized immune response in the patient. The local immune reaction in HL is by far the most prominent among all tumors, with the exception of so called T-cell-rich B-cell lymphoma, a subtype of large-cell B-cell lymphoma. The general immune response in patients with HL is best described as an acquired cellular immune deficiency, most likely a result of the presence of tumor, although some data in the literature suggest a preexisting immune deficiency. The cellular origin of Reed-Sternberg (RS) cells in classical and nodular lymphocyte-predominant HL is discussed elsewhere. RS cells and their mononuclear variants can be considered as clones of neoplastic B cells that, by secreting potent cytokines/chemokines, not only cause the symptoms of HL but also promote their own growth and evade immune surveillance. The characteristic histologic features of HL--the prominent inflammatory response, the influx of eosinophils, and the presence of fibrosis and sclerosis--may also result from the expression of a range of surface molecules and the production of cytokines and chemokines by RS cells.

Hodgkin Disease↗

Genetic analysis of 2 cases of clear cell renal cancer in 2 sisters.

Two sisters affected with renal cell carcinoma (RCC) is an extremely rare finding, and may indicate a hereditary pattern or the presence of other predisposing factors. We describe here 2 sisters presenting with clear cell renal cell cancer. Examination for von Hippel-Lindau (VHL)-related features and tuberous sclerosis (M. Bourneville) was negative and both had a normal constitutional karyotype. Cytogenetic analysis of the tumor tissue of both patients showed a translocation involving chromosomes 3 and 5, resulting in loss of 3p sequences and gain of part of 5q. The 5q breakpoints were similar, but the breakpoints at 3p appeared to differ. Allelic imbalance analysis supported our observations. Microsatellite analysis revealed that both sisters inherited different chromosome 3 parental alleles. For chromosome 5, 3 different haplotypes could be deduced, but the chromosome 5 alleles overrepresented in the different tumor tissues were from different parental origin. The development of the 2 RCCs in these 2 sisters thus cannot be explained by the inheritance of a mutated VHL gene located at 3p25, nor by the inheritance of other gene defects at chromosomes 3p or 5q. Although the chance that 2 sisters develop sporadic RCC is very low, in the presented case it is probably coincidental or related to another genetic predisposition.

Carcinoma, Renal Cell↗

A cosmid and cDNA fine physical map of a human chromosome 13q14 region frequently lost in B-cell chronic lymphocytic leukemia and identification of a new putative tumor suppressor gene, Leu5.

B-cell chronic lymphocytic leukemia (B-CLL) is a human hematological neoplastic disease often associated with the loss of a chromosome 13 region between RB1 gene and locus D13S25. A new tumor suppressor gene (TSG) may be located in the region. A cosmid contig has been constructed between the loci D13S1168 (WI9598) and D13S25 (H2-42), which corresponds to the minimal region shared by B-CLL associated deletions. The contig includes more than 200 LANL and ICRF cosmid clones covering 620 kb. Three cDNAs likely corresponding to three different genes have been found in the minimally deleted region, sequenced and mapped against the contigged cosmids. cDNA clone 10k4 as well as a chimeric clone 13g3, codes for a zinc-finger domain of the RING type and shares homology to some known genes involved in tumorigenesis (RET finger protein, BRCA1) and embryogenesis (MID1). We have termed the gene corresponding to 10k4/13g3 clones LEU5. This is the first gene with homology to known TSGs which has been found in the region of B-CLL rearrangements.

Amino Acid Sequence↗