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At least 199 records · Page 11Linked to original sources
PubMed1990

Double-blind comparison of intravaginal prostaglandin E2 gel and "chip" for preinduction cervical ripening.

The intravaginal application of prostaglandin E2 for preinduction cervical ripening has proved to be advantageous in the management of patients with an unfavorable cervix. The purpose of this double-blind randomized investigation was to compare the efficacy and safety of two methods of prostaglandin E2 delivery. Patients who were to have preinduction cervical ripening because of an unfavorable cervix (Bishop score less than or equal to 4) were randomly assigned to be given a single dose of prostaglandin E2 as either 2.5 mg of gel or a 3.0 mg "chip" intravaginally in a placebo-controlled manner. Sixty-nine patients received the active prostaglandin E2, 34 in the gel group and 35 in the "chip" group. The groups were similar in maternal age, race, parity, gestational age, and initial Bishop score. Both forms of prostaglandin E2 were easy to administer and helpful in priming an unfavorable cervix. The need for, duration of, and maximum dose of oxytocin were similar in both groups. Cesarean delivery because of failed induction occurred in 5 of 35 (14.3%) patients receiving a "chip" and 4 of 34 (11.8%) receiving the gel. However, patients receiving a "chip" experienced a 20% (7/35) incidence of hyperstimulation, compared with 2.9% (1/36) in those receiving the gel (p less than 0.05). The only case requiring immediate cesarean delivery because of intractable uterine hyperstimulation received a "chip." We conclude that both methods were effective for cervical ripening, but the lower incidence of uterine hyperstimulation seen with the gel would suggest that it is preferable to the "chip."

Administration, Intravaginal↗
PubMed1988

Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer.

Sixty patients with FIGO stage IIb, IIc, III and IV ovarian cancer were entered into a randomized Phase III study of cyclophosphamide 600 mg/m2 with cisplatin 100 mg/m2, iproplatin 240 mg/m2 or carboplatin 300 mg/m2. Dose modifications were made according to renal function and myelotoxicity. The arms containing carboplatin (CBDCA) and iproplatin (CHIP) were not shown to be significantly different from the cisplatin containing arm with regard to response rate, duration of response and survival. Subjective toxicity showed that cisplatin and cyclophosphamide therapy was associated with more nausea and vomiting (P = 0.0005). The duration of vomiting showed a significant increase with successive courses of chemotherapy for the cisplatin containing arm only (P less than 0.003). The cyclophosphamide/CHIP combination caused significantly more diarrhoea (P less than 0.0006). Alopecia was more severe (P less than 0.02), and neurotoxicity was more common, in patients who received cyclophosphamide and cisplatin (paraesthesiae P = 0.0007, tinnitus P less than 0.00005, deafness P = 0.0018). All three combinations caused cumulative toxicity on haemoglobin (Hb) (P less than 0.001 for each treatment), leukocyte count (WCC) (P less than 0.0005 for each treatment), and platelet count (P less than 0.0005 for each treatment). The degree of fall in Hb for each course of therapy was greater in the cisplatin containing arm compared with the CHIP and CBDCA arms which were not significantly different from each other (P = 0.0005). For WCC the cisplatin/cyclophosphamide regimen was significantly less toxic than CHIP/cyclophosphamide, with CBDCA/cyclophosphamide falling between the two and not being significantly different from either (P = 0.0005). The CHIP containing arm caused more thrombocytopenia than the other arms which were of equal toxicity (P less than 0.0005). Serum creatinine showed a gradual significant overall rise with each course of cisplatin/cyclophosphamide therapy (P less than 0.0005), whereas the CBDCA arm showed no change and the CHIP arm showed a small fall in serum creatinine after most courses of therapy. This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. The CHIP/cyclophosphamide regimen caused more thrombocytopenia and diarrhoea. The CHIP and CBDCA containing arms caused more leukopenia than the cisplatin containing regimen. Either iproplatin or carboplatin would be an acceptable alternative to cisplatin in chemotherapy regimens, and would result in reduced toxicity.

Aged↗
PubMed2005

Cytotoxicity test based on electrochemical impedance measurement of HepG2 cultured in microfabricated cell chip.

This paper presents the use of electrochemical impedance measurement on a cell chip to monitor cell growth as a consequence of treatment with potentially cytotoxic agents. The cell chip consists of an eight-well cell culture chamber incorporated with a three-electrode system on each well. The gold electrode for impedance measurements is fabricated by sputtering on polycarbonate film. Human hepatocellular carcinoma cell (HepG2) is adapted to cytotoxicity test using the cell chip. Although the relatively small quantity of cells on the electrode has been measured indirectly, the cell chip can monitor toxic effects on the HepG2 cells cultured in the cell chip continuously and detect cellular behavior without multiple reagents. The cells in the stationary phase after plating are used for the cytotoxicity experiment and the impedance is decreased after treatments with several toxicants, such as tamoxifen and menadione, indicating the detachment of dead cells. These results reveal that the microfabricated cell chip system provides an easy and real-time monitoring method for cytotoxicity test.

Carcinoma, Hepatocellular↗
PubMed2005

Micropillar array chip for integrated white blood cell isolation and PCR.

We report the fabrication of silicon chips containing a row of 667 pillars, 10 by 20 microm in cross-section, etched to a depth of 80 microm with adjacent pillars being separated by 3.5 microm. The chips were used to separate white blood cells from whole blood in less than 2 min and for subsequent PCR of a genomic target (eNOS). Chip fluid dynamics were validated experimentally using CoventorWare microfluidic simulation software. The amplicon concentrations were determined using microchip capillary electrophoresis and were >40% of that observed in conventional PCR tubes for chips with and without pillars. Reproducible on-chip PCR was achieved using white blood cell preparations isolated from whole human blood pumped through the chip.

Cell Separation↗
PubMed2005

Disposable polydimethylsiloxane/silicon hybrid chips for protein detection.

This paper presents disposable protein analysis chips with single- or four-chamber-constructed from poly(dimethylsiloxane) (PDMS) and silicon. The chips are composed of a multilayer stack of PDMS layers that sandwich a silicon microchip. This inner silicon chip features an etched array of micro-cavities hosting polymeric beads. The sample is introduced into the fluid network through the top PDMS layer, where it is directed to the bead chamber. After reaction of the analyte with the probe beads, the signal generated on the beads is captured with a CCD camera, digitally processed, and analyzed. An established bead-based fluorescent assay for C-reactive protein (CRP) was used here to characterize these hybrid chips. The detection limit of the single-chamber protein chip was found to be 1 ng/ml. Additionally, using a back pressure compensation method, the signals from each chamber of the four-chamber chip were found to fall within 10% of each other.

C-Reactive Protein↗
PubMed2005

Microfluidic pH-sensing chips integrated with pneumatic fluid-control devices.

This paper presents a microfluidic chip capable of performing precise continuous pH measurements in an automatic mode. The chip is fabricated using micro-electro-mechanical-systems (MEMS)-based techniques and incorporates polydimethylsiloxane (PDMS) microstructures, pH-sensing electrodes and pneumatic fluid-control devices. Through its enhanced microchannel design and use of pneumatic fluid-control devices, the microfluidic chip reduces the dead volume of the sample and increases the pumping rate. The maximum pumping rate of the developed micro-pump is 28 microL/min at an air pressure of 10 psi and a driving frequency of 10 Hz. The total sample volume consumed in each sensing operation is just 0.515 microL. As a result, the developed chip reduces the sample volume compared to conventional large-scale pH-sensing systems. The microfluidic chip employs the electrochemical sensing method to conduct precise pH level measurements. The sensing electrodes are fabricated by sputtering a layer of SiO(2)-LiO(2)-BaO-TiO(2)-La(2)O(3) (SLBTLO) onto platinum (Pt) electrodes and the pH value of the sample is evaluated by measuring the potential difference between the sensing electrodes and a reference electrode. Additionally, the integration of the microfluidic chip with a pneumatic fluid-control device facilitates automatic sample injection and a continuous sensing operation. The developed system provides a valuable tool with which to examine pH values in a wide range of biomedical and industrial applications.

Electrochemistry↗
PubMed2006

Fabrication of a bio-MEMS based cell-chip for toxicity monitoring.

A bio-MEMS based cell-chip that can detect a specific toxicity was fabricated by patterning and immobilizing bioluminescent bacteria in a microfluidic chip. Since the emitted light intensity of bioluminescent bacteria changed in response to the presence of chemicals, the bacteria were used as the toxicity indicator in this study. A pattern of immobilized cells was successfully generated by photolithography, utilizing a water-soluble and negatively photosensitive polymer, PVA-SbQ (polyvinyl alcohol-styrylpyridinium) as an immobilization material. Using the recombinant Escherichia coli (E. coli) strain, GC2, which is sensitive to general toxicity, the following were investigated for the immobilization: an acceptable dose of long-wavelength UV light, the biocompatibility of the polymer, and the effect of the chip-environment. We found that 10 min of UV light exposure, the toxicity of polymer (SPP-H-13-bio), and the other chip-environment did not inhibit cell metabolism significantly for making a micro-cell-chip. Detection of a specific toxicity was demonstrated by simply immobilizing the bioluminescent bacteria, DK1, which increased bioluminescence in the presence of oxidative damage in the cells. An injection of hydrogen peroxide of 0.88 mM induced 10-fold increase in bioluminescent intensity confirming the capability of the chip for toxicity monitoring.

Dose-Response Relationship, Drug↗
PubMed2006

Isotachophoresis preconcentration integrated microfluidic chip for highly sensitive genotyping of the hepatitis B virus.

The genotyping of hepatitis B virus (HBV) has become recently a valuable tool not only for epidemiological reasons but also for the clinical practice. Conventional methods for HBV genotyping typically include amplification of the target DNA sequences with a two-round nested PCR followed by separation of the amplified fragments by gel electrophoresis. A microfluidic chip that couples isotachophoresis (ITP) preconcentration and zone electrophoresis (ZE) separation may provide great advantages for sensitive, rapid and cost-effective clinical analysis. In this study, an HBV genotyping method with only one amplification round was developed by the application of the ITP-ZE chip. All the analysis steps of the ITP-ZE separation including sample injection, stacking and separation were performed continuously, controlled by sequential high-voltage switching. A 2.1cm sample plug was preconcentrated between discontinuous buffers in ITP process, followed by ZE separation. Sensitivity enhancement was obtained through the increase of sample loading volume. The average LOD value of the ITP-ZE microfluidic chip was determined to be 0.0021pg/muL. In a large-scale HBV genotyping test, single round PCR products were analyzed by ITP-ZE microfluidic chip, and the results were compared with that of the conventional method. Among the 200 cases studied, the classification rate obtained with microfluidic chip was 93%, which was 6% higher than that obtained with the conventional method. Method with ITP-ZE chip analysis provides HBV genotyping information in reduced PCR amplification time with higher detection rate when compared with conventional method. This method holds great potential for extrapolation to the abundance of similar molecular biology-based techniques in clinical diagnosis.

Base Sequence↗
PubMed2006

Co-chaperone CHIP promotes aggregation of ataxin-1.

Recent studies demonstrated that co-chaperone/E3 ligase CHIP (C-terminus of hsp70-interacting protein) mediates the ubiquitylation and suppresses the aggregation of polyglutamine (polyQ) proteins, such as huntingtin or ataxin-3. In this study, we investigated the effects of CHIP on the degradation of another polyQ protein ataxin-1. Interestingly CHIP associates not only with the polyQ-expanded ataxin-1 but also with the normal ataxin-1. Moreover, by enhancing ataxin-1 ubiquitylation, CHIP over-expression leads to a reduction in the solubility of ataxin-1 and thus increases the aggregate formation, especially that of polyQ-expanded ataxin-1. Domain analysis revealed that the TPR domain is required for the promotion of aggregation. By contrast, other co-chaperones or E3 ligases, such as BAG-1 or parkin, did not show similar effects on the aggregation of ataxin-1. Importantly, the effect of CHIP is impaired by the mutation of Ser776 of ataxin-1 whose phosphorylation is crucial for ataxin-1 aggregation. Our findings suggest that the role of CHIP in aggregation of polyQ proteins greatly varies depending on the context of full-length polyQ proteins.

Amino Acid Sequence↗
PubMed2005

Protein ubiquitination: CHIPping away the symmetry.

CHIP is a ubiquitin ligase implicated in the degradation of misfolded proteins. In the November 23 issue of Molecular Cell, identified CHIP as a protein that interacts with the ubiquitin E2 complex Ubc13-Uev1A, which catalyzes the synthesis of Lys-63-linked polyubiquitin chains. Although the ubiquitin ligase activity of CHIP requires its dimerization through the U box domain, the crystal structure of the CHIP-E2 complex reveals that the protomers in the CHIP homodimer adopt distinct conformations such that only one U box of CHIP interacts with Ubc13.

Catalysis↗
PubMed2006

Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity.

The ubiquitin-proteasome system (UPS) is involved in the pathogenetic mechanisms of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Dorfin is a ubiquitin ligase (E3) that degrades mutant SOD1 proteins, which are responsible for familial ALS. Although Dorfin has potential as an anti-ALS molecule, its life in cells is short. To improve its stability and enhance its E3 activity, we developed chimeric proteins containing the substrate-binding hydrophobic portion of Dorfin and the U-box domain of the carboxyl terminus of Hsc70-interacting protein (CHIP), which has strong E3 activity through the U-box domain. All the Dorfin-CHIP chimeric proteins were more stable in cells than was wild-type Dorfin (Dorfin(WT)). One of the Dorfin-CHIP chimeric proteins, Dorfin-CHIP(L), ubiquitylated mutant SOD1 more effectively than did Dorfin(WT) and CHIP in vivo, and degraded mutant SOD1 protein more rapidly than Dorfin(WT) does. Furthermore, Dorfin-CHIP(L) rescued neuronal cells from mutant SOD1-associated toxicity and reduced the aggresome formation induced by mutant SOD1 more effectively than did Dorfin(WT).

Amyotrophic Lateral Sclerosis↗
PubMed2003

Comparison of standard capillary and chip separations of sodium dodecylsulfate-protein complexes.

Conditions for converting a set of five standard proteins to electrochemically active sodium dodecylsulfate (SDS) complexes were worked out with the aim of using such complexes for conductivity detection with a a chip electrophoresis system. The results obtained were compared with standard capillary electrophoresis (37 cm (effective length 30 cm) x 75 microm I.D. capillary, 10 kV, negative polarity at the inlet). The chip separations were run at 500 V per chip (100 V/cm) as compared to the standard capillary arrangement, which was run at 266.6 V/cm. For the capillary set-up the protein complexes were prepared in aqueous solution (Milli-Q water) made 10 mM with respect to SDS. If the SDS concentration was increased to 50 mM, the separation in the capillary was incomplete. On the other hand with the chip system both approaches yielded acceptable results. The chip separations were slightly (but not distinctly) shorter and offered better separations than the standard set-up. The concentration of the surfactant used for the preparation the complexes results in alternations of the elution sequence, which is preserved if the chip separation is used instead of the capillary set-up. Apparently the full capacity of protein-SDS binding is not exploited for the preparation of the adducts.

Electrophoresis, Capillary↗
PubMed1990

Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group.

A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further.

Aged↗
PubMedDate not supplied

[Reference population values for the Spanish Child Health and Illness Profile-Adolescent Edition (CHIP-AE) using a representative school-based sample].

AIM: The Child Health and Illness Profile (CHIP-AE) is a generic health status instrument for adolescents aged 12-19 years adapted for use in Spain. The aim of this study was to obtain reference population values of the Spanish version of the CHIP-AE. METHODS: The CHIP-AE was administered to a representative sample of adolescents from schools in Barcelona. The sample was selected by using cluster-sampling, stratified by type of school (public or private) and an ecological socioeconomic index (Indice de Capacidad Familiar: low, middle, and high). The CHIP-AE scores were standardized to a mean of 20 and a standard deviation (SD) of 5. Means and percentiles were computed. Means were compared by age, gender, and socioeconomic status using analysis of variance. RESULTS: The response rate was 81% (n = 902). The distribution of the CHIP-AE scores presented a wide range with scores generally skewed toward positive health status. Nevertheless, the results suggest that the sample selected from a general population was not free of health problems. Twenty-five percent of adolescents presented scores below 17.2 in the domain of discomfort, indicating an effect size of 0.56 standardized SD units. The distribution of scores in the reference samples from Barcelona was similar to the original results in Baltimore (USA), with some marginal differences in individual risks. CONCLUSIONS: The CHIP-AE systematically gathers information on health domains in adolescents. The results from this reference sample will allow comparisons with adolescents from other regions, and/or with different health problems, as well as description of inequalities in health during adolescence.

Adolescent↗
PubMed2004

Novel biosensor chip for simultaneous detection of DNA-carcinogen adducts with low-temperature fluorescence.

A monoclonal antibody (MAb)-gold biosensor chip with low-temperature laser-induced fluorescence detection for analysis of DNA-carcinogen adducts is described. Optimization of the detection limit, dynamic range, and biosensing applicability of the MAb-gold biosensor chip was achieved by: (1) using dithiobis(succinimidyl propionate (DSP)) as a protein linker and (2) employing recombinant protein A to provide oriented immobilization of the MAbs. The use of DSP, which has a short methylene chain length, led to faster protein binding kinetics and higher protein surface density than a longer dithiobis(succinimidyl undecanoate) (DSU) linker. The incorporation of recombinant protein A increased the distance between the oriented MAb-bound analytes and the gold surface. The increased distance minimized fluorescence quenching, resulting in about a 10-fold increase in the fluorescence signal in comparison with a chip without protein A. The improved chip architecture was used to demonstrate that biosensing of two structurally similar benzo[a]pyrene (BP)-derived DNA adducts, BP-6-N7Gua and BP-diolepoxide-10-N2dG, bound to two specific MAbs immobilized from a mixture at the same address on the chip, is feasible. These mutagenic adducts are formed by one-electron oxidation and monooxygenation pathways, and are depurinating and stable DNA adducts, respectively. It is shown that the DNA adducts can be easily identified at the same address using time-resolved, low-temperature laser-based fluorescence spectroscopy. The current limit of detection is in the low femtomole range. These results indicate that a single biosensor chip consisting of a Au/DSP/protein A/MAb nano-assembly, with analyte-specific MAbs and low-temperature fluorescence detection should be suitable for simultaneous detection and quantitation of the above adducts, as well as the luminescent antigens for which selective MAbs exist.

Benzo(a)pyrene↗
PubMed1998

Electroconducting polymers for the construction of DNA or peptide arrays on silicon chips.

We wish to show in this paper new developments and new applications of the pyrrole copolymerization process allowing the addressing of pyrrole-modified biomolecules on microelectrode arrays. Two main developments are described: the first one concerns the development of multiplexed silicon chips bearing 128 microelectrodes instead of 48 for the passive chips. The second one deals with new applications of this grafting process concerning not only DNA chips but peptide chips too. In this way, copolymerization of pyrrole peptides on the chip (leading to peptide chip) and their immunological detection is illustrated. This technology shows a high dimensional resolution and a real versatility.

Animals↗
PubMed2002

CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.

Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.

Animals↗
PubMed2000

Voltammetry on microfluidic chip platforms

Microfluidic chip devices are shown to be attractive platforms for performing microscale voltammetric analysis and for integrating voltammetric procedures with on-chip chemical reactions and fluid manipulations. Linear-sweep, square-wave, and adsorptive-stripping voltammograms are recorded while electrokinetically "pumping" the sample through the microchannels. The adaptation of voltammetric techniques to microfluidic chip operation requires an assessment of the effect of relevant experimental variables, particularly the high voltage used for driving the electroosmotic flow, upon the background current, potential window, and size or potential of the voltammetric signal. The exact potential window of the chip detector is dependent upon the driving voltage. Manipulation of the electroosmotic flow opens the door to hydrodynamic modulation (stopped-flow) and reversed-flow operations. The modulated analyte velocity permits compensation of the microchip voltammetric background. Reversal of the driving voltage polarity offers extended residence times in the detector compartment. Rapid square-wave voltammetry/flow injection operation allows a detection limit of 2 x 10(-12) mol (i.e., 2 pmol) of 2,4,6-trinitrotoluene (TNT) in connection with 47 nL of injected sample. The ability of integrating chemical reactions with voltammetric detection is demonstrated for adsorptive stripping measurements of trace nickel using the nickel-dimethylglyoxime model system. The voltammetric response is characterized using catechol, hydrazine, TNT, and nickel as test species. The ability to perform on-chip voltammertic protocols in advantageous over nanovial voltammetric operations that lack a liquid-handling capability. Coupling the versatility of microfluidic chips with the rich information content of voltammetry thus opens an array of future opportunities.

Journal Article↗