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PubMed2005

Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes.

A major hallmark of the polyglutamine diseases is the formation of neuronal intranuclear inclusions of the disease proteins that are ubiquitinated and often associated with various chaperones and proteasome components. But, how the polyglutamine proteins are ubiquitinated and degraded by the proteasomes are not known. Here, we demonstrate that CHIP (C terminus of Hsp70-interacting protein) co-immunoprecipitates with the polyglutamine-expanded huntingtin or ataxin-3 and associates with their aggregates. Transient overexpression of CHIP increases the ubiquitination and the rate of degradation of polyglutamine-expanded huntingtin or ataxin-3. Finally, we show that overexpression of CHIP suppresses the aggregation and cell death mediated by expanded polyglutamine proteins and the suppressive effect is more prominent when CHIP is overexpressed along with Hsc70.

Animals↗
PubMed2006

A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control.

In SCF (Skp1/Cullin/F-box protein) ubiquitin ligases, substrate specificity is conferred by a diverse array of F-box proteins. Only in fully assembled SCF complexes, it is believed, can substrates bound to F-box proteins become ubiquitinated. Here we show that Fbx2, a brain-enriched F-box protein implicated in the ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2. CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins, including unassembled NMDA receptor subunits. These findings indicate that CHIP acts with Fbx2 in a novel ubiquitination pathway that links CHIP to glycoprotein quality control in neurons. In addition, they expand the repertoire of pathways by which F-box proteins can regulate ubiquitination and suggest a new role for PEST domains as a protein interaction motif.

Amino Acid Sequence↗
PubMed2002

Ethyl cellulose and polyethylene glycol-based sustained-release sparfloxacin chip: an alternative therapy for advanced periodontitis.

This study reports the development of a sustained-release system of sparfloxacin for use in the treatment of periodontal disease. A sustained-release sparfloxacin device was formulated, based on ethyl cellulose (EC) 10 cps, polyethylene glycol (PEG) 4000, and diethyl phthalate (DEPh). It will hereafter be called the sparfloxacin chip (SRS chip). The chip has dimensions of 10 mm length, 2 mm width, and 0.5 mm thickness. The in vitro drug release pattern and clinical evaluation of the formulations were studied. Reports of the short-term clinical study show that the use of the SRS chip may cause complete eradication of the pathogenic bacteria in the periodontal pockets of patients who have chronic generalized periodontitis. In this clinical study, the baseline and follow-up measurements of various clinical indices, such as oral hygiene index(es), plaque index, sulcular depth component of periodontal disease index, gingival crevicular fluid flow measurement, and dark field microscopic examinations of oral pathogens in plaque samples were studied. Significant improvements were observed in many parameters of the treatment group compared with the placebo group.

Analysis of Variance↗
PubMed1998

Study V: Children's Interview for Psychiatric Syndromes (ChIPS): psychometrics in two community samples.

OBJECTIVE: To determine sensitivity and specificity of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) revised Children's Interview for Psychiatric Syndromes (ChIPS) in nonclinical samples. METHOD: Participants were 40 children 6 to 18 years of age from a community sample (n = 22) or a bereaved sample 1 to 2 years following the death of a parent (n = 18). ChIPS and the Diagnostic Interview for Children and Adolescents (DICA-R-C) were administered in a Latin Square design. A consensus conference (CC) of child psychopathology experts determined presence or absence of syndromes or symptoms after reviewing assessment materials not including ChIPS. RESULTS: Sensitivity is commensurate with epidemiologic base rates (17.5% of participants endorsed at least one syndrome). Low base rate kappas and percentage agreement were calculated to determine agreement on symptom or syndrome endorsement for 20 disorders. For syndrome analyses, over half the kappas could not be calculated due to 100% agreement on absence. For symptom analyses, 3 of 20 kappas could not be calculated (100% agreement on absence). Eleven of ChIPS/DICA-R-C symptom kappas were significant (p < 0.04), 2 of 17 had 95% agreement (kappas, p < 0.08), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). Thirteen of 17 ChIPS/CC symptom kappas were significant (p < 0.04), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). CONCLUSION: ChIPS' psychometrics in nonclinical samples compares favorably with that of other structured interviews.

Adolescent↗
PubMed2006

Ultrasensitive DNA chip: gene expression profile analysis without RNA amplification.

We have developed a new DNA chip whose substrate has a unique minute columnar array structure made of plastic. The DNA chip exhibits ultrahigh sensitivity, up to 100-fold higher than that of reference DNA chips, which makes it possible to monitor gene expression profiles even with very small amounts of RNA (0.1-0.01 microg of total RNA) without amplification. Differential expression ratios obtained with the new DNA chip were validated against those obtained with quantitative real-time PCR assays. This novel microarray technology would be a powerful tool for monitoring gene expression profiles, especially for clinical diagnosis.

Gene Expression Profiling↗
PubMed2000

From DNA biosensors to gene chips.

Wide-scale DNA testing requires the development of small, fast and easy-to-use devices. This article describes the preparation, operation and applications of biosensors and gene chips, which provide fast, sensitive and selective detection of DNA hybridization. Various new strategies for DNA biosensors and gene chips are examined, along with recent trends and future directions. The integration of hybridization detection schemes with the sample preparation process in a 'Lab-on-a-Chip' format is also covered. While the use of DNA biosensors and gene chips is at an early stage, such devices are expected to have an enormous effect on future DNA diagnostics.

Biosensing Techniques↗
PubMed2001

A flexible light-directed DNA chip synthesis gated by deprotection using solution photogenerated acids.

Oligonucleotide microarrays or oDNA chips are effective decoding and analytical tools for genomic sequences and are useful for a broad range of applications. Therefore, it is desirable to have synthesis methods of DNA chips that are highly flexible in sequence design and provide high quality and general adoptability. We report herein, DNA microarray synthesis based on a flexible biochip method. Our method simply uses photogenerated acid (PGA) in solution to trigger deprotection of the 5'-OH group in conventional nucleotide phosphoramidite monomers (i.e. PGA-gated deprotection), with the rest of the reactions in the synthesis cycle the same as those used for routine synthesis of oligonucleotides. The complete DNA chip synthesis process is accomplished on a regular DNA synthesizer that is coupled with a UV-VIS projection display unit for performing digital photolithography. Using this method, oDNA chips containing probes of newly discovered genes can be quickly and easily synthesized at high yields in a conventional laboratory setting. Furthermore, the PGA-gated chemistry should be applicable to microarray syntheses of a variety of combinatorial molecules, such as peptides and organic molecules.

DNA↗
PubMed1989

A phase II study of carboplatin and CHIP in patients with metastatic colon carcinoma.

Fifty-six patients were treated in each arm of a study comparing CHIP and carboplatin for the therapy of previously untreated metastatic colorectal carcinoma. There were one partial response (2%) with CHIP and two partial responses (4%) with carboplatin. Side effects were significantly more severe with CHIP than with carboplatin. The most common side effect for both drugs was vomiting followed by hematologic side effects. Sixteen percent of the patients receiving CHIP and 9% of those receiving carboplatin had life-threatening side effects. Neither drug offers significant activity in metastatic colorectal carcinoma.

Aged↗
PubMed1993

Traumatic pneumomediastinum in a child secondary to corn chip perforation of the esophagus.

Esophageal perforations, while an infrequent form of trauma in the pediatric population, are of concern because of their life-threatening complications. If not recognized and treated promptly, esophageal injuries can result in mediastinitis and death. An unusual case is presented, describing traumatic esophageal perforation in a child resulting from laceration by an ingested corn chip. A study is reported investigating the rigidity of three types of these popular snack chips. Stress testing and statistical analysis of the resultant measurement data indicated that the three brands of chips were equally rigid. The mean force of compression required to fracture the chips was approximately three pounds, a force great enough to damage the fragile structures of the upper aerodigestive system. Physicians and parents alike should be aware of the possible dangers of this type of snack food to avert the possibility of esophageal injury with its resultant morbidity and potential mortality.

Child↗
PubMed2003

Validity of the Spanish version of the Child Health and Illness Profile-Adolescent Edition (CHIP-AE).

OBJECTIVES: To assess the structural, convergent, discriminant, and criterion validity of the Spanish version of the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) and to compare results with the U.S. version. SUBJECTS: A sample of adolescents aged 12 to 19 attending schools and representative of the school-aged population in Barcelona, Spain (n = 902). MEASURES: Exploratory factor analyses were performed, and results compared with the U.S. version. The Child Depression Inventory (CDI) and the State-Trait Anxiety Inventory (STAIC) were administered to a subgroup of adolescents to assess convergent and discriminant validity. Criterion validity was assessed by using receiver operating characteristic (ROC) curves to examine the ability of the CHIP-AE academic performance subdomain to predict school grades. RESULTS: The Spanish version has 6 defined domains with a factor structure showing minor differences from the U.S. version. Higher correlations were found between the CDI and STAIC and CHIP-AE subdomains of emotional discomfort and self-esteem (range. 0.48-0.80, P<0.01) than with scales measuring dissimilar concepts. The area under the ROC curve was 0.83 (95% confidence interval, 0.75-0.92) for the number of failed subjects (none/one or more) related to academic performance. CONCLUSIONS: The underlying theoretical model of the Spanish version of the CHIP-AE functions well in Spain, and the Spanish version has acceptable levels of convergent, discriminant, and criterion validity. Sensitivity to change and the use of the health profiles need to be assessed.

Achievement↗
PubMed2004

Nonuniform hybridization: a potential source of error in oligonucleotide-chip experiments with low amounts of starting material.

Low amounts of starting material are a significant limitation of gene-expression profiling of microprepared pathologic specimens. Linear RNA amplification has become the method of choice to overcome this problem. Thus, transcriptomal analyses by oligonucleotide-chips or cDNA microarrays are now feasible with labeled complementary RNA generated from total RNA samples in the lower nanogram range. However, in case of oligonucleotide-chips, it has been underestimated so far that individual complementary RNA molecules are shorter in length than and display a 3' bias in comparison to the sequence stretch represented by oligonucleotides on the chip. This can lead to incorrect interpretation of raw data. We have analyzed this problem testing ex vivo-microprepared endothelial cells with Affymetrix GeneChips U133A. Only a small subset of housekeeping genes showed adequate uniform hybridization. We developed a software tool for objective evaluation of oligonucleotide-chips based on automated analysis of as well as normalization to this subset of housekeeping genes. We analyzed the gene expression profile of microprepared lymphatic vascular endothelial cells. We show that optimized normalization prevented exclusion of angiopoietin-2, a lymphatic endothelial marker, from the lymphovascular transcriptome.

Endothelial Cells↗
PubMed2004

Neuron-semiconductor chip with chemical synapse between identified neurons.

Noninvasive electrical stimulation and recording of neuronal networks from semiconductor chips is a prerequisite for the development of neuroelectronic devices. In a proof-of-principle experiment, we implemented the fundamental element of such future hybrids by joining a silicon chip with an excitatory chemical synapse between a pair of identified neurons from the pond snail. We stimulated the presynaptic cell (VD4) with a chip capacitor and recorded the activity of the postsynaptic cell (LPeD1) with a transistor. We enhanced the strength of the soma-soma synapse by repetitive capacitor stimulation, establishing a neuronal memory on the silicon chip.

Animals↗
PubMed2004

A self-tuning method for one-chip SNP identification.

Current methods for interpreting oligonucleotide-based SNP-detection microarrays, SNP chips, are based on statistics and require extensive parameter tuning as well as extremely high-resolution images of the chip being processed. We present a method, based on a simple data-classification technique called nearest-neighbors that, on haploid organisms, produces results comparable to the published results of the leading statistical methods and requires very little in the way of parameter tuning. Furthermore, it can interpret SNP chips using lower-resolution scanners of the type more typically used in current microarray experiments. Along with our algorithm, we present the results of a SNP-detection experiment where, when independently applying this algorithm to six identical SARS SNP chips, we correctly identify all 24 SNPs in a particular strain of the SARS virus, with between 6 and 13 false positives across the six experiments.

Algorithms↗
PubMed2005

A system-on-chip digital pH meter for use in a wireless diagnostic capsule.

This paper describes the design and implementation of a system-on-chip digital pH meter, for use in a wireless capsule application. The system is organized around an 8-bit microcontroller, designed to be functionally identical to the Motorola 6805. The analog subsystem contains a floating-electrode ISFET, which is fully compatible with a commercial CMOS process. On-chip programmable voltage references and multiplexors permit flexibility with the minimum of external connections. The chip is designed in a modular fashion to facilitate verification and component re-use. The single-chip pH meter can be directly connected to a personal computer, and gives a response of 37 bits/pH, within an operating range of 7 pH units.

Algorithms↗
PubMed1987

Chip pile workers and mould exposure. A preliminary clinical and hygienic survey.

Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases of allergic alveolitis have been reported in Finland. Eight non-smoking workers, six on chip piles and two on bark piles, were examined to study the immunological and clinical response to continuous mould spore exposure. The spore exposure ranged between 10(4) and 10(5) spores/m3. Three of the six chip pile workers had precipitating serum antibodies against Aspergillus fumigatus. The three antibody-positive workers had a tendency to decreased total pulmonary diffusion capacity and vital capacity. Significant respiratory symptoms were not noted. Long-term spore exposure may include an occupational health risk to chip pile workers.

Adult↗
PubMed2006

Oligonucleotide DNA chips are useful adjuncts in epigenetic studies of glioblastomas.

Several studies have suggested that hypermethylation and hypomethylation of CpG islands within the promoters and 5' exons of tumor-related genes are closely associated with carcinogenesis. However, large-scale analysis of candidate genes has been hampered by the lack of a high throughput approach for analyzing methylation patterns. Using methylation-specific oligonucleotide (MSO) chips, we evaluated the methylation patterns of eight samples of fresh frozen glioblastoma tissue. The MSO chip used contained DNA probes with the CpG sites of p16 (p16INK4A, CDKN2A), MGMT (O6-Methylguanine-DNA-methyltransferase), APC (adenomatous polyposis coil), RASSF1A (human RAS effect homolog), which are usually hypermethylated in cancer cells and MAGE (melanoma antigen), which is usually hypomethylated in cancer cells. We selected CpG sites for analysis; 28 CpG sites (263 bp) for p16, 26 CpG sites (249 bp) for MGMT, 16 CpG sites (195 bp) for APC, 22 CpG sites (262 bp) for RASSF1A and 18 CpG sites (235 bp) for MAGE. We then constructed primer sets not including CpG sites. Bisulfite modification of genomic DNA, methylation specific PCR, hybridization and image scan with data analysis and sequencing of the bisulfite modified DNA were carried out. Of the eight glioblastomas, hypermethylation of the 5'-CpG sites of the MGMT were found in two, RASSF1A were found in five, and p16 and APC genes were not found in any cases and hypomethylation of that of the MAGE was found in eight cases. These results obtained from the oligo DNA chip study were correlated well with the sequencing data of bisulfite modified genomic DNA except in regard to the RASSF1A and MAGE genes. The devised MSO DNA chip is a useful tool for studies on methylation.

Base Sequence↗
PubMed2004

U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy.

Neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated and ubiquitylated tau, are exhibited at regions where neuronal loss occurs in neurodegenerative diseases; however, the mechanisms of NFT formation remain unknown. Molecular studies of frontotemporal dementia with parkinsonism-17 demonstrated that increasing the ratio of tau with exon 10 insertion induced fibrillar tau accumulation. Here, we show that carboxyl terminus of Hsc70-interacting protein (CHIP), a U-box protein, recognizes the microtubule-binding repeat region of tau and preferentially ubiquitylates four-repeat tau compared with three-repeat tau. Overexpression of CHIP induced the prompt degradation of tau, reduced the formation of detergent-insoluble tau and inhibited proteasome inhibitor-induced cell death. NFT bearing neurons in progressive supranuclear palsy, in which four-repeat tau is a component, showed the accumulation of CHIP. Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons.

Animals↗
PubMed1992

Contribution of autogeneic membranous bone chips and bone paste to healing of rabbit skull defects.

In skeletal surgery, bone chips and bone paste are often used to facilitate bony repair. However, no comparative investigation between these forms of bone graft implantation has been undertaken. In this study four trephine skull defects were produced in each of 14 adult rabbits and inlays of bone paste and two separate amounts of bone chips were then implanted in each animal. The results were compared relative to a control defect and assessed by gross inspection, light microscopy, and contact radiography after periods of 4 and 15 wk. Bone chips offered only minor advantages over controls in the defects investigated and differences in bony regeneration between the diversified amounts of bone chips were negligible. After bone paste implantation, a cellular and mature bone was rapidly produced. The clinical significance of these findings is discussed.

Animals↗