Search PubMed⌕ Search

Biomedical subjects

J D Chen

Publications and source records attributed to J D Chen.

At least 127 records · Page 7Linked to original sources

Time-frequency representation of the electrogastrogram--application of the exponential distribution.

The aim of this paper was to examine the applicability of the exponential distribution for the time-frequency representation of the electrogastrogram (EGG). The EGG is a noninvasive measurement of the electrical activity of the stomach by placing electrodes on the abdominal skin. Quantitative analysis of the EGG has relied on spectral methods. The normal frequency of the EGG in humans is 3 cycles/min. Electrical dysrhythmia observed in the EGG is associated with motor disorders of the stomach. The exponential distribution was applied in this work for the estimation of EGG frequency and the detection of dysrhythmia in the EGG. A series of computer simulations was conducted, demonstrating the reliability of the exponential distribution in the analysis of nonstationary electrical signals of the stomach. Applications of the exponential distribution in the spectral analysis of typical EGG's were presented. The results showed that there is a great potential for the use of the exponential distribution in EGG analysis.

Computer Simulation↗

Dibutyryl cyclic AMP modulates keratinocyte migration without alteration of integrin expression.

Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. It has been demonstrated that cAMP inhibits keratinocyte proliferation when used at high concentrations. Nevertheless, new recent reports have demonstrated that cAMP may stimulate or inhibit keratinocyte growth depending upon the concentration used. Studies to examine the influence of cAMP upon the migration of other cell types have been contradictory. To determine the direct effect of dibutyryl cAMP (DBcAMP) upon human keratinocyte migration, we used a quantitative locomotion assay using a wide range of DBcAMP concentrations. We found a bi-phasic effect of DBcAMP on keratinocyte migration across connective tissue matrices. Keratinocyte locomotion on the matrices was promoted at 10(-5) M and 10(-6) M of DBcAMP, but not at higher or lower concentrations. Time-course experiments demonstrated that the effect of DBcAMP on keratinocyte locomotion and proliferation occurred independently. Fluorescence-activated cell sorter analysis demonstrated that the effect of DBcAMP on the migration of human keratinocytes was independent from the modulation of integrin receptors. Although the cellular mechanisms by which DBcAMP promotes keratinocyte migration is unclear, the addition of DBcAMP or TPA to keratinocyte cultures enhanced the synthesis of a 92-kDa metalloproteinase in association with enhanced cellular migration. These observations suggest a possible link between metalloproteinase expression and cellular migration.

Bucladesine↗

A novel 105-kDa lamina lucida autoantigen: association with bullous pemphigoid.

Several cases have been reported of patients with immunemediated subepidermal blistering disorders whose autoantibodies react to antigens present on both the dermal and epidermal side of 1 M NaCl-split skin. In this report, we identify, localize, and characterize the basement membrane zone antigen corresponding to the dermal staining in a patient whose serum stains both the dermal and epidermal side of 1 M NaCl-split skin. This patient's serum contains autoantibodies directed against a 105-kilodalton(kDa) dermal antigen and the 230-kDa epidermal (bullous pemphigoid) antigen. This novel 105-kDa protein was previously identified as the sole antigen in another patient with a unique bullous disease whose autoantibodies were directed against only the dermal side of 1 M NaCl-split skin. This 105-kDa antigen was identical by one- and two-dimensional immunoblot analysis in these two patients. By immunoblot analysis, autoantibodies from our patient labeled a 105-kDa protein within various extracts of human skin basement membrane. Immunoblot analyses using epitope-selected autoantibodies directed against the 105-kDa protein demonstrated that this antigen is independent and distinct from other known basement membrane antigens. The 105-kDa antigen is an extracellular matrix component of the basement membrane, which is synthesized and secreted by both keratinocytes and fibroblasts. Identical electrophoretic migration of cellular and secreted forms of the protein suggested there is no major post-translational modification of the protein. Immunomapping of normal human skin fractured through the dermal-epidermal junction by incubation in 1 M NaCl or by suction blistering demonstrated that the location of the 105-kDa antigen within the basement membrane zone is between the bullous pemphigoid antigens and two other lamina lucida components, laminin and nicein. These data demonstrate clearly that a subepidermal autoimmune bullous disease may have autoantibodies directed against two distinct components of the dermal-epidermal junction.

Aged↗

Type VII collagen specifically binds fibronectin via a unique subdomain within the collagenous triple helix.

Type VII collagen is the major component of anchoring fibrils, structures within basement membranes beneath stratified squamous epithelium thought to mediate the adherence of the epidermis to the dermis of human skin. Type VII collagen has affinity for fibronectin. The interaction between type VII collagen and fibronectin is mediated through the collagen-binding domain on the amino terminus of fibronectin. Heretofore, the domain on the type VII collagen molecule that binds to fibronectin was not known. In this study, we mapped the binding site of fibronectin to a specific subdomain of the triple helical collagenous region of type VII collagen, immediately adjacent to the small carboxyl terminal non-collagenous domain. This fibronectin-binding site within the type VII collagen molecule lies between nucleotide residues 615 and 1161.

Amino Acid Sequence↗

Serosal and cutaneous recordings of gastric myoelectrical activity in patients with gastroparesis.

The aims of this study were to 1) investigate gastric myoelectrical activity in patients with gastroparesis, 2) validate the cutaneous electrogastrogram (EGG) in tracking the frequency change of the gastric slow wave, and 3) investigate the effect of electrical stimulation on gastric myoelectrical activity. Gastric myoelectrical activity was recorded in 12 patients with documented gastroparesis using serosal electrodes for > 200 min in each subject. All recordings were made at least 4 days after surgery. Each session consisted of a 30-min recording in the fasting state and a 30-min recording after a test meal. The test meal (liquid or mixed) was selected according to patient's tolerance. Electrical stimulation was performed in three subjects via the serosal electrodes at a frequency of 3 cycles/min. Gastric myoelectrical activity was recorded using serosal electrodes in each session. The serosal recording showed slow waves of 2.5 to 4.0 cycles/min in all 12 subjects. Absence of spikes was noted in 11 of the 12 subjects. The simultaneous serosal and cutaneous recording of gastric myoelectrical activity showed that the frequency of the EGG was exactly the same as that of the serosal recording. Liquid meals resulted in a significant decrease in slow-wave frequency (Student's t test, P = 0.006), and the EGG accurately reflected this change. Electrical stimulation had no effect on the frequency of the gastric slow wave and did not induce spikes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human keratinocytes make uniquely linear phagokinetic tracks.

The migration of human keratinocytes is dramatically influenced by the type of extracellular matrix in contact with the cells: collagen induces the cells to produce long, linear migration tracks. In this study, a migration assay and computer-assisted morphometry were used to quantitate the extent of migration and the linearity of the migration tracks for a variety of cell types. Only human keratinocytes and HT-1080 fibrosarcoma cells produced both high levels of migration (migration index > 30) and highly linear tracks (track linearity > 4.5). Human keratinocytes and HT-1080 cells share at least two other features: both synthesize copious amounts of extracellular matrix components, and both synthesize high levels of collagenase that degrades basement membrane (type IV) collagen. However, zymogram studies of collagenase production do not yield any characteristic collagenase profile which might distinguish these two types of cells from other normal and metastatic cells.

Cell Movement↗

Human keratinocyte migration on type IV collagen. Roles of heparin-binding site and alpha 2 beta 1 integrin.

BACKGROUND: The migration of human keratinocytes is an early and important event in the re-epithelialization of cutaneous wounds. Type IV collagen, a ubiquitous basement membrane component, promotes keratinocyte migration. EXPERIMENTAL DESIGN: In this study, we sought to identify specific sites within the type IV collagen molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. We first examined purified fragments of the type IV collagen molecule as substrates for keratinocytes in a phagokinetic migration assay. We then tested several synthetic peptides derived from the triple-helical region of type IV collagen, as well as antibodies against specific integrin subunits, for their ability to either support or inhibit keratinocyte migration on matrices of both type IV collagen and relevant peptide derivatives. RESULTS: Keratinocytes migrated on the triple-helical fragment to the same extent as they did on the native type IV collagen. The amino-terminal 7S and the carboxy-terminal NC1 regions of type IV collagen failed to support keratinocyte migration. In addition, Hep III peptide was active both in inhibiting keratinocyte migration on type IV collagen and in serving as a substrate matrix for migration. Peptide containing the amino acid sequence RGD did not influence cell migration on type IV collagen. A specific monoclonal antibody against the alpha 2 beta 1 integrin receptor significantly inhibited keratinocyte migration on matrices of both type IV collagen and Hep III peptide. CONCLUSIONS: Keratinocyte migration on type IV collagen involves the interaction of the alpha 2 beta 1 receptor with the Hep III region of the type IV collagen molecule.

Binding Sites↗

Identification of gastric contractions from the cutaneous electrogastrogram.

OBJECTIVE: The objective of this study was to investigate whether gastric contractions in the fasting and fed state can be identified from the cutaneous electrogastrogram. METHODS: Simultaneous measurements of gastric myoelectrical and manometric activities were made in 10 healthy female volunteers from 1:00 AM to 9:45 AM. For manometric recording, a catheter incorporating solid state transducers was used. Cutaneous electrogastrography (EGG) was used for myoelectrical recording. All EGG data from 1:00 AM to 7:30 AM that occurred during motor quiescence, all EGG data that occurred during antral contractions, and 2-h EGG data after breakfast given at 7:30 AM were quantitatively analyzed and compared with each other. The EGG in three specific periods (fasting without antral contractions, fasting with contractions, and postprandial) was characterized by four parameters that include frequency, power, and stabilities of the frequency and power. RESULTS: 1) the peak power of the postprandial EGG was, respectively, 12.5 dB (about 2-fold increase in amplitude) and 6.8 dB (about 1-fold increase in amplitude) higher than that during motor quiescence (p < 0.05) and motor activity in the fasting state; 2) the dominant frequency of the postprandial EGG was, respectively, 6% and 13% higher than that during motor quiescence and motor activity (p < 0.05) in the fasting state; 3) the peak power of the fasting EGG was 48% more unstable during motor activity than motor quiescence (p < 0.05); 4) the stability of the EGG frequency was not significantly different during the three different periods. CONCLUSION: The EGG provides important and useful information for the assessment of gastric motility. An unstable EGG peak power is indicative of gastric contractions in the fasting state. An increase in EGG peak power and/or dominant frequency after a solid test meal suggests a normal postprandial gastric motility.

Adult↗

Functional ecdysone receptor is the product of EcR and Ultraspiracle genes.

Although the biological activity of the insect moulting hormone ecdysone, is manifested through a hormonally regulated transcriptional cascade associated with chromosomal puffing, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor (EcR) is by itself incapable of high-affinity DNA binding or transcriptional activation. Rather, these activities are dependent on heterodimer formation with Ultraspiracle (USP) the insect homologue of vertebrate retinoid X receptor. Here we report that native EcR and USP are co-localized on ecdysone-responsive loci of polytene chromosomes. Moreover, we show that natural ecdysones selectively promote physical association between EcR and USP, and conversely, that high-affinity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties. These results redefine the ecdysone receptor as a dynamic complex whose activity may be altered by combinatorial interactions among subunits and ligand.

Animals↗

Stepwise assembly of hyperaggregated forms of Drosophila zeste mutant protein suppresses white gene expression in vivo.

The zeste gene is involved in two chromosome pairing-dependent phenomena: transvection and the suppression of white gene expression. Both require the ability of zeste protein to multimerize, dependent on three interlaced hydrophobic heptad repeats in the C-terminal domain. The first step is dimerization through a leucine zipper. Two other heptad repeats are then required to form higher multimers. The zeta(1) mutation, which causes the pairing-dependent suppression of white, creates a new hydrophobic nucleus that allows the formation of a new and larger aggregate. The zeta(op6) mutation, which suppresses even unpaired copies of white, makes even larger aggregates. The phenotypic suppression of white by a series of mutants is strictly correlated with hyperaggregation and the larger the hyperaggregates, the weaker the requirement for the pairing of white. Hyperaggregation of the Z1 protein in vitro is suppressed by co-translation with the C-terminal peptide of wild-type protein, lacking the DNA-binding domain. This C-Z+ peptide also complements the zeta(1) allele in vivo and restores normal color, demonstrating that zeste product also exists in a multimeric complex in the cell. Complementation in vivo is strictly correlated with the prevention of hyperaggregation of the zeste mutant products in vitro, supporting the interpretation that excessive association of zeta(1) and zeta(op6) proteins is responsible for their repression of white gene expression.

ATP-Binding Cassette Transporters↗

Multimerization of the Drosophila zeste protein is required for efficient DNA binding.

The Drosophila zeste protein forms multimeric species in vitro through its C-terminal domain. Multimerization is required for efficient binding to DNA containing multiple recognition sequences and increasing the number of binding sites stimulates binding in a cooperative manner. Mutants that can only form dimers still bind to a dimeric site, but with lower affinity. Mutations or progressive deletions from the C-terminal show that when even dimer formation is prevented, DNA-binding activity is lost. Surprisingly, binding activity is regained with larger deletions that leave only the DNA-binding domain. Additional protein sequences apparently inhibit DNA binding unless they permit multimerization. The DNA-binding domain peptides bind strongly even to isolated recognition sequences and they bind as monomers. The ability of various zeste peptides to stimulate white gene expression in vivo shows that multimeric forms are the functional species of the zeste product in vivo. The DNA-binding domain peptide binds well to DNA in vitro, but it cannot stimulate white gene expression in vivo. This failure may reflect the need for an activation domain or it may be caused by indiscriminate binding of this peptide to non-functional isolated sites. Multimerization increases binding specificity, selecting only sites with multiple recognition sequences.

ATP-Binding Cassette Transporters↗

Acute and chronic neurological symptoms among paint workers exposed to mixtures of organic solvents.

The purpose of this study was to determine the prevalence rates of acute and chronic neurologic symptoms among paint workers and the association of such symptoms with the severity of exposure to mixtures of solvents. Two paint manufacturing factories and 25 various kinds of spray painting factories were selected for study. Air concentrations of organic solvents were measured by personal samplers and were analyzed by gas chromatography. A total of 196 workers were given a screening neurological examination and a questionnaire on acute and chronic neurologic symptoms. A detailed personal medical history and a profile on alcohol consumption and medication were also included. The results showed that xylenes and toluene were the major solvents found in almost all the air samples with average contents of 50 and 24% on a weight basis of 73 air samples. We classified workers according to different exposure patterns and different air concentrations of breathing zones: high (8-hr hygienic effect, 0.25-9.86; median, 1.66), short-term high (hygienic effect, 0-3.38; median, 0.12), and low (hygienic effect, 0-0.38; median, 0.12). All workers showed no overt neurological signs such as ataxic gait, poor coordination, or muscle weakness. After excluding those workers who consumed more than 280 g of alcohol per week (n = 8), took antihypertensive medications (n = 4), or were treated with antipsychotic agents (n = 1), we found that the severity of exposure was associated with acute symptoms of headache and chest tightness and chronic symptoms of dizziness, easy fatigability, depressed mood, and palpitation. There was no association between peripheral neurological symptoms and the severity of exposure. Workers in the high exposure group were 2.7 times more likely to develop two or more acute symptoms and 3.3 times more likely to develop three or more chronic symptoms of the central nervous system than the low exposure group. After modeling by multiple logistic regression, we concluded that exposure to a medium level of mixtures of solvents (hygienic effect exceeding 1.66) may produce acute and chronic central neurological symptoms.

Acute Disease↗

Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen by increasing the alpha 2 integrin subunit.

The migration of human keratinocytes across the would bed is an early and critical event in the reepithelialization of cutaneous wounds. Epidermal growth factor (EGF) has been shown to accelerate the healing of fresh, split-thickness cutaneous wounds when applied topically. The mechanism(s) by which this accelerated healing occurs remains unknown. Using an assay that directly evaluates human keratinocyte locomotion without confounding the possibility of cell proliferation, we examined the influence of EGF on human keratinocyte motility. Both recombinant epidermal growth factor (rEGF) and transforming growth factor-alpha (TGF-alpha) promoted human keratinocyte locomotion when the cells were apposed to connective tissue matrices of collagen or fibronectin, important components of the wound bed. Other growth factors studied did not enhance keratinocyte migration. Blocking the EGF/TGF-alpha receptor on the cell surface of keratinocytes with specific antibody inhibited the stimulation of keratinocyte locomotion by rEGF and TGF-alpha. Flow cytometry analysis of keratinocytes migrating on type I collagen in the presence of rEGF or TGF-alpha revealed increased expression of the alpha 2 integrin subunit on the keratinocyte surface. The alpha 2 beta 1 integrin mediates keratinocyte migration on collagens type I and IV, and inhibition of migration via antibody blockade of the alpha 2 beta 1 integrin can be partially overcome by increasing the concentration of rEGF present in the medium. Our study demonstrates that the growth-independent stimulation of keratinocyte locomotion via regulation of integrin expression may be one mechanism by which EGF accelerates the reepithelialization of human cutaneous wounds.

Basement Membrane↗

Adaptive cancellation of the respiratory artifact in surface recording of small intestinal electrical activity.

In the human small intestine there is omnipresent electrical activity with a frequency of 0.15-0.2 Hz. The electrical activity of the small intestine can be measured by surface electrodes placed on the abdominal skin. The most annoying problem in the surface electrical recording is the respiratory artifact which is not discernible from the small intestinal signal. The frequency of the respiration is about 0.2-0.4 Hz, which is very close to that of small intestinal activity, making the use of the conventional bandpass filtering impractical. In this paper a selective frequency domain adaptive filter was proposed for the cancellation of the respiratory artifact. The basic principle of the selective frequency domain adaptive filter is that only selected filter weights are adapted based on the frequency characteristics of the respiratory artifact. Therefore, a substantial reduction of computation is achieved. A series of computer simulations was conducted for the optimization of the system parameters and for the investigation of the system performance. It was demonstrated in this paper that the selective frequency domain adaptive filter is as effective as, but more efficient than, the conventional frequency domain adaptive filter. The adaptive system for the cancellation of the respiratory artifact based on the selective frequency domain adaptive filter is very efficient in computation, has a fast convergence (about 100 adaptations), substantial reduction of the respiratory artifact and little effect (or distortion) on the small intestinal electrical signal.

Computer Simulation↗

Spectral analysis of episodic rhythmic variations in the cutaneous electrogastrogram.

Electrical activity of the stomach can be measured using surface electrodes. The cutaneous recording of gastric electrical activity is called the electrogastrogram (EGG). Gastric electrical dysrhythmic events associated with abnormal conditions of the stomach may be detected from the EGG. An adaptive spectral analysis method which is based on autoregressive moving average modeling has previously been developed. The aim of this paper is to demonstrate the ability of the previous method in detecting gastric dysrhythmic events from the EGG. A series of bench tests stimulating typical problems with the analysis of nonstationary electric potentials was conducted. The application of the adaptive spectral analysis method to dysrhythmic events and rhythmic variations of the gastric slow wave is presented in this paper. The adaptive spectral analysis approach provides several advantages: narrow frequency peaks permitting more precise frequency identification, determination of changes in frequency components at any time point, and enhanced interpretation of cutaneous EGG recordings.

Algorithms↗

Measurement of electrical activity of the human small intestine using surface electrodes.

Electrical activity of the human small intestine is usually measured by implanted or intraluminal electrodes. The application of these invasive techniques is, however, very limited. In this paper, a noninvasive technique is introduced to measure electrical activity of the small intestine by placing electrodes on the abdominal skin over the small intestine. Surface recordings were obtained in ten healthy volunteers, three patients with total gastrectomy and five patients with gastroparesis (a slight degree of paralysis of the mucosal coat of the stomach) with implanted electrodes on the serosa of the duodenum. An omnipresent 9-12 cpm electrical activity was observed in all surface recordings. Our findings from the surface electrodes were consistent with those reported in the literature via implanted or intubated electrodes. It is concluded that the technique described in this paper provides a noninvasive way to measure electrical activity of the small intestine. It may have potential application in medical research and clinical diagnosis.

Adult↗