Biomedical subjects

E Chen

Publications and source records attributed to E Chen.

At least 37 records · Page 2Linked to original sources

PubMed2001

A novel clathrin homolog that co-distributes with cytoskeletal components functions in the trans-Golgi network.

A clathrin homolog encoded on human chromosome 22 (CHC22) displays distinct biochemistry, distribution and function compared with conventional clathrin heavy chain (CHC17), encoded on chromosome 17. CHC22 protein is upregulated during myoblast differentiation into myotubes and is expressed at high levels in muscle and at low levels in non-muscle cells, relative to CHC17. The trimeric CHC22 protein does not interact with clathrin heavy chain subunits nor bind significantly to clathrin light chains. CHC22 associates with the AP1 and AP3 adaptor complexes but not with AP2. In non-muscle cells, CHC22 localizes to perinuclear vesicular structures, the majority of which are not clathrin coated. Treatments that disrupt the actin-myosin cytoskeleton or affect sorting in the trans-Golgi network (TGN) cause CHC22 redistribution. Overexpression of a subdomain of CHC22 induces altered distribution of TGN markers. Together these results implicate CHC22 in TGN membrane traffic involving the cytoskeleton.

Cells, Cultured↗

PubMed2001

Effect of RGD coating on osteocompatibility of PLGA-polymer disks in a rat tibial wound.

Osteocompatibility of porous polylactic-glycolic acid (PLGA) disks coated with synthetic peptides was assessed in 5-mm diameter unicortical tibial osseous wounds in rats. The coatings consisted of various ratios of peptides including the tripeptide arginine-glycine-aspartic acid (RGD) and the inactive arginine-glycine-glutamic acid (RGE). When left empty, the tibial wounds healed spontaneously with proliferation of intramedullary woven bone within 1 week. The reactive bone was resorbed, and by 3 weeks, the cortical wound was healed with lamellar bone, and the medullary space was repopulated with marrow. When PLGA disks were implanted there was a delay in repair with reduced bone fill and no bone bridging at 3 weeks. When disks were coated with increasing amounts of RGD peptide, there was a biphasic effect on osteocompatibility and on osseous ingrowth. Evaluation at 10 days showed a dose-dependent increase, with 1.5-fold greater osteocompatibility (p < 0.05) and 1.6-fold more osseous ingrowth into the polymer (p < 0.01) than uncoated disks. With more RGD and with undiluted RGE, osteocompatibility and osseous ingrowth were the same as with uncoated disks. At 3 weeks, there were no significant differences among all the groups. These data indicate that RGD coating enhanced early stages of osteocompatibility and ingrowth.

Animals↗

PubMed2001

A computational model of postoperative knee kinematics.

A mathematical model for studying the passive kinematics of total knee prostheses can be useful in computer-aided planning and guidance of total joint replacement. If the insertion location and neutral length of knee ligaments is known, the passive kinematics of the knee can be calculated by minimizing the strain energy stored in the ligaments at any angular configuration of the knee. Insertions may be found intraoperatively, or may come from preoperative 3D medical images. The model considered here takes into consideration the geometry of the prosthesis and patient-specific information. This model can be used to study the kinematics of the knee joint of a patient after total joint replacement. The model may be useful in preoperative planning, computer-aided intraoperative guidance, and the design of new prosthetic joints.

Arthroplasty, Replacement, Knee↗

PubMed2001

Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2.

The activated B-cell factor (ABF)-1 cDNA was initially isolated from Epstein-Barr virus (EBV)-infected B cells and codes for a DNA-binding protein belonging to the basic helix-loop-helix (bHLH) family of transcription factors. In this study, we characterized the nuclear localization signal of ABF-1, mapped two distinct transcriptional repression domains, and identified one ABF-1-interacting protein, Id-2. By examining the subcellular location of deletion mutants of ABF-1 fused to green fluorescent protein (GFP), critical regions involved in nuclear localization were determined. Analysis of GFP-tagged ABF-1 deletion mutants revealed two separate regions capable of directing nuclear localization. One region mapped to the N-terminal amino acids 71 to 103, whereas the second region localized to the C-terminal bHLH domain. Transient transfection of ABF-1 deletion mutants demonstrated that the N-terminal amino acids 1 to 40 and the bHLH domain function together to achieve maximum repression of E2A activity. Taken together, these results indicate that ABF-1 is a nuclear transcriptional repressor with two distinct regions that function in a synergistic fashion to attenuate E2A-mediated gene activation.

Basic Helix-Loop-Helix Proteins↗

PubMed2001

Model system for evaluation of alternative splicing: exon skipping.

Alternative splicing of the primary RNA transcript is a common mechanism for generating protein diversity. A model system was developed to study this process in vitro that is useful for evaluation of splicing of transcripts expressed in cells that do not grow well in culture. The system was used to analyze skipping of exon 4 of the amelogenin message, normally expressed in ameloblast cells for a short interval during tooth enamel development. Amelogenins are highly conserved proteins resulting from extensive alternative splicing, with domains involved in a range of functions, including mineral formation and intercellular signaling. In the bovine gene, the very short intron 4 was predicted to inhibit inclusion of exon 4, because in murine ameloblasts, exon 4 is detectably included in mRNA, and intron 4 is longer than the bovine counterpart. Bovine intron 4 was lengthened, and this size increase enhanced exon 4 inclusion sixfold to eightfold, although splice site selection was inaccurate. Intron length, therefore, is not the sole determinant controlling amelogenin exon 4 inclusion, and cis-acting inhibitory elements may also be involved in exon skipping. This vector system allows evaluation of splicing of a tissue-specific RNA by focusing on exons of interest through transfection of heterologous cultured cells without complications attributable to background transcription of the gene being evaluated.

Alternative Splicing↗

PubMed2001

Thinning of the papillomacular bundle in the glaucomatous eye and its influence on the reference plane of the Heidelberg retinal tomography.

PURPOSE: To measure the thickness of the papillomacular bundle in glaucomatous eyes with good visual acuity and to evaluate the influence of an adjusted reference plane on the Heidelberg retinal tomography result. METHODS: The thickness of the papillomacular bundle was measured with optical coherence tomography in both eyes of eight patients with asymmetric glaucoma. The eye with less glaucomatous damage with normal visual field served as the control. The difference in the thickness of the papillomacular bundle between the control eye and the glaucomatous eye was used to correct the reference plane of Heidelberg retinal tomography. RESULTS: The thickness of the papillomacular bundle in glaucomatous eyes was reduced (P = 0.00037) and was 33.9 +/- 16.5 microm thinner than control eyes. A corrected reference plane in Heidelberg retinal tomography caused an increased classification value (-0.683 +/- 0.164), implying that more glaucoma damage was detected after the correction. In one case the value was shifted from normal to glaucomatous after an adjustment of the reference plane. CONCLUSION: The thickness of the papillomacular bundle is decreased in glaucomatous eyes, though these eyes have good visual acuity. Evaluation of glaucoma with Heidelberg retinal tomography using the standard reference plane may underestimate the glaucoma damage.

Aged↗

PubMed2001

Differential antifungal activity of isomeric forms of nystatin.

When nystatin is placed in RPMI and other biological fluids, there is loss of pure nystatin, with the development of two distinguishable chromatographic peaks, 1 and 2. Peak 1 appears identical to commercially prepared nystatin. By nuclear magnetic resonance (NMR) and mass spectral analysis, peak 2 appears to be an isomer of peak 1. The isomers are quantitatively and fully interconvertible. Formation of peak 2 is accelerated at a pH of >7.0 and ultimately reaches a near 55:45 (peak 1/peak 2 ratio) mixture. We sought to determine the relative activities of peaks 1 and 2 against Candida spp. Peak 2 consistently showed higher MICs when it was the predominant form during the experiment. Time-kill analyses showed that peak 2 required > or =8 x the concentration of peak 1 to produce a modest and delayed killing effect, which was never of the same magnitude as that produced by peak 1. In both types of assays, the activity of peak 2 corresponded with intra-assay formation of peak 1. Both MIC measurements and time-kill analysis suggest that peak 2 has considerably less activity, if any at all, against Candida spp. Peak 2 may serve as a reservoir for peak 1.

Antifungal Agents↗

PubMed2001

Cognitive appraisal biases: an approach to understanding the relation between socioeconomic status and cardiovascular reactivity in children.

We tested the hypothesis that lower socioeconomic status (SES) children display heightened cardiovascular reactivity during stressful situations because they are more likely to appraise a wide variety of social situations, including ambiguous ones, as threatening. A sample of 201 children and adolescents, half White and half African American, were assessed initially. Ninety of these children were retested an average of 3 years later. At both time points, children were interviewed about appraisals of hostile intent and feelings of anger in response to scenarios with negative or ambiguous outcomes. Cardiovascular reactivity to 3 laboratory stress tasks was measured. Initially, lower SES was associated with greater hostile intent appraisal and anger during ambiguous scenarios across all participants. In addition, responses to ambiguous scenalios partially mediated the relation between SES and vascular reactivity. Longitudinally, low SES African American participants showed higher mean intensity of hostile intent appraisals during ambiguous scenarios, and these appraisals mediated the SES-reactivity relationship. These findings suggest that the way in which children appraise ambiguous social situations plays an important role in the relation between SES and cardiovascular reactivity.

Adolescent↗

PubMed2001

Treatment effects on carbon dioxide retention in patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: This study was designed to examine respiratory control in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), with or without CO(2) retention. METHODS: We recruited 10 body mass index-matched, apnea-hypopnea index-matched, age-matched, and lung function-matched OSAHS patients, according to their awake PaCO(2). Five patients were hypercapnic (PaCO(2), > or = 45 mm Hg), and five patients were eucapnic. Hypoxic responses (the ratio of the change in minute ventilation [DeltaV(E)] to the change in arterial oxygen saturation [DeltaSaO(2)] and the ratio of the change in mouth occlusion pressure over the first 100 ms of inspiration against an occluded airway [DeltaP(0.1)] to DeltaSaO(2)) and hypercapnic responses (DeltaV(E)/DeltaPCO(2) ratio and DeltaP(0.1)/DeltaPCO(2) ratio) were tested during wakefulness before treatment in all 10 patients, and before and during treatment (at 2, 4, and 6 weeks) with pressure support in the hypercapnic group. RESULTS: Hypercapnic patients had lower mean (+/- SD) DeltaV(E)/DeltaSaO(2) ratio than eucapnic patients (-0.17 +/- 0.04 vs -0.34 +/- 0.04 L /min/%SaO(2), respectively), lower mean DeltaP(0.1)/DeltaSaO(2) ratio (-0.04 +/- 0.02 vs -0.14 +/- 0.03 cm H(2)O/%SaO(2), respectively), and lower DeltaP(0.1)/DeltaPCO(2) ratio (0.23 +/- 0.1 vs 0.49 +/- 0.1 cm H(2)O/mm Hg, respectively) [p < 0.05]. After receiving noninvasive ventilation treatment, the hypercapnic and hypoxic responses of the hypercapnic patients increased. At 4 to 6 weeks, values for both responses had increased to within the normal range and PaCO(2) had fallen to < 45 mm Hg, while weight was unchanged. CONCLUSIONS: Depressed chemoresponsiveness plays a role that is independent of obesity in the development of CO(2) retention in some OSAHS patients, and it may be a response to sleep-disordered breathing.

Adult↗

PubMed2001

The integrin-mediated cyclic strain-induced signaling pathway in vascular endothelial cells.

The irregular distribution of plaque in the vasculature results from the interaction of local hemodynamic forces with the vessel wall. One well-characterized force is cyclic circumferential strain, the repetitive pulsatile pressure distention on the arterial wall. This review summarizes current research, which has aimed to elicit the signal transduction pathway by which cyclic strain elicits functional and structural responses in endothelial cells; specifically, it summarizes the signaling pathway that begins with the reorganization of integrins. One method by which these extracellular matrix receptors affect signal transduction is through their ability to initiate the process of phosphorylation on tyrosine residues of cytoplasmic protein kinases, including focal adhesion kinase. The strain-induced pathway appears to also involve ras and the mitogen-activated protein kinase family of enzymes, and preliminary data suggests a role for src as well. Ultimately, it is the regulation of gene expression through the modulation of transcription factors that allows endothelial cells to respond to changes in local hemodynamics.

Blood Pressure↗

PubMed2000

Tetrasomy 15q25-->qter: cytogenetic and molecular characterization of an analphoid supernumerary marker chromosome.

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).

Abnormalities, Multiple↗

PubMed2000

Rapid up-regulation of peptide elongation factor EF-1alpha protein levels is an immediate early event during oxidative stress-induced apoptosis.

Hydrogen peroxide (H(2)O(2)) induces apoptosis in cultured cells, in a dose-dependent manner. Treatment with H(2)O(2) causes decreased mitochondrial respiration, along with DNA degradation and the formation of an oligonucleosomal ladder, all hallmarks of apoptotic cell death. In this report, we investigate alterations in expression of a peptide elongation factor, EF-1alpha, during oxidative challenge. EF-1alpha protein levels undergo rapid increase upon treatment with H(2)O(2); however, whereas sublethal doses of H(2)O(2) stimulate only transient increases of EF-1alpha protein levels, lethal doses produce sustained elevation of EF-1alpha levels. Furthermore, pretreatment of H9c2(2-1) cells with transcriptional inhibitors fails to abolish the oxidant-induced increase in EF-1alpha, and Northern blotting analysis reveals that EF-1alpha mRNA levels remain steady throughout the H(2)O(2) treatment period, suggesting that the up-regulation of EF-1alpha is mediated posttranscriptionally. Transient transfection with an antisense EF-1alpha cDNA protects against hydrogen peroxide-mediated cytotoxicity in proportion to the degree of repression of EF-1alpha protein levels, suggesting that up-regulation of EF-1alpha plays a role in expediting the execution of the apoptotic program in response to oxidative stress.

Actins↗

PubMed2000

Four DAZ genes in two clusters found in the AZFc region of the human Y chromosome.

The DAZ genes are candidate fertility factors that lie within the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. The number of DAZ genes has been difficult to determine, in part because the nucleotide sequences of the DAZ genes are nearly identical. Here, fluorescence in situ hybridization and characterization of BAC clones revealed four full-length DAZ genes on the human Y chromosome. They exist in two clusters, each comprising an inverted pair of DAZ genes (3' <-- 5'::5' --> 3'). Analysis of genomic sequences and testicular transcripts suggested that three or four DAZ genes are translated. Each gene contains at least seven tandem copies of a previously described, 2.4-kb repeat unit that encodes 24 amino acids. In addition, two DAZ genes contain tandem copies of a 10.8-kb repeat unit that encodes the RNA-binding domain, which appears to be multimerized in some DAZ proteins. Combining our present results with previous studies, we can reconstruct several steps in the evolution of the DAZ genes on the Y chromosome. In the ancestral Y-chromosomal DAZ gene, amplification of both intragenic repeats began before the human and cynomolgus (Old World) monkey lineages diverged. During subsequent evolution, an inverted duplication of this modified gene occurred. Finally, the resulting two-gene cluster was duplicated, generating the two-cluster/four-gene arrangement found on modern human Y chromosomes.

Base Sequence↗

PubMed2000

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Journal Article↗

PubMed2000

The p24 proteins are not essential for vesicular transport in Saccharomyces cerevisiae.

To investigate the factors involved in the sorting of cargo proteins into COPII endoplasmic reticulum (ER) to Golgi apparatus transport vesicles, we have created a strain of S. cerevisiae (p24Delta8) that lacks all eight members of the p24 family of transmembrane proteins (Emp24p, Erv25p, and Erp1p to Erp6p). The p24 proteins have been implicated in COPI and COPII vesicle formation, cargo protein sorting, and regulation of vesicular transport in eukaryotic cells. We find that p24Delta8 cells grow identically to wild type and show delays of invertase and Gas1p ER-to-Golgi transport identical to those seen in a single Deltaemp24 deletion strain. Thus, p24 proteins do not have an essential function in the secretory pathway. Instead, they may serve as quality control factors to restrict the entry of proteins into COPII vesicles.

Base Sequence↗

PubMed2000

Loss of PTEN facilitates HIF-1-mediated gene expression.

In glioblastoma-derived cell lines, PTEN does not significantly alter apoptotic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGF-1-induced angiogenic gene expression by regulating Akt activation of HIF-1 activity. Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. In addition, Akt activation leads to HIF-1alpha stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1alpha stabilization. We propose that loss of PTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.

Apoptosis↗

PubMed2000

A five-year longitudinal study of the regional cerebral metabolic changes of a schizophrenic patient from the first episode using Tc-99m HMPAO SPECT.

This is a naturalistic study of the relationship between cerebral metabolic activity, clinical symptoms and treatment response in a schizophrenic patient for 5 years from the onset of her illness. Serial technetium-99m-HMPAO brain SPECT was used to measure regional cerebral metabolism. The Cambridge Neurological Inventory and neuropsychological tests (WAIS-R verbal subscales, Wisconsin Card Sorting Test, semantic verbal fluency, logical memory in Weschler Memory Scale) were used for neurocognitive assessment. Under-activity of the left temporal area was observed in the course of patient illness despite remission of the psychotic symptoms. Bilateral prefrontal metabolic under-activity was noted at the emergence of negative symptoms, executive neurocognitive dysfunction and the treatment-resistant state. After response to clozapine, the right prefrontal activity returned to a normal level. Our findings suggested that persistent left temporal underactivity detected by SPECT despite clinical remission may indicate a vulnerability for further relapses and development of a treatment-resistant state. Treatment-resistant state, negative symptoms and executive neurocognitive deficit may involve abnormal prefrontal metabolic activity and can be alleviated in clozapine-responsive patients.

Adult↗

PubMed2000

Effect of eyelid botulinum toxin injection on lacrimal drainage.

PURPOSE: To determine the effect of eyelid botulinum toxin injection on the lacrimal drainage and to assess the use of botulinum toxin in dry eye conditions. METHODS: Prospectively, three test groups were examined and one lacrimal system investigated in each person in each group. Botulinum toxin A (3.75 IU) was injected into the medial part of 13 lower eyelids of 13 normal test subjects and the medial part of nine lower eyelids in nine patients with dry eyes. A dose of 2.5 IU was injected into the medial part of 10 lower eyelids and the medial part of 10 upper eyelids of 10 patients with dry eyes. The drop test was used to determine the lacrimal drainage capacity and the blink output, before and after the injection. The subjective effect of the botulinum toxin injection on eye comfort was investigated. RESULTS: Three weeks after lower eyelid botulinum toxin injection, the mean blink output was reduced to 64% (1.19 of 1.87; P <.001) and 70% (0.94 of 1.35; P <.001) of the baseline values in the groups of normal subjects and patients, respectively. After injection in both the upper and lower eyelid, the mean blink output was reduced to 38% (0.54 of 1.41; P <.001) of the baseline value. The patients with dry eyes reported an improved eye comfort in six of nine cases after injection in the lower eyelid and in seven of 10 cases after injection in both the upper and lower eyelid. Adverse effects included one case of increased discomfort for 3 weeks after injection. CONCLUSION: Injection of botulinum toxin into the medial part of the eyelids decreased the lacrimal drainage, suggesting a new way to treat dry eye conditions. Further studies are required to assess the clinical value of this treatment.

Adult↗