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Biomedical subjects

E Park

Publications and source records attributed to E Park.

At least 19 recordsLinked to original sources

Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with APPL during Drosophila development.

beta-Amyloid precursor protein binding protein 1 (APP-BP1) was previously identified based on its binding to the carboxyl terminal of beta-amyloid precursor protein. In this report, we have discovered that a mutation of dAPP-BP1 (Drosophila ortholog of APP-BP1) hinders tissue development, causes apoptosis in imaginal disc cells, and blocks the NEDD8 conjugation pathway. We show that dAPP-BP1 specifically binds the intracellular domain of APP-like protein (APPL). The dAPP-BP1 mutation partially suppresses the abnormal macrochaete phenotype of Appl(d), while overexpression of dAPP-BP1 causes abnormal macrochaetes. When APPL is overexpressed, the normal bristle pattern in the fly thorax is disturbed and apoptosis is induced in wing imaginal discs. APPL overexpression phenotypes are enhanced by reducing the level of dAPP-BP1. APPL overexpression is shown to inhibit the NEDD8 conjugation pathway. APPL-induced apoptosis is rescued by overexpression of dAPP-BP1. Our data suggest that APPL and dAPP-BP1 interact antagonistically during Drosophila development.

Amino Acid Sequence↗

Characterization of squid-processing byproduct hydrolysate and its potential as aquaculture feed ingredient.

The squid (Loligo pealei) byproduct composed of heads, viscera, skin, fins, and small tubes was subjected to hydrolysis at 55 degrees C and natural pH (6.8) using endogenous proteases. Squid hydrolysate was characterized during the course of hydrolysis for changes in the degree of hydrolysis, viscosity, electrophoretic pattern of proteins and peptides, and amino acid and fatty acid profiles. The change in viscosity can be used to monitor the progress of protein hydrolysis up to the molecular mass of 26.63 kDa. The 2 h hydrolysis resulted in a 2-fold increase in the total free amino acids and yielded hydrolysate with protein molecular mass of < or =45 kDa having feed attractability and good amino acid and fatty acid profiles with high contents of essential amino acids and fatty acids. Such hydrolysis-induced changes can make squid byproduct hydrolysate a good source of aquaculture feed ingredient, especially for a starter diet for larval fish.

Amino Acids↗

Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children.

To determine incidence of invasive Haemophilus influenzae type b (Hib) disease in a defined population of Jeonbuk Province, Korea, children <5 years were evaluated in prospective, population-based surveillance of invasive bacterial diseases using standardized methods for patient referral, clinical evaluation and laboratory testing (optimized culture, latex agglutination, polymerase chain reaction). Vaccine utilization was assessed with vaccination histories of patients in surveillance, monthly data on Hib vaccine distribution and a coverage survey of clinic patients in study population. From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. The annual suspected bacterial meningitis incidence was 258.4/100,000 <5 years and the probable/confirmed Hib meningitis incidence was 6.0/100,000 <5 years. Pneumococcal meningitis incidence was 2.1/100,000 <5 years and Group B streptococcal meningitis incidence was 0.17/1000 live births. A total of 69,589 Hib vaccine doses were distributed during the study. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was leading cause of bacterial meningitis yet bacterial pathogens were identified in only 4% of abnormal CSF. These findings may reflect truly low incidence, presumptive antibiotic treatment, partial Hib immunization, or incomplete clinical evaluations. Given the apparent Hib meningitis burden in Jeonbuk Province, additional studies to describe other invasive Hib syndromes, Hib-associated mortality and disability, and economic impact of Hib disease will be useful to guide public health decisions regarding routine Hib vaccine introduction.

Adolescent↗

Physiological studies on vasoactive intestinal peptide in rat small bowel isografts.

BACKGROUND: Vasoactive intestinal peptide (VIP) is released by stimulation of nonadrenergic noncholinergic (NANC) inhibitory nerves. In order to evaluate the function of VIP in jejunal isografts, we examined the enteric nerve responses in isografted rat jejunum compared with normal jejunum. METHODS: Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 8). As controls, normal segments of the jejunum were obtained from nontransplanted Lewis rats (n = 20). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers and VIP. RESULTS: The isografted jejunum was more strongly innervated by excitatory nerves, especially NANC excitatory nerves, than the normal jejunum (P <.05). VIP mediated relaxation reactions of NANC inhibitory nerves in the normal but to a lesser extent in the isografted jejunum (P <.05). CONCLUSIONS: The increased NANC excitatory nerves and the decreased effects of VIP in mediating NANC inhibitory nerves may largely relate to the peristaltic abnormalities seen in the isografted LEW rat jejunum.

Animals↗

Changes in glial cell white matter AMPA receptor expression after spinal cord injury and relationship to apoptotic cell death.

Increasing evidence suggests that AMPA receptors (AMPARs) play a key role in mediating excitotoxic cell damage after acute spinal cord injury (SCI). However, the role of glial AMPARs in posttraumatic white matter injury requires further clarification. In the present study we examined the changes in AMPAR expression after SCI, the cellular distribution of these changes, and their association with apoptosis. Western blots revealed expression of GluR1, 3, and 4, but not GluR2, in spinal cord white matter. Immunohistochemistry was used to examine the distribution of AMPARs in spinal cord white matter. Quantification of AMPAR-expressing cells in spinal cord white matter indicated predominantly GluR3 expression in oligodendrocytes and predominantly GluR4 expression in astrocytes. A clip compression model of SCI was used to examine the changes in AMPAR expression in dorsal column white matter after injury. Quantitative analysis of GluR3 levels of expression indicated a significant decrease at 3 days postinjury compared to uninjured animals, followed by a recovery of expression by 2 weeks. GluR4 subunits followed a similar expression pattern. Gene message expression of GluR3 and GluR4 flip/flop mRNA splice variants exhibited a pattern of expression that correlated with protein expression. GluR3-expressing glia appeared to be more susceptible to apoptosis than GluR4-expressing cells. A large decline in GluR3-expressing oligodendrocytes suggests that this subunit may be associated with the induction of apoptosis in white matter glia, thus contributing to secondary injury mechanisms.

Alternative Splicing↗

Particulate exposure and size distribution from wood burning stoves in Costa Rica.

Biomass fuel is the most common energy source for cooking and space heating in developing countries. Biomass fuel combustion causes high levels of indoor air pollutants including particulates and other combustion by-products. We measured indoor air quality in 23 houses with a wood burning stove in rural residential areas of Costa Rica. Daily PM2.5, PM10 and CO concentrations, and particle size distribution were simultaneously measured in the kitchen. When a wood burning stove was used during the monitoring period, average daily PM2.5 and PM10 concentrations were 44 and 132 microg/m3, respectively. Average CO concentrations were between 0.5 and 3.3 ppm. All houses had a particle size distribution of either one or two peaks at around 0.7 and 2.5 microm aerodynamic diameters. The particulate levels increased rapidly during cooking and decreased quickly after cooking. The maximum peak particulate levels ranged from 310 to 8170 microg/m3 for PM2.5 and from 500 to 18900 microg/m3 for PM10 in all houses. Although the 24-h particulate levels in this study are lower than the National Ambient Air Quality Standards of PM2.5 and PM10, it is important to note that people, especially women and children, are exposed to extremely high levels of particulates during cooking.

Adult↗

Analytical solutions of contaminant transport from finite one-, two-, and three-dimensional sources in a finite-thickness aquifer.

Analytical study of contaminant transport from a finite source in a finite-thickness aquifer is most useful in hydrological and environmental sciences and engineering but rarely investigated in previous studies. This paper provides analytical solutions of contaminant transport from one-, two-, and three-dimensional finite sources in a finite-thickness aquifer using Green's function method. A library of unpublished analytical solutions with different finite source geometry is provided. A graphically integrated MATLAB script is developed to calculate the temporal integrations in the analytical solutions and obtain the final solutions of concentration. The analytical solutions are examined by reproducing the solutions of some special cases discussed in previous studies. The sensitivities of the line source solutions to source geometry, dispersion coefficients, and distance to the source are tested. The contaminant concentration in the near field is found to be sensitive to the source geometry and anisotropy of the dispersion coefficients. The contaminant concentration in the far field is found to be much less sensitive to the source geometry. The physical insights of the analytical solutions are interpreted.

Chemical Phenomena↗

Prospective assessment of estrogen replacement therapy and cognitive functioning: atherosclerosis risk in communities study.

Studies of humans have not confirmed the suggestion from animal studies that estrogen replacement therapy may have an inverse relation with cognitive function decline. Because many of these studies have been marred by design or methodological problems, such as a small sample size, failure to control for confounding variables, or the use of a cross-sectional design, the present study was conducted in a large cohort of middle-aged postmenopausal women participating in the Atherosclerosis Risk in Communities (ARIC) Study. The study population consisted of 2,859 women aged 48-67 years, whose cognitive function was tested at the second (1990-1992) and fourth (1996-1998) visits of the ARIC Study using three instruments: the Delayed Word Recall Test, Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised, and Word Fluency Test. After multiple adjustment, no consistent patterns of cognitive changes between the two cohort visits could be detected according to current use or duration of use of estrogen replacement therapy. Thus, the results of the present study do not support the hypothesis that estrogen replacement therapy may slow age-related cognitive decline, at least as it applies to relatively young postmenopausal women.

Aged↗

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury.

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

Animals↗

Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Base Sequence↗

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery.

PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Adolescent↗

Characterization and regulation of Schizosaccharomyces pombe gene encoding thioredoxin.

A cDNA coding thioredoxin (TRX) was isolated from a cDNA library of Schizosaccharomyces pombe by colony hybridization. The 438 bp EcoRI fragment, which was detected by Southern hybridization, reveals an open reading frame which encodes a protein of 103 amino acids. The genomic DNA encoding TRX was also isolated from S. pombe chromosomal DNA using PCR. The cloned sequence contains 1795 bp and encodes a protein of 103 amino acids. However, the C-terminal region obtained from the cDNA clone is -Val-Arg-Leu-Asn-Arg-Ser-Leu, whereas the C-terminal region deduced from the genomic DNA appears to contain -Ala-Ser-Ile-Lys-Ala-Asn-Leu. This indicates that S. pombe cells contain two kinds of TRX genes which have dissimilar amino acid sequences only at the C-terminal regions. The heterologous TRX 1C produced from the cDNA clone could be used as a subunit of T7 DNA polymerase, while the TRX 1G from the genomic DNA could not. The upstream sequence and the region encoding the N-terminal 18 amino acids of the genomic DNA were fused into the promoterless beta-galactosidase gene of the shuttle vector YEp357 to generate the fusion plasmid pYKT24. Synthesis of beta-galactosidase from the fusion plasmid was found to be enhanced by hydrogen peroxide, menadione and aluminum chloride. It indicates that the expression of the cloned TRX gene is induced by oxidative stress.

Aluminum Chloride↗

Assessment of the total number of human transcription units.

Variation in the estimates of the number of genes encoded by the human genome (28,000-120,000) attests to the difficulty of systematically identifying human genes. Sequencing of human chromosome 22 (Chr22) provided the first comprehensive, unbiased view of an entire human chromosome, and intensive analysis of this sequence identified 545 genes and 134 pseudogenes that had similarity or identity to known proteins and/or ESTs and which were listed in the gene annotation (http://www.sanger.ac.uk/HGP/Chr22). This analysis yielded an estimate of approximately 36,000 functional expressed genes in the human genome (and 9000 pseudogenes). However, a key uncertainty in this estimate was that hundreds of additional genes beyond those annotated in the Chr22 sequence are predicted by the gene prediction program Genscan, an unknown number of which might represent additional expressed genes. To determine what fraction of these "predicted novel genes" (PNGs) represents expressed human genes, we used a sensitive RT-PCR assay to detect predicted transcripts in 17 tissues and one cell line. Our results indicate that at least 5000-9000 additional human genes which lack similarity to known genes or proteins exist in the human genome, increasing baseline gene estimates to approximately 41,000-45,000.

Chromosomes, Human, Pair 22↗

The development of a decisional balance measure of physician smoking cessation interventions.

BACKGROUND: Decreasing the prevalence of smoking is an important health care goal, and there is evidence that physicians' advice to quit is an important motivator for patients. However, fewer than half of smokers report that they have ever been advised to quit. This study was conducted to develop a decisional balance measure for physician delivery of smoking cessation interventions. METHODS: This study included a convenience sample of 155 primary care physicians. A decisional balance measure was developed using item generation and development, pilot testing, and principal components analyses. Validity was established by relating the decisional balance measure to a previously validated item of counseling behavior and to physician stage of readiness to deliver smoking cessation counseling. RESULTS: Based on principal components analyses and item analyses, the final measure consisted of 10 Pro and 10 Con items with coefficient alpha of 0.83 and 0.86. The Pros and Cons scales were significantly associated with self-reported counseling to patients who smoke and to stage of readiness to deliver smoking cessation counseling. CONCLUSIONS: A decisional balance measure of physician smoking cessation interventions can be used to assist investigators in developing effective interventions to enhance the delivery of smoking cessation interventions in primary care settings.

Adult↗

Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities.

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the regulation of fibrinolysis. We carried out a cross-sectional study to assess the association of soluble thrombomodulin (sTM) with peripheral artery disease (PAD) in a stratified random sample (n=863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. PAD was more common in black than in white participants and associated with classical risk factors in an expected manner; positively with age, smoking, hypertension, diabetes (P=0.05), and LDL-cholesterol, and inversely with HDL-cholesterol. Significant positive associations were observed also with fibrinogen and white blood cell count. Overall, the sTM concentration was not a significant predictor of PAD. The association was, however, modified by the level of factor VIII:C in whites (P=0.002 for the interaction), but not in blacks. Protein C was inversely associated with PAD prevalence (odds ratio 0.33, 95% CI 0.18--0.61, P=0.0004). sTM was inversely associated with plasminogen, but no associations with t-PA, PAI-1, or D-dimer were seen. In conclusion, the present results provide some additional evidence on the role of thrombomodulin-protein C pathway in atherosclerotic disease and support our earlier observation on interaction between sTM and factor VIII:C.

Black or African American↗