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Biomedical subjects

J W Jung

Publications and source records attributed to J W Jung.

At least 19 recordsLinked to original sources

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Adult↗

Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins.

In the present study, we examined whether the bone morphogenetic proteins (BMPs), which are important in the developmental specification of transmitter type in certain classes of neurons, might also play a role in signaling the differentiation of a dopaminergic (DA) phenotype. We found that BMP-2, -4 and -6 were each capable of inducing, in a dose and time dependent manner, moderate levels of the DA enzyme tyrosine hydroxylase (TH) in cultured neurons from the mouse embryonic striatum. In contradistinction to other TH-inducing agents, BMPs initiated de novo TH expression without the required synergy of exogenous growth factors or co-activating substances and in neurons presumably aged (E16) beyond the critical period for induction. However, the appearance of TH in induced cells was short-lived (24 h) and could not be prolonged by repeated supplementation with the BMPs. Inhibitors of the mitogen-activated protein kinase (MAPK/ERK) signaling pathway, PD98059 and apigenin, did not prevent TH induction by BMP-4, as they did other TH inducing agents, indicating that the MAPK/ERK pathway does not mediate BMPs effects on TH expression. We conclude that BMP-2, -4 and -6 can be added to the expanding inventory of agents capable of inducing TH, making them potentially important in the specification of a DA phenotype in stem/precursor cells for the treatment of Parkinson's disease.

Animals↗

IgE binding components in Tetranychus urticae and Panonychus ulmi-derived crude extracts and their cross-reactivity with domestic mites.

BACKGROUND: Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers. OBJECTIVE: To evaluate IgE binding components in T. urticae and P. ulmi-derived crude extracts and their cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers. METHODS: Thirty-one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross-reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting. RESULTS: A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae-specific IgE binding was completely inhibited by 100 microg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi-specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%). CONCLUSION: There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.

Adult↗

Differential regulation of cAMP-mediated gene transcription and ligand selectivity by MC3R and MC4R melanocortin receptors.

Melanocortins are known to be involved in the regulation of feeding behavior. These hormones mediate their effects through G-protein-coupled receptors by stimulating adenylate cyclase. In this study we describe the functional response of melanocortin 4 receptor (MC4R) and melanocortin 3 receptor (MC3R) in HEK 293T cells, by using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE) as a monitor of intracellular cAMP levels and cAMP-regulated gene expression. We were able to show that MC4R and MC3R expressed in the human cell line HEK 293T stimulate transcription induced by stimulation with different analogs of alpha-melanocyte-stimulating hormone (alpha-MSH) at different levels. In our assay of CRE-mediated gene transcription activity, alpha-MSH-ND was the most efficient alpha-MSH analog for MC4R whereas NDP-MSH was the most efficient for MC3R. Changing the His6 residue of alpha-MSH-ND to Gln or Lys markedly decreased CRE-mediated luciferase activity for MC3R compared with MC4R. On analysis by modeling the receptor-ligand complex by NMR, [Gln6]alpha-MSH-ND and [Lys6]alpha-MSH-ND showed different conformational interactions between MC3R and MC4R. Furthermore, the maximum coupling efficiency of MC4R and MC3R to G proteins was different; MC4R showed only 30-50% of the maximum activity induced by MC3R. In total, our results suggest that a differential receptor-ligand interaction is involved and that the relative interactions of MC3R and MC4R with G protein are possibly quantitatively and qualitatively different.

Adrenocorticotropic Hormone↗

Solution structure of a designed amphipathic antimicrobial synthetic peptide, PGAa.

A designed peptide, PGAa showed an excellent antifungal activity as well as an efficient bactericidal activity toward gram-positive, especially in the pathogenic yeast Candida albicans 28838. The solution structures of PGAa have been determined both in 40% TFE/water solution and DPC micelle by CD and NMR spectroscopy. Based on NOEs, vicinal coupling constants, backbone amide exchange rates, and chemical shift indices, PGAa formed a long amphipathic alpha-helical conformation in both TFE and DPC micelle environments, spanning the residues Ile(2)-Ala(19) in TFE and Lys(5)-Ala(19) in DPC micelle, respectively. Solution structures suggested that the hydrophobic residues would interact with the fatty acyl chains of the lipid bilayer, while the positively charged side-chains exposed to aqueous environments. Therefore, we conclude that the alpha-helical structure as well as the highly amphiphatic nature of PGAa peptide may play a critical role in its antimicrobial activity as well as selectivities in different species.

1,2-Dipalmitoylphosphatidylcholine↗

Association of HLA-DRB1(*)07 and DRB1(*)04 to citrus red mite (Panonychus citri) and house dust mite sensitive asthma.

BACKGROUND: Specific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers. OBJECTIVE: The aim of this study was to evaluate whether susceptibility or resistance to CRM-induced asthma was associated with HLA-DRB1 gene. METHODS: DNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety-one adults with CRM-sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA-DRB1 alleles were carried out using PCR-based methods. RESULTS: Allelic frequency of HLA-DRB1(*)07 was higher in the CRM-sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM-sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA-DRB1 gene-encoded antigens between the two groups. CONCLUSION: HLA-DRB1 genes may be involved in the development of CRM-induced asthma. In addition, HLA-DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM-exposed adults.

Adult↗

The active site and substrates binding mode of malonyl-CoA synthetase determined by transferred nuclear Overhauser effect spectroscopy, site-directed mutagenesis, and comparative modeling studies.

The active sites and substrate bindings of Rhizobium trifolii molonyl-CoA synthetase (MCS) catalyzing the malonyl-CoA formation from malonate and CoA have been determined based on NMR spectroscopy, site-directed mutagenesis, and comparative modeling methods. The MCS-bound conformation of malonyl-CoA was determined from two-dimensional-transferred nuclear Overhauser effect spectroscopy data. MCS protein folds into two structural domains and consists of 16 alpha-helices, 24 beta-strands, and several long loops. The core active site was determined as a wide cleft close to the end of the small C-terminal domain. The catalytic substrate malonate is placed between ATP and His206 in the MCS enzyme, supporting His206 in its catalytic role as it generates reaction intermediate, malonyl-AMP. These findings are strongly supported by previous biochemical data, as well as by the site-directed mutagenesis data reported here. This structure reveals the biochemical role as well as the substrate specificity that conservative residues of adenylate-forming enzymes have.

Adenosine Triphosphate↗

Identification of residues essential for a two-step reaction by malonyl-CoA synthetase from Rhizobium trifolii.

Malonyl-CoA synthetase (MCS) catalyses the formation of malonyl-CoA in a two-step reaction consisting of the adenylation of malonate with ATP followed by malonyl transfer from malonyl-AMP to CoA. In order to identify amino acid residues essential for each step of the enzyme, catalysis based on chemical modification and database analysis, Arg-168, Lys-170, and His-206 were selected for site-directed mutagenesis. Glutathione-S-transferase-fused enzyme (GST-MCS) was constructed and mutagenized to make R168G, K170M, R168G/K170M and H206L mutants, respectively. The MCS activity of soluble form GST-MCS was the same as that of wild-type MCS. Circular dichroism spectra for the four mutant enzymes were nearly identical to that for the GST-MCS, indicating that Arg-168, Lys-170 and His-206 are not important for conformation but presumably for substrate binding and/or catalysis. HPLC analysis of products revealed that the intermediate malonyl-AMP is not accumulated during MCS catalysis and that none of the mutant enzymes accumulated it either. Kinetic analysis of the mutants revealed that Lys-170 and His-206 play a critical role for ATP binding and the formation of malonyl-AMP, whereas Arg-168 is critical for formation of malonyl-CoA and specificity for malonyl-AMP. Molecular modelling based on the crystal structures of luciferase and gramicidin S synthetase 1 provided MCS structure which could fully explain all these biochemical data even though the MCS model was generated by comparative modelling.

Adenosine Triphosphate↗

Multivariate non-parametric methods for Mann-Whitney statistics to analyse cross-over studies with two treatment sequences.

A non-parametric strategy for the analysis of ordinal data from cross-over studies with two treatment sequences and d(> or = 2) periods is examined through Mann-Whitney rank measures of association. For each period, these statistics estimate the probability of larger response for a randomly selected patient in one group relative to a randomly selected patient in the other group. Such estimates are as well formed for comparisons between groups for u pairs of periods with the same treatment. Methods for U-statistics are used to produce a consistent estimate of the covariance matrix for the (d + u) Mann-Whitney estimates. The effects of periods and treatments on the respective Mann-Whitney estimates are evaluated through linear (or log-linear) models. For estimation of the parameters in these models, a modified weighted least squares method is applied through a (2d - 1) < or = (d + u) dimensional basis which effectively addresses potentially near singularities in the estimated covariance matrix of the Mann-Whitney estimates. The proposed methods are applicable to response variables with an interval or an ordered categorical scale. Their scope additionally has capabilities for controlling strata in the design of a cross-over study or concomitant variables for which covariance adjustment is of interest for reduction of variance. Applications of the methods are illustrated through three cross-over studies with different specifications for the two sequences of two treatments during two to four periods.

Animals↗

Solution structure of a sweet protein single-chain monellin determined by nuclear magnetic resonance and dynamical simulated annealing calculations.

Single-chain monellin (SCM), which is an engineered 94-residue polypeptide, has proven to be as sweet as native two-chain monellin. SCM is more stable than the native monellin for both heat and acidic environments. Data from gel filtration HPLC and NMR indicate that the SCM exists as a monomer in aqueous solution. The solution structure of SCM has been determined by nuclear magnetic resonance (NMR) spectroscopy and dynamical simulated annealing calculations. A stable alpha-helix spanning residues Phe11-Ile26 and an antiparallel beta-sheet formed by residues 2-5, 36-38, 41-47, 54-64, 69-75, and 83-88 have been identified. The sheet was well defined by backbone-backbone NOEs, and the corresponding beta-strands were further confirmed by hydrogen bond networks based on amide hydrogen exchange data. Strands beta2 and beta3 are connected by a small bulge comprising residues Ile38-Cys41. A total of 993 distance and 56 dihedral angle restraints were used for simulated annealing calculations. The final simulated annealing structures ( k) converged well with a root-mean-square deviation (rmsd) between backbone atoms of 0.49 A for secondary structural regions and 0.70 A for backbone atoms excluding two loop regions. The average restraint energy-minimized (REM) structure exhibited root-mean-square deviations of 1.19 A for backbone atoms and 0.85 A for backbone atoms excluding two loop regions with respect to 20 k structures. The solution structure of SCM revealed that the long alpha-helix was folded into the concave side of a six-stranded antiparallel beta-sheet. The side chains of Tyr63 and Asp66 which are common to all sweet peptides showed an opposite orientation relative to H1 helix, and they were all solvent-exposed. Residues at the proposed dimeric interface in the X-ray structure were observed to be mostly solvent-exposed and demonstrated high degrees of flexibility.

Algorithms↗

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: identification of a novel mutation.

A 5-month-old Korean boy who presented with lethargy and cardiomyopathy was diagnosed with very long chain acyl coenzyme A dehydrogenase (VLCAD) deficiency by organic acid, fatty acid, acylcarnitine, and molecular genetic analysis. The patient was a compound heterozygote for mutations in the VLCAD gene. One allele contains a 3-bp deletion in exon 6, deleting glutamic acid in codon 130 (E130del ); this allele is of paternal origin. The patient's maternally derived allele is a novel mutation, C1843T in exon 20, which creates a premature termination codon (R615stop ). Although molecular genetic characterization of VLCAD deficiency is limited to a few patients, heterogeneity of mutations is already apparent. However, the E130del is a relatively frequent mutant allele, which has been noted in 2 previously identified patients. The 2 mutant alleles in our patient appear to be responsible for his severe and fatal clinical manifestations.

Acyl-CoA Dehydrogenase, Long-Chain↗

Spider mite allergy in apple-cultivating farmers: European red mite (Panonychus ulmi) and two-spotted spider mite (Tetranychus urticae) may be important allergens in the development of work-related asthma and rhinitis symptoms.

BACKGROUND: Recent investigations have suggested that the citrus red mite (Panonychus citri) is the most important allergen affecting citrus-cultivating farmers with asthma, allergic rhinitis, or both. OBJECTIVE: We sought to evaluate type I hypersensitivity to spider mites, particularly the European red mite (Panonychus ulmi) and the two-spotted spider mite (Tetranychus urticae), and to determine the relationship between hypersensitivity to spider mites and respiratory dysfunction. METHODS: We performed a cross-sectional survey. Questionnaires were given, and skin prick tests for 11 inhalant allergens common in Korea and 2 species of spider mites (European red mite and two-spotted spider mite) were performed in 725 apple-cultivating farmers in Korea. RESULTS: Results of skin prick tests in the apple farmers indicated that European red mite (23.2%) was the most common sensitizing allergen, followed by Tyrophagus putrescentiae (21.2%), two-spotted spider mite (16.6%), Dermatophagoides farinae (16.3%), D pteronyssinus (14.4%), cockroach (13.1%), and Hop Japanese (Humulus Japonicus) pollen (12.0%). Positive skin responses (mean wheal size >/=3 mm) to one or more of 13 inhalant allergens were found in 48.2% of farmers tested, whereas 40 subjects (8.6%) had an isolated skin response to the spider mites. Among 119 farmers with work-related asthmatic symptoms, the positive skin response rates to European red mite and two-spotted spider mite were 40.4% and 27.0%, respectively. These figures were significantly higher than those found among farmers without work-related symptoms (19.1% and 14.1%, respectively; P <.01). The prevalence of work-related asthma symptoms was higher in farmers with positive skin responses to spider mites than in those with negative skin responses to spider mites and those with positive skin responses to any allergen tested (31.4% vs 15.0% vs 21.0%, respectively; P <.05). CONCLUSION: Spider mites, particularly European red mite and 2-spotted spider mite, are common sensitizing allergens in apple-cultivating farmers. These spider mites may be important causative allergens in the development of work-related respiratory symptoms in these workers.

Administration, Inhalation↗

A linear model method for rank measures of association from longitudinal studies with fixed conditions (visits) for data collection and more than two groups.

Several statistical methods are available for the analysis of responses with ordinal categories or continuous distributions for the respective visits in longitudinal studies. This paper discusses an alternative nonparametric strategy for studies with more than two groups through Mann-Whitney rank measures of association for all pairs of groups. The proposed method is based on U-statistic theory, and it applies a linear or linear logistic model to the Mann-Whitney estimators for the probabilities of better response for each group relative to each of the others. In addition, the ways of adjusting for covariables and managing stratification factors are explained. Analysis of parallel dose-response relationships for two treatments is illustrated for the proposed method with data from a multicenter study with repeated measurements. A nonparametric estimator for relative potency is provided from the method.

Algorithms↗

Stress, social support, and substantiated maltreatment in the second and third years of life.

OBJECTIVE: The purpose of this research was to determine whether risk factors for a maltreatment report in the first year of life, especially the interaction of life event stress and social support, persist into the second and third years of life. METHOD: Predominantly low income mothers who had been interviewed shortly after the birth of infants in a longitudinal cohort were re-interviewed around the infants' first birthdays, and reports to North Carolina's Central Registry of Child Abuse and Neglect were tracked for substantiated maltreatment reports. RESULTS: Variables significantly associated with a substantiated maltreatment report in the second or third year of life (p < .01) were first year maltreatment reports and participation in Medicaid. Three interactions between a stressful life event indicator variable and a social support indicator variable were significant predictors of substantiated second or third year reports (p < .05). CONCLUSIONS: Even in the presence of significant risk factors from the first year of life, life event stress can increase the risk of a substantiated maltreatment report in the second or third years of life, but social support may moderate the effect of life events.

Adolescent↗

Age-related changes of water content in the rat skin.

The water content of the skin is greatly influenced by ground substances, which may be responsible for wrinkling and laxity of the skin accompanying the cutaneous aging. Therefore, water content in the skin is presumed to be a critical determinant in cutaneous aging. This study was aimed at clarifying the change in water content and the content of glycosaminoglycans (GAG) of rat skin in relation to aging. Sprague-Dawley rats were divided into 6 groups: 1-, 3-, 6-, 12-, 18- and 24-month-old groups. Two-to-three grams of skin tissue samples were taken from the back, and a half of sample was dried at 160 degrees C for 30 min with electronic moisture balance, and water content was assessed as decreased weight by heating. To measure change of GAG of the rat skin, another half of samples were extracted with 0.1 M sodium phosphate buffer (pH 7.4 NaPB) and 2 M guanidine-HCl/Tris buffer (pH 7.4). The resultant insoluble pellet was dried at 50 degrees C in a drying over for 72 h after two washings and the dry weight was recorded. The amount of sulfated GAG in the skin extracts was measured by alcian blue precipitation assay, and the amount of uronic acid (UA) was assayed in the skin tissue extracts and the dried skin using the carbazole reaction. The water content of the rat skin decreased with age, and a similar decreasing pattern in the amount of sulfated GAG and UA of the rat skin tissue was observed with aging. One hundred times of UA was obtained in dry rat skin tissue, as compared with that of the skin extracts. In conclusion, there occurs a significant decrease of water content in the aged rat skin, which may be related to the change of GAG with intrinsic aging of the skin.

Animals↗

Pericaval fat collection that mimics thrombosis of the inferior vena cava: demonstration with use of multi-directional reformation CT.

PURPOSE: To evaluate the causes for localized fat collection that seemed to be within the subdiaphragmatic inferior vena cava (IVC) on axial computed tomographic (CT) scans. MATERIALS AND METHODS: Six consecutive patients with presumed intracaval fat collection at routine abdominal CT (n = 2) or thin-section CT of the lung (n = 4) were studied prospectively with helical CT. Three patients had chronic liver diseases. Multi-directional, two-dimensional, reformatted images were obtained from the helical CT data for identification of the relation between the IVC and fat collection. Six patients without intracaval fat collection were studied as control subjects. RESULTS: On axial CT scans, the fat collection had a round or oval shape (in four of six patients) and was located posteromedial to the IVC (in four of six patients). On coronal reformatted images, the fat collection was outside the IVC between the diaphragm and subdiaphragmatic IVC, which was contiguous to the fat around the subdiaphragmatic esophagus. In the fat collection group, the IVC angled toward the right and narrowed to half in diameter as it passed down to the diaphragm. In the control group, the IVC was straight, although the diameter decreased similarly. CONCLUSION: A localized fat collection adjacent to the subdiaphragmatic IVC that mimics intracaval fat on axial CT scans is due to acute angulation of the IVC, which is probably a result of anatomic variation, chronic liver disease, or both.

Adipose Tissue↗

Risk of child abuse or neglect in a cohort of low-income children.

The purposes of this research were to identify risk factors for reported child abuse or neglect and to examine the roles of stress and social support in the etiology of child maltreatment. Mothers of newborn infants with biomedical and sociodemographic risk factors were recruited from community and regional hospitals and local health departments in 42 counties of North and South Carolina selected for geographic distribution and for large numbers of such newborns. For every four such mothers, the next mother to deliver an otherwise normal newborn was sought. Mothers were interviewed shortly after giving birth, and state Central Registries of Child Abuse and Neglect were reviewed when each infant was 1 year of age. Eight hundred forty-two of 1,111 recruited mothers were successfully interviewed in their homes between March 1986 and June 1987. Seven hundred forty-nine North Carolina births who resided in the state more than 6 months were eligible for inclusion in the analysis. Logistic regression with backward elimination procedures was used in the analysis. Maternal education (p < .01), number of other dependent children in the home (p < .01), receipt of Medicaid (p < .01), maternal depression (p < .05), and whether the maternal subject lived with her own mother at age 14 years (p < .05) were the best predictors of a maltreatment report. Further examination revealed an interaction effect between stressful life events, as measured by life event scores, and social well-being (p < .01). For children born at risk for social and/or medical problems, extreme low income (participation in public income support programs), low maternal education, maternal depression, the presence of any other young children in the home, and a mother's separation at age 14 years from her own mother significantly predict child maltreatment reports in the first year of life. In addition, stressful life events, even if perceived positively, may increase or decrease the risk of maltreatment reports, depending upon the presence of social support.

Adolescent↗