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Biomedical subjects

K M Chung

Publications and source records attributed to K M Chung.

At least 19 recordsLinked to original sources

Differential roles of spinal cholera toxin- and pertussis toxin-sensitive G proteins in nociceptive responses caused by formalin, capsaicin, and substance P in mice.

The aim of the present study is to characterize the roles of spinal cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G proteins in the regulation of various nociceptive responses. The effects of intrathecal (i.t.) pretreatments with CTX and PTX on the formalin (subcutaneous)-, capsaicin (i.t.)-, and substance P (SP; i.t.)-induced nociceptive behaviours were examined in mice. Pretreatment with CTX (i.t.; 24 h before) significantly and dose-dependently (0.05-0.5 microg) suppressed both the first and second phases of the formalin-induced nociceptive behaviour. On the other hand, pretreatment with PTX (i.t., 6 days before) at the same doses (0.05-N0.5 microg) did not affect the formalin-induced response. Capsaicin (i.t., 0.5 microg)- and SP (i.t., 0.7 microg)-induced nociceptive behaviours were attenuated by the pretreatment with CTX. In addition, SP-induced nociceptive response was also attenuated by the pretreatment with PTX. However, the capsaicin-induced nociceptive response was not influenced by PTX pretreatment. These findings suggest that, at the spinal cord level, CTX-sensitive G-proteins are involved in the formalin-, capsaicin-, and SP-induced nociceptive behavioural responses, whereas PTX-sensitive G proteins are involved in SP-induced nociceptive response.

Animals↗

ORE9, an F-box protein that regulates leaf senescence in Arabidopsis.

Senescence is a sequence of biochemical and physiological events that constitute the final stage of development. The identification of genes that alter senescence has practical value and is helpful in revealing pathways that influence senescence. However, the genetic mechanisms of senescence are largely unknown. The leaf of the oresara9 (ore9) mutant of Arabidopsis exhibits increased longevity during age-dependent natural senescence by delaying the onset of various senescence symptoms. It also displays delayed senescence symptoms during hormone-modulated senescence. Map-based cloning of ORE9 identified a 693-amino acid polypeptide containing an F-box motif and 18 leucine-rich repeats. The F-box motif of ORE9 interacts with ASK1 (Arabidopsis Skp1-like 1), a component of the plant SCF complex. These results suggest that ORE9 functions to limit leaf longevity by removing, through ubiquitin-dependent proteolysis, target proteins that are required to delay the leaf senescence program in Arabidopsis.

Abscisic Acid↗

A conceptual model of child psychopathology: implications for understanding attention deficit hyperactivity disorder and treatment efficacy.

Highlights the desirability of using a theoretical framework for guiding the design and evaluation of therapeutic interventions for children with attention deficit hyperactivity disorder (ADHD). A general conceptual model is introduced and used to evaluate ADHD treatment outcome research. Treatments designed to target the substrate level (pharmacological interventions) result in broad, robust improvement in both core and peripheral areas of functioning. Those targeting hypothesized core features of the disorder (i.e., attention, impulsivity-hyperactivity) produce corresponding improvement in core and peripheral outcome measures with the exception of studies employing cognitive-behavior therapy. Those targeting peripheral features of the disorder effect change only in corresponding peripheral areas of functioning. Implications for clinical practice are discussed, and an alternative conceptual model of ADHD is introduced and compared with existing models.

Attention↗

Internalizing behavior problems and scholastic achievement in children: cognitive and behavioral pathways as mediators of outcome.

Examined a conceptual model in which dual developmental pathways (behavioral and cognitive) are hypothesized to account for the relation among internalizing behavior problems, intelligence, and later scholastic achievement using a cross-sectional sample of 325 children. Classroom behavior and select aspects of cognitive functioning (vigilance, short-term memory) were hypothesized to mediate the relations among internalizing problems, IQ, and long-term scholastic achievement. Hierarchical tests applied to a nested series of models demonstrated that (a) individual differences in measured intelligence among children are associated with variations in classroom performance and cognitive functioning, (b) classroom performance and cognitive functioning make unique contributions to prediction of later achievement over and above the influence of intelligence, (c) anxious/depressive features are correlated but separable constructs, and (d) anxiety/depression and withdrawal contribute to prediction of classroom performance and cognitive functioning over and above the effects of intelligence. Classroom performance and cognitive functioning thus appear to mediate the effects of internalizing behaviors as well as intelligence. Particular attention to the presence and potential impact of social withdrawal on children's functioning, both alone and concomitant with anxiety/depression, appears warranted during the course of clinical evaluations owing to the strong continuity among these variables.

Adolescent↗

Differential modulatory roles of cholera toxin and pertussis toxin in the regulation of pain responses induced by excitatory amino acids administered intrathecally in mice.

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in excitatory amino acids induced pain response. Intrathecal (i.t.) injection of glutamate (20 microg), N-methyl-D-aspartic acid (NMDA; 60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 13 ng), and kainic acid (12 ng) showed pain response. Pretreatment with CTX (0.05 and 0.5 microg, i.t.) attenuated pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t. in a dose-dependent manner. On the other hand, i.t. pretreatment with PTX further increased the pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t., especially at the dose of 0.5 microg. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play opposite roles in modulating the pain response induced by spinally administered. Furthermore, CTX- and PTX-sensitive G-proteins appear to modulate pain response induced by stimuli of both NMDA and non-NMDA glutamate receptors.

Adjuvants, Immunologic↗

Nonstructural protein 5A of hepatitis C virus inhibits the function of karyopherin beta3.

It has been suggested that nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) plays a role in the incapacitation of interferon by inactivation of RNA-dependent protein kinase PKR. In order to further investigate the role of NS5A, we tried to identify cellular proteins interacting with NS5A by using the yeast two-hybrid system. The karyopherin beta3 gene was isolated from a human liver cell library as a protein interacting with NS5A. The protein-protein interaction between NS5A and karyopherin beta3 was confirmed by in vitro binding assay and an in vivo coimmunoprecipitation method. The effect of NS5A on the karyopherin beta3 activity was investigated using a yeast cell line containing mutations in both PSE1 and KAP123, genes that are homologous to the human karyopherin beta3 gene. Human karyopherin beta3 complemented the loss of the PSE1 and KAP123 functions, supporting growth of the double mutant cells. However, expression of NS5A hampered the growth of the double mutant cells supplemented with human karyopherin beta3. On the other hand, expression of NS5A by itself had no effect on the growth of the double mutant expressing wild-type yeast PSE1. This indicates that NS5A may inhibit karyopherin beta3 function via protein-protein interaction. The role of NS5A in HCV replication is discussed.

Animals↗

Upgrading the science and technology of assessment and diagnosis: laboratory and clinic-based assessment of children with ADHD.

Reviews the usefulness of clinic-based and laboratory-based instruments and paradigms for diagnosing attention deficit hyperactivity disorder (ADHD) and monitoring treatment effects. Extant literature examining the performance of normal children and those with ADHD on an extensive range of neurocognitive tests, tasks, and experimental paradigms indicates that particular types of instruments may be more reliable than others with respect to detecting between-group differences. We review task parameters that may distinguish the more reliable from less reliable instruments. The value of clinic-based and laboratory-based instruments for monitoring treatment response in children with ADHD is questionable when evaluated in the context of ecologically relevant variables such as classroom behavior and academic functioning. We present a general conceptual model to highlight conceptual issues relevant to designing clinic-based and laboratory-based instruments for the purposes of diagnosing and monitoring treatment effects in children with ADHD. Application of the model to currently conceptualized core variables indicates that attention and impulsivity-hyperactivity may represent correlative rather than core features of the disorder. We discuss implications of these findings for designing the next generation of clinic-based and laboratory-based instruments.

Attention Deficit Disorder with Hyperactivity↗

Subcellular localization of hepatitis C viral proteins in mammalian cells.

We determined the subcellular localization of hepatitis C viral (HCV) proteins as a first step towards the understanding of the functions of these proteins in the mammalian cell (CHO-K1). We used fluorescence emitted from green fluorescent protein (GFP)-fused to the viral proteins to determine the subcellular localization of the viral proteins. We found that most of the viral proteins were excluded from the nucleus. Core exhibited a globular pattern near the nucleus. NS2 was concentrated in the perinuclear space. NS4A accumulated in the ER and the Golgi regions. NS3 was detected in the nucleus as well as the cytoplasm, when it was expressed by itself. However, NS3 became restricted to the cytoplasm, when it was produced together with NS4A. NS4B showed a spot-like pattern throughout the cytoplasm. NS5A and NS5B were distributed throughout the cytoplasm in a mesh-like pattern. These results can provide a basis for further investigations into the functions of the HCV proteins.

Animals↗

Analysis of the C-terminal region of Arabidopsis thaliana APETALA1 as a transcription activation domain.

APETALA1 (AP1) of Arabidopsis thaliana is a transcription factor controlling flower development. AP2 is a member of the MADS (MCM1, AGAMOUS, DEFICIENS, SRF) superfamily, which plays important roles in differentiation in plants and animals. MADS domains, which function most importantly in DNA binding, are found in all major eukaryotic kingdoms. In plants, MADS domain-containing proteins also possess a region of moderate sequence similarity named the K domain, which is involved in protein-protein interaction. Little is known about the function of a third, highly variable, domain designated the C domain, as it resides at the C terminus of the MADS proteins of plants. Here we report that the C-terminal domain of Arabidopsis thaliana AP1 and its homologues perform a transcriptional activation function. The C-terminal region of AP1 is composed of at least two separable transcriptional activation domains that function synergistically.

Amino Acid Sequence↗

Effects of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse.

The present study was designed to investigate the modulatory effects of blockade of spinal histamine receptors on antinociception induced by supraspinally administered mu-epsilon-, delta-, and kappa-opioid receptor agonists. The effects of intrathecal (i.t.) injections with cyproheptadine [a histamine-1 (H1) receptor antagonist], ranitidine (a H2 receptor antagonist), or thioperamide (a H3 receptor antagonist) injected i.t., on the antinociception induced by morphine (a mu-receptor antagonist), beta-endorphin (an epsilon-receptor agonist), D-Pen(2,5)-enkephalin (DPDPE, a delta-receptor agonist) or trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohxyl] benzeocetamide (U50,488H, a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick test. The i.t. injection of cyproheptadine (from 0.31 to 62 nmole), ranitidine (from 0.28 to 56 nmole), or thioperamide (from 0.24 to 48 nmole) alone did not show any antinociceptive effect. The i.t. pretreatment with cyproheptadine or thioperamide dose-dependently attenuated the inhibition of the tail-flick response induced by i.c.v. administered morphine (0.6 nmole), b-endorphin (0.03 nmole), DPDPE (1.5 nmole), and U50,488H (130 nmole). In addition, the i.t. pretreatment with ranitidine dose-dependently attenuated the inhibition of the tail-flick response induced by morphine, b-endorphin and U50,488H without affecting DPDPE-induced response. Our results suggest that spinal histamine H1 and H3 receptors may involved in the production of antinociception induced by supraspinally applied morphine, b-endorphin, DPDPE and U50,488H. Spinal H2 receptors appear to be involved in supraspinally administered morphine, b-endorphin- and U50,488H-induced antinociception but not DPDPE-induced antinociception.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Differential modulation by baclofen on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the formalin test.

Our previous studies have demonstrated that supraspinal GABAergic receptors are differentially involved in the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hot-plate tests. These two models employed a phasic, thermal nociceptive stimulus. The present study was designed to examine the possible involvement of supraspinal GABAergic receptors in opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed the almost complete inhibitory effects against the hyperalgesic response in both phases. Muscimol (75-100 ng) and baclofen (5-10 ng) injected i.c.v. produced the hypoalgesic response in the both phases. The hypoalgesic response induced by muscimol and baclofen observed during the second phase was more pronounced than that observed during the second phase. Baclofen (2.5 ng), at the dose which did not affect the hyperalgesic response, resulted in a significant reversal of the i.c.v. administered beta-endorphin-induced hypoalgesic response observed during the second, but not the first, phase. However, the hypoalgesic response induced by i.c.v. administered morphine was not changed by the same dose of muscimol or baclofen injected i.c.v. Our results indicate that, at the supraspinal level, GABA(B)receptors appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin test model.

Analgesics, Opioid↗

Fundus magnification produced during direct ophthalmoscopy of the corrected eye.

The clinical significance of fundus magnification produced during direct ophthalmoscopy of the corrected eye has not been fully established. Based on paraxial ray tracing, fundus magnification (M) can be defined by a simple equation, M = (K'/4) x (Fs/K), where K' is the dioptric axial power of the eye, Fs is the correcting thin lens power and K is the ocular ametropia. Refractive myopes produce greater fundus magnification than axial myopes, whereas refractive hyperopes produce lower fundus magnification than axial hyperopes. If we assume 15 x fundus magnification as our standard magnification for an emmetropic reduced eye, then wearing glasses or putting the focusing lens at or close to the anterior focus of the eye is able to achieve the standard magnification for axial myope and axial hyperope, whereas wearing contact lenses is able to achieve the standard magnification for refractive myope and refractive hyperope. Vertex distance has greater influence on fundus magnification produced during direct ophthalmoscopy than other funduscopic techniques. In conclusion, the newly defined formula has clinical applications during direct ophthalmoscopy.

Eyeglasses↗

Splenic injury following colonoscopy.

Splenic injury following colonoscopy is rare but can be fatal and easily overlooked. A case of colonoscopic splenic injury is presented to highlight its potentially fatal complication. The risk factors, underlying mechanism, possible measures of prevention, diagnosis, and treatment are also discussed.

Journal Article↗

Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A feasible mechanism of unwinding duplex RNA.

Crystal structure of RNA helicase domain from genotype 1b hepatitis C virus has been determined at 2.3 A resolution by the multiple isomorphous replacement method. The structure consists of three domains that form a Y-shaped molecule. One is a NTPase domain containing two highly conserved NTP binding motifs. Another is an RNA binding domain containing a conserved RNA binding motif. The third is a helical domain that contains no beta-strand. The RNA binding domain of the molecule is distinctively separated from the other two domains forming an interdomain cleft into which single stranded RNA can be modeled. A channel is found between a pair of symmetry-related molecules which exhibit the most extensive crystal packing interactions. A stretch of single stranded RNA can be modeled with electrostatic complementarity into the interdomain cleft and continuously through the channel. These observations suggest that some form of this dimer is likely to be the functional form that unwinds double stranded RNA processively by passing one strand of RNA through the channel and passing the other strand outside of the dimer. A "descending molecular see-saw" model is proposed that is consistent with directionality of unwinding and other physicochemical properties of RNA helicases.

Acid Anhydride Hydrolases↗

Crystallization and preliminary X-ray crystallographic analysis of the helicase domain of hepatitis C virus NS3 protein.

The NS3 protein of hepatitis C virus (HCV) is thought to be essential for viral replication. The N-terminal domain of the protein contains protease activity and the C-terminal domain contains nucleotide triphosphatase and RNA helicase activity. The RNA helicase domain of HCV NS3 protein was purified by using affinity-column chromatographic methods, and crystallized by using the microbatch crystallization method under oil at 277 K. The crystals belong to primitive trigonal space group P3121 or P3221 with cell dimensions of a = b = 93.3, c = 104.6 A. The asymmetric unit contains one molecule of the helicase domain, with the crystal volume per protein mass (Vm) of 2.50 A3 Da-1 and solvent content of about 50.8% by volume. A native data set to 2.3 A resolution was obtained from a frozen crystal indicating that the crystals are quite suitable for structure determination by multiple isomorphous replacement.

Amino Acid Sequence↗