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Biomedical subjects

H Kang

Publications and source records attributed to H Kang.

At least 19 recordsLinked to original sources
PubMed2003

Does psychological vulnerability determine health-care utilization in fibromyalgia?

OBJECTIVES: Patients with fibromyalgia (FM) undergo multiple testing and referral to specialists, and often use complementary/alternative medicine (CAM) services. The objectives of the study were: (i) to document health service utilization, and (ii) to examine whether psychological vulnerability was associated with visits to physicians and CAM providers. METHODS: Women (N = 178) with a diagnosis of primary FM completed a psychosocial test measuring pain, perceived stress, global psychological distress, sexual abuse history, co-morbidity and disability due to FM. Subjects also completed a health services questionnaire, documenting visits to physicians and CAM providers during the previous 6 months. Psychological vulnerability was operationalized as obtaining high scores on psychological distress, perceived stress and reporting at least one abusive event. RESULTS: The average number of visits was 7.2 to physicians and 11.3 to CAM providers. CONCLUSIONS: The number of physician visits was significantly associated with more co-morbidity. Psychologically vulnerable subjects were more likely to use CAM services than those not so classified.

Adult↗
PubMed2003

Developmental hemispheric asymmetry of interregional metabolic correlation of the auditory cortex in deaf subjects.

The functional connectivity of the auditory cortex might be altered in deaf subjects due to the loss of auditory input. We studied the developmental changes of functional connectivity of the primary auditory cortex (A1) in deaf children, deaf adults, and normal hearing adults by examining interregional metabolic correlation with (18)F-FDG PET. The mean activity of FDG uptake in the cytoarchitectonically defined A1 region served as a covariate in the interregional and interhemispheric correlation analysis. A1 metabolic rate was correlated with that of the ipsilateral superior temporal lobe in both normal and deaf subjects. This correlated area was larger in deaf children than in deaf or normal hearing adults. Concerning the functional connectivity of A1, a hemispheric asymmetry was found in that the extent of interregional correlation was clearly larger in the right than in the left hemisphere. This asymmetry was particularly pronounced in the younger deaf children. Both extent and asymmetry of the functional connectivity of A1 subsided with age. Contrary to this, a correlation between the left and the right primary auditory cortices was absent in younger deaf children but became apparent as they grew older.

Adolescent↗
PubMed2003

The effects of hyaluronic acid on fibronectin fragment mediated cartilage chondrolysis in skeletally mature rabbits.

OBJECTIVE: Intraarticular Na-Hyaluronate (HA) exerts a beneficial effect on adolescent rabbits after fibronectin fragment (Fn-f) mediated cartilage injury. We extended our studies to a population of rabbits which have reached full skeletal maturity. DESIGN: Adult male NZW rabbits received an injury with Fn-f and no further treatment; an injection of HA followed by Fn-f injury, or Fn-f injury followed by a single or weekly intraarticular injection of HA. All animals were sacrificed 38 days after receiving the Fn-f injury. After sacrifice, proteoglycan (PG) content was determined from articular cartilage from the medial femoral condyles and tibial plateaus. The patellae were processed for histology. RESULTS: Cartilage PG contents were significantly reduced after Fn-f injection (P=0.0167) and were only slightly improved with HA pre-treatment. However, post-treatment with HA resulted in significant improvements in cartilage PG content when compared to Fn-f only (single HA, P=0.01; weekly HA,P =0.01). Loss of Safranin-O staining, cell loss, osteophyte formation and inflammation were present in the patellae following Fn-f injection. Pre-treatment with HA reduced these changes. More significant protection of cartilage and restoration of Fn-f injury were noted in animals receiving post-treatment with HA. CONCLUSIONS: These results suggest that 38 days after Fn-f injury the lost PG content induced by Fn-f injection is substantially restored by weekly post-treatment with intraarticular HA in rabbits that have reached full skeletal maturity.

Animals↗
PubMed2003

Degradation of phenanthrene and naphthalene by a Burkholderia species strain.

Burkholderia sp. TNFYE-5 was isolated from soil for the ability to grow on phenanthrene as sole carbon and energy source. Unlike most other phenanthrene-degrading bacteria, TNFYE-5 was unable to grow on naphthalene. Growth substrate range experiments coupled with the ring-cleavage enzyme assay data suggest that TNFYE-5 initially metabolizes phenanthrene to 1-hydroxy-2-naphthoate with subsequent degradation through the phthalate and protocatechuate and beta-ketoadipate pathway. A metabolite in the degradation of naphthalene by TNFYE-5 was isolated by high-pressure liquid chromatography (HPLC) and was identified as salicylate by UV-visible spectral and gas chromatography-mass spectrometry analyses. Thus, the inability to degrade salicylate is apparently one major reason for the incapability of TNFYE-5 to grow on naphthalene.

Biodegradation, Environmental↗
PubMed2002

Self-aggregates of poly(2-hydroxyethyl aspartamide) copolymers loaded with methotrexate by physical and chemical entrapments.

Amphiphilic copolymers based on poly(2-hydroxyethyl aspartamide) (PHEA) formed self-aggregates for the entrapment and release of methotrexate (MTX) by physical entrapment and chemical conjugation. In physical entrapment, MTX was partitioned into hydrophobic domains in self-aggregates of PHEA grafted with octadecyl chains (PHEA-C18) and the amount of the entrapped drug increased linearly by 3.39 mg per the degree of substitution of grafted octadecyl groups. The amphiphilic nature of the drug induced a large initial release in the buffer medium, irrespective of the amount of octadecyl chains. However, PEG-grafted PHEA-C18 copolymers conjugated with MTX, ConG, formed a micelle-like structure by self-association of the conjugates and suppressed the initial large release. The alkyl grafting lowered the CAC, meaning enhancement of aqueous stability. The release was accelerated in pH 10.0 by rapid hydrolysis of ester linkage by base-catalyzed cleavage, while it was significantly reduced at pH 5.0.

Antimetabolites, Antineoplastic↗
PubMed2001

Effects of elevated CO2 on fen peat biogeochemistry.

Effects of elevated atmospheric CO2 concentration on northern peatland biogeochemistry was studied in a short-term experiment. Eight intact soil cores (11-cm diameter x 40-cm depth) with Juncus and Festuca spp. were collected from a calcareous fen in north Wales. Half of the cores were incubated under 350 ppm CO2 concentration, whilst the other four cores were maintained at 700 ppm CO2. After a 4-month incubation, significantly higher biomass (root + shoot + algal mat) was determined under elevated CO2 conditions. Higher emissions of N2O and CO2, and higher concentration of pore-water DOC (dissolved organic carbon) were also observed under elevated CO2. However, no significant differences were found in CH4 emission or soil enzyme activities (beta-glucosidase, phosphatase, and N-acetylglucosaminidase) in the bulk soil. Overall, the results suggest that elevated CO2 would increase the primary productivity of the fen vegetation, and stimulate N2O and CO2 emissions as a consequence of an enhanced DOC supply from the vegetation to the soil microbes.

Carbon↗
PubMed2001

Expression of hMLH1 is inactivated in the gastric adenomas with enhanced microsatellite instability.

Microsatellite instability (MSI) and frameshift mutations in the genes containing coding nucleotide repeats have been reported in a subset of gastric adenomas, however the inactivation profiles of DNA mismatch repair genes in MSI-positive gastric adenomas have not been characterized. To address the origin of MSI in gastric adenomas, expressions of hMLH1 and hMSH2 were explored in 86 gastric adenomas. Gastric carcinomas, of which 16 were MSI-positive and 22 MSI-negative, were used as controls. MSI was found in 15 (17%) of gastric adenomas. Absent or decreased hMLH1 expression by immunohistochemistry was noted in most of the MSI-positive adenomas (13/15, 87%) and carcinomas (14/16, 88%), and all of these tumours showed methylation of the hMLH1 gene promoter. In contrast, rare inactivation of hMLH1 expression was found in MSI-negative adenomas (3/71, 4%) and carcinomas (2/22, 9%). Intense expression of hMSH2 gene product was observed in most of the gastric adenomas and carcinomas regardless of MSI status. These findings indicate that the inactivation of hMLH1 gene expression by promoter methylation is an early event and might be the origin of MSI-positive gastric adenomas.

Adaptor Proteins, Signal Transducing↗
PubMed2001

An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory.

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dependent transcription. To investigate the role of this kinase in neuronal plasticity and memory, we generated transgenic mice in which the expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to the postnatal forebrain. In these transgenic mice, activity-induced CREB phosphorylation and c-Fos expression were significantly attenuated. Hippocampal late LTP (L-LTP) was also impaired, whereas basic synaptic function and early LTP (E-LTP) were unaffected. These deficits correlated with impairments in long-term memory, specifically in its consolidation/retention phase but not in the acquisition phase. These results indicate that neural activity-dependent CaMKIV signaling in the neuronal nucleus plays an important role in the consolidation/retention of hippocampus-dependent long-term memory.

Amino Acid Substitution↗
PubMed2001

Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation.

Protein phosphatase 5 (PP5) exhibits low basal activity due to the autoinhibitory properties of its N-terminal and C-terminal domains but can be activated approximately 40-fold in vitro by polyunsaturated fatty acids. To identify residues involved in regulating PP5 activity, we performed scanning mutagenesis of its N-terminal tetratricopeptide repeat (TPR) domain and deletion mutagenesis of its C-terminal domain. Mutating residues in a groove of the TPR domain that binds to heat shock protein 90 had no effect on basal phosphatase activity. Mutation of Glu-76, however, whose side chain projects away from this groove, resulted in a 10-fold elevation of basal activity without affecting arachidonic acid-stimulated activity. Thus, the interface of the TPR domain involved in PP5 autoinhibition appears to be different from that involved in heat shock protein 90 binding. We also observed a 10-fold elevation of basal phosphatase activity upon removing the C-terminal 13 amino acids of PP5, with a concomitant 50% decrease in arachidonic acid-stimulated activity. These two effects were accounted for by two distinct amino acid deletions: deleting the four C-terminal residues (496-499) of PP5 had no effect on its activity, but removing Gln-495 elevated basal activity 10-fold. Removal of a further three amino acids had no additional effect, but deleting Asn-491 resulted in a 50% reduction in arachidonic acid-stimulated activity. Thus, Glu-76 in the TPR domain and Gln-495 at the C-terminus were implicated in maintaining the low basal activity of PP5. While the TPR domain alone has been thought to mediate fatty acid activation of PP5, our data suggest that Asn-491, near its C-terminus, may also be involved in this process.

Amino Acids↗
PubMed2001

Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the lumen of sarcoplasmic reticulum.

HRC (histidine-rich Ca(2+) binding protein) has been identified from skeletal and cardiac muscle and shown to bind Ca(2+) with high capacity and low affinity. While HRC resides in the lumen of the sarcoplasmic reticulum, the physiological function of HRC is largely unknown. In the present study, we have performed co-immunoprecipitation experiments and show that HRC binds directly to triadin, which is an integral membrane protein of the sarcoplasmic reticulum. Using a fusion protein binding assay, we further identified the histidine-rich acidic repeats of HRC as responsible for the binding of HRC to triadin. These motifs may represent a novel protein-protein interaction domain. The HRC binding domain of triadin was also localized by fusion protein binding assay to the lumenal region containing the KEKE motif that was previously shown to be involved in the binding of triadin to calsequestrin. Notably, the interaction of HRC and triadin is Ca(2+)-sensitive. Our data suggest that HRC may play a role in the regulation of Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin.

Amino Acid Sequence↗
PubMed2001

Assessment of substrate specificity of hepatitis G virus NS3 protease by a genetic method.

The RNA genome of hepatitis G virus (HGV) encodes a large polyprotein that is processed to mature proteins by viral-encoded proteases. The HGV NS3 protease is responsible for the cleavage of the HGV polyprotein at four different locations. No conserved sequence motif has been identified for the cleavage sites of the NS3 protease. To determine the substrate specificity of the NS3 protease, amino acid sequences cleaved by the NS3 protease were obtained from randomized sequence libraries by using a screening method referred to as GASP (Genetic Assay for Site-specific Proteolysis). Based on statistical analyses of the obtained cleavable sequences, a consensus substrate sequence was deduced: Gln-Glu-Thr-Leu-Val downward arrow Ser, with the scissile bond located between Val and Ser. The relevance of this peptide as a cleavable substrate was further supported by molecular modeling of the NS3 protease. Our result would provide an insight on the molecular activity of the NS3 protease and may be useful for the design of substrate-based inhibitors.

Base Sequence↗
PubMed2001

The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-kappa b in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7.

Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappa B (NF kappa B) and was essential for the previously described NF kappa B transactivation by palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NF kappa B, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF kappa B in oxLDL-treated, resting macrophage cells.

Animals↗
PubMed2001

An improved strategy for a genetic assay for site-specific proteolysis.

We have previously reported a genetic assay that is suitable for the study of substrate specificity of a protease in vivo, and herein present a simplified version of the method. In this procedure, expressed in Saccharomyces cerevisiae by using the constitutive alcohol dehydrogenase promoter is a fusion protein in which a transcription factor is linked to the intracellular domain of an integral membrane protein by a protease substrate sequence. Following this, a protease is expressed by using the inducible GAL promoter in the same yeast cells. The cleavage of the substrate sequence by the specific protease results in the release of the transcription factor and subsequent activation of reporter genes in nucleus. Since the expression of a protease is strictly under the control of the inducible GAL promoter, false substrate sequences that are cleaved by endogenous yeast proteases can be easily recognized and eliminated from further characterization. This suggests that the modified strategy provides an efficient tool for the analysis of substrate sequences of a protease in vivo.

Endopeptidases↗
PubMed2001

Even-odd alternation in mass spectrum of thymine and uracil clusters: evidence of intracluster photodimerization.

Multiphoton ionization of thymine and uracil clusters generated by a supersonic molecular beam gave rise to a remarkable alternation of mass spectral intensities between even- and odd-numbered clusters. Such alternation was observed in clusters of up to 30 molecules. Excitation to the two lowest electronically excited states seemed to be a strong prerequisite. In view of the well known photodimerization reaction of thymine and uracil in the bulk phase, it is proposed that such alternation in the mass spectral intensity resulted from formation of photodimer units within the cluster on intense UV irradiation. Several analogues of thymine with no known propensity for photodimerization in the bulk phase did not exhibit any sign of such alternation in the cluster mass spectrum. The intrinsic UV window for photodimerization, and hence photoinduced mammalian mutagenesis, was estimated to be approximately 210-280 nm, significantly narrower than the previously reported bulk values of 150-300 nm.

DNA↗
PubMed2001

Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit.

Calmodulin-dependent protein kinase IV (CaMKIV) is a key mediator of Ca(2+)-induced gene expression. In this study, CaMKIV was found to directly associate with and phosphorylate the nuclear factor-kappaB (NFkappaB) component p65 both in vitro and in vivo. The phosphorylation of p65 by CaMKIV resulted in recruitment of transcription coactivator cAMP-response element-binding protein-binding protein and concomitant release of corepressor silencing mediator for retinoid and thyroid hormone receptors, as demonstrated by the glutathione S-transferase pull down and mammalian two hybrid assays. In addition, cotransfection of CaMKIV resulted in cytosolic translocation of the silencing mediator for retinoid and thyroid hormone receptors. Consistent with these results, cotransfected CaMKIV dramatically stimulated the NFkappaB transactivation in mammalian cells. From these results, NFkappaB is suggested to be a novel downstream effector molecule of CaMKIV.

Animals↗
PubMed2001

Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability.

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of colorectal and gastric carcinomas. This study describes the analysis of MSI-positive colorectal (39 cases) and gastric carcinomas (36 cases) for the presence of frameshift mutations of the six genes known to be involved in DNA repair and containing mononucleotide repeats in their coding region. Our mutational study of the 75 MSI-positive tumors revealed frequent mutations in hRAD50 (23 cases, 31%), BLM (16 cases, 21%), and hMSH6 (16 cases, 21%); rare mutations in BRCA1 (1 case, 1%) and ATM (3 cases, 4%); and no mutation in NBS1. In contrast, no frameshift mutation was found in 60 MSI-negative colorectal and gastric carcinomas. The mutation of hRAD50, a gene that is involved in the response to cellular DNA damage and forms a complex with hMRE11 and NBS1, has not been reported previously. Our results suggest that frameshift mutations of hRAD50, BLM, and hMSH6 are selected and play a role in the tumorigenesis of colorectal and gastric carcinomas with MSI. The MSI targeting of the hRAD50 and BLM genes represents an additional link between MSI and DNA repair because alteration of these genes could accelerate defective DNA repair.

Acid Anhydride Hydrolases↗
PubMed2001

Pregnancy outcomes among U.S. Gulf War veterans: a population-based survey of 30,000 veterans.

PURPOSE: We evaluated an association between veterans' Gulf War service and reported adverse pregnancy outcomes. METHODS: We conducted a health survey in which selected reproductive outcomes of a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared to those of 15,000 non-Gulf veteran controls. RESULTS: Male Gulf veterans, compared with their non-Gulf veteran controls, reported a significantly higher rate of miscarriage (odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.32-1.99). Female Gulf veterans also reported more miscarriages than their respective controls, although their excess was not statistically significant (OR= 1.35; CI = 0.97-1.89). Both men and women deployed to the Gulf theater reported significant excesses of birth defects among their liveborn infants. These excess rates also extended to the subset of "moderate to severe" birth defects [males: OR= 1.78 (CI = 1.19-2.66); females: OR = 2.80 (CI = 1.26-6.25)]. No statistically significant differences by deployment status were found among men or women for stillbirths, pre-term deliveries or infant mortality. CONCLUSION: The risk of veterans reporting birth defects among their children was significantly associated with veteran's military service in the Gulf War. This observation needs to be confirmed by a review of medical records to rule out possible reporting bias.

Abortion, Spontaneous↗