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Biomedical subjects

J K Kim

Publications and source records attributed to J K Kim.

At least 73 records · Page 4Linked to original sources

Sino-aortic denervation alters the hemodynamic response to exercise in hypertensive rats.

The effect of sino-aortic denervation (SAD) on the heart rate (HR), arterial pressure (AP) and regional blood flow responses during dynamic exercise was examined in spontaneously hypertensive rats (SHR). Intact (n= 14) and SAD (n= 17) rats were instrumented with arterial catheters and mesenteric and iliac Doppler ultrasonic flow probes. After recovery, all rats underwent a graded exercise test. Heart rate increased significantly during exercise in intact and SAD rats. There was no significant difference in the steady state heart rate response to exercise in the intact and SAD rats. Arterial pressure increased during exercise in the intact rats. In sharp contrast, arterial pressure decreased during exercise in the SAD rats. Iliac vascular conductance increased during exercise in the intact and SAD rats. The increase in iliac vascular conductance during exercise was significantly greater in the SAD rats. Mesenteric vascular conductance decreased during exercise in the intact and SAD rats. The decrease in mesenteric vascular conductance during exercise was significantly attenuated in the SAD rats. Results suggest that functioning arterial baroreceptors are required for the typical hemodynamic responses during dynamic treadmill running in hypertensive rats.

Animals↗

Removal of unburned carbon from coal fly ash using a pneumatic triboelectrostatic separator.

A pneumatic triboelectrostatic beneficiation system of fly ash was studied using a continuous, bench-scale electroseparator composed of two vertical electrode plates and an ejector-tribocharger. Tests were conducted to evaluate the charge density and the separation efficiency at various operating conditions. It was found that the higher charge densities were obtained at (1) the air flow rate of 1.75 m3/min. (2) the feed rate of less than 50 kg/h. and (3) the relative humidity of less than 30% with use of a stainless ejector tribocharger. With these optimum conditions, the clean ash of less than LOI 3% was recovered with a yield over 75% when operated at the diffuser slit gap of 4mm, the diffuser outlet velocity of 16.1-18.6 m/s, and the distance of 15 cm between diffuser slit and splitter. The optimum feed rate was found to be 740 kg/h per m2 of electrode surface area, which can be used as a scale-up factor of electroseparator.

Air Pollutants↗

Generation and characterization of recombinant ScFv antibodies detecting Eimeria acervulina surface antigens.

In our previous attempt to generate monoclonal antibodies (MAbs) against coccidia parasites that more accurately reflect the natural avian humoral immune response, we produced two chicken B-cell hybridomas, 5D11 and 2-1. While both cell lines secreted antibodies reactive with sporozoites of Eimeria acervulina, they were produced in yields too low to conduct meaningful in vivo studies. To circumvent this problem, we produced four single chain variable fragment (scFv) antibodies from the V(H) and V(L) genes of hybridomas 5D11 and 2-1. The concentration of these recombinant antibodies expressed in E. coli and purified to homogeneity was 5-6 mg/L. Three of the antibodies exhibited antigen binding specificity to Eimeria surface antigens equivalent to that of the native MAbs. Nucleotide sequence analysis of the V(L) genes from hybridomas 5D11 and 2-1 and genomic DNA revealed vestiges of gene conversion with V(lambda) pseudogenes. These recombinant scFv antibodies will prove useful for further characterization of natural Eimeria surface antigens as potential vaccine candidates.

Animals↗

Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development.

Srg3 (SWI3-related gene product) is a mouse homolog of yeast SWI3, Drosophila melanogaster MOIRA (also named MOR/BAP155), and human BAF155 and is known as a core subunit of SWI/SNF complex. This complex is involved in the chromatin remodeling required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. We generated mice with a null mutation in the Srg3 locus to examine its function in vivo. Homozygous mutants develop in the early implantation stage but undergo rapid degeneration thereafter. An in vitro outgrowth study revealed that mutant blastocysts hatch, adhere, and form a layer of trophoblast giant cells, but the inner cell mass degenerates after prolonged culture. Interestingly, about 20% of heterozygous mutant embryos display defects in brain development with abnormal organization of the brain, a condition known as exencephaly. Histological examination suggests that exencephaly is caused by the failure in neural fold elevation, resulting in severe brain malformation. Our findings demonstrate that Srg3 is essential for early embryogenesis and plays an important role in the brain development of mice.

Animals↗

Abdominopelvic actinomycosis involving the gastrointestinal tract: CT features.

PURPOSE: To assess the computed tomographic (CT) features of abdominopelvic actinomycosis involving the gastrointestinal tract. MATERIALS AND METHODS: CT scans were analyzed in 18 patients with pathologically proved abdominopelvic actinomycosis involving the gastrointestinal tract. Eight patients had a history of using intrauterine contraceptive devices. Bowel site, wall thickness, length, bowel involvement patterns, inflammatory infiltration, and features of peritoneal or pelvic mass, if present, were evaluated at CT. RESULTS: Of the gastrointestinal tract, the sigmoid colon was most commonly involved (50%). All patients showed concentric (n = 15) or eccentric (n = 3) bowel wall thickening, with a mean thickness of 1.2 cm and a mean length of 8.3 cm. The thickened bowel enhanced homogeneously in nine patients and heterogeneously in the other nine. Inflammatory infiltration was mostly diffuse and severe. In 17 patients, a peritoneal or pelvic mass (mean maximum diameter, 3.2 cm) was seen adjacent to the involved bowel and appeared to be heterogeneously enhanced in most cases; infiltration into the abdominal wall was seen in four patients. CONCLUSION: Actinomycosis should be included in the differential diagnosis when CT scans show bowel wall thickening and regional pelvic or peritoneal mass with extensive infiltration, especially in patients with abdominal pain, fever, leukocytosis, or long-term use of intrauterine contraceptive devices.

Actinomycosis↗

Intracranial arteriovenous malformations: real-time auto-triggered elliptic centric-ordered 3D gadolinium-enhanced MR angiography--initial assessment.

Auto-triggered elliptic centric-ordered three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography was compared with 3D multiple overlapping thin-slab acquisition time-of-flight (TOF) MR angiography in the evaluation of intracranial arteriovenous malformations (AVMs) in 10 patients. Intraarterial digital subtraction angiography (DSA) was the reference standard. Gadolinium-enhanced MR angiograms were found to be equivalent to DSA images in AVM component depiction in 70%--90% of cases and were consistently superior to TOF MR angiograms.

Adolescent↗

Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4.

Using cre/loxP gene targeting, transgenic mice with muscle-specific inactivation of the GLUT4 gene (muscle GLUT4 KO) were generated and shown to develop a diabetes phenotype. To determine the mechanism, we examined insulin-stimulated glucose uptake and metabolism during hyperinsulinemic-euglycemic clamp in control and muscle GLUT4 KO mice before and after development of diabetes. Insulin-stimulated whole body glucose uptake was decreased by 55% in muscle GLUT4 KO mice, an effect that could be attributed to a 92% decrease in insulin-stimulated muscle glucose uptake. Surprisingly, insulin's ability to stimulate adipose tissue glucose uptake and suppress hepatic glucose production was significantly impaired in muscle GLUT4 KO mice. To address whether these latter changes were caused by glucose toxicity, we treated muscle GLUT4 KO mice with phloridzin to prevent hyperglycemia and found that insulin-stimulated whole body and skeletal muscle glucose uptake were decreased substantially, whereas insulin-stimulated glucose uptake in adipose tissue and suppression of hepatic glucose production were normal after phloridzin treatment. In conclusion, these findings demonstrate that a primary defect in muscle glucose transport can lead to secondary defects in insulin action in adipose tissue and liver due to glucose toxicity. These secondary defects contribute to insulin resistance and to the development of diabetes.

Adipose Tissue↗

Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways.

Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant phosphorylation sites are difficult to identify in cultured cells and to validate in isolated tissues. Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser307, which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1. To monitor phosphorylation of Ser307 in various cell and tissue backgrounds, we prepared a phosphospecific polyclonal antibody designated alphapSer307. This antibody revealed that TNF-alpha, IGF-1, or insulin stimulated phosphorylation of IRS-1 at Ser307 in 3T3-L1 preadipocytes and adipocytes. Insulin injected into mice or rats also stimulated phosphorylation of Ser307 on IRS-1 immunoprecipitated from muscle; moreover, Ser307 was phosphorylated in human muscle during the hyperinsulinemic euglycemic clamp. Experiments in 3T3-L1 preadipocytes and adipocytes revealed that insulin-stimulated phosphorylation of Ser307 was inhibited by LY294002 or wortmannin, whereas TNF-alpha-stimulated phosphorylation was inhibited by PD98059. Thus, distinct kinase pathways might converge at Ser307 to mediate feedback or heterologous inhibition of IRS-1 signaling to counterregulate the insulin response.

Animals↗

Prevention of fat-induced insulin resistance by salicylate.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.

Animals↗

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4(+/-) mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.

Adipocytes↗

Exposure rate as a determinant of the synergistic interaction of heat combined with ionizing or ultraviolet radiation in cell killing.

A synergistic interaction of hyperthermia with ionizing or UV light (254 nm) radiation was analyzed in experiments with yeast cells. For a fixed dose rate of radiation, the synergism was shown to be observed only within a definite temperature range (40-45 degrees C), inside of which there was an optimal temperature to achieve the highest synergism. The effectiveness of the synergistic interaction was smaller for haploid cells than for diploid cells. Experimental data from diploid yeast cells evidenced the significance of the exposure rate in the synergistic interaction of heat combined with ionizing or ultraviolet radiation. The data show that the less is the intensity of radiation, the lower is the temperature that should be used to provide some definite, or highest, synergistic interaction with the radiation. To demonstrate the significance of this rule for other cellular systems, the results of other authors published for bacterial spores and mammalian cells are discussed. Calculations from these results have confirmed the revealed relationship between the dose rate and the exposure temperature. On this basis, it is inferred that synergism may take place at small intensities of harmful environmental factors existing in the biosphere. Hence, any assessment of the health or environmental risks should take into account synergistic interactions between harmful agents.

Cell Survival↗

Clinical features and prognosis of acute aortic intramural hemorrhage compared with those of acute aortic dissection: a single center experience.

The clinical manifestations and natural history of acute aortic intramural hemorrhage are not well characterized. Therefore, we have evaluated the differences in the clinical features and prognosis between acute intramural hemorrhage and acute classic aortic dissection. One hundred two consecutive patients with acute aortic syndrome were diagnosed between November 1994 and May 1999. The clinical features, treatment modalities and survival of these patients were analyzed. Thirty one of the 102 patients (30%) had intramural hemorrhage and 71 (70%) had aortic dissection. Patients with intramural hemorrhage were older than those with aortic dissection (mean ages 67 and 55 years, respectively) (p < 0.001), and intramural hemorrhage showed a lower proportion of type A than did aortic dissection (32% and 58%, respectively) (p = 0.018). The incidence of severe complications was significantly lower in patients with intramural hemorrhage than in those with aortic dissection (19% and 27%, respectively) (p < 0.001). Mean follow-up duration was 23.1+/-16.0 months. The overall death rate for patients with intramural hemorrhage (2 / 31; 6%) tended to be lower than those with aortic dissection (14 / 71; 20%) (p = 0.104). The Stanford classification and treatment modalities were not correlated with death. Late follow-up imaging studies in intramural hemorrhage showed partial to complete resolution of intramural hematoma (9 / 15; 60%). In this study, intramural hemorrhage was fairly common, more frequent among older patients, had a lower proportion of type A, and showed a lower incidence of severe complications and a more favorable prognosis in terms of mortality, than aortic dissection.

Acute Disease↗

Molecular screening for fragile X syndrome in mentally handicapped children in Korea.

Fragile X syndrome is one of the most common forms of inherited mental retardation and is caused by the expansion of the CGG trinucleotide repeats in the FMR-1 gene. This study was aimed to facilitate the molecular screening of fragile X syndrome in Korean children with mental retardation of unknown etiology. The subjects were tested by Expand Long Template PCR system in the presence of 7-deaza-dGTP, and then by Southern blot analysis. The PCR method provided rapid and reliable results for the identification of fragile X negative and positive patients. One hundred one mentally retarded children (78 males and 23 females) were screened by PCR amplification, which detected only one abnormal sample. The PCR-positive case was confirmed by the CGG repeat expansion on Southern blot analysis with a positive cytogenetic result. In conclusion, Expand Long Template PCR may be used as the first screening test for detecting the fragile X syndrome.

Adolescent↗

Increased levels of circulating autoantibodies to cultured human bronchial epithelial cell in adult patients with nonatopic asthma.

The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma has been proposed by earlier studies. To evaluate the possible involvement of autoimmune response against bronchial epithelial cell in the pathogenesis of nonatopic asthma, we measured circulating autoantibodies to cultured human bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent assay. We used stored serum samples form 38 age-matched healthy controls, 26 adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and 12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies to bronchial epithelial cell were significantly higher in patients with nonatopic asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that levels of circulating IgG autoantibodies to bronchial epithelial cell were increased in adult patients with nonatopic asthma. Further studies are needed to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.

Adult↗

Characterization of UV-irradiated dense/porous collagen membranes: morphology, enzymatic degradation, and mechanical properties.

Collagen-based membranous materials of various shapes (gel, film, sponge) are known to be the most promising materials in terms of facilitating the regeneration of dermal defects. In this study, dense and porous collagen membranes were fabricated using air-drying and freeze-drying processes, respectively, and the effect of ultraviolet (UV) radiation on the degree of membrane crosslinking was evaluated by in vitro biodegradation and mechanical testing. A non-irradiated membrane group was used as the negative control and a glutaraldehyde (GA) treated group as the positive control. Scanning electron microscopy showed that, as the freezing temperature decreased to -196 degrees C, the resultant mean pore sizes also decreased; optimal pore size was obtained at a freezing temperature of -70 degrees C. In vitro biodegradation and mechanical testing demonstrated that GA treatment or 4 hours of exposure to UV radiation significantly increased both resistance to collagenase and mechanical strength versus the untreated controls, regardless of the collagen membrane type (dense or porous). Our results suggest that UV treatment is a useful tool for the fabrication of collagen membranes designed to be used as dermal dressings.

Animals↗

The predictive parameters of erythropoietin hyporesponsiveness in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: The present study was aimed at investigating the predictive parameters of erythropoietin (epoetin) hyporesponsiveness in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: We studied 40 patients with end-stage renal disease who had been receiving CAPD for at least 6 months and epoetin therapy for at least more than 2 months. Pearson's simple correlation and multiple stepwise linear regression analysis was used to discover what parameter can predict epoetin resistance. We expressed epoetin resistance index (ERI) as weekly epoetin dose/hematocrit/body weight'. The dose of epoetin is titrated by about 25% every 2 to 4 weeks to maintain a target hematocrit level between 33% and 36%. RESULTS: We analyzed the relationship between ERI and other predictive parameters by Pearson's correlation. These results showed ERI has a statistically significant correlation with transferrin saturation (TS) (r = -0.327, p = 0.042), total weekly Kt/Vurea (r = -0.423, p = 0.018), serum albumin level (r = -0.458, p = 0.003), normalized protein catabolic rate (nPCR) (r = -0.479, p = 0.006), normalized protein equivalent of total nitrogen appearance (nPNA) (r = -0.488, p = 0.005) and serum C-reactive protein (CRP) (r = 0.332, p = 0.036). Regression analysis was performed using stepwise linear regression for multiple variables to discover the most independent variable which is correlated with ERI. ERI was entered as a dependent variable, whereas the other parameters (age, duration of peritoneal dialysis, serum albumin level, CRP, serum ferritin, total weekly Kt/Vurea, nPCR, nPNA, serum iPTH, serum aluminium, TS) were entered as independent variables. This analysis showed CRP is the most significant variable and, if CRP is excluded, nPNA is the significant variable. CRP has a statistically significant correlation with serum albumin level (r = -0.418, p = 0.007) and total weekly Kt/Vurea (r = -0.366, p = 0.043). High CRP group has more increased level of ERI (p < 0.05), age (p < 0.05) and serum creatinine level (p < 0.05) than normal control, but more decreased level of serum albumin (p < 0.01) and serum iron levels (p < 0.05). CONCLUSION: These results indicate that CRP is the most important predictor of epoetin hyporesponsiveness.

Adult↗

Retinal vein occlusion in two patients with primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (APS) is a disease producing vascular thrombus with antiphospholipid antibody without association with autoimmune diseases as systemic lupus erythematosus. Retinal vein occlusion is a rare vascular manifestation in primary APS. We describe 2 cases of primary APS presenting with developing blurred vision. Each had central retinal vein occlusion and high titer of IgG anticardiolipin antibody.

Adult↗

Mutational definition of RNA-binding and protein-protein interaction domains of heterogeneous nuclear RNP C1.

The heterogeneous nuclear ribonucleoprotein (hn- RNP) C proteins, among the most abundant pre-mRNA-binding proteins in the eukaryotic nucleus, have a single RNP motif RNA-binding domain. The RNA-binding domain (RBD) is comprised of approximately 80-100 amino acids, and its structure has been determined. However, relatively little is known about the role of specific amino acids of the RBD in the binding to RNA. We have devised a phage display-based screening method for the rapid identification of amino acids in hnRNP C1 that are essential for its binding to RNA. The identified mutants were further tested for binding to poly(U)-Sepharose, a substrate to which wild type hnRNP C1 binds with high affinity. We found both previously predicted, highly conserved residues as well as additional residues in the RBD to be essential for C1 RNA binding. We also identified three mutations in the leucine-rich C1-C1 interaction domain near the carboxyl terminus of the protein that both abolished C1 oligomerization and reduced RNA binding. These results demonstrate that although the RBD is the primary determinant of C1 RNA binding, residues in the C1-C1 interaction domain also influence the RNA binding activity of the protein. The experimental approach we described should be generally applicable for the screening and identification of amino acids that play a role in the binding of proteins to nucleic acid substrates.

Amino Acid Sequence↗