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Biomedical subjects

Y Kang

Publications and source records attributed to Y Kang.

At least 19 recordsLinked to original sources

Effects of electro-acupuncture on the expression of c-jun and c-fos in spared dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats.

This study evaluated the plastic changes of c-jun and c-fos in the right sixth lumbar dorsal root ganglion (L6 DRG), Rexed's lamina II in representative spinal segments L3, L5, and L6 and in the nucleus dorsalis (ND) at L3 segments after electro-acupuncture (EA) in cats subjected to removal of L1-L5 and L7-S2 DRG. Following dorsal root ganglionectomy, there was a significant increase in the density of c-jun immunoreactivity in the neurons and glia in spinal lamina II and in the ND; there was also marked elevation in the expression of c-fos in ND. In both cases there was no change in the c-jun and c-fos immunoreactivity in the DRG. After EA in the operated animals, there was an up-regulation in the expression of c-jun in the L6 DRG and the associated spinal lamina II; however, increased c-fos expression was detected only in the L6 DRG. Western blot and RT-PCR were also performed to quantitatively explore the mRNA and protein expression changes in the spinal dorsal horn and associated DRG. Following partial deafferentation, there was a significant increase in the protein level of both c-jun and c-fos in the dorsal horn, while, in both cases there was no change in c-jun and c-fos protein and mRNA in the DRG. After EA in the operated animals, both c-jun protein and its mRNA in the L6 DRG as well as the associated dorsal horn of L6 spinal segment were upregulated, but increased c-fos protein and its mRNA was observed only in the L6 DRG. These findings suggested that c-jun and c-fos might be related to the acupuncture promoted spinal cord plasticity as reported previously.

Animals↗

Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3.

Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.

Cell Line, Transformed↗

Functional roles of 5-hydroxytryptamine 3/4 receptors in neurons of rat dorsal motor nucleus of the vagus.

In neurons of dorsal motor nucleus of the vagus that is involved in the gastric motility and possibly emesis, application of 5-hydroxytryptamine produces membrane depolarization, and suppresses spike-repolarization and spike-afterhyperpolarization, suggesting divergent effects of 5-hydroxytryptamine through activating multiple subtypes of 5-hydroxytryptamine receptors. However, only the role of 5-hydroxytryptamine 2A receptors has been established to be responsible for the depolarization, and the mechanisms underlying the modulation of spikes remain unknown although a role of 5-hydroxytryptamine 4 receptors was implicated in modulations of spikes. There is now increasing evidence for the role of 5-hydroxytryptamine receptors in neurons involved in generating emesis following administration of anticancer drug. Since antagonists of 5-hydroxytryptamine 3/4 receptors are widely used as anti-emetic drugs, we have reevaluated the functional roles of 5-hydroxytryptamine 3/4 receptors of dorsal motor nucleus of the vagus neurons, especially in modulating transient outward currents that are presumed to be involved in spike-repolarization and spike-afterhyperpolarization. Whole-cell patch-clamp recordings were made from the dorsal motor nucleus of the vagus neurons, which were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine injected into a bundle of abdominal vagus nerves. Under a voltage-clamp condition, dorsal motor nucleus of the vagus neurons expressed a prominent A-like current. The activation of 5-hydroxytryptamine 3 receptors reversibly increased the resting membrane conductance while the activation of 5-hydroxytryptamine 4 receptors led to an almost irreversible decrease in the A-like current. A long-lasting suppression of A-like current by transient activation of 5-hydroxytryptamine 4 receptors would result in a long-lasting increase in the excitability of dorsal motor nucleus of the vagus neurons, which might be involved in generation of the long-lasting facilitation of gastric motility or in generation of the long-lasting gastric relaxation through the activation of enteric non-adrenergic non-cholinergic neurons as implicated in the delayed emesis induced by anticancer drugs.

4-Aminobenzoic Acid↗

Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone.

INTRODUCTION: In assessing cervical fractures of the proximal femur, this in vitro quantitative computed tomography (QCT) study had three objectives: to compare QCT to dual-energy X-ray absorptiometry (DXA) for predicting the failure load of the proximal femur, to compare the contributions of density and geometry to bone failure load, and to compare the contributions of cortical and trabecular bone to bone failure load. A novel three-dimensional (3D) analysis tool [medical image analysis framework (MIAF-Femur)] was used to analyze QCT scans. METHODS: The proximal ends of 28 excised femurs were studied (1) using QCT to separately measure bone mineral density (BMD) and geometric variables of trabecular and cortical bone, (2) using mechanical tests to failure in a stance configuration, and (3) using DXA to measure BMD. The variables were described with mean, standard deviation, and range. Correlation matrix and multivariate linear models were computed. RESULTS: Among correlations, cortical thicknesses of the femoral neck were significantly correlated with femoral failure load, especially of the inferoanterior quadrant (r2=0.41; p<0.001), as was cortical volume at the "extended neck" (r2=0.41; p<0.001). Femoral failure load variance was best explained by a combination of QCT variables. Combining densitometric and geometric variables measured by QCT explained 76% of femoral failure load variance compared with 69% with the DXA model. Geometric variables (measured by QCT) explained 43% of femoral failure load variance compared with 72% for densitometric variables (measured by QCT). A model including only trabecular variables explained 52% of femoral failure load variance compared with 59% for a model including only cortical variables. CONCLUSION: The QCT-MIAF reported here provides analysis of both geometric and densitometric variables characterizing cortical and trabecular bone. Confirmation of our results in an independent sample would suggest that QCT may better explain failure load variance for cervical fracture than the gold standard DXA-provided BMD.

Absorptiometry, Photon↗

Basiliximab induction in adult liver transplant recipients with 93% rejection-free patient and graft survival at 24 months.

Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid many of the adverse events associated with polyclonal antibodies and significantly impact on rejection-free long-term survival in orthotopic liver transplantation (OLTx). We describe our experience with the use of basiliximab induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression. Forty-six consecutive deceased donor primary OLTx were analyzed. All patients received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate mofetil was also used as indicated. The mean follow-up period was 17.9 months. Forty-three patients remained rejection-free during follow-up. The actuarial patient and graft survival rate at 2 years was 93%. The rate of histology-proven hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results were compared to a historical group of 46 OLTx recipients on tacrolimus-based immunosuppression without basiliximab induction. The historical group had a rejection rate of 34% with lower patient and graft survival rates of 71.74% and 69.5%, respectively, at 24 months as well as a higher histological HCV recurrence rate of 77% (17/22), with three patients progressing to graft failure within 2 years. CMV infection and disease developed in 4.5% of the patients. Although PTLD was not observed, three recipients with hepatocellular carcinoma (HCC) developed and died of metastatic HCC. Induction with basiliximab in combination with tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and improves rejection-free survival rate after OLTx without increasing the incidence of CMV, PTLD, or HCV recurrence.

Adult↗

Detection of hepatitis A virus from clotting factors implicated as a source of HAV infection among haemophilia patients in Korea.

To investigate the causal relationship of blood clotting factors and hepatitis A virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we performed a 1:3 matched case-control study and molecular detection of HAV from clotting factors and patients. The epidemiological investigation showed that one lot of clotting factor VIII was related epidemiologically to patients with hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval between injections. We examined 17 sera collected from seven patients and 124 lots of blood clotting factors (factor VIII and factor IV) by HAV reverse transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five clotting factors and six sera. The HAV sequence of one of the factor VIII samples was identical to the sequences found in three patients' sera. Findings from the laboratory and epidemiological studies suggested that the clotting factor was causally related to HAV infection in three haemophilia patients.

Adolescent↗

Measurements of in-air output ratios for a linear accelerator with and without the flattening filter.

The in-air output ratio (Sc) for photon beams from linear accelerators describes the change of in-air output as a function of the collimator settings. The physical origin of the Sc is mainly due to the change in scattered radiation that can reach the point of measurement as the geometry of the head changes. The flattening filter (FF) and primary collimator are the major sources of scattered radiation. The change in amount of backscattered radiation from the collimator into the beam-monitoring chamber also contributes to the variation of output. In this work, we measured the Sc and backscatter factors (Sb) into the beam-monitoring chamber for a linear accelerator with and without the FF. We measured the Sc with a Farmer-type chamber in a miniphantom at the depth of 10 g/cm2 for 6- and 18-MV x-ray beams from a Varian Clinac 2100EX linear accelerator. The Sb were measured with a universal pulse counter and a diode array with build-in counting hardware and software. The head scatter component (Sh) was then derived from the relationship Sc= Sh x Sb, where Sb was the linear fit of measured results. Significant differences were observed for Sc with and without the FF. Within the range of experimental uncertainty, the Sb was similar with and without the FF. The variations in Sh differed significantly over the range of field sizes of 3 X 3 to 40 X 40 cm2 with and without the FF; for the 6-MV beam, it was 8% vs 3%, and for the 18-MV beam, 7% vs 1%. By analyzing the contributions of backscatter factor and total in-air output ratios with and without the FF, we directly gained insight into the contributions of different components to the total variations in Sc of a linear accelerator. Sc, Sb, and Sh are basic and useful dosimetric quantities for delivery of intensity-modulated radiation therapy using a linear accelerator operating in a mode without the FF.

Air↗

Development of a COPD severity score.

OBJECTIVE: Treatment of chronic obstructive pulmonary disease (COPD) is based on symptom control. This suggests that COPD severity can be determined by analyzing treatment intensity. The objective of this analysis was to develop and validate a severity score for adult COPD based on treatments. RESEARCH DESIGN: Using principal components analysis, a COPD severity score was developed using data based on treatments extracted from an employer claims database (development group). Variables included were identified from literature review and clinical expert opinion. External validity was tested in a separate group of adult chronic bronchitis patients in whom principal components analysis was re-conducted and factor loadings were compared to the development group. Construct validity was tested by comparing the incidence of acute exacerbations of chronic bronchitis (AECB) in patients with high and lower severity scores. To illustrate the use of the COPD severity score, effectiveness of alternative AECB antibiotic treatments was compared in a separate patient sample categorized by severe versus mild/moderate COPD. RESULTS: In the development group (n = 2068), principal components analysis produced a single main factor for severity scoring. Of the 12 variables contributing to this factor, the 6 with the highest factor loadings were treatment related. The factor performed similarly in the external validity group (n = 9127) as it did in the development group. In construct validity testing, severe COPD patients were 4 times more likely to have AECB episodes than mild/moderate patients. Patients with severe COPD and an AECB were more likely to fail treatment with antibiotics than those with mild/moderate COPD. Based on the COPD severity score developed, we found that treatment of patients with severe COPD and an AECB with fluoroquinolones was more likely to result in treatment failure than treatment with macrolides (OR = 2.01; p = 0.03). CONCLUSIONS: The analysis was successful in developing and validating a method to score COPD severity based on treatments. This method may prove useful in providing insights about the benefits of COPD treatments.

Anti-Bacterial Agents↗

Cloning and expression of ARMC3_v2, a novel splicing variant of the human ARMC3 gene.

ARM genes, whose polypeptide consist of Armadillo/beta-catenin-like repeats (ARM) domain(s), exist ubiquitously from fly to vertebrates. These genes have multiple functions in signal transduction, development, cell adhesion and mobility, tumor initiation and metastasis. In this study, we have isolated a novel splicing variant of ARMC3 from human fetal brain, which is 2439 bp, encoding a 688-amino acid polypeptide that contains three typical ARM domains. The cDNA called ARMC3_v2 and the original called ARMC3_v1 (GeneBank: BC039312) are both located on the human chromosome 10p12.23. RT-PCR analysis in our work showed that ARMC3_v2 was detected in human skeletal muscle, liver, spleen and thymus; in contrast, ARMC3_v1 in skeletal muscle, lung, prostate and testis.

Amino Acid Sequence↗

Ion detection with photonic crystal microcavities.

We have experimentally demonstrated a cation and anion sensor by using short linear photonic crystal microcavities with an embedded quantum dot active region. The photonic crystal microcavity covered with an ion-selective polymer forms a submicrometer optical detection system sensitive to small changes of perchlorate anion (ClO4(-)) and calcium cation (Ca2+) concentrations.

Journal Article↗

Joule heating induced transient temperature field and its effects on electroosmosis in a microcapillary packed with microspheres.

The Joule heating induced transient temperature field and its effect on the electroosmotic flow in a capillary packed with microspheres is analyzed numerically using the control-volume-based finite difference method. The model incorporates the coupled momentum equation for the electroosmotic velocity, the energy equations for the Joule heating induced temperature distributions in both the packed column and the capillary wall, and the mass and electric current continuity equations. The temperature-dependent physical properties of the electrolyte solution are taken into consideration. The characteristics of the Joule heating induced transient development of temperature and electroosmotic flow fields are studied. Specifically, the simulation shows that the presence of Joule heating causes a noticeable axial temperature gradient in the thermal entrance region and elevates a significant temperature increment inside the microcapillary. The temperature changes in turn greatly affect the electroosmotic velocity by means of the temperature-dependent fluid viscosity, dielectric constant, and local electric field strength. Furthermore, the model predicts an induced pressure gradient to counterbalance the axial variation of the electroosmotic velocity so as to maintain the fluid mass continuity. In addition, under specific conditions, the present model is validated by comparing with the existing analytical model and experimental data from the literature.

Journal Article↗

Identifying site-specific metastasis genes and functions.

Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression. Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of primary breast cancers revealed a subset of site-specific metastasis genes that are selected for early in tumor progression. High expression of these genes predicts the propensity for lung metastasis independently of several classic markers of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.

Animals↗

Retroviral delivery of GAD-IgG fusion construct induces tolerance and modulates diabetes: a role for CD4+ regulatory T cells and TGF-beta?

Previous studies have demonstrated that antigen-specific tolerance could be induced by lipopolysaccharide (LPS)-stimulated B cells retrovirally transduced with an immunoglobulin-antigen (or epitope-containing peptide) fusion construct. To investigate the mechanism of this gene therapy system, we now adapted this approach to immunotherapy of spontaneous diabetes in nonobese diabetic (NOD) mice, a T-cell-mediated autoimmune disease triggered, in part, by a pathogenic response to glutamate decarboxylase (GAD) 65. We demonstrate that LPS-stimulated splenocytes, retrovirally transfected with GAD-IgG fusion construct, induce a significant antigen-specific hyporesponsiveness at both cellular and humoral levels and reduce the incidence of diabetes in female NOD mice. Parallel with disease protection, we observed a prolonged increase of the numbers of CD4+CD25+ T cells in the periphery of GAD-IgG-treated mice, compared to those treated with a control IgG vector, both in the prediabetic period and persisting even 8 months after gene therapy. This increase appeared to be induced by the repeated stimulation of the antigen in the periphery instead of a result of differentiation of T-cell precursor in the thymus. Moreover, CD4+CD25+ T cells induced by GAD-IgG fusion construct were capable of suppressing the proliferative response of CD4+CD25- T cells in vitro; and ablation of the activity of CD4+CD25+ T cells by blocking antibody against CD25 could reverse GAD-specific T-cell hyporesponsiveness. These results suggested that CD4+CD25+ T-cell subset induced in GAD-IgG-treated NOD mice represented the regulatory or suppressive CD4+CD25+ T cells (Treg) and might play an important role in the induction and maintenance of tolerance in NOD mice. Furthermore, the numbers of splenic CD4+CD62L+ regulatory T cells in GAD-IgG-treated mice during the prediabetic period and serum TGF-beta levels in 34-38-week-old GAD-IgG-protected mice were also increased, compared to control IgG-treated ones. Therefore, we propose that the induction of tolerance and the prevention of diabetes incidence in NOD female mice induced by the GAD-IgG fusion construct may require CD4+ regulatory T cells, and the possible mediation of TGF-beta.

Animals↗

L-type Ca(2+) channel expression along feline smooth muscle oesophagus.

Muscle from the proximal smooth muscle (SM) oesophagus of the cat demonstrates contractions of greater amplitude and greater sensitivity to cholinergic stimulation than muscle from the distal SM oesophagus. In the light of the central role of calcium influx in SM contractility, we hypothesized that regional differences in oesophageal contractility may be associated with differential expression of L-type calcium channels (L(Ca)) along the SM oesophagus. L(Ca) expression was compared between proximal and distal regions of the circular SM oesophagus by Western blots. Patch clamp technique was utilized to study L(Ca) currents. Muscle strip studies assessed L(Ca) contribution to contractile activity. The protein expression of L(Ca) and L(Ca) current density was greater in the proximal than distal region. L(Ca) voltage and time-dependent activation and inactivation curves were similar in cells from both regions. Stimulation of muscle strips with acetylcholine (ACh) in the presence of tetrodotoxin resulted in contractions of greater amplitude in the proximal region. The L(Ca) agonist Bay K 8644 caused a greater increase in ACh-induced contraction amplitude in muscle strips from the proximal region. Therefore, regional myogenic differences in L(Ca) expression along the circular SM oesophageal body exist and may contribute to the nature of oesophageal contractions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Production of gamma-linolenic acid by disrupted mycelia of Mortierella isabellina.

AIMS: To optimize the production of linolenic acid by disrupted mycelia of Mortierella isabellina. METHODS AND RESULTS: Effects of incubation conditions such as incubation time, pH of reaction mixture, concentration of Mg2+ or malate and incubation temperature on production of linolenic acid were studied. The production of gamma-linolenic acid reached 224 mg g-1 dry cells when the reaction mixture was composed of 1.0 g (dry mycelial mass) of disrupted mycelia of M. isabellina, 50 ml (50 mmol l(-1)) potassium phosphate buffer supplemented with 0.312 mmol l(-1) of Mg2+ and 10 mmol l(-1) of malate, pH 7.0 and incubated at 5 degrees C for 1 day. CONCLUSIONS: Incubation temperature, concentration of Mg2+ and malate showed major effects on the increased linolenic acid production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights conditions for increasing gamma-linolenic acid production by cell-free mycelia of M. isabellina and an insight into rapidly gaining high production of polyunsaturated fatty acids.

Culture Media↗

Application of endoscopy for a midbrain tumor.

OBJECTIVE AND IMPORTANCE: It has been difficult to obtain a biopsy of a midbrain lesion. In addition, proper cerebrospinal fluid diversion should be secured because progressing tumor in the midbrain causes obstructive hydrocephalus. We report on the superiority of flexible neuroendoscopy to treat progressing midbrain tumor. CLINICAL PRESENTATION: A 64-year-old man presented with an occasional double vision. A magnetic resonance imaging scan disclosed an enhancing lesion in the midbrain. INTERVENTION: We performed a neuroendoscopic biopsy of the tumor and third ventriculostomy. Neuroendoscopy confirmed a bulging of the posterior commissure, which caused stenosis of the entrance of the aqueduct. Histological examination of the specimen obtained disclosed a diffuse astrocytoma. No permanent postoperative complications occurred although the patient felt slight double vision for 2 days after the operation. Conventional radiation therapy was supplemented. CONCLUSION: Flexible neuroendoscopic biopsy with third ventriculostomy was a less-invasive and safer alternative for the progressing midbrain tumor bulging into the ventricles.

Astrocytoma↗

Unsuccessful third ventriculostomy for occlusive hydrocephalus.

For non-communicating hydrocephalus, neuroendoscopic third ventriculostomy has become a major choice. But sometimes, the procedure results in failure. Typically, impairment of a distal CSF absorption, a preexisting arachnoid membrane just below the fenestrated site and a glial scarring of fenestrated site were pointed out as a factors of failure. On the other side, the intraventricular pressure dynamics of a functioning third ventriculostomy is in the process of study. Recently some reports have noticed the importance of the flow of CSF into the prepontine cistern, mimicking the flow through the aqueduct of Sylvius. We report an unsuccessful trial of third ventriculostomy in a case with huge posterior fossa tumor.

Aged↗