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Biomedical subjects

H Kang

Publications and source records attributed to H Kang.

At least 73 records · Page 4Linked to original sources

Effects of substance P and vasoactive intestinal peptide on interferon-gamma and interleukin-4 production in severe atopic dermatitis.

BACKGROUND: Recent studies have demonstrated that two T cell-derived lymphokines, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), play a crucial role in the pathogenesis of atopic dermatitis (AD). It is known that neuropeptides, such as substance P (SP) and vasoactive intestinal peptide (VIP), have various immunomodulatory effects. Elevated levels of these neuropeptides and increased staining of SP positive nerve fibers have been reported in AD patients. OBJECTIVE: The study was designed to examine the effects of SP and VIP on the production of IFN-gamma and IL-4. The aim of the study was to establish whether these neuropeptides acted to affect cytokine release in the peripheral blood mononuclear cells (PBMCs) of AD patients. METHODS: The effects of SP and VIP on the production of IFN-gamma and IL-4 in phytohemagglutinin stimulated PBMC cultures over a 48-hour period were analyzed by enzyme-linked immunosorbent assay in 15 AD patients. Non-atopic individuals were used as a control group. RESULTS: Base cytokine profiles of AD patients showed significantly decreased IFN-gamma and increased IL-4 when weighed against non-atopic controls. Compared with controls, SP had a significant percentage enhancing effect on both IFN-gamma and IL-4 production at concentrations of 10(-8) M and 10(-6) M, however, this IFN-gamma up-regulatory effect of SP was reversed by spantide, a SP antagonist. The ratios of IFN-gamma: IL-4 production were significantly elevated in the SP treated AD group. Although VIP had no specific noticeable effects on the IFN-gamma and IL-4 production. CONCLUSIONS: Our data may suggest that SP has an influence on the immunomodulation of AD patient by regulating IFN-gamma production, either directly or indirectly. Vasoactive intestinal peptide, on the other hand, has no modulatory effects on the cytokine production of AD patients.

Adolescent↗

Induction of tumor necrosis factor-alpha and inducible nitric oxide synthase fails to prevent toxoplasmic encephalitis in the absence of interferon-gamma in genetically resistant BALB/c mice.

Following infection with Toxoplasma gondii, certain strains of mice, such as BALB/c, are genetically resistant to development of toxoplasmic encephalitis (TE) and establish a latent chronic infection as do humans. Thus, these animals appear to be a suitable model to analyze the mechanism of resistance to TE. Since the mechanism for their genetic resistance is unknown, we examined the role of interferon-gamma (IFN-gamma) tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in the resistance using BALB/c-background IFN-gamma-deficient (IFN-gamma(-/-)) mice. IFN-gamma(-/-) and control mice were infected with the ME49 strain of T. gondii and treated with sulfadiazine to establish chronic infection. After discontinuing sulfadiazine, the IFN-gamma(-/-) mice all died, whereas the control mice all survived. Histological studies revealed remarkable inflammatory changes associated with large numbers of tachyzoites in brains of the IFN-gamma(-/-) mice but not in the control mice after discontinuation of sulfadiazine. Large amounts of mRNA for tachyzoite-specific SAG1 were detected in brains of only the IFN-gamma(-/-) mice. IFN-gamma mRNA was detected in brains of only the control mice, whereas mRNA for TNF-alpha and iNOS were detected in brains of both strains of mice. The amounts of the mRNA for TNF-alpha and iNOS did not differ between these mice. Treatment of IFN-gamma(-/-) mice with recombinant IFN-gamma prevented development of TE. These results demonstrate that IFN-gamma is crucial for genetic resistance of BALB/c mice against TE and that TNF-alpha and iNOS are insufficient to prevent TE in the absence of IFN-gamma.

Animals↗

Reproducibility and complications in gene searches: linkage on chromosome 6, heterogeneity, association, and maternal inheritance in juvenile myoclonic epilepsy.

Evidence for genetic influences in epilepsy is strong, but reports identifying specific chromosomal origins of those influences conflict. One early study reported that human leukocyte antigen (HLA) markers were genetically linked to juvenile myoclonic epilepsy (JME); this was confirmed in a later study. Other reports did not find linkage to HLA markers. One found evidence of linkage to markers on chromosome 15, another to markers on chromosome 6, centromeric to HLA. We identified families through a patient with JME and genotyped markers throughout chromosome 6. Linkage analysis assuming equal male-female recombination probabilities showed evidence for linkage (LOD score 2.5), but at a high recombination fraction (theta), suggesting heterogeneity. When linkage analysis was redone to allow independent male-female thetas, the LOD score was significantly higher (4.2) at a male-female theta of.5,.01. Although the overall pattern of LOD scores with respect to male-female theta could not be explained solely by heterogeneity, the presence of heterogeneity and predominantly maternal inheritance of JME might explain it. By analyzing loci between HLA-DP and HLA-DR and stratifying the families on the basis of evidence for or against linkage, we were able to show evidence of heterogeneity within JME and to propose a marker associated with the linked form. These data also suggest that JME may be predominantly maternally inherited and that the HLA-linked form is more likely to occur in families of European origin.

Alleles↗

Identification of natural rubber and characterization of rubber biosynthetic activity in fig tree.

Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and (13)C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent K(m) values of 2.8 and 228 microM, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg(2+) ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree.

Cations, Divalent↗

EGF receptor and p21WAF1 expression are reciprocally altered as ME-180 cervical carcinoma cells progress from high to low cisplatin sensitivity.

Cell cycle regulators and signal transduction pathways can influence apoptotic sensitivity of tumor cells, and we previously described an association between EGFr overexpression, reduced DNA repair activity, and increased apoptotic sensitivity of ME-180 cervical carcinoma cells toward cis-diammedichloroplatinum (cDDP; K. Nishikawa, et al., Cancer Res., 52: 4758-4765, 1992). In the present study, the characteristics of ME-180 cells selected for high or low apoptotic sensitivity to cDDP (or camptothecin) were examined and compared to determine whether signal transduction components and cell cycle regulation were distinct in these isogenic drug response variant populations. As ME-180 cells progressed from high to low cDDP sensitivity [IC50 approximately 80 ng/ml in cDDP sensitive (PT-S) to approximately 2000 ng/ml in cDDP-resistant (Pt-R) cells], there was a significant decrease in EGFr expression that paralleled the relative reduction in cDDP apoptotic responsiveness (approximately 30-fold). cDDP-resistant cells had the slowest rate of growth and more effectively reduced DNA adduct levels following cDDP exposure than parental cells. Cellular levels of the cell cycle inhibitor p21WAF1 inversely correlated with cDDP responsiveness with high levels of p21WAF1 expressed in drug-resistant Pt-R cells in the absence of elevated p53. cDDP stimulated a 2-fold increase in p53 levels in both drug-sensitive and drug-resistant cells but caused a delayed reduction in p21WAF1 levels, suggesting p53-independent regulation of p21WAF1 in ME-180 cells. Activation of EGFr in Pt-R cells stimulated cell cycle progression (2-fold), reduced p21WAF1 levels (>2-fold), and increased sensitivity to cDDP (3-fold), suggesting that receptor signaling enhanced the efficacy of cDDP to induce cell death by relieving cell cycle restriction. These results demonstrate that the transition of ME-180 cells from a drug-sensitive to drug-resistant phenotype correlates with reciprocal changes in EGFr and p21WAF1 expression and provides additional evidence that the pathways controlled by these proteins may contribute to some forms of drug resistance.

Apoptosis↗

[Effects of stress level on the biomechanical behavior of the temporomandibular joint disc in domestic pigs].

This study aimed to examine the responses of the temporomandibular joint (TMJ) disc against compression, to clarify the property of viscoelasticity and permeability of the disc, and to provide experimental data for further analyzing the mechanism of stress dissipation within the TMJ disc. With the use of confined compression mechanics and biphasic theory, creep experiments on eight TMJ discs of four domestic pigs were performed under three stress levels(0.07 MPa, 0.13 MPa and 0.30 MPa). The results showed that at 0.07 stress level, the compressive stiffness at 2 seconds of the anterior band(AB), intermediate zone(IZ) and posterior band(PB) of the disc was 4.48 MPa, 3.93 MPa and 6.31 MPa, respectively; the coefficient K of permeability was 0.272 x 10(-12) m4/NS, 0.30 x 10(-12) m4/NS, and 0.042 x 10(-12) m4/NS. At 0.30 Mpa level, the compressive stiffness increased to 14.07 MPa, 13.68 Mpa and 14.00 MPa; the coefficient K lowered to 0.017 x 10(-12) m4/NS, 0.012 x 10(-12) m4/NS and 0.005 x 10(-12) m4/NS. In conclusion, the TMJ disc has viscoelastic and biobiphasic properties against compression. The stiffness of the disc increases with the increment of stress level but the coefficient of permeability decreases. These findings demonstrate that the modulation of stress and of permeability may be two important factors influencing stress dissipation and shock absorption behavior of the disc during compressive and impact loads.

Animals↗

[Biomechanics of temporomandibular joint].

Temporomandibular joint (TMJ) is one of the most intricate and complicate loading joints in the human body. Articular cartilage is characteristic of low infiltrative, porous viscoelastic material. In physiological condition, there is a stress-absorbing architecture system in the TMJ cartilage, which consists of collagen-proteoglycan-water gel network. TMJ disc is a specific connective tissue as stress concentration absorber between condyle and articular fossa, but it does not belong to fibrocartilage. Retrodiscal tissue has high compliance of which the role is to play volume-compensating mechanism in joint movement. Lateral wall is a complexed structure out of ligament and capsule with weak tensile strength and tensile rigidity. Therefore, prolonged oral parafunction will result in joint fatigue and failure.

Biomechanical Phenomena↗

[A clinical and epidemiological study of 86 cases on abused children].

OBJECTIVE: To study the clinical and epidemiological manifestations on abused children, in order to find ways of prevention. METHODS: Retrospective study was carried out clinically and epidemiologically on 86 cases abused children from 1998.1 - 1999.12. RESULTS: The sex ratio (male:female) in the abused children was 0.76:1. Most cases were 3 - 16 years olds. Abuse incidences were most commonly occurred in spring and winter, accounted for 32.56% and 33.72% respectively. Most abuses happened physically (45.34%), predominantly involved skin (30.23%) and parenchyma (11.27%). Mental abuse accounted for 24.41%. 14 cases resulted in death (16.27%). 55 (64%) of the abusers were illiterate or with poor education. CONCLUSION: The abused sites mostly involved skin and parenchyma, but also caused harm to children's mental health, even causing deaths. Most abused children were female and abusers had lower cultural background. Thus, we need to provide a sounding board, to work on child abuse preventin.

Adolescent↗

[Tensile mechanics of mandibular condylar cartilage].

OBJECTIVE: To study the biomechanical properties of the mandibular condyle cartilage and determine its functional importance. METHODS: Eight condyle specimens of the four pig temporomandibular joints were obtained by autopsy and stored in sealed plastic bags at -20 degrees C. These pigs were healthy, aged 1 year +/- 2 months. In the coronal direction, 300 microns wide, rectangular cartilage-bone specimens were prepared on the right condyles using specified knife. In the sagittal direction, rectangular cartilage-bone specimens with the same width were obtained on the left condyles. Standard rectangular testing specimens were prepared from cartilage-bone specimens in a microtome kept at -20 degrees C (300 microns wide and 250 microns thick). The specimens were inserted in a soft-tissue uniaxial tensile test machine and immersed in a bath of Ringer's solution at room temperature. Preconditioning of the specimens was carried out prior to the uniaxial tensile experiment and the specimens were elongated to failure with the constant strain rate (0.05 mm/s). The resulting mean values were curved fitted with Fung's two-parameter (A, B) exponential stress strain equation using a nonlinear regression program. RESULTS: The data obtained showed that a typical nonlinear biomechanical behavior of the condyle cartilage. Toe-region and quasi-linear zone were obvious on the experimental stress strain relation curve. Theoretically fitted parameter A and B were 0.47 and 4.13 (coronally) and 0.60 and 4.70 (sagittally). The sagittal specimens showed greater tensile stress (2.92 MPa), tensile stiffness (9.04 MPa), energy absorption (6.02 N.mm) but less tensile strain (37.34%) than that of the coronal specimens (2.15 MPa, 6.55 MPa, 4.91 N.mm, and 41.12%). The differences were statistically significant (P < 0.05). CONCLUSION: The mandibular condyle cartilage is a kind of biophasic material which shows nonlinear viscoelastic behavior, anistrophic characteristics in biomechanical function and high ability to resist tensile stress in the longitudinal direction.

Animals↗

[A biomechanical study on the retrodiscal tissue of human temporomandibular joint].

In order to investigate the biomechanical properties and functional mechanism of the retrodiscal tissue (RT) of human temporomandibular joint (TMJ), we conducted a uniaxial tensile test on thirteen RT specimens taken from eight fresh TMJs of the human cadavers aged between 8-15 years (m = 11.8 yrs). The experimental data were analyzed in conjunction with the Quasi-Linear Viscoelastic Theory as proposed by Fung YC to characterize the time-dependent behaviour and the constitutive relationship of the RT. The results showed that the physiological biphasic zone of stress-strain curve lied within 20%-30% strain levels. The elastic modulus (MPa), tensile strength(MPa) and strain to failure(%) were high. There were significant differences in strain to yielding and energy resorption (N.mm) between lateral and medial RT. There was a good agreement between theoretical prediction value and experimental result within 6% strain level. These data suggest that there would be a higher passive deformation and lower safety storage of strength in the RT which could be related to anterior displacement of the TMJ disc and that Fung's Theory can adequately describe the stress-time behaviour and the constitutive relationship of the RT within lower strain rate.

Adolescent↗

FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells.

Protein-tyrosine kinases p56(Lck), SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential components in T-cell activation. Another lymphoid-specific adaptor FYB/SLAP has also been identified as a predominant binding partner of SLP-76 and the Src kinase FYN-T, although its role in the activation process has been unclear. In this study, we demonstrate that FYN-T selectively phosphorylates FYB providing a template for the recruitment of FYN-T and SLP-76 SH2 domain binding. This interaction is unusual in its distinct cytoplasmic localization and its long term stable kinetics of phosphorylation. Furthermore, we demonstrate for the first time that the co-expression of all three components of the FYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cell receptor-driven interleukin 2 transcription activity. These findings document the existence of a T-cell receptor-regulated FYN-T-FYB pathway that interfaces with the adaptor SLP-76 and up-regulates lymphokine production in T-cells.

Adaptor Proteins, Signal Transducing↗

Isolation, characterization, and functional analysis of a novel cDNA clone encoding a small rubber particle protein from Hevea brasiliensis.

Biochemical evidence reported so far suggests that rubber synthesis takes place on the surface of rubber particles suspended in the latex of Hevea brasiliensis. We have isolated and characterized a cDNA clone that encodes a protein tightly bound on a small rubber particle. We named this protein small rubber particle protein (SRPP). Prior to this study, this protein was known as a latex allergen, and only its partial amino acid sequence was reported. Sequence analysis revealed that this protein is highly homologous to the rubber elongation factor and the Phaseolus vulgaris stress-related protein. Southern and Northern analyses indicate that the protein is encoded by a single gene and highly expressed in latex. An allergenicity test using the recombinant protein confirmed that the cloned cDNA encodes the known 24-kDa latex allergen. Neither ethylene stimulation nor wounding changed the transcript level of the SRPP gene in H. brasiliensis. An in vitro rubber assay showed that the protein plays a positive role in rubber biosynthesis. Therefore, it is likely that SRPP is a part of the rubber biosynthesis machinery, if not the rubber polymerase, along with the rubber elongation factor.

Allergens↗

The effect of external electron beam on neointima in rat carotid artery injury model.

PURPOSE: Endovascular irradiation with either a gamma or a beta source has shown to reduce neointimal proliferation. However, the effect of external-beam radiation on neointimal hyperplasia is controversial. The objective of this study was to determine the effect of external-beam irradiation with different doses on neointimal hyperplasia in the rat carotid artery injury model. METHODS AND MATERIALS: Twenty-seven Sprague-Dawley rats underwent endothelial denudation injury by 2F Fogarty balloons on carotid artery. Immediately after the injury, rats were irradiated externally using 6-MeV electrons. Rats were grouped according to the radiation doses, 0 Gy as controls (n = 5), 5 Gy (n = 5), 10 Gy (n = 5), 15 Gy (n = 6), and 20 Gy (n = 6). Then, rats were sacrificed after 2 weeks and the carotid arteries were perfusion-fixed in paraformaldehyde. External elastic lamina (EEL) area, lumen area, maximal intimal thickness (MIT), and intimal area (IA) of the injured segments were measured on the basis of histomorphometry. RESULTS: In EEL and lumen area, there was no statistically significant difference between the irradiated groups and the controls. In MIT and IA, low-dose radiation (5 Gy and 10 Gy) did not induce any significant reduction. High-dose radiation (15 Gy and 20 Gy), however, reduced MIT and IA significantly. CONCLUSION: External electron beam reduced the intimal area, and the inhibition of neointimal proliferation was dependent upon radiation doses. This study suggests that the minimal effective dose for the inhibition of neointimal hyperplasia following denudation injury in the rat carotid model is between 10 Gy and 15 Gy.

Animals↗

TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii.

We previously reported that genetic susceptibility of mice to peroral infection with T. gondii is associated with CD4+ T cell-dependent, interferon (IFN)-gamma-mediated necrosis of their small intestine. We examined the role of tumour necrosis factor (TNF)-alpha and nitric oxide (NO), in addition to IFN-gamma. At 7 days after infection, a marked increase in CD4+ T cells was observed in lamina propria mononuclear cells (LPC) of the small intestine as compared with normal mice, and significantly greater amounts of mRNA for IFN-gamma, TNF-alpha, and inducible NO synthase (iNOS) were detected in LPC of the small intestine of infected than uninfected animals. Treatment of infected mice with anti-TNF-alpha monoclonal antibody (mAb) or the iNOS inhibitor, aminoguanidine, prevented necrosis and prolonged time to death. Infected iNOS-targeted mutant mice did not develop the disease whereas infected, control mice did. Treatment with anti-TNF-alpha mAb did not affect the expression of IFN-gamma in the LPC but inhibited expression of iNOS in the infected mice, indicating the role of TNF-alpha in the induction of iNOS. These results suggest that NO induced by a combination of IFN-gamma and TNF-alpha through activation of iNOS is a critical mediator of intestinal pathology and contributes to early mortality in genetically susceptible mice.

Administration, Oral↗