Biomedical subjects

K H Yang

Publications and source records attributed to K H Yang.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparison of brain responses between frontal and lateral impacts by finite element modeling.

This study was conducted to investigate differences in brain response due to frontal and lateral impacts based on a partially validated three-dimensional finite element model with all essential anatomical features of a human head. Identical impact and boundary conditions were used for both the frontal and lateral impact simulations. Intracranial pressure and localized shear stress distributions predicted from these impacts were analyzed. The model predicted higher positive pressures accompanied by a relatively large localized skull deformation at the impact site from a lateral impact when compared to a frontal impact. Lateral impact also induced higher localized shear stress in the core regions of the brain. Preliminary results of the simulation suggest that skull deformation and internal partitions may be responsible for the directional sensitivity of the head in terms of intracranial pressure and shear stress response. In previous experimental studies using subhuman primates, it was found that a lateral impact was more injurious than a frontal impact. In this study, shear stress in the brain predicted by the model was much higher in a lateral impact in comparison with a frontal impact of the same severity. If shear deformation is considered as an injury indicator for diffuse brain injuries, a higher shear stress due to a lateral impact indicate that the head would tend to have a decreased tolerance to shear deformation in lateral impact. More research is needed to further quantify the effect of the skull deformation and dural partitions on brain injury due to impacts from a variety of directions and at different locations.

Biomechanical Phenomena↗

PubMed2001

Genetic variants of the serotonin system and weight change during clozapine treatment.

Clozapine-induced weight gain may impair health and affect patient compliance. The aim of this study is to investigate the relationship between the genetic variants of the serotonin system and clozapine-induced body weight change (BWC). Ninety-three treatment-resistant schizophrenic patients were weighed monthly for 4 months during clozapine treatment. At the conclusion of treatment, patients had gained an average of 2.4 kg body weight, with BWC ranging from -17.5 to +12.9 kg. The levels of the serotonin transporter variants, serotonin 2A, serotonin 2C and serotonin 6, demonstrated no statistically significant relationship to BWC. Patients with a lower initial body mass index demonstrated a greater weight gain associated with clozapine treatment. Further exploration of the neurotransmitters implicated in the antipsychotic-induced BWC is important in order to reduce the morbidity and noncompliance associated with weight gain.

Adolescent↗

PubMed2001

Qi therapy as an intervention to reduce chronic pain and to enhance mood in elderly subjects: a pilot study.

Qi therapy (or external Qi) is an oriental complementary therapy preventing, curing disease and strengthens health and improving the human potentiality through regulation of body. It is increasingly being used to improve the quality of life, but there is little direct evidence of its efficacy. This study assessed the effects of Qi therapy (QT) on reducing pain and enhancing mood states in elderly subjects with chronic pain. We studied 40 elderly participants with chronic pain, who were randomly allocated to receive QT (n=20) or standard care (n=20). The experimental group receives Qi therapy twice a week for 2 weeks (total 4 times), and control group received general care at the same time and the same amount of duration. We measured pain level and Profile of Mood State (POMS) to explore participants' response to Qi therapy. There was a significant reduction in pain (p<0.0001) after QT and an improved positive mood state (p<0.0001). These findings suggest that Qi therapy may have a role in helping the elderly to cope with their pain and mood disturbances.

Affect↗

PubMed2001

Evidence for an association between polymorphism in the serotonin-2A receptor variant (102T/C) and increment of N100 amplitude in schizophrenics treated with clozapine.

Using event-related potentials (ERPs), a reduction in the auditory N100, N200 and P300 amplitude has been found in schizophrenic patients and may represent some pathophysiological deficit. Therefore, we investigated whether the genetic variant of the serotonin-2A receptor is associated with ERP change after clozapine treatment in schizophrenic patients. Ninety-nine schizophrenic patients were included in the study. The results demonstrated that patients with 102C/C genotype have higher N100 amplitude than other patients after clozapine treatment. Our findings suggested that serotonin-2A receptor polymorphism may relate to clozapine response in schizophrenic patients. An objective and reliable tool like ERPs to assess patients' treatment response may afford more consistent results in pharmacogenetic studies.

Adult↗

PubMed2001

Stimulation of fracture healing in a canine ulna full-defect model by low-intensity pulsed ultrasound.

Because no report has been issued on the healing effects of low-intensity pulsed ultrasound on moderate to large fracture gaps, we performed an experimental study using a canine ulna full-defect model. Ten mongrel male dogs were divided into two groups: a small defect group and large defect group. The defects were made on the middle one third of both ulnae and one side only was randomly selected for ultrasound sonication, at 1 MHz, 200 microsecond bursting sine wave in 50 mW/cm2 spacial average and temporal average. Sonication was started on the day after surgery and applied for 15 minutes once a day for six days a week. In the small defect group, the means of the radiologic scores, as described by Lane and Sandhu, were 0.6, 4.4, and 8.4 in the control side and 1.8, 6.0, and 10.4 in the treatment side one, three, and five months after the operation, respectively (p=0.0372). In the large defect model, the corresponding means were 2.2, 3.4, and 6.0 in the control side and 3.3, 5.4, and 9.2 in the treatment side (p= 0.009). Low-intensity pulsed ultrasound enhanced new bone formation in small and large full-defects and decreased the incidence of nonunion in the large defect model.

Animals↗

PubMed2001

Prodigiosin blocks T cell activation by inhibiting interleukin-2Ralpha expression and delays progression of autoimmune diabetes and collagen-induced arthritis.

Prodigiosin (PDG) was previously reported to be a T cell-specific immunosuppressant. Here we describe the mechanism of action of PDG in T cells and the effect of PDG on autoimmune diseases. PDG selectively suppresses concanavalin A (Con A)-induced T cell proliferation, but has little effect on lipopolysaccharide-induced proliferation of B cells and nitric oxide production of macrophages. Although PDG does not block interleukin (IL)-2 production, it efficiently inhibits interleukin-2 receptor alpha-chain (IL-2Ralpha) expression, and this results in a disruption of the IL-2/IL-2R signaling pathway, on which a great part of the regulation of T cell activation depends. PDG blocks T cell differentiation into effector helper T cells secreting interferon-gamma and IL-4 as well as into effector cytotoxic T lymphocytes expressing perforin, which is at least in part resulting from inhibition of the IL-2/IL-2R signaling. PDG indirectly blocks signal transducer and activator of transcription activation by inhibiting cytokine signalings in Con A-activated T cells, although it does not inhibit the activation of nuclear factor-kappaB, nuclear factor of activated T cells, and activator protein-1. As direct evidence of immunosuppression in vivo, we show that PDG markedly reduced blood glucose levels and cellular infiltration into the pancreatic islets in nonobese diabetic mice, and that it also delays the onset of collagen-induced arthritis in DBA/1 mice. In conclusion, our results demonstrate that PDG has a unique mode of action, namely, that it blocks T cell activation by inhibiting primarily IL-2Ralpha expression in the IL-2/IL-2R signaling, and show that this compound represents a promising immunosuppressant candidate for the treatment of autoimmune diseases.

Animals↗

PubMed2000

Association study of a functional serotonin transporter gene polymorphism with schizophrenia, psychopathology and clozapine response.

Serotonin is implicated in the pathogenesis of schizophrenia. Following serotonin release, the serotonin transporter (5-HTT) is the major determinant of serotonin inactivation. The present study tested the hypothesis that a biallelic polymorphism in the 5' regulatory region of the 5-HTT gene (5-HTTLPR) confers susceptibility to schizophrenia, association with the clinical manifestations of schizophrenia or clozapine response. 90 treatment-resistant schizophrenic patients were assessed using the Brief Psychiatric Rating Scale before and after clozapine treatment. The results demonstrated that the 5-HTTLPR variants did not play a major role in the susceptibility, clinical manifestations or clozapine response in schizophrenia.

Adult↗

PubMed2000

2-Amino-3-methylimidazo[4,5-f]quinoline inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells by blocking p38 kinase activation.

We show that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic amine, significantly inhibits nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages. The decrease in NO production was found to correlate well with a decrease in inducible NO synthase (iNOS) mRNA expression as demonstrated by Northern blot analysis. Treatment of RAW 264.7 cells with IQ selectively inhibited the activation of NF-kappaB/Rel, an important transcription factor of iNOS gene expression, while neither AP-1 nor Oct was affected by IQ. Since iNOS transcription has been shown recently to be under the control of the p38 kinase signaling cascade, we assessed the effect of IQ on p38 kinase activation. Treatment of RAW 264.7 with IQ inhibited LPS-stimulated p38 kinase phosphorylation in a dose-related manner. IQ also inhibited the p38 kinase activity. Collectively, this series of experiments indicates that IQ inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Based on our findings, the most likely mechanism that can account for this biological effect involves the negative regulation of NF-kappaB/Rel and p38 kinase pathway.

Animals↗

PubMed2000

Dexamethasone inhibits IL-1 beta gene expression in LPS-stimulated RAW 264.7 cells by blocking NF-kappa B/Rel and AP-1 activation.

In the present study, the mechanism by which dexamethasone (DEX) inhibited IL-1beta gene expression in bacterial lipopolysaccharide (LPS)-activated RAW 264.7 cells was investigated. The decrease in LPS-induced IL-1beta mRNA expression was demonstrated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Since the promoter in IL-1beta gene contains binding motifs for NF-kappaB/Rel, AP-1, NF-IL6, and CREB/ATF, which appear to be important in LPS-mediated IL-1beta induction, the effects of DEX on the activation of these transcription factors were examined. Treatment of DEX to RAW 264.7 cells induced a dose-related inhibition of NF-kappaB/Rel and AP-1 in chloramphenicol acetyltransferase activity, while neither NF-IL6 nor CREB/ATF activation was affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of NF-kappaB/Rel and AP-1 proteins to their cognate DNA sites as measured by electrophoretic mobility shift assay (EMSA). DEX treatment caused a significant reduction in nuclear c-rel, p65, and p50 protein contents, and these decreases were paralleled by the accumulation of cytoplasmic c-rel, p65, and p50. DEX treatment of RAW 264.7 cells did not inhibit the nuclear translocation of c-jun and c-fos. We found that the inhibition of IL-1beta production by DEX is not related to p38, which is important in the IL-1beta induction. These results suggest that DEX may inhibit IL-1beta gene expression by a mechanism involving the blocking of LPS-induced NF-kappaB/Rel and AP-1 activation.

Animals↗

PubMed2000

Chlorophyllin suppression of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells.

Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, functions as an anticarcinogen and antioxidant. In the present study, we investigated the effect of CHL on nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with CHL inhibited nitric oxide production in the LPS-stimulated RAW 264. 7 cells in a dose-related manner. Competitive RT-PCR analysis, using a DNA competitor as an internal standard, demonstrated that the treatment with 1, 10, and 50 microM CHL decreased LPS-induced iNOS mRNA expression in a concentration-dependent manner. Since the expression of the iNOS gene is mainly regulated by NF-kappaB, we then examined the effects of CHL on the NF-kappaB DNA binding activity, using an electrophoretic mobility shift assay. CHL down-regulated the NF-kappaB DNA binding on its cognate recognition site at the concentrations just noted. Employing a transfection and reporter gene expression system with p(NF-kappaB)(3)-chloramphenicol acetyl transferase (CAT), the treatment of CHL produced a dose-dependent inhibition of CAT activity in RAW 264.7 cells. Furthermore, CHL partially restored LPS-decreased IkappaBalpha, an inhibitory protein against NF-kappaB activation, in the cytosolic extract from the LPS-treated cells determined by immunoblot analysis. CHL also protected the hydroxyl radical-induced cytotoxicity in RAW 264.7 cells, indicating its antioxidant effect. These results suggest that CHL suppresses the nitric oxide production and iNOS mRNA expression mediated by the inhibition of NF-kappaB activation, and its action mechanism may be based on its antioxidant effect.

Animals↗

PubMed2000

2-Acetylaminofluorene suppresses immune response through the inhibition of nuclear factor-kappaB activation during the early stage of B cell development.

2-Acetylaminofluorene (AAF), an arylamide carcinogen, has been known to inhibit humoral and cell-mediated immune response by lipopolysaccharide (LPS). In the current study we demonstrate that AAF induced the down-regulation of protein kinase C (PKC) that is a key enzyme in the pathways leading to LPS-induced B-cell proliferation, while having no inhibitory effect on intracellular cAMP in spleen cells. Additionally, to identify the mechanism of action of AAF during B-cell development, we determined the effects of AAF on LPS-induced nuclear factor-kappaB (NF-kappaB) activation in 70Z/3 murine pre-B cells, CH12 murine mature B cells and S194 murine plasmacytoma cells. LPS-induced NF-kappaB activation, which is dependent on PKC, was inhibited by pretreatment with AAF for 2 h in the nuclei of 70Z/3 murine pre-B cells by detection of NF-kappaB specific DNA-protein binding. Conversely, AAF barely inhibited the constitutive NF-kappaB binding activity in mature B-cells, S194 and CH12. To confirm the effect of AAF on NF-kappaB activation, a chloramphenicol acetyl transferase (CAT) expression vector containing multiple copies of the NF-kappaB element (pCAT(kappaB)(3)) was transiently transfected into 70Z/3 or S194 cells, and assessed for inducible CAT activity. AAF treatment of 70Z/3 cells resulted in a significant inhibition of CAT activity induced by LPS. However, AAF exhibited no inhibitory effect on constitutive CAT activity in mature B cells, S194, indicating that AAF no longer has suppressive effects on the immune response in differentiated B cells. Taken together, these results suggest that AAF may act to suppress immune response by blocking the activation of PKC and nuclear expression of NF-kappaB at the early stage of B cell development.

2-Acetylaminofluorene↗

PubMed2000

Suppression of IL-2 and IL-4 gene expression by nodularin through the reduced NF-AT binding activity.

Nodularin is a cyclic peptide produced by cyanobacteria. In the present study, the inhibitory effect of nodularin on T lymphocyte functions was demonstrated. Direct addition of nodularin to B6C3F1 mouse splenocyte cultures produced a concentration-dependent inhibition of the lymphoproliferative response to concanavalin A stimulation. Nodularin inhibited PMA plus ionomycin (Io)-induced IL-2 mRNA expression in murine splenocytes and thymocytes as determined by quantitative/competitive RT-PCR. To further characterize the mechanism for the transcriptional regulation of IL-2, the binding activity of transcription factors, NF-AT, AP-1, NF-kappaB, and Oct, was evaluated by electrophoretic mobility shift assays in mouse splenocytes. Nodularin reduced the NF-AT binding activity in PMA/Io-induced splenocytes, but no significant effect was observed on AP-1, NF-kappaB, or Oct binding activity. Nodularin also inhibited IL-4 mRNA expression in PMA/Io-stimulated murine splenocytes. These results suggest that T lymphocyte is a possible cellular target of nodularin, and the inhibitory effect of nodularin on T-cell specific transcription factor NF-AT induces T-cell dysfunction, which leads to a diminution in IL-2 and IL-4 gene transcription.

Animals↗

PubMed2000

Inconsistency between severe substantia nigra degeneration with Lewy bodies and clinical parkinsonism in dementia patients: a cliniconeuropathological study.

In a retrospective cliniconeuropathological study, we reviewed all the cases received in our dementia brain bank during a 4-year period to determine if all patients with severe substantia nigra (SN) degeneration and SN Lewy bodies (LBs) exhibited prominent signs of parkinsonism and were treated for parkinsonism during the disease course. The SN of 426 cases were graded for microscopic degeneration using a semiquantitative five-tiered scale, with grade 0 indicating normal and grade 4 the most severe degeneration. Twenty-nine cases with grade 3 (16) or grade 4 (13) SN degeneration with SN LBs and clinical records were identified. Ten had been treated for parkinsonism (6 grade 3, 4 grade 4) and 19 had not. Whereas most of the patients had exhibited signs of end-stage parkinsonism during their last year, 1 grade 3 and 2 grade 4 patients apparently never exhibited prominent signs of parkinsonism during the course of their dementia. No clear neuropathological differences were noted between these patients that did not have prominent signs and a control group of six patients with clinical Parkinson's disease with dementia (parkinsonism onset at least 1 year before dementia onset). We conclude that in patients with dementia there is an inconsistent relationship between the expression of clinical parkinsonism during life and severe SN degeneration with LBs identified at necropsy.

Aged↗

PubMed2000

Qualitative analysis of neck kinematics during low-speed rear-end impact.

OBJECTIVE: To analyze neck kinematics and loading patterns during rear-end impacts. DESIGN: The motion of each cervical vertebra was captured using a 250 frame/s X-ray system during a whole body rear-end impact. These data were analyzed in order to understand different phases of neck loading during rear-end impact. BACKGROUND: The mechanism of whiplash injury remains largely unknown. An understanding of the underlying kinematics of whiplash is crucial to the identification of possible injury mechanisms before countermeasures can be designed. METHODS: Metallic markers were inserted into the vertebral bodies and spinous processes of each of the seven cervical vertebrae. Relative displacement-time traces between each pair of adjacent cervical vertebrae were calculated from X-ray data. Qualitative analyses of the kinematics of the neck at different phase of impact were performed. RESULTS: The neck experiences compression, tension, shear, flexion and extension at different cervical levels and/or during different stages of the whiplash event. CONCLUSIONS: Neck kinematics during whiplash is rather complicated and greatly influenced by the rotation of the thoracic spine, which occurs as a result of the straightening of the kyphotic thoracic curvature. RELEVANCE: Understanding the complicated kinematics of a rear-end impact may help clinicians and researchers shed some light on potential mechanisms of whiplash neck injury.

Acceleration↗

PubMed2000

Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia.

Schizophrenic patients with the apolipoprotein E (APOE = gene; apoE = protein) epsilon4 allele exhibited lower psychosis scores than patients without the epsilon4 allele in previous reports. The present study tested the hypothesis that the APOE epsilon4 allele confers association with the clinical manifestations of schizophrenia or clozapine response. A total of 95 schizophrenic patients who were treatment resistant were included in the study. The results demonstrated that the presence of the APOE epsilon4 allele did not influence the response to clozapine in schizophrenic patients, neither was the baseline psychopathology related to the APOE epsilon4 allele. Given the multiple functions of the apoE protein in the brain, further study of the influence of APOE on CNS medication response is needed.

Adult↗

PubMed2000

Endoscopic bone graft for delayed union and nonunion.

We performed endoscopic bone grafting for eight patients of delayed union and nonunion which developed after femoral and humeral shaft fractures. The mean interval from initial intervention to endoscopic bone grafting was 7.3 months. Six patients of delayed union and nonunion healed at 4.1 months on average. Two patients had unsatisfactory healing and eventually underwent non-endoscopic revisional surgery. There was no intraoperative on postoperative complication. Endoscopic bone grafting can be a less invasive alternative, obtaining rapid bone union in cases of compromised healing of the diaphyseal fracture.

Adult↗

PubMed2000

Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells.

We previously reported that immunosuppressive cannabinoids inhibited interleukin (IL)-2 steady-state mRNA expression and secretion by phorbol-12-myristate-13-acetate plus ionomycin-activated mouse splenocytes and EL4 murine T-cells. Here we show that inhibition of IL-2 production by cannabinol, a modest central nervous system-active cannabinoid, is mediated through the inhibition of IL-2 gene transcription. Moreover, electrophoretic mobility shift assays demonstrated that cannabinol markedly inhibited the DNA binding activity of nuclear factor of activated T-cells (NF-AT) and activator protein-1 (AP-1) in a time- and concentration-dependent manner in activated EL4 cells. The inhibitory effects produced by cannabinol on AP-1 DNA binding were quite transient, showing partial recovery by 240 min after cell activation and no effect on the activity of a reporter gene under the control of AP-1. Conversely, cannabinol-mediated inhibition of NF-AT was robust and sustained as demonstrated by an NF-AT-regulated reporter gene. Collectively, these results suggest that decreased IL-2 production by cannabinol in EL4 cells is due to the inhibition of transcriptional activation of the IL-2 gene and is mediated, at least in part, through a transient inhibition of AP-1 and a sustained inhibition of NF-AT.

Animals↗

PubMed2000

Analogue pattern matching in a dendritic spine model based on phosphorylation of potassium channels.

Modification of potassium channels by protein phosphorylation has been shown to play a role in learning and memory. If such memory storage machinery were part of dendritic spines, then a set of spines could act as an 'analogue pattern matching' device by learning a repeatedly presented pattern of synaptic activation. In this study, the plausibility of such analogue pattern matching is investigated in a detailed circuit model of a set of spines attached to a dendritic branch. Each spine head contains an AMPA synaptic channel in parallel with a calcium-dependent potassium channel whose sensitivity depends on its phosphorylation state. Repeated presentation of synaptic activity results in calcium activation of protein kinases and subsequent channel phosphorylation. Simulations demonstrate that signal strength is greatest when the synaptic input pattern is equal to the previously learned pattern, and smaller when components of the synaptic input pattern are either smaller or larger than corresponding components of the previously learned pattern. Therefore, our results indicate that dendritic spines may act as an analogue pattern matching device, and suggest that modulation of potassium channels by protein kinases may mediate neuronal pattern recognition.

Animals↗