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Biomedical subjects

K H Yang

Publications and source records attributed to K H Yang.

At least 109 records · Page 6Linked to original sources

Structure-antigenicity relationship of peptides from the pre-S2 region of the hepatitis B virus surface antigen.

Peptide antigenicity against the pre-S2 region of the hepatitis B virus surface antigen was studied using a pre-S2 specific anti-hepatitis B virus mouse monoclonal antibody (H8 mAb) and synthetic peptides by competitive ELISA. The mAb showed preferences for long peptides with the sequence 120/123-145, though the mAb binding region was located in the sequence 130-145 from the analysis of a conjugation study. The N-terminal residues 120/123-129 play an important role for the maintenance of the highly antigenic structure of the B cell epitope. Among these, the N-terminal hydrophilic residues 124-126 and hydrophobic residue 127 were important, whereas residues 120-122 did not affect antigenicity. Residues 131 and 141 appeared to be critical for the mAb binding. The relationship between peptide structure and antigenicity was also investigated by probing the secondary structure of the peptides by circular dichroism. Highly antigenic peptides elicited more ordered structure in 20% trifluoroethanol than less antigenic peptides. The results suggested that peptide antigenicities against H8 mAb are closely related to the B-cell epitope conformations of peptides.

Amino Acid Sequence↗

Suppressive effects of 2-acetylaminofluorene on concanavalin A-stimulated murine splenocyte proliferation in vitro: inhibition of interleukin-2 receptor expression.

Treatment of 2-acetylaminofluorene (AAF) to murine splenocyte culture produced a dose-related suppression on the lymphoproliferative response to concanavalin A (Con A). The amount of interleukin 2 (IL-2) activity in the culture supernatants was increased when AAF was treated for 48 hr. Since IL-2 activity did not increase if AAF was treated for the last 4 hr of a 48-hr culture period, the increase of IL-2 activity in culture supernatants did not appear to be due to the leakage of IL-2 from intracellular pool. Treatment of colchicine, an agent known to increase IL-2 activity in culture supernatants by inducing the cytoskeletal structure modification, increased IL-2 activity in splenocyte culture supernatants in 4 hr treatment. Meanwhile, the IL-2 receptor alpha (IL-2R alpha) positive cell population was decreased by the treatment of AAF. These results suggested that suppressive effects of AAF on the lymphoproliferative response to Con A in murine splenocyte culture may be associated with the inhibition of IL-2 receptor expression.

2-Acetylaminofluorene↗

Suppression of TCDD-induced cytochrome P450 IA1 activity by staurosporine in mouse primary hepatocyte cultures and hepatoma cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced cytochrome P450 IA1 activity in mouse primary hepatocyte cultures and mouse hepatoma Hepa-1 cells. Pretreatment with staurosporine, a protein kinase C inhibitor, inhibited TCDD-activated cytochrome P450 IA1 expression dose-dependently in both culture systems. Staurosporine also decreased P450IA1 protein synthesis which was detected using western immunoblot. Increased transcription of CYP1A1 gene by TCDD was also suppressed by staurosporine treatment. However, tyrphostin AG213, a specific tyrosine kinase inhibitor, had no effects on TCDD-induced cytochrome P450 expression. These results suggest that protein kinase C signal transduction may be involved in the cytochrome P450 induction mechanism by TCDD.

Alkaloids↗

The C-reactive protein (CRP) in patients with long bone fractures and after arthroplasty.

Between March 1991 and February 1992 serial serum C-reactive protein (CRP) levels were measured prospectively for three weeks in 57 consecutive patients with fractures of long bones, and also in 11 patients who had undergone primary total hip or knee arthroplasty. A semi-quantitative capillary floculation method was used for measuring the CRP level. The highest values were usually recorded 2-3 days after trauma or operation, and the CRP was nearly normal by three weeks. In the patients with long bone fractures the amplitude of CRP response was affected by the type of treatment. Lower values were observed in those patients treated conservatively than in those who underwent operation, but the profile of CRP response was similar, regardless of the type of treatment. The CRP response was also affected by the severity of the trauma in conservatively treated patients, but in those who underwent operation the CRP response was similar, regardless of the severity of the injury. In patients with primary total hip or knee arthroplasty the pattern of CRP response after operation was similar to that in the patients with long bone fractures who underwent surgical treatment. Awareness of the natural course of the CRP response after fracture and arthroplasty may help in the diagnosis of early post-traumatic and postoperative complications, especially infections.

Adolescent↗

Hepatocyte growth factor enhances B-cell activity.

Hepatocyte growth factor (HGF), is one of the growth factors induced and secreted into the serum of partially hepatectomized or hepatotoxin-treated mice that mediates regeneration of hepatic tissue. Results are presented here demonstrating that in addition to hepatotrophic effects, HGF also possesses immunologic activity. In particular, addition of HGF to B6C3F1 mouse spleen cell cultures enhanced humoral immune responses by augmenting the ability of B-cells to secrete immunoglobulin.

Animals↗

Mouse interferon gamma pretreated hepatocytes conditioned media suppress cytochrome P-450 induction by TCDD in mouse hepatoma cells.

Mouse interferon gamma (IFN-G) markedly suppressed 7-ethoxyresorufin o-deethylase (EROD) activity when added at the same time as TCDD in mouse primary hepatocyte cultures. IFN-G, however, had no effect on EROD induction by TCDD in Hepa-1 cells, a mouse hepatoma cell line, or Hepa-1 cells cocultured with Kupffer cells when added directly to the culture. EROD induction by TCDD in Hepa-1 cells was suppressed when cells were cultured with IFN-G pretreated mouse hepatocytes conditioned media. The magnitude of suppression was related to the dose of IFN-G and the density of hepatocytes used for the preparation of the conditioned media. Treatment of the monoclonal antibody against IFN-G to the conditioned media did not block the suppression of EROD induction. The suppressive effect of IFN-G pretreated hepatocytes conditioned media on EROD induction, however, was blocked when the conditioned media was heated or treated with trypsin. These results suggested that IFN-G pretreated mouse hepatocytes may release a soluble protein factor(s) which suppressed the EROD induction by TCDD in Hepa-1 cells.

Animals↗

Suppression of the in vitro immune response by 7,12-dimethylbenz[a]anthracene in mouse splenocytes co-cultured with rat hepatocytes.

7,12-Dimethylbenz[a]anthracene (DMBA) produced a dose-related suppression of in vitro polyclonal antibody response to lipopolysaccharide in mouse splenocytes co-cultured with rat hepatocytes. Addition of alpha-naphthoflavone (ANF), the cytochrome P-450 inhibitor, to the coculture reversed the DMBA-induced immunosuppression. The amount of [3H]DMBA bound to splenocyte DNA increased in a time-dependent manner up to 4 hr of co-culture and treatment of ANF reduced the binding. The addition of extracellular DNA to the co-culture prevented the suppression of the antibody response by DMBA. These results suggested that reactive metabolite(s) of DMBA were released from hepatocytes and that the suppression of the antibody response by DMBA is mediated via these reactive intermediate(s). DNA represents the primary macromolecular target for the reactive intermediate(s) of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Cloning of a Clostridium botulinum type B toxin gene fragment encoding the N-terminus of the heavy chain.

Two lambda gt11 clones of the toxin gene of Clostridium botulinum type B were identified by the monoclonal antibody specific to the heavy chain of type B toxin. Neither of the expressed fusion proteins from the lysates of lysogenic E. coli Y1089 showed any botulinal toxic activity. One of the clones hybridized to the oligonucleotide probe which was synthesized according to the amino acid sequence of N-terminus of heavy chain. The sequence analysis revealed that highly homologous regions in N-terminus of heavy chain exist among botulinum neurotoxins (type A, B) and tetanus toxin on the amino acid sequence level.

Amino Acid Sequence↗

Importance of hepatocyte culture conditions in dimethylnitrosamine-induced suppression of antibody response in the mixed cultures of murine hepatocytes and splenocytes.

The role of the hepatocyte culture media in dimethylnitrosamine (DMN)-induced suppression of antibody responses by splenocytes against sheep erythrocytes (SRBCs) was investigated using the mixed culture system of murine hepatocytes and murine splenocytes. It was observed that hormone-supplemented complete media was required for hepatocyte cultures to optimally activate DMN to its immunosuppressive form(s). In the absence of the hormone supplement, the concentration of DMN required to produce a 50% suppression (IC50) was increased by over 10-fold (i.e., compare the IC50 in complete media of less than 0.5 mM to the IC50 in basal media of almost 10.0 mM). In contrast, the activation of cyclophosphamide (cytoxan, CTX), which was used in these studies as a comparative control, was not affected by the absence of the hormone supplement. These results indicate that the observed effect on the activation of DMN was not due to a generalized loss of metabolic capability of hepatocytes cultured without hormones. To examine the role of drug metabolizing capabilities of hepatocytes in the differential activation of DMN, we compared phase I and phase II enzyme activities of hepatocytes cultured for 24 h in either basal media or hormone-supplemented complete media. Our results indicated that there was a significant decrease of phase I monooxygenase activities of cultured hepatocytes when compared to freshly isolated hepatocytes. However, our results failed to show any difference in the activities of hepatocytes cultured in the two media. Most notably, there was no difference in the activity of either high- or low-affinity DMN demethylase, as measured by the generation of formaldehyde. We observed a similar profile with phase II conjugative capabilities, specifically sulfotransferase and glucuronyltransferase. These results indicate that the activation of DMN to its immunosuppressive form(s) can be modulated in the co-culture system by culturing hepatocytes under different conditions. Because we failed to show any differences in the metabolic capabilities of hepatocytes cultured under the two media conditions, the results suggest that the modulation of immunosuppressive activity may not be related to a change in the generation of the immunosuppressive metabolite(s).

Animals↗

Induction of cytochrome P-450 by dimethyl sulfoxide in primary cultures of adult rat hepatocytes.

Treatment of hepatocyte cultures with dimethyl sulfoxide (DMSO) induced P-450IIE1-specific aniline 4-hydroxylase activity and P-450IA1-specific ethoxyresorufin O-deethylase activity at a concentration of 0.1% (v/v). The P-450IIB-specific pentoxyresorufin O-deethylase activity was induced only at the 2% (v/v) level. Dot blot analysis of the total cellular RNA and cycloheximide treatment of the culture suggested that induction of ethoxyresorufin O-deethylase activity by DMSO may be due to the increase of de novo synthesis of the P-450IA1 protein, not to accumulation of mRNA in the hepatocyte culture.

Aniline Hydroxylase↗

Computer simulation of occupant neck response to airbag deployment in frontal impacts.

A mathematical simulation was performed to study the potential of head and neck injury to an unbelted driver restrained by an airbag. The baseline study represented a 50th percentile male dummy driving in a compact car with the steering wheel perpendicular to the floor. The vehicle was moving at 48 km/hour at the time of impact. Model predictions were compared with sled test results. The data agreed reasonably well. A parametric study was performed to study the effect of changing the steering wheel angle and the size of the airbag. It was found that when the standard 20 degrees angle steering wheel was used, neck joint torques were decreased by 22 percent while the resultant head acceleration increased 41 percent from the base line study. When the vertical dimension of the airbag was reduced by 10 percent, neck joint torques were increased by 14 percent, while head acceleration showed a slight decrease of 9 percent.

Acceleration↗

Effect of porcine bone morphogenetic protein on healing of bone defect in the rabbit radius.

Segmental long bone defects due to infection or trauma is a difficult problem to manage in patients. We studied the effect of porcine bone morphogenetic protein (pBMP) on healing of defects in the rabbit radius. Porcine BMP was separated and purified from the tibia and femur of pigs by repeated solubilization and precipitation of the protein with different concentrations of urea and GuHCl. The osteoinductive activity of pBMP was confirmed by bioassay using No. 615 mice. In rabbits, about a 15 mm length of radii were removed and 20 mg of pBMP was implanted in the defected area with fibrin sealant (FS), while only FS was implanted in controls. Union of the affected area was observed in 6 weeks in the experimental side. There was no definite evidence of bone bridging across the affected area in the controls. This suggests that pBMP has a bone forming activity in other species and the clinical use of pBMP in treating patients with segmental bone defects is promising.

Animals↗

Relationship between lower limb dynamics and knee joint pain.

To test the hypothesis that appropriate and timely neuromuscular control of limb motions plays an important role in the preservation of joint health, we kinematically and kinetically examined the behavior of the legs of young adult subjects at heel strike during natural walking. We compared a group of 18 volunteers, who, we presumed, were preosteoarthrotic because of mild, intermittent, activity-related knee joint pain, with 14 age-matched asymptomatic normal subjects. The two groups of subjects exhibited similar gait patterns with equivalent cadences, walking speeds, terminal stance phase knee flexion, maximum (peak) swing angular velocity, and overall shape of the vertical ground reaction. However, our instrumentation detected statistically significant differences between the two groups within a few milliseconds of heel strike. In the knee pain group, the heel hit the floor with a stronger impact in this brief interval. Just before heel strike, there was a faster downward velocity of the ankle with a larger angular velocity of the shank. The follow-through of the leg immediately after heel strike was more violent with larger peak axial and angular accelerations of the leg echoed by a more rapid rise of the ground reaction force. This sequence of events represents repetitive impulsive loading, which consistently provoked osteoarthrosis in animal experiments. We refer to this micro-incoordination of neuromuscular control not visible to the naked eye as "microklutziness."

Adult↗

Early predictor of the efficacy of immunoprophylaxis against perinatal hepatitis B transmission: analysis of prophylaxis failure.

To research early predictors of the efficacy of the ongoing mass immunoprophylaxis against perinatal hepatitis B virus (HBV) transmission in Taiwan and to analyse the possible causes of immunoprophylaxis failure, 52 hepatitis Be antigen (HBeAg)-positive carrier mothers were recruited for the study. Maternal blood samples were taken at the first and third trimesters and delivery. Umbilical blood was collected and venous blood samples were taken at 4, 7, 11 and 14 months of age. Serum hepatitis B surface antigen (HBsAg) and antibody titres, HBeAg titre and HBV-DNA concentration were analysed. All the umbilical cord blood samples were negative for HBsAg. Among the 52 vaccinated infants, four were poor responders (anti-HBs less than 10 mIU ml-1 before vaccine booster). Another five infants became HBsAg-positive by 4 months of age and remained carriers. All these five carrier mothers were HBV-DNA-positive and three of them had risk factors related to maternal-fetal haemorrhage during pregnancy or delivery. The remaining 43 infants showed protective anti-HBs level (greater than 10 mIU ml-1) by 4 months of age. Three mothers out of these 43 cases also had the same haemorrhage risk factors during pregnancy or delivery, but were HBV-DNA-negative. Therefore, the anti-HBs level at 4 months is a predictor of the success of immunoprophylaxis. It may be helpful to distinguish HBV-DNA-positive carrier mothers among HBeAg-positive ones, to avoid inducing more maternal-fetal haemorrhage in such cases during pregnancy or delivery. Otherwise, additional hepatitis B immune globulin may be indicated in such cases to raise the successful prevention rate.

Carrier State↗

Effects of sinefungin and 5'-deoxy-5'-S-isobutyl-adenosine on lipopolysaccharide-induced proliferation and protein N-methylation of arginyl residues in murine splenic lymphocytes.

The effects of sinefungin (SF) and 5'-deoxy-5'-S-isobutyl-adenosine (SIBA) on lymphoproliferation and protein N-methylation of arginyl residues were investigated in splenic lymphocyte culture in vitro. Both SF and SIBA produced a dose-related inhibition of the lymphoproliferative response to lipopolysaccharide (LPS). The time-course of the inhibition indicated that SIBA had a more inhibitory effect than that of SF at short incubation periods, but SF showed more inhibition when the incubation was prolonged. The effects of SF and SIBA on the lymphoproliferative response corresponded with their effects on the protein N-methylation of arginyl residues by protein methylase I.

Adenosine↗

Mechanism of disc rupture. A preliminary report.

Lumbar intervertebral disc herniation is thought to be related to senescent changes in the nucleus pulposus except in rare instances of trauma. This investigation provides the first in vitro model of disc prolapse that reliably ruptures discs under physiologically reasonable stress. Fourteen vertebral motion segments with intact posterior elements were loaded repetitively at 1.5 Hz in a combination of flexion (7 degrees), rotation (less than 3 degrees), and compression (1,334 N) for an average of 6.9 hours (range, 3.0-13.0 hours) in a materials testing machine. Loading was terminated when reaction force leveled off for more than 1 hour. Ten discs failed through annular protrusions, and four failed by nuclear extrusion through annular tears, supporting the hypothesis that intervertebral disc prolapse is peripheral in origin. The annulus fibrosus is the site of primary pathologic change.

Humans↗

Differentiation of human motion data using combined spline and least squares concepts.

A differentiation method, which combines the concepts of least squares and splines, has been developed to analyze human motion data. This data smoothing technique is not dependent on a choice of a cut-off frequency and yet it closely reflects the nature of the phenomenon. Two sets of published benchmark data were used to evaluate the new algorithm.

Algorithms↗

Malignant glomus tumor originating in the superior mediastinum--an immunohistochemical and ultrastructural study.

An extremely rare case of malignant glomus tumor originating in the superior mediastinum was evaluated immunohistochemically and ultrastructurally. A 78-year-old woman who had been suffering from dysphagia and dyspnea had poorly-defined soft tissue mass, 4.5 x 2.5cm, in the superior mediastinum with direct invasion into the esophagus, trachea, and bilateral thyroid glands. This case is believed to be unique in several respects. There were neither recognizable findings of benign glomus tumor nor sarcomatous areas, in contrast to the previously reported cases. A definite direct invasion into the surrounding organs was identified. We therefore interpreted this case as primary malignant glomus tumor, not as glomangiosarcoma arising in a benign glomus tumor.

Actins↗