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Biomedical subjects

W N Huang

Publications and source records attributed to W N Huang.

9 recordsLinked to original sources

Elevation of plasma interleukin-18 concentration is associated with insulin levels in patients with systemic lupus erythematosus.

We previously reported that systemic lupus erythematosus (SLE) patients have a higher risk of insulin resistance and abnormal insulin secretion. Recent studies demonstrated that interleukin (IL)-18, a novel pro-inflammatory cytokine, may be involved in triggering the inflammatory processes in SLE and the concentrations of circulating IL-18 in SLE patients were significantly higher than those in healthy subjects. IL-12 has a synergistic effect with IL-18, and both cytokines are inducers of interferon (IFN)-gamma. The objective of this study was to identify the effect of fasting insulin levels on circulating concentrations of IL-18, IL-12 and IFN-gamma in patients with SLE. Plasma levels of proinflammatory Th-1 cytokines were determined by enzyme-linked immunosorbent assay in a total of 70 female SLE patients and 34 age-matched healthy females. Insulin resistance (IR) and secretion were evaluated by homeostasis model assessment (HOMA). All patients were further classified into subgroups based on the quartiles of fasting insulin levels. SLE patients with fasting insulin levels in the top quartile compared with other quartiles had significantly higher plasma levels of IL-18. The presence of insulin auto-antibodies (IAA) in SLE patients had no influence on plasma levels of IL-18. In addition, fasting insulin levels and HOMA IR were positively correlated with IL-18 in all SLE patients, respectively. In conclusion, elevated circulating IL-18 concentrations corresponded with increases in fasting insulin levels and the status of insulin resistance in patients with SLE.

Adult↗

Association of brachial-ankle pulse wave velocity with cardiovascular risk factors in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. Increasing arterial stiffness is closely associated with atherosclerotic cardiovascular diseases, and pulse wave velocity (PWV) is considered to be an indicator of arterial stiffness. The objective of this study was to identify the relationship between brachial-ankle pulse wave velocity (baPWV) and cardiovascular risk factors in patients with SLE. Age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBS), plasma lipid profile, plasma homocysteine, thiobarbituric acid reactive substances (TBARS), baPWV, ankle-brachial index (ABI), and SLE-related factors were determined in a total of 83 SLE patients (12 males and 71 females). All SLE patients were further classified into two subgroups according to baPWV value (baPWV < 1400 cm/s, n=37 versus baPWV > 1400 cm/s, n=46). The mean baPWV value of studied SLE patients was 1520 +/- 381 cm/s. Age, BMI, SBP, DBP, FBS, TBARS and homocysteine levels were significantly higher in SLE patients with baPWV value > 1400cm/s than in SLE patients with baPWV value < 1400cm/s. In addition, baPWV correlated significantly with age, SBP, DBP, FBS and homocysteine. Moreover, stepwise multiple regression analysis showed that age and SBP were independently associated with baPWV. The results of this study indicate a possible link between vascular stiffness measured by baPWV and cardiovascular risk factors in patients with SLE.

Adult↗

Structures of heparin-derived disaccharide bound to cobra cardiotoxins: context-dependent conformational change of heparin upon binding to the rigid core of the three-fingered toxin.

Glycosaminoglycans (GAGs) have been suggested to be a potential target for cobra cardiotoxin (CTX) with high affinity and specificity via a cationic belt at the concave surface of the polypeptide. The interaction of GAGs, such as high-molecular weight heparin, with CTXs not only can induce aggregation of CTX molecules but also can enhance their penetration into membranes. The binding of short chain heparin, such as a heparin-derived disaccharide [DeltaUA2S(1-->4)-alpha-D-GlcNS6S], to CTX A3 from Taiwan cobra (Naja atra), however, will not induce aggregation and was, therefore, investigated by high-resolution (1)H NMR. A novel heparin binding site on the convex side of the CTX, near the rigid disulfide bond-tightened core region of Cys38, was identified due to the observation of intermolecular NOEs between the protein and carbohydrate. The derived carbohydrate conformation using complete relaxation and conformational exchange matrix analysis (CORCEMA) of NOEs indicated that the glycosidic linkage conformation and the ring conformation of the unsaturated uronic acid in the bound state depended significantly on the charge context of CTX molecules near the binding site. Specifically, comparative binding studies of several heparin disaccharide homologues with two CTX homologues (CTX Tgamma from Naja nigricollis and CTX A3) indicated that the electrostatic interaction of N-sulfate of glucosamine with NH(3)(+)zeta of Lys12 and of the 2-O-sulfate of the unsaturated uronic acid with NH(3)(+)zeta of Lys5 played an important role. These results also suggest a model on how the CTX-heparin interaction may regulate heparin-induced aggregation of the toxin via the second heparin binding site.

Animals↗

Heparin reduces the alpha-helical content of cobra basic phospholipase A(2) and promotes its complex formation.

The interaction of phospholipase A(2) (PLA(2)) with glycosaminoglycans (GAGs) has recently attracted attention in view of its implication on inflammation and cell proliferation. By using Fourier Transformed Infrared (FTIR) spectroscopic measurements, we demonstrate here that binding of cobra basic phospholipase A(2) from Naja nigricollis (N-PLA(2)) to heparin may induce a significant conformational change observed in the amide I region of the enzyme's alpha-helical and beta-sheet structure. It is observed that notable conformational change of N-PLA(2) due to heparin binding occurs only when heparin's chain length is at least an octasaccharide as evidenced by circular dichroism and optical density measurements. This correlation may be an important factor in the aggregation of N-PLA(2) and N-PLA(2)-heparin complexes. Heparin induced change in conformation of PLA(2) is suggested to be a notable link in understanding the diversity in PLA(2) activity when rendered to the extracellular matrix of cell membranes that is full of GAG molecules.

Animals↗

[Observation and analyses on voice changes in the normal aged].

OBJECTIVE: To measure the voice samples of the normal aged in order to systemically study the features of the voice changes. METHOD: To collect and analyze 146 voice samples of the normal aged with sonogram. RESULT: The fundamental frequency of the voice of the aged decreases and rises in the male more than 80 years older. The low frequency harmonics are regulation and the intensity is strong in the formant of the aged. The difference reduces in voice between male and female. The harmonics to noise ratio tends downwards and the amplitude perturbation quotient tends upwards along with the growth of age in the aged male. The changes of the above-mentioned parameters are not significant in the aged female. CONCLUSION: The voice changes are normal physiological ones in the normal aged. The changes of the parameters are used to evaluate normal aged voice and abnormal one. The changes show that the function in the aged phonation tends to decline to a certain extent and it must be protected and be trained.

Aged↗

Lipoprotein-induced prostacyclin production in endothelial cells and effects of lipoprotein modification.

Although lipoprotein modification has been implicated in atherogenesis, the effect of modified forms of lipoproteins on vascular cell function has not been fully resolved. We have investigated lipoprotein-induced prostaglandin production by macrovascular endothelial cells. This study delineates early responses of endothelial cells after exposure to native and modified forms of the lipoproteins. Modification of lipoproteins by oxidation or glycation significantly affected the capacity of lipoproteins to induce prostacyclin (PGI2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL3) caused higher production of PGI2 in the short term (4-24 h) but reached similar levels as HDL3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI2 production in endothelial cells, and this may have an influence on vascular function in disease states such as diabetes and atherosclerosis. Although the changes appear to contradict data from long-term in vivo studies, these results from in vitro studies may reflect the situation in very early lesion development. GlcLDL, while causing an increase in endothelial cell PGI2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.

Analysis of Variance↗

Fusion of sphingomyelin vesicles induced by proteins from Taiwan cobra (Naja naja atra) venom. Interactions of zwitterionic phospholipids with cardiotoxin analogues.

Egg sphingomyelin vesicles were used to assay aggregation/fusion activities of proteins from Taiwan (Naja naja atra) venom to avoid the problem of phospholipase A2 contamination during protein purification. It led to the identification of a new cardiotoxin (CTX) analogue protein (CTX V) with major aggregation/fusion, but few hemolysis, activities. On the contrary, cardiotoxin (CTX III) induced significant hemolysis of human red blood cells but exhibited few aggregation/fusion activities. To study the structure/activity relationship of these CTX-induced processes, the amino acid sequence of CTX V was determined and its aggregation/fusion activity was compared with that of CTX III by transmission electron microscopy, quasielastic laser light scattering, differential scanning calorimetry, and fluorescence spectroscopy. The results show that the CTX-induced fusion process at temperatures slightly above that of the gel to liquid-crystalline phase transition of sphingomyelin vesicles can ultimately convert small sonicated vesicles into large fused vesicles with sizes of 1-2 microns. The abilities of CTX V to induce the leakage of sphingomyelin vesicles content and to cause the fusion of vesicles are approximately 10-fold higher than those of CTX III. Based on the CTX structures determined in the present and other studies, it is suggested that the amino acid residue X within the well conserved sequence of -Cys-Pro-X-Gly-Lys-Gln-Leu-Cys- plays a role in the interaction of CTX with lipid molecules. The lipid phase transition could further enhance the protein-lipid interaction in the process leading to the fusion of vesicles.

Amino Acid Sequence↗

Expression and clinical significance of antinuclear antibody in hepatitis C virus infection.

BACKGROUND: The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY: Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS: Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS: Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.

Alkaline Phosphatase↗