Biomedical subjects

S F Cheng

Publications and source records attributed to S F Cheng.

At least 19 recordsLinked to original sources

PubMed2006

Study of different methods for enhancing the nitrate removal efficiency of a zero-valent metal process.

This study explores the effect of several enhancing methods, namely acid wash pretreatment, ultrasound treatment and addition of nickel catalyst on the nitrate removal efficiency of three zero-valent metals--iron, aluminium and zinc. It is hoped that by learning about the major reaction pathways of nitrate removal with zero-valent metals and the main factors influencing the reactivity of those zero-valent metals, optimum process conditions may be identified. The study results show that direct transfer of electrons is the major reaction pathway. Thus increasing a clean, fresh metal surface and decreasing the thickness of the diffusion layer to accelerate mass transfer are the main determinants of reaction rate. In the absence of a clean, fresh metal surface, the catalytic reaction of nickel becomes the primary removal pathway.

Aluminum↗

PubMed2004

Rational pharmacotherapy in the diabetic hypertension: analysis-prescribing patterns in a general hospital in Taiwan.

OBJECTIVES: To examine prescribing at a 2800-bed hospital, also providing ambulatory services for 9000 visits per day, with a view to assessing the extent to which it followed international guidelines for treating diabetic hypertension. METHOD: Patients receiving antidiabetic and antihypertensive drugs concomitantly during the 4-week study period were included. RESULT: Of the 5015 eligible patients, most received combination antidiabetic therapy. Oral antidiabetic agents used alone or in combination included (in descending order) metformin, glibenclamide, gliclazide, glipizide, glimepiride and alpha-glucosidase inhibitors. Gliclazide accounted for most of the oral antidiabetic drug expenditure. Sulfonylurea plus metformin was the most popular regimen. Prescriptions for long-acting sulfonylureas did not differ between elderly and younger patients. For blood pressure control, calcium-channel blockers were most commonly used alone and overall, although current guidelines suggest that they should be second-line treatments. Inappropriate use of immediate-release nifedipine was noted. The combination, atenolol >100 mg/day and hydrochlorothiazide 50 mg/day (or an equivalent) were extensively used. Among 54.7% patients treated with combination antihypertensives, calcium-channel blockers and an angiotensin-converting enzyme inhibitor were most commonly used. CONCLUSION: Most diabetic hypertensive patients were treated with combination therapy for glucose and blood pressure control. Prescriptions for antihypertensive drugs often differed from current guidelines, especially in the choice of agents and their combinations.

Aged↗

PubMed2001

Conformation and interaction with the membrane models of the amino-terminal peptide of influenza virus hemagglutinin HA2 at fusion pH.

Conformations of a 48-mer peptide corresponding to the amino-terminal region of influenza HA2 in aqueous and membranous environments were studied. In aqueous solution the peptide was found to be oligomeric and its helicity was enhanced at higher concentrations. The conformation in phospholipid bilayer and insertion depth into the sodium dodecyl sulfate (SDS) micelle for the fusion peptide were in line with those determined for the amino-terminal 25-mer analog. The turn of residues 28-31 found in the crystal structure of hemagglutinin at neutral pH persisted in the presence of SDS at pH 5.0. Except for the turn, conformational lability of the amino portion of HA2 is suggested by comparison of the secondary structure determined herein with that obtained with the influenza fusion protein crystallized in the aqueous phase at neutral pH. The backbone amide proton exchange experiment suggested an interaction with the micellar surface for the segment carboxy-terminal to the fusion peptide domain.

Amino Acid Sequence↗

PubMed2001

Feasibility of using metals to remediate water containing TCE.

The feasibility of treating underground water contaminated by a chlorinated organic compound with bimetallics Fe/ Ni, Zn/Ni and Zn single metal was studied. Column tests to simulate a reactive permeable wall in a funnel-and-gate system were used. Research results indicated that bimetallic Fe0/Ni0 and Zn0/Ni0 all had a very strong degraded power to trichloroethylene (TCE) at concentration up to 25 mg/l under different flow rates (27 cm/day-20 m/day). Furthermore, the concentrations of TCE and various ions in the treated effluent were nearly lower than the values specified in related standards for drinking water in Taiwan. These results showed that this technique could be effectively and safely used as an underground water remediation process.

Environmental Pollution↗

PubMed2001

The leucine zipper motif of the envelope glycoprotein ectodomain of human immunodeficiency virus type 1 contains conformationally flexible regions as revealed by NMR and circular dichroism studies in different media.

A 43-mer peptide derived from the coiled coil domain of the transmembrane glycoprotein, gp41, of human immunodeficiency virus type 1, was synthesized. Light scattering measurements suggested that the peptide molecules likely exist in the aqueous solution in trimeric form. Circular dichroism experiments showed a moderate helix population enhancement for the peptide in 80% methanol solution relative to helicity in sodium dodecyl sulfate micellar suspension. NMR spectroscopy indicated that the N-terminal section of the peptide was conformationally more sensitive to the medium. The conformationally labile regions contain residues implicated in gp41-gp120 association. Our data support the idea that the coiled coil region is responsible for oligomerization of the gp41 ectodomain and suggest a site of conformational isomerization following receptor binding-induced gp120 dissociation from gp41.

Amino Acid Sequence↗

PubMed2000

The amino-terminal region of the fusion peptide of influenza virus hemagglutinin HA2 inserts into sodium dodecyl sulfate micelle with residues 16-18 at the aqueous boundary at acidic pH. Oligomerization and the conformational flexibility.

The conformation and interactions with membrane mimics of the NH(2)-terminal fragment 1-25 of HA2, HA2-(1-25), of influenza virus were studied by spectroscopic methods. Secondary structure analysis of circular dichroism data revealed 45% helix for the peptide at pH 5.0. Tryptophan fluorescence quenching by acrylamide and NMR experiments established that the Trp(14) is inside the vesicular interior and residues 16-18 are at the micellar aqueous boundary. NBD fluorescence enhancement of the NH(2)-terminal labeled fluorophore on the vesicle-bound peptide indicated that the NH(2) terminus of the fusion peptide was located in the hydrophobic region of the lipid bilayer. No significant change in insertion depth was observed between pH 5.0 and 7.4. Collectively, these spectroscopic measurements pointed to an equilibrium between helix and non-helix conformations, with helix being the dominant form, for the segment in the micellar interior. The conformational transition may be facilitated by the high content of glycine, a conformationally flexible amino acid, within the fusion peptide sequence. Self-association of the 25-mer peptide was observed in the N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine SDS-gel electrophoresis experiments. Incorporating the NMR signal attenuation, fluorescence, and gel electrophoresis data, a working model for the organization of the fusion peptide in membrane bilayers was proposed.

Amino Acid Sequence↗

PubMed2000

A helix initiation motif, XLLRA, is stabilized by hydrogen bond, hydrophobic and van der Waals interactions.

Five partially overlapping synthetic peptides containing the N-terminal portion of the leucine zipper (LZ)-like domain of human immunodeficiency virus envelope glycoprotein gp41 were used to deduce the helix initiation site. Circular dichroism (CD) data suggested a strong helix-inducing motif, LLRA. The coupling constant and nuclear Overhauser effect (NOE) results obtained from nuclear magnetic resonance experiments in 20% trifluoroethanol aqueous solution at 280 K for the four decapeptides under study suggested that the motif XLLRA, where X is a group or an amino acid residue capable of forming hydrogen bond to arginine, constitutes a helix nucleation core. A similar conclusion was reached for a pentadecapeptide in water, suggesting that the result was not dependent on both chain length and the helix promoting medium. Detailed analysis of NOE and CD data from the four decapeptides indicated that the acetyl group and asparagine had a strong tendency to be helix N-capping, in confirmation of previous studies. Molecular modeling using restraints derived from NOE data showed that van der Waals, hydrophobic interactions and hydrogen bonds contribute synergetically to the stability of the core structure. The concept of nucleation core consisting of a few amino acids may be generally applied in proton design and folding studies.

Amino Acid Motifs↗

PubMed2000

The enhancement methods for the degradation of TCE by zero-valent metals.

Batch tests were performed to compare the degradation rates of TCE on Fe0 and Zn0. Our results indicated that the degradating capability of Zn0 to TCE was nearly 10 times higher than that of Fe0. On the other hand, the degradation rates of Fe0 or Zn0 in conjunction with other metals for reduction of TCE was investigated. The selected metals were nickel (Ni0) and palladium (Pd0) both of which have a strong enhancement effect. The reduction rates of Zn0/Pd0 and Zn0/Ni0 for TCE were the fastest. Fe0 that had lost its surface activity could be activated again by the addition of Pd0 or Ni0.

Ethane↗

PubMed1999

Proline affects oligomerization of a coiled coil by inducing a kink in a long helix.

The structural effect of a proline in a helix in trifluoroethanol (TFE)/water medium was examined on a 29-mer peptide and its proline analog derived from the leucine zipper (LZ)-like motif of gp41 (the transmembrane glycoprotein of HIV-1) by NMR and circular dichroism (CD) spectroscopies. Lower helical content was found for the proline mutant from the CD study. NMR data show that distortion of the helix by proline is local and occurs mainly on the N-terminal side of the substitution site. Molecular dynamics computation exhibits a bending of the helical axis of 30 degrees +/- 10 degrees, in agreement with X-ray diffraction results. Light-scattering experiments indicated that the average aggregation number of the proline-substituted mutant is substantially lower than that of the wild-type peptide. From the ratio of dissociation constants of the wild-type and the proline mutant peptides, the difference in free energy of trimeric formation is calculated to be 2.1 kcal/mol. Thermal stability, helicity, and the average aggregation number for the helix oligomers were found to be correlated. The structural alteration and the reduced coiled coil stability may account for the deficiency in the biological functions of the proline mutants of gp41 and in the inhibitory action of proline-substituted peptides. These effects may also be important in unraveling the roles played by proline in transmembrane proteins.

Amino Acid Motifs↗

PubMed1999

Biophysical characterization of the structure of the amino-terminal region of gp41 of HIV-1. Implications on viral fusion mechanism.

A peptide of 51 amino acids corresponding to the NH2-terminal region (5-55) of the glycoprotein gp41 of human immunodeficiency virus type 1 was synthesized to study its conformation and assembly. Nuclear magnetic resonance experiments indicated the sequence NH2-terminal to the leucine zipper-like domain of gp41 was induced into helix in the micellar solution, in agreement with circular dichroism data. Light scattering experiment showed that the peptide molecules self-assembled in water into trimeric structure on average. That the peptide molecules oligomerize in aqueous solution was supported by gel filtration and diffusion coefficient experiments. Molecular dynamics simulation based on the NMR data revealed a flexible region adjacent to the hydrophobic NH2 terminus of gp41. The biological significance of the present findings on the conformational flexibility and the propensity of oligomerization of the peptide may be envisioned by a proposed model for the interaction of gp41 with membranes during fusion process.

Amino Acid Sequence↗

PubMed1998

Determination of the binding constant of a protein kinase C substrate, NG(28-43), to sodium dodecyl sulfate via the diffusion coefficient measured by pulsed field gradient nuclear magnetic resonance.

The binding affinity of a protein kinase C substrate, neurogranin peptide NG(28-43), to a sodium dodecyl sulfate micelle was analyzed quantitatively by the diffusion coefficient (Da) of the peptide determined by pulsed field gradient NMR. By use of a two-state model, the fraction of the peptide in the bound state, and hence the binding constant, can be estimated. The obtained binding constant is within the same order of magnitude as those reported for similar systems using other techniques. The present method may be generalized to measure the formation constants of other peptide:micelle complexes.

Binding Sites↗

PubMed1998

Determination of the equilibrium micelle-inserting position of the fusion peptide of gp41 of human immunodeficiency virus type 1 at amino acid resolution by exchange broadening of amide proton resonances.

The exchange broadening of backbone amide proton resonances of a 23-mer fusion peptide of the transmembrane subunit of HIV-1 envelope glycoprotein gp41, gp41-FP, was investigated at pH 5 and 7 at room temperature in perdeuterated sodium dodecyl sulfate (SDS) micellar solution. Comparison of resonance peaks for these pHs revealed an insignificant change in exchange rate between pH 5 and 7 for amide protons of residues 4 through 14, while the exchange rate increase at neutral pH was more prominent for amide protons of the remaining residues, with peaks from some protons becoming undetectable. The relative insensitivity to pH of the exchange for the amide protons of residues 4 through 14 is attributable to the drastic reduction in [OH-] in the micellar interior, leading to a decreased exchange rate. The A15-G16 segment represents a transition between these two regimes. The data are thus consistent with the notion that the peptide inserts into the hydrophobic core of a membrane-like structure and the A15-G16 dipeptide is located at the micellar-aqueous boundary.

Amino Acid Sequence↗

PubMed1997

The FLG motif in the N-terminal region of glucoprotein 41 of human immunodeficiency virus type 1 adopts a type-I beta turn in aqueous solution and serves as the initiation site for helix formation.

NMR and CD studies were carried out on a peptide representing the hydrophobic N-terminal domain of envelope glycoprotein of human immunodeficiency virus type-1 in solutions of varying polarity. It was found that in aquaeous solution the amide proton of glycine in the FLG motif resonated at a considerably high field and its chemical shift, within the limit of experimental precision, had a temperature coefficient of zero in the range studied. The upfield shift of NH of the glycine could be largely attributed to the ring-current effect of phenylalanine in the FLG motif that participated in a type-1 beta turn with a short Cbeta(i)-NH(i+2) distance. The slower proton-deuterion exchange for the glycine amide proton relative to that of other glycines was consistent with a folded structure for the motif in aquaeous solution. Results of the molecular simulation showed that this proton was shielded from the solvent by non-polar side chains of the amino acid residues surrounding the turn stabilized by hydrophobic interactions, thus explaining the zero temperature coefficient of the proton chemical shift. The structural stabilizing effect of the hydrophobic interaction was supported by the behavior of the proton in less polar Me2SO solution, in which the anomaly in the chemical shift and its temperature coefficient was less prominent. Detailed secondary-structure analysis suggested that the beta turn of the FLG motif may act as an initiation core for helix formation, probably because the turn readily transforms into helical form.

Amino Acid Sequence↗

PubMed1997

NMR and circular dichroism studies on the conformation of a 44-mer peptide from a CD4-binding domain of human immunodeficiency virus envelope glycoprotein.

Two-dimensional NMR, circular dichroism (CD) experiments and molecular modeling were performed to study the secondary structure of a 44-mer peptide fragment derived from the C4 region of gp120 of human immunodeficiency virus in aqueous solution. It was found a nascent helical structure exists following a type I turn near the N-terminus of the peptide. The proline residue in the turn appears to serve as a helix initiator. The helical structure was in fast dynamic equilibrium with beta- or random coil form on the NMR scale. A reverse turn was identified at a section containing two consecutive proline residues. A nascent helical structure has been detected for the region near the C-terminus of the 44-mer peptide. Higher helical content for the peptide is also indicated by CD studies on TFE titration. Thus it is proposed that, in more apolar medium, the Pro-Pro turn and the segment amino-terminal to it, spanning about 20 amino acids, may be converted into helix structure. Moreover, the region near the C-terminus of the peptide may also be induced into helix, so that a helix-turn-helix structure may be formed in the C4 domain of gp120. A helical wheel representation of this stretch shows amphipathicity of the helix. The biological implication of the conformational adaptibility of the peptide was discussed.

Amino Acid Sequence↗

PubMed1997

The amino-terminal fusion domain peptide of human immunodeficiency virus type 1 gp41 inserts into the sodium dodecyl sulfate micelle primarily as a helix with a conserved glycine at the micelle-water interface.

A peptide based on the N-terminal fusion domain of gp41 of human immunodeficiency virus type 1 (HIV-1) and its tryptophan analog were synthesized to examine the secondary structure in the micellar environment. Nuclear magnetic resonance (NMR), circular dichroism and electron paramagnetic resonance experiments indicated that the gp41 fusion peptide inserted into the micelle primarily as a helix (59%), with substantial beta-structure (26.7%). Deep penetration of the peptide into the apolar hydrocarbon core was supported by the results of fluorescence experiments in which the tryptophan analog exhibited a blue shift of about 30 nm in the presence of a sodium dodecyl sulfate micelle, in 1,2-dimyristoyl-rac-glycero-3-phosphocholine, and in 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine vesicular solutions. The results of spin label-attenuated 1H resonance experiments show that the region C-terminal to G16, which contains a turn structure, exhibited substantial interaction with the micelle, suggesting that it lies on the surface of micelle. Molecular simulation based on data from NMR experiments revealed a flexible hinge at residues 15 and 16 (alanine and glycine, respectively) from the N terminus of the peptide located at the micelle-solution interface. The highly conserved A15-G16 dipeptide may play a role in the function of fusion domain of HIV-1 envelope glycoprotein.

Amino Acid Sequence↗

PubMed1996

Characterization of conformation and dynamics of CD4 Fragment (81-92) TYICEVEDQKEE and its benzylated derivative by 1H NMR spectroscopy and molecular modeling: Relevance of conformation to biological function.

Two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy experiments were carried out to determine the conformation of a CD4 fragment (81-92) TYICEVEDQKEE and its di-benzylated analogue in aqueous solution. The refined structures obtained by use of distance geometry and simulated annealing for both peptides revealed a marked departure from that of the corresponding sequence within the D1D2 fragment of CD4 determined by x-ray crystal studies. Near the amino terminus of both peptides, a distinct loop exists that is stabilized by the hydrophobic interaction between the side chains of the amino acids in the region. For the parent peptide and Cys84 and Glu85 dibenzylated analogues, the orientation of the loop is different with respect to the reverse turn formed by Val86 through Gln89. In particular, the side chains of Val86 point in different directions for these two peptide analogues. The C- terminus of both peptide analogues exhibits a faster motional characteristic. The deuterium-proton exchange experiment showed a very slowly exchanged Gln89 backbone NH for the di-benzylated peptide, suggesting its participation in the hydrogen bond to Val86 C=O. The negatively charged side chains of Glu87 and Asp88 are found to jut out, similar to the crystal structure. The difference between the two peptides in inhibiting the syncytium formation is postulated to arise from the more defined Val86-Gln89 turn and the orientation of the apolar side chains of the residues in the stretch thought to participate in the cell-fusion process.

Amino Acid Sequence↗

PubMed1996

On the importance of van der Waals interaction in the groove binding of DNA with ligands: restrained molecular dynamics study.

Comparison of interaction energy between an oligonucleotide and a DNA-binding ligand in the minor and major groove modes was made by use of restrained molecular dynamics. Distortion in DNA was found for the major groove mode whereas less significant changes for both ligand and DNA were detected for the minor groove binding after molecular dynamics simulation. The conformation of the ligand obtained from the major groove modes resembles that computed with the ligand soaked in water. The van der Waals contact energy was found to be as significant as electrostatic energy and more important for difference in binding energy between these two binding modes. The importance of van der Waals force in groove binding was supported by computations on the complex formed by the repressor peptide fragment from the bacteriophage 434 and its operator oligonucleotide.

Bacteriophages↗

PubMed1995

A model for mixed virus disease: co-infection with Moloney murine leukemia virus potentiates runting induced by polyomavirus (A2 strain) in Balb/c and NIH Swiss mice.

Polyomavirus was originally isolated by Ludwick Gross from a mixture that also contained a murine retrovirus. A possible pathogenic interaction between polyomavirus and an endogenous mouse retrovirus locus (mtv-7) in polyomavirus-induced cancer has also been reported. To study potential interactive effects of polyomavirus (Py) and Moloney murine leukemia retrovirus (M-MuLV), newborn Balb/c and NIH Swiss mice were infected with high titer wild-type Py (A2 strain) and M-MuLV. Dramatically stunted growth (runting) occurred in 100% of the doubly inoculated mice, while much lower frequency of runting occurred in animals infected with Py alone and not at all with M-MuLV-infected mice. In situ hybridization for Py DNA showed ongoing Py replication and inflammation in kidneys (atypical of most mice singly infected by Py) of runted doubly inoculated mice. In addition, high Py viral replication continued well past the usual acute stage termination. M-MuLV replication was also initially inhibited in bone marrow by simultaneous Py infection. No M-MuLV replication was seen in singly or doubly infected mouse kidneys. Runting was very rapid, observable within 2 days after co-infection, arguing against an adaptive or antigen-specific immunological mechanism. One possibility was that a cytokine-driven acute response mechanism was involved. Supporting this view, RNAse protection assays for various cytokine RNAs showed that several were specifically elevated in kidneys of doubly infected mice. Three patterns were observed: (1) IL-6 was elevated in doubly infected mice early after infection (7 days), but it declined at later times (19 days); (2) IFN-gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3) TNF-alpha, IL-12p40, and possibly TNF-beta were elevated only at late times. While the cytokines in the third category might be indicative of infiltrating inflammatory cells, it seems possible that cytokines in the first or second categories might be involved in establishing runting and ongoing polyoma DNA replication in the doubly infected mice.

Animals↗