Search PubMed⌕ Search

Biomedical subjects

S Guan

Publications and source records attributed to S Guan.

53 records · Page 3Linked to original sources

Collision-induced dissociation for mass spectrometric analysis of biopolymers: high-resolution Fourier transform ion cyclotron resonance MS4.

Efficient collision-induced dissociation multistage tandem high-resolution mass spectrometry of peptide ions is demonstrated for the first time. Specifically, four-stage Fourier transform ion cyclotron resonance collision-induced dissociation tandem-in-time MS4 is demonstrated for bradykinin quasimolecular ions, MH+, produced by matrix-assisted laser desorption/ionization. We combine off-resonant excitation and ion axialization to improve the efficiency of parent ion dissociation and product ion collection and detection at every MS stage. We observe successive loss of water/ammonia from the C-terminus to leave an (MH-NH3/H2O)+ ion in the second stage, followed by successive losses of the next two amino acids, arginine and phenylalanine. High mass resolving power is achieved throughout all four MS stages, in an experiment that consumes approximately 10 pmol of peptide and takes only approximately 5 min. We project that it should be possible to automate this experiment for high-speed sequencing of biopolymers.

Biopolymers↗

MS/MS with high detection efficiency and mass resolving power for product ions in Fourier transform ion cyclotron resonance mass spectrometry.

We present a new FT-ICR method for MS/MS of trapped ions. Parent ions isolated in the source trap of a dual-trap FT-ICR/MS instrument are subjected to off-resonance dipolar excitation to promote collision-induced dissociation (CID), while product ions are simultaneously axialized by broad-band azimuthal quadrupolar excitation in the presence of argon collision gas. In this way, radial diffusional loss of product ions is greatly reduced; moreover, the axialized product ions may then be efficiently transferred to the analyzer trap for high-resolution detection. Significant improvements in FT-ICR detection efficiency, mass resolving power (m/delta m > or = 20,000 at m/z < or = 1000), and mass accuracy (< or = 50 ppm for peptide fragments of m/z < or = 1000) are demonstrated for CID product ions of the cyclic peptide, gramicidin S.

Amino Acid Sequence↗

Wide-mass-range axialization for high-resolution Fourier-transform ion cyclotron resonance mass spectrometry of externally generated ions.

Ions generated in both continuous and pulsed-mode external ion sources are injected into an open-ended cylindrical Fourier-transform ion cyclotron resonance ion trap by means of an electrostatic ion guide consisting of concentric cylinder and wire electrodes to which a potential difference is applied. Broadband axialization during ion injection improves ion trapping efficiency by reducing the ion off-axis displacement. Significant improvements in both signal-to-noise ratio and mass resolving power, along with high mass selectivity are demonstrated for ions generated by external Cs+ secondary ion mass spectrometry or by matrix-assisted laser desorption/ionization.

Cesium↗

[Detection of anti-BB antibodies in human sera by VIDAS system].

Lyme disease is an infectious disease just known in the latest decade. The sera of people from various origins were detected for Anti-BB antibodies (IgM+IgG) by VIDAS system. The results are as follows: Of 83 sera from the health-cared people, 8 were positive (9.6%); of 20 sera from the patients clinical diagnosed as tuberculosis, none was positive; of 46 sera from the patients clinical diagnosed or suspected as node diseases, 4 were positive (8.7%); of 57 sera from the patients with various ophthalmologic diseases, 13 were positive (22.8%); of 15 sera from the patients with stomatologic diseases, 4 were positive (26.7%); of 17 sera from the patients with various diseases including dermomyositis, liver and spleen swelling, undefined febrile diseases; lung cancer, lung shadow, etc.), 2 were positive (11.8%); of 16 sera from the people highly suspected with lyme disease living in the epidemic areas of Xin Jiang and Hei Long Jiang provinces, 12 were positive (75%). The same 165 sera samples were detected at the same time by VIDAS System and IFA, 24 were positive by VIDAS System (14.5%), and 131 positive by IFA (79%), the accordance rate was only 32.7%.

Antibodies, Bacterial↗

Elimination of frequency drift from Fourier transform ion cyclotron resonance mass spectra by digital quadrature heterodyning: ultrahigh mass resolving power for laser-desorbed molecules.

At sufficiently low pressure, FT-ICR mass resolving power is no longer pressure-limited. Rather, the observed spectral peaks are broadened by ion cyclotron frequency drift during the detection period, due to change in shape of the coherently orbiting ion packet during detection. The frequency drift may be quantitated by Fourier transformation of each of a series of consecutive segments of the time-domain ICR signal, followed by fitting the frequency vs time behavior to a polynomial in time. Correction for that frequency drift is then achieved by a digital quadrature procedure, followed by multiplication by a weight factor which removes the frequency drift. We demonstrate a 750-fold reduction in FT-ICR mass spectral peak width for pseudomolecular (M+K)+ ions of laser-desorbed leucine enkephalin (m/delta m = 1,300,000)! Moreover, correction based on the frequency drift of ions of a given m/z also corrects for frequency drift of ions of other m/z values, as demonstrated for isotopic peaks from (M+K)+ from gramicidin S (m/z 1179). Narrowing of the FT-ICR mass spectral peaks results in a corresponding increase in peak height-to-noise ratio as well. In addition, we propose a theoretical model for frequency drift during detection of the ion cyclotron resonance signal. Simultaneous relaxation of coherent cyclotron motion and compression of the axial distribution of an initially radially coherent ion packet account for ion cyclotron frequency drift during detection. The potential energy generated by mutual ion-ion Coulomb repulsions varies with ion cyclotron orbital radius as ions undergo collisional damping.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclotrons↗

Thin gold film-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry of biomolecules.

A new thin gold film-assisted (TGFA) laser desorption/ionization (LDI) technique has been combined with Fourier transform ion cyclotron resonance (FT-ICR) high-resolution mass analysis. A thermally labile organic sample is coated onto a thin gold film deposited on a glass plate and desorbed and ionized by Nd:YAG laser irradiation. The wavelength for maximum light absorption may be tuned by varying the thickness of the metal film; e.g., a 10-nm-thick gold film absorbs maximally near the Nd:YAG fundamental wavelength (1064 nm). A key advantage of the method is the stability of the gold film, which facilitates deposition of samples from any of a variety of solvent systems. Coupled with recently introduced quadrupolar excitation and collisional cooling for ion axialization, TGFA-LDI FT-ICR mass spectra provide high sensitivity (e.g., 100-fmol single-shot detection limit and mass resolving power, m/delta m approximately 113,000, for (M+K)+ ions from gramicidin S at m/z 1180).

Cellobiose↗

Enhanced mass resolving power, sensitivity, and selectivity in laser desorption Fourier transform ion cyclotron resonance mass spectrometry by ion axialization and cooling.

Ion cooling and axialization produced by azimuthal quadrupolar excitation in the presence of ion-neutral collisions are applied to laser desorption Fourier transform ion cyclotron resonance mass spectrometry (LD/FT/ICR-MS). With this technique, the large kinetic and internal energies of ions generated by laser desorption processes can be cooled effectively by collisions of ions with neutral argon atoms (at > 5 x 10(-7) Torr). After sufficient cooling in the source compartment of a dual ion trap, the axialized ions may be transferred to the analyzer compartment for detection at much lower pressure (and thus much higher mass resolving power). Enhancements in both FT/ICR mass resolving power and sensitivity are observed; moreover, ion isolation with high selectivity at high pressure is also demonstrated.

Argon↗

Stored waveform inverse Fourier transform axial excitation/ejection for quadrupole ion trap mass spectrometry.

A general method for high-resolution ion excitation, ejection, and isolation is developed from linear response theory for resonant dipolar excitation of the axial z-oscillatory motion of ions in a quadrupole (Paul) ion trap operated in rf-only mode. For a spatially uniform dipolar excitation field, the ion z-oscillation amplitude is directly proportional to the amplitude of the Fourier component of the excitation at the axial oscillation frequency of that ion. Thus, one may specify an arbitrary z-motion frequency-domain spectrum by applying a time-domain stored waveform obtained from the inverse Fourier transform of the corresponding frequency-domain excitation spectrum. The stored waveform inverse Fourier transform (SWIFT) waveform may be tailored for selective ejection or excitation of ions of arbitrary mass-to-charge ratio ranges. The method includes all other possible excitation/ejection waveforms (e.g., single frequency, frequency sweep) as special cases. The effect of collisional damping during excitation is included in the analytical solution of the ion response.

Algorithms↗

Multiply pulsed collision gas for ion axialization in Fourier-transform ion cyclotron resonance mass spectrometry.

We present a new multiply pulsed collision-gas technique for ion axialization for Fourier-transform ion cyclotron resonance (FTICR) high-resolution mass analysis. Ions are axialized in the source trap of a dual-trap FTICR spectrometer by azimuthal quadrupolar irradiation for several tens of seconds at a steady-state pressure maintained by repeated pulses of collision gas (argon), followed by removal of the collision gas and detection at a much lower pressure after transfer to the analyzer trap. Magnitude-mode FTICR mass resolving power, m/delta m approximately 1,770,000, for [M+K]+ ions from laser-desorbed/ionized leucine enkephalin at m/z 594 is demonstrated. This mass resolving power is the highest yet reported for a peptide with any type of laser desorption/ionization mass analyzer.

Argon↗

Renin, angiotensinogen, and kallikrein gene expression in two-kidney Goldblatt hypertensive rats.

An imbalance in the activity of the vasopressor renin-angiotensin and vasodepressor kallikrein-kinin systems may play an important role in the pathogenesis of hypertension after unilateral renal artery constriction. To test this hypothesis, we examined the expression of the renin, angiotensinogen (Ao), and tissue kallikrein genes 7 and 25 days after placement of a 0.25-mm clip on the left renal artery of rats. One week after clipping, renin mRNA levels were 4.6-fold higher in the clipped and 50% lower in the nonclipped kidneys compared with kidneys from sham-operated rats. At 25 days, renin mRNA levels in the clipped kidneys were not different from sham kidneys, but were suppressed to almost undetectable levels in the nonclipped kidneys. Steady-state Ao mRNA levels in the clipped kidneys were not different from those of nonclipped or sham kidneys at either 7 or 25 days. However, at 25 days, Ao mRNA levels were lower in the liver (70%), left ventricle (55%), and aorta (45%) of clipped than sham-operated rats. The expression of the renal kallikrein gene was unchanged at 7 days and was suppressed by 50% at 25 days. These results are consistent with the notion that activation of the intrarenal renin-angiotensin system occurs during the initial phase of the two-kidney, one-clip hypertension model. The renal kallikrein gene, in marked contrast to renin, becomes downregulated in the chronic phase. The differential regulation of renin-angiotensin and kallikrein genes may be an important pathogenetic factor in renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

Dietary Na and ACE inhibition effects on renal tissue angiotensin I and II and ACE activity in rats.

This study was designed to improve and validate methods for the accurate and consistent quantitation of angiotensin (ANG) I and II levels in rat kidney and to determine the effects on renal ANG I and II of changes in dietary sodium intake and ANG-converting enzyme (ACE) inhibition. Kidneys from pentobarbital-anesthetized rats were rapidly removed and homogenized in methanol before extraction and purification of ANG peptides by solid-phase extraction and high-performance liquid chromatography (HPLC). Recoveries of 125I-ANG I and II were greater than 80%. Reversed-phase HPLC of the partially purified methanol extract showed that greater than 75% of the ANG I- and greater than 82% of the ANG II-like immunoreactivity coeluted with ANG I and II, respectively. Dietary sodium deprivation (0.003 meq/g) and excess (1.34 meq/g) for 7 days significantly (P less than 0.01) increased and decreased renal ANG I (296 +/- 30 and 82.6 +/- 15.8 vs. 161 +/- 18 fmol/g) and ANG II (216 +/- 16 and 45.6 +/- 11.8 vs. 98 +/- 16 fmol/g) contents, respectively. Plasma ANG I and II levels showed similar changes. ACE activity was significantly upregulated by sodium deprivation in both kidney (44% increase) and plasma (30% increase). In rats fed normal chow, infusion of enalaprilat for 1 h abolished plasma ACE activity but decreased renal ACE activity by only 58%. ACE inhibition increased renal and plasma ANG I levels 2.8- and 12-fold, respectively, and decreased renal and plasma ANG II levels 75-78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats.

Renal tissue angiotensin I (Ang I) and II (Ang II) content and angiotensin converting enzyme activity were assessed in both kidneys during initial (7 days) and maintenance (25 days) phases of two-kidney, one clip hypertension in rats. At 7 and 25 days, systolic arterial pressure was 146 +/- 2 and 170 +/- 7 mm Hg, respectively. After 7 days, Ang I content of clipped kidneys was 64% and 70% higher (p < 0.001) than in nonclipped and sham-operated kidneys, respectively, when compared with levels in kidneys from sham-operated rats. In kidneys harvested 25 days after clipping one renal artery, Ang I and Ang II contents in clipped kidneys were increased 102% and 24% (p < 0.01), respectively. Ang II content was also 32% higher in nonclipped kidneys. Angiotensin converting enzyme activity in nonclipped kidneys was greater (p < 0.05) than that in either clipped (46% higher) or sham-operated kidneys (57% higher). Plasma Ang I and Ang II levels were elevated at 7 days but were not different at 25 days in clipped rats. These results demonstrate a dissociation between intrarenal and circulating levels of Ang I and Ang II and suggest that qualitatively different mechanisms may be responsible for the elevated intrarenal Ang II levels during the initial and maintenance phases of renal hypertension.

Angiotensin I↗

[Stability examination of the inclusion compounds of 8 Chinese medicinal volatile oils with beta-cyclodextrin].

The content, hence the stability of volatile oils and their main components in the inclusion compounds of 8 Chinese medicinal volatile oils with beta-cyclodextrin have been examined with different storage times. The 8 Chinese medicines are Vitex negundo var. heterophylla, Notopterygium incisum, Alpinia officinarum, Atractylodes lancea, Pogostenon cablin, Asarum heterotropoides var. mandshuricum, Schizonepeta tenuifolia and Amomum villosum.

Cyclodextrins↗

Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells.

Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity.

Animals↗