Melvin Blaze - Academia.edu (original) (raw)

Papers by Melvin Blaze

Analytical Chemistry, Apr 16, 2012

Experiments were performed to examine the feasibility of mass spectrometry (MS) depth profiling o... more Experiments were performed to examine the feasibility of mass spectrometry (MS) depth profiling of animal tissue by ∼75 fs, 800 nm laser pulses to expose underlying layers of tissue for subsequent MS analysis. Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) was used to analyze phospholipids and proteins from both intact bovine eye lens tissue and tissue ablated by ultrashort laser pulses. Laser desorption postionization mass spectrometry (LDPI-MS) with 10.5 eV single photon ionization was also used to analyze cholesterol and other small molecules in the tissue before and after laser ablation. Scanning electron microscopy was applied to examine the ablation patterns in the tissue and estimate the depth of the ablation craters. Ultrashort pulse laser ablation was found to be able to remove a layer of several tens of micrometers from the surface of eye lens tissue while leaving the underlying tissue relatively undamaged for subsequent MS analysis. MS analysis of cholesterol, phospholipids, peptides, and various unidentified species did not reveal any chemical damage caused by ultrashort pulse laser ablation for analytes smaller than ∼6 kDa. However, a drop in intensity of larger protein ions was detected by MALDI-MS following laser ablation. An additional advantage was that ablated tissue displayed up to an order of magnitude higher signal intensities than intact tissue when subsequently analyzed by MS. These results support the use of ultrashort pulse laser ablation in combination with MS analysis to permit depth profiling of animal tissue.

Analytical Chemistry, Oct 10, 2012

The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small mo... more The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small molecule quantification is demonstrated here. The N-methylpiperazine acetamide of (MPA) ampicillin was adsorbed into polyelectrolyte multilayer surface coatings composed of chitosan and alginate, both high molecular weight biopolymers. These MPA-ampicillin spiked multilayers were then shown to inhibit the growth of E. faecalis biofilms that play a role in early stage infection of implanted medical devices. Finally, LDPI-MS imaging using 7.87 eV single photon ionization was found to detect MPA-ampicillin with the multilayers before and after biofilm growth with limits of quantification and detection of 0.6 and 0.3 nmoles, respectively. The capabilities of LDPI-MS imaging for small molecule quantification are compared to those of MALDI-MS. Furthermore, these results indicate that 7.87 eV LDPI-MS imaging should be applicable to quantification of a range of small molecular species on a variety of complex organic and biological surfaces. Finally, while MS imaging for quantification was demonstrated here using LDPI, it is a generally useful strategy that can be applied to other methods.

Rapid Communications in Mass Spectrometry, May 4, 2021

Mixed-mode reversed-phase/anion exchange liquid chromatography is useful for separations of mixtu... more Mixed-mode reversed-phase/anion exchange liquid chromatography is useful for separations of mixtures containing anions (e.g. ionized acids). However, when using this form of liquid chromatography with mass spectrometry detection, the bleed of amine-containing hydrolysis products from the columns may cause ion suppression or enhancement. Methods: Using electrospray ionization tandem quadrupole mass spectrometry detection, we determined the ion suppression or enhancement caused by column bleed for three mixed-mode reversed-phase/weak anion-exchange columns containing stationary phases that differ in chemical structure. Two of the stationary phases are based on silica particles, while the third uses ethylene-bridged hybrid organic/inorganic particles, which have improved hydrolytic stability. Mixtures of acidic and basic analytes were combined with the chromatography flow postcolumn, both with and without a column, and their mass spectrometry ion signal responses (peak areas) were determined. The ratio of signal response with and without a column is the matrix factor. Positive ion electrospray measurements were carried out using 0.1% formic acid (pH $ 2.7) as a mobile phase additive, and 10mM ammonium formate (pH $ 6.4) was used for negative ion electrospray detection. Results: The matrix factors under both positive and negative ionization modes were closest to 1 (0.74-1.16) for the hybrid particle-based columns, showing minimal ion suppression or enhancement. In contrast, the silica-based columns gave matrix factors ranging from 0.04 to 1.86, indicating high levels of ion suppression or enhancement. These results may be explained by the differences in the structures of the stationary phases, which affect the relative amounts of hydrolysis products that elute from the columns. Conclusions: The low levels of mass spectrometry ion suppression or enhancement caused by column bleed from the hybrid particle-based columns should allow for accurate quantitative mass spectrometric detection combined with mixed-mode reversed-phase/weak anion-exchange chromatography.

Journal of Nutrition, May 1, 2018

Background: Higher-protein meals (>25 g protein/meal) have been associated with enhanced satiety ... more Background: Higher-protein meals (>25 g protein/meal) have been associated with enhanced satiety but the role of amino acids is unclear. Leucine has been proposed to stimulate satiety in rodents but has not been assessed in humans. Objective: We assessed the acute effects of lower-protein nutrition bars, enhanced with a leucine peptide (LP), on postprandial appetite sensations in combination with plasma leucine and peptide YY (PYY) in healthy women. Methods: Utilizing a double-blind randomized crossover design, 40 healthy women [28 ± 7.5 y; body mass index (BMI, in kg/m 2): 23.5 ± 2.4] consumed the following isocaloric (180 kcal) pre-loads on 3 separate visits: control bar [9 g protein with 0 g added LP (0-g LP)] or treatment bars [11 g protein with 2 g added LP (2-g LP) or 13 g protein with 3 g added LP (3-g LP)]. Pre-and postprandial hunger, desire to eat, prospective food consumption (PFC), fullness, and plasma leucine were assessed every 30 min for 240 min. Plasma PYY was assessed hourly for 240 min (n = 24). Results: Main effects of time (P < 0.0001) and treatment (P < 0.03) were detected for postprandial hunger, desire to eat, PFC, and fullness. Post hoc analyses revealed that the 2-g and 3-g LP bars elicited greater increases in fullness and greater decreases in PFC compared with 0-g LP (all, P < 0.05) with no differences between the 2-g and 3-g LP bars. The 2-g bar elicited greater decreases in hunger and desire to eat compared with the 0-g LP bar (both, P ≤ 0.01), whereas 3-g LP did not. Appetite incremental areas under the curves (iAUCs) and PYY outcomes were not different between bars. A treatment × time interaction was detected for plasma leucine with increases occurring in a leucine-dose-dependent manner (P < 0.0001). Conclusion: Despite the dose-dependent increases in plasma leucine following the consumption of lower-protein bars enhanced with LP, only the 2-g LP bar elicited consistent postprandial changes in select appetite sensations compared with the 0-g LP bar. This study was registered on clinicaltrials.gov as NCT02091570.

Analyst, 2012

The heptapeptide ARHPHPH was identified from biofilms and planktonic cultures of two different st... more The heptapeptide ARHPHPH was identified from biofilms and planktonic cultures of two different strains of Enterococcus faecalis, V583 and ATCC 29212, using matrix assisted laser desorption ionization mass spectrometry (MALDI-MS). ARHPHPH was also imaged at the boundary of cocultured, adjacent E. faecalis and Escherichia coli (ATCC 25922) biofilms, appearing only on the E. faecalis side. ARHPHPH was proteolyzed from κ-casein, a component in the growth media, by E. faecalis microbes. Additionally, top down and bottom up proteomic approaches were combined to identify and spatially locate multiple proteins within intact E. faecalis V583 biofilms by MALDI-MS. The resultant tandem MS data were searched against the NCBInr E. faecalis V583 database to identify thirteen cytosolic and membrane proteins which have functional association with the cell surface. Two of these proteins, enolase and GAPDH, are glycolytic enzymes known to display multiple functions in bacterial virulence in related bacterial strains. This work illustrates a powerful approach for discovering and localizing multiple peptides and proteins within intact biofilms.

Analytical Chemistry, 2011

The Journal of nutrition, Jan 20, 2018

Higher-protein meals (>25 g protein/meal) have been associated with enhanced satiety but the r... more Higher-protein meals (>25 g protein/meal) have been associated with enhanced satiety but the role of amino acids is unclear. Leucine has been proposed to stimulate satiety in rodents but has not been assessed in humans. We assessed the acute effects of lower-protein nutrition bars, enhanced with a leucine peptide (LP), on postprandial appetite sensations in combination with plasma leucine and peptide YY (PYY) in healthy women. Utilizing a double-blind randomized crossover design, 40 healthy women [28 ± 7.5 y; body mass index (BMI, in kg/m2): 23.5 ± 2.4] consumed the following isocaloric (180 kcal) pre-loads on 3 separate visits: control bar [9 g protein with 0 g added LP (0-g LP)] or treatment bars [11 g protein with 2 g added LP (2-g LP) or 13 g protein with 3 g added LP (3-g LP)]. Pre- and postprandial hunger, desire to eat, prospective food consumption (PFC), fullness, and plasma leucine were assessed every 30 min for 240 min. Plasma PYY was assessed hourly for 240 min (n = 24...

Rapid Communications in Mass Spectrometry

The British journal of nutrition, 2016

Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular functi... more Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0-7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30-65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective ...

The British journal of nutrition, 2016

Objectives: To determine the degree of non-enzymatic collagen cross-linking of human crown dentin... more Objectives: To determine the degree of non-enzymatic collagen cross-linking of human crown dentin treated with various cross-linking agents used at different exposure times. Methods: Dentin surfaces were analyzed using attenuated total reflectance fourier transform-infrared spectroscopy (ATR-FTIR). Spectra were recorded using a FTLA2000 Series spectrometer (ABB Bomem Inc.) in the range of 400-4000 cm-1 using single-beam with 4 cm-1 resolution and averaging 256 scans. Spectra from the same sections (N=5) were obtained at different timepoints: undemineralized, demineralized surface (20-sec 35% phosphoric acid), cumulative exposure to cross-linking agents: 5% glutaraldehyde, carbodiimide/N-Hydroxysuccinimide (5.75%/1.38% w:v in water), and grape seed extract (6.5 % and 30% GSE w:v in water) for 30-sec, 60-sec, 2-min, 5-min and 10-min. The data was statistically analyzed by Kruskal-Wallis test, followed by Mann-Whitney analysis for independent samples (cross-linking agents), and Wilcoxo...

Molecular Diversity, 2005

Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently... more Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.

The Analyst, 2012

Analytical Chemistry, 2012

Experiments were performed to examine the feasibility of MS depth profiling of animal tissue bỹ 7... more Experiments were performed to examine the feasibility of MS depth profiling of animal tissue bỹ 75 fs, 800 nm laser pulses to expose underlying layers of tissue for subsequent MS analysis. Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) was used to analyze phospholipids and proteins from both intact bovine eye lens tissue and tissue ablated by ultrashort laser pulses. Laser desorption postionization (LDPI-MS) with 10.5 eV single photon ionization was also used to analyze cholesterol and other small molecules in the tissue before and after laser ablation. Scanning electron microscopy was applied to examine the ablation patterns in the tissue and estimate the depth of the ablation craters. Ultrashort pulse laser ablation was found able to remove a layer of several tens of micrometers from the surface of eye lens tissue while leaving the underlying tissue relatively undamaged for subsequent MS analysis. MS analysis of cholesterol, phospholipids, peptides, and various unidentified species did not reveal any chemical damage caused by ultrashort pulse laser ablation for analytes smaller than ~6 kDa. However, a drop in intensity of larger protein ions was detected by MALDI-MS following laser ablation. An additional advantage was that ablated tissue displayed up to an order of magnitude higher signal intensities than intact tissue when subsequently analyzed by MS. These results support the use of ultrashort pulse laser ablation in combination with MS analysis to permit depth profiling of animal tissue.

Analytical Chemistry, 2012

The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small mo... more The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small molecule quantification is demonstrated here. The N-methylpiperazine acetamide (MPA) of ampicillin was adsorbed into polyelectrolyte multilayer surface coatings composed of chitosan and alginate, both high molecular weight biopolymers. These MPA-ampicillin spiked multilayers were then shown to inhibit the growth of Enterococcus faecalis biofilms that play a role in early stage infection of implanted medical devices. Finally, LDPI-MS imaging using 7.87 eV single-photon ionization was found to detect MPA-ampicillin within the multilayers before and after biofilm growth with limits of quantification and detection of 0.6 and 0.3 nmol, respectively. The capabilities of LDPI-MS imaging for small molecule quantification are compared to those of MALDI-MS. Furthermore, these results indicate that 7.87 eV LDPI-MS imaging should be applicable to quantification of a range of small molecular species on a variety of complex organic and biological surfaces. Finally, while MS imaging for quantification was demonstrated here using LDPI, it is a generally useful strategy that can be applied to other methods.

Analytical Chemistry, 2011

The small molecular analyte 3,5-dibromotyrosine (Br 2 Y) and chitosan-alginate polyelectrolyte mu... more The small molecular analyte 3,5-dibromotyrosine (Br 2 Y) and chitosan-alginate polyelectrolyte multilayers (PEM) with and without adsorbed Br 2 Y were analyzed by laser desorption postionization mass spectrometry (LDPI-MS). LDPI-MS using 7.87 eV laser and tunable 8 -12.5 eV synchrotron vacuum ultraviolet (VUV) radiation found that desorption of clusters from Br 2 Y films allowed detection by ≤8 eV single photon ionization. Thermal desorption and electronic structure calculations determined the ionization energy of Br 2 Y to be ~8.3±0.1 eV and further indicated that the lower ionization energies of clusters permitted their detection at ≤8 eV photon energies. However, single photon ionization could only detect Br 2 Y adsorbed within PEMs when using either higher photon energies or matrix addition to the sample. All samples were also analyzed by 25 keV Bi 3 + secondary ion mass spectrometry (SIMS), with the negative ion spectra showing strong parent ion signal which complemented that observed by LDPI-MS. However, the negative ion SIMS appeared strongly dependent on the high electron affinity of this specific analyte and the analyte's condensed phase environment.

Analytical Chemistry, Apr 16, 2012

Analytical Chemistry, Oct 10, 2012

Rapid Communications in Mass Spectrometry, May 4, 2021

Journal of Nutrition, May 1, 2018

Analyst, 2012

Analytical Chemistry, 2011

The Journal of nutrition, Jan 20, 2018

Rapid Communications in Mass Spectrometry

The British journal of nutrition, 2016

Molecular Diversity, 2005

The Analyst, 2012

Analytical Chemistry, 2012

The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small mo... more The potential of laser desorption postionization mass spectrometry (LDPI-MS) imaging for small molecule quantification is demonstrated here. The N-methylpiperazine acetamide (MPA) of ampicillin was adsorbed into polyelectrolyte multilayer surface coatings composed of chitosan and alginate, both high molecular weight biopolymers. These MPA-ampicillin spiked multilayers were then shown to inhibit the growth of Enterococcus faecalis biofilms that play a role in early stage infection of implanted medical devices. Finally, LDPI-MS imaging using 7.87 eV single-photon ionization was found to detect MPA-ampicillin within the multilayers before and after biofilm growth with limits of quantification and detection of 0.6 and 0.3 nmol, respectively. The capabilities of LDPI-MS imaging for small molecule quantification are compared to those of MALDI-MS. Furthermore, these results indicate that 7.87 eV LDPI-MS imaging should be applicable to quantification of a range of small molecular species on a variety of complex organic and biological surfaces. Finally, while MS imaging for quantification was demonstrated here using LDPI, it is a generally useful strategy that can be applied to other methods.

Analytical Chemistry, 2011