Ray Perkins - Academia.edu (original) (raw)
Papers by Ray Perkins
Journal of Biological Chemistry, 1981
Functional Proteomics, 2018
Proteases drive the life cycle of all proteins, ensuring the transportation and activation of new... more Proteases drive the life cycle of all proteins, ensuring the transportation and activation of newly minted, would-be proteins into their functional form while recycling spent or unneeded proteins. Far from their image as engines of protein digestion, proteases play fundamental roles in basic physiology and regulation at multiple levels of systems biology. Proteases are intimately associated with disease and modulation of proteolytic activity is the presumed target for successful therapeutics. "Proteases: Pivot Points in Functional Proteomics" examines the crucial roles of proteolysis across a wide range of physiological processes and diseases. The existing and potential impacts of proteolysis-related activity on drug and biomarker development are presented in detail. All told the decisive roles of proteases in four major categories comprising 23 separate subcategories are addressed. Within this construct, 15 sets of subject-specific, tabulated data are presented that include identification of proteases, protease inhibitors, substrates, and their actions. Said data are derived from and confirmed by over 300 references. Cross comparison of datasets indicates that proteases, their inhibitors/promoters and substrates intersect over a range of physiological processes and diseases, both chronic and pathogenic. Indeed, "Proteases: Pivot Points …" closes by dramatizing this very point through association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity, cardiovascular and metabolic disease, cancer, neurodegeneration, and bacterial self-defense.
4open, 2020
Based on high quality surgery and scientific data, scientists and surgeons are committed to prote... more Based on high quality surgery and scientific data, scientists and surgeons are committed to protecting patients as well as healthcare staff and hereby provide this Guidance to address the special issues circumstances related to the exponential spread of the Coronavirus disease 2019 (COVID-19) during this pandemic. As a basis, the authors used the British Intercollegiate General Surgery Guidance as well as recommendations from the USA, Asia, and Italy. The aim is to take responsibility and to provide guidance for surgery during the COVID-19 crisis in a simplified way addressing the practice of surgery, healthcare staff and patient safety and care. It is the responsibility of scientists and the surgical team to specify what is needed for the protection of patients and the affiliated healthcare team. During crises, such as the COVID-19 pandemic, the responsibility and duty to provide the necessary resources such as filters, Personal Protective Equipment (PPE) consisting of gloves, flui...
The Journal of Physical Chemistry, 1984
Detection hors phase a 90° des spectres RPE de R-4 tetramethyl-2,2,6,6 piperidinoxyle-1 (avec R=O... more Detection hors phase a 90° des spectres RPE de R-4 tetramethyl-2,2,6,6 piperidinoxyle-1 (avec R=OH, NH 2 , H 2 ou O) et de R-2 dihethyl-5,5 pyrrolidinoxyle-1 (avec R=COOH, CH 3 , CD 3 , OH ou OD), en solution aqueuse. Constantes de couplage superhyperfin des electrons avec les protons en γ et δ dans les composes piperidiniques. Conformations stables et interconversion de conformations
Journal of Magnetic Resonance (1969), 1983
Phloretin is a lipophilic compound which has been widely studied as a broad spectrum effector of ... more Phloretin is a lipophilic compound which has been widely studied as a broad spectrum effector of metabolite transport in red blood cells (RBC). Phloretin effects on the organization of lipids in the RBC membrane are investigated using the spin-labeled fatty acids, 5 and 16-nitroxyl stearate (5-NS and 16-N& respectively). Phloretin at different concentrations produced biphasic effects on the lineshape of the EPR response from 16-N!I-labeled RBC. The dependence of these changes on the flat cell orientation with respect to the magnetic field suggested that phloretin promoted lipid order at low concentrations (5 to 40 N) and disorder at high concentrations (40 to 250 &). The biphasic effects of phloretin occurred at concentrations which parallel its dual actions on metabolite transfer. Phloretin generally inhibits transport (protein-mediated) and stimulates diffusion (lipid-mediated) processes. The spectroscopic effects were best characterized through second-harmonic, in-phase detection. The possible contribution of other factors to the spectroscopic changes is discussed. When RBC were spin labeled with 5-NS, higher concentrations of the probe were required for adequate detection and only monophasic effects of phoretin were observed. The results suggest that membrane lipids are important in phloretin effects on transport and diffusion processes. l Recipients of a postdoctoral fellowship from the Muscular Dystrophy Association.
Proceedings of the National Academy of Sciences, 1980
It has been postulated that the degenerative process in dystrophic muscle results from increased ... more It has been postulated that the degenerative process in dystrophic muscle results from increased concentrations of free radicals, peroxides, or lipid hydroperoxides. Therefore, the reduction of the free radical tanol (2,2,6,6-tetramethyl-4-piperidinol-1-oxyl) by extracts of muscles of dystrophic and normal chickens was studied. Pectoral (white) and thigh (red) muscles were used. For initial rate measurements, the various muscle extracts were added to an equal volume of 0.2 mM tanol. Reaction mixtures were introduced into the EPR cavity in a standard aqueous flat cell. Rates were measured by continuously monitoring the decrease in signal amplitude of the center (MI = 0) solution tanol EPR resonance line (in-phase first harmonic absorption signal). With extracts from dystrophic white muscle, the reduction rate was 75% faster than normal, whereas in dystrophic red muscle extracts the rate was normal. This agreed with previous observations that white muscle is more severely affected tha...
Journal of Labelled Compounds and Radiopharmaceuticals, 1981
p i p e r i d i n y l)maleimide has been prepared to improve sensitivity and resolution in its ES... more p i p e r i d i n y l)maleimide has been prepared to improve sensitivity and resolution in its ESR spectrum. The synthesis involved modifications of procedures known for the corresponding protonated analog. Spectral data are presented for the product to establish isotopic purity. A five-fold enhancement of the ESR signal for the title compound relative to the proton counterpart has been observed.
Chemical Physics Letters, 1980
Abstract The spin label, perdeuterio-N-(1-oxy 1-2, 2, 6, 6-tetramenthyl-4-piperidinyl) maleimide ... more Abstract The spin label, perdeuterio-N-(1-oxy 1-2, 2, 6, 6-tetramenthyl-4-piperidinyl) maleimide (DMSL) was synthesized and its EPR and saturation transfer EPR spectra were compared to those of the hydrogen analogue, HMSL-The labels were studied as freely ...
Chemical Physics Letters, 1980
ENDOR spectra of the spin label N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) maleimide bound to l... more ENDOR spectra of the spin label N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) maleimide bound to lyophilized human oxyhemoglobin suggest a principal element of 3.7 MHz for the largest proton hyperfine tensor. The absence of orientation selection justifies the use of an isotropic ...
Chemical Physics, 1974
... t6 des Sciences de Paris. *S Alfred P. Sloan Fellow. spins with the applied Zee man modulatio... more ... t6 des Sciences de Paris. *S Alfred P. Sloan Fellow. spins with the applied Zee man modulation field into the stochastic Liouville equation for the spin density matrix. ... We easily find: d(J dr = ss(J (A w) V, W sin r, (4a) dV dr fiV, + (. ) U, W cos (4b) dWfdT = aW+a+V0iV. ...
Chemical Physics, 1976
A density matrix-transition rate matrix formalism is employed to compute the eight unique electro... more A density matrix-transition rate matrix formalism is employed to compute the eight unique electron paramagnetic resonance signals at the first two harmonics of the applied Zeeman modulation. Calculations arc carried out for conditions appropriate for investigating spin-labeled biomoleculcs with partially saturating microwave tields and Zeeman modulation amplitudes comparable to resonance linewidths. Spectra are computed for rotational correlation times ranging from 10-' to 10e3 s and for modulation frequencies of 50 and 100 kHz. These simulations indicate that of the eight signals the in-phase dispersion signal at the first harmonic of the modulation and the out-of-phase dispersion signal at the tirst harmonic afford the best sensitivity to molecular motion and the largest signal amplitudes. It is suggested that study of these signals is the method of choice for monitoring slowly tumbling spin labels when signal-to-noise considerations are critical. The conclusions derived from computer simulations arc borne out by experimental measurements performed on 10m3 M solutions of the steroid spin label 17&hydroxy~',4'dimethylspiro-[5a_andro~an~-3,Z'~xazo~din]-3'~xyl in see-butyfhenaene.
Biochemistry, 1982
Electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies were us... more Electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies were used to characterize the binding of spin-labeled fatty acid (SLFA) to bovine serum albumin (BSA). Association constants of three stearic acid derivatives labeled with a nitroxyl radical at C-5, C-12, or C-16 were estimated by EPR spectroscopy as the ratio of SLFA to BSA was increased from about 0 to 9. The values were compared to those for unmodified stearate. With all three SLFA, it was apparent that the nitroxyl residue modified the binding pattern. For SLFA:BSA ratios up to
Proceedings of the National Academy of Sciences, 1978
Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-di... more Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to diffe...
The Journal of Membrane Biology, 1980
Proceedings of The National Academy of Sciences, 1978
Saturation transfer electron paramagnetic resonance and the spin label 2(3-carboxypropyl)4,4-dime... more Saturation transfer electron paramagnetic resonance and the spin label 2(3-carboxypropyl)4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne
Journal of Biological Chemistry, 1981
Functional Proteomics, 2018
Proteases drive the life cycle of all proteins, ensuring the transportation and activation of new... more Proteases drive the life cycle of all proteins, ensuring the transportation and activation of newly minted, would-be proteins into their functional form while recycling spent or unneeded proteins. Far from their image as engines of protein digestion, proteases play fundamental roles in basic physiology and regulation at multiple levels of systems biology. Proteases are intimately associated with disease and modulation of proteolytic activity is the presumed target for successful therapeutics. "Proteases: Pivot Points in Functional Proteomics" examines the crucial roles of proteolysis across a wide range of physiological processes and diseases. The existing and potential impacts of proteolysis-related activity on drug and biomarker development are presented in detail. All told the decisive roles of proteases in four major categories comprising 23 separate subcategories are addressed. Within this construct, 15 sets of subject-specific, tabulated data are presented that include identification of proteases, protease inhibitors, substrates, and their actions. Said data are derived from and confirmed by over 300 references. Cross comparison of datasets indicates that proteases, their inhibitors/promoters and substrates intersect over a range of physiological processes and diseases, both chronic and pathogenic. Indeed, "Proteases: Pivot Points …" closes by dramatizing this very point through association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity, cardiovascular and metabolic disease, cancer, neurodegeneration, and bacterial self-defense.
4open, 2020
Based on high quality surgery and scientific data, scientists and surgeons are committed to prote... more Based on high quality surgery and scientific data, scientists and surgeons are committed to protecting patients as well as healthcare staff and hereby provide this Guidance to address the special issues circumstances related to the exponential spread of the Coronavirus disease 2019 (COVID-19) during this pandemic. As a basis, the authors used the British Intercollegiate General Surgery Guidance as well as recommendations from the USA, Asia, and Italy. The aim is to take responsibility and to provide guidance for surgery during the COVID-19 crisis in a simplified way addressing the practice of surgery, healthcare staff and patient safety and care. It is the responsibility of scientists and the surgical team to specify what is needed for the protection of patients and the affiliated healthcare team. During crises, such as the COVID-19 pandemic, the responsibility and duty to provide the necessary resources such as filters, Personal Protective Equipment (PPE) consisting of gloves, flui...
The Journal of Physical Chemistry, 1984
Detection hors phase a 90° des spectres RPE de R-4 tetramethyl-2,2,6,6 piperidinoxyle-1 (avec R=O... more Detection hors phase a 90° des spectres RPE de R-4 tetramethyl-2,2,6,6 piperidinoxyle-1 (avec R=OH, NH 2 , H 2 ou O) et de R-2 dihethyl-5,5 pyrrolidinoxyle-1 (avec R=COOH, CH 3 , CD 3 , OH ou OD), en solution aqueuse. Constantes de couplage superhyperfin des electrons avec les protons en γ et δ dans les composes piperidiniques. Conformations stables et interconversion de conformations
Journal of Magnetic Resonance (1969), 1983
Phloretin is a lipophilic compound which has been widely studied as a broad spectrum effector of ... more Phloretin is a lipophilic compound which has been widely studied as a broad spectrum effector of metabolite transport in red blood cells (RBC). Phloretin effects on the organization of lipids in the RBC membrane are investigated using the spin-labeled fatty acids, 5 and 16-nitroxyl stearate (5-NS and 16-N& respectively). Phloretin at different concentrations produced biphasic effects on the lineshape of the EPR response from 16-N!I-labeled RBC. The dependence of these changes on the flat cell orientation with respect to the magnetic field suggested that phloretin promoted lipid order at low concentrations (5 to 40 N) and disorder at high concentrations (40 to 250 &). The biphasic effects of phloretin occurred at concentrations which parallel its dual actions on metabolite transfer. Phloretin generally inhibits transport (protein-mediated) and stimulates diffusion (lipid-mediated) processes. The spectroscopic effects were best characterized through second-harmonic, in-phase detection. The possible contribution of other factors to the spectroscopic changes is discussed. When RBC were spin labeled with 5-NS, higher concentrations of the probe were required for adequate detection and only monophasic effects of phoretin were observed. The results suggest that membrane lipids are important in phloretin effects on transport and diffusion processes. l Recipients of a postdoctoral fellowship from the Muscular Dystrophy Association.
Proceedings of the National Academy of Sciences, 1980
It has been postulated that the degenerative process in dystrophic muscle results from increased ... more It has been postulated that the degenerative process in dystrophic muscle results from increased concentrations of free radicals, peroxides, or lipid hydroperoxides. Therefore, the reduction of the free radical tanol (2,2,6,6-tetramethyl-4-piperidinol-1-oxyl) by extracts of muscles of dystrophic and normal chickens was studied. Pectoral (white) and thigh (red) muscles were used. For initial rate measurements, the various muscle extracts were added to an equal volume of 0.2 mM tanol. Reaction mixtures were introduced into the EPR cavity in a standard aqueous flat cell. Rates were measured by continuously monitoring the decrease in signal amplitude of the center (MI = 0) solution tanol EPR resonance line (in-phase first harmonic absorption signal). With extracts from dystrophic white muscle, the reduction rate was 75% faster than normal, whereas in dystrophic red muscle extracts the rate was normal. This agreed with previous observations that white muscle is more severely affected tha...
Journal of Labelled Compounds and Radiopharmaceuticals, 1981
p i p e r i d i n y l)maleimide has been prepared to improve sensitivity and resolution in its ES... more p i p e r i d i n y l)maleimide has been prepared to improve sensitivity and resolution in its ESR spectrum. The synthesis involved modifications of procedures known for the corresponding protonated analog. Spectral data are presented for the product to establish isotopic purity. A five-fold enhancement of the ESR signal for the title compound relative to the proton counterpart has been observed.
Chemical Physics Letters, 1980
Abstract The spin label, perdeuterio-N-(1-oxy 1-2, 2, 6, 6-tetramenthyl-4-piperidinyl) maleimide ... more Abstract The spin label, perdeuterio-N-(1-oxy 1-2, 2, 6, 6-tetramenthyl-4-piperidinyl) maleimide (DMSL) was synthesized and its EPR and saturation transfer EPR spectra were compared to those of the hydrogen analogue, HMSL-The labels were studied as freely ...
Chemical Physics Letters, 1980
ENDOR spectra of the spin label N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) maleimide bound to l... more ENDOR spectra of the spin label N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) maleimide bound to lyophilized human oxyhemoglobin suggest a principal element of 3.7 MHz for the largest proton hyperfine tensor. The absence of orientation selection justifies the use of an isotropic ...
Chemical Physics, 1974
... t6 des Sciences de Paris. *S Alfred P. Sloan Fellow. spins with the applied Zee man modulatio... more ... t6 des Sciences de Paris. *S Alfred P. Sloan Fellow. spins with the applied Zee man modulation field into the stochastic Liouville equation for the spin density matrix. ... We easily find: d(J dr = ss(J (A w) V, W sin r, (4a) dV dr fiV, + (. ) U, W cos (4b) dWfdT = aW+a+V0iV. ...
Chemical Physics, 1976
A density matrix-transition rate matrix formalism is employed to compute the eight unique electro... more A density matrix-transition rate matrix formalism is employed to compute the eight unique electron paramagnetic resonance signals at the first two harmonics of the applied Zeeman modulation. Calculations arc carried out for conditions appropriate for investigating spin-labeled biomoleculcs with partially saturating microwave tields and Zeeman modulation amplitudes comparable to resonance linewidths. Spectra are computed for rotational correlation times ranging from 10-' to 10e3 s and for modulation frequencies of 50 and 100 kHz. These simulations indicate that of the eight signals the in-phase dispersion signal at the first harmonic of the modulation and the out-of-phase dispersion signal at the tirst harmonic afford the best sensitivity to molecular motion and the largest signal amplitudes. It is suggested that study of these signals is the method of choice for monitoring slowly tumbling spin labels when signal-to-noise considerations are critical. The conclusions derived from computer simulations arc borne out by experimental measurements performed on 10m3 M solutions of the steroid spin label 17&hydroxy~',4'dimethylspiro-[5a_andro~an~-3,Z'~xazo~din]-3'~xyl in see-butyfhenaene.
Biochemistry, 1982
Electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies were us... more Electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies were used to characterize the binding of spin-labeled fatty acid (SLFA) to bovine serum albumin (BSA). Association constants of three stearic acid derivatives labeled with a nitroxyl radical at C-5, C-12, or C-16 were estimated by EPR spectroscopy as the ratio of SLFA to BSA was increased from about 0 to 9. The values were compared to those for unmodified stearate. With all three SLFA, it was apparent that the nitroxyl residue modified the binding pattern. For SLFA:BSA ratios up to
Proceedings of the National Academy of Sciences, 1978
Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-di... more Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to diffe...
The Journal of Membrane Biology, 1980
Proceedings of The National Academy of Sciences, 1978
Saturation transfer electron paramagnetic resonance and the spin label 2(3-carboxypropyl)4,4-dime... more Saturation transfer electron paramagnetic resonance and the spin label 2(3-carboxypropyl)4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne