Cynthia Husted - Academia.edu (original) (raw)

Papers by Cynthia Husted

Magnetic Resonance in Medicine, 1993

We have obtained high‐field (11.7 Tesla), high‐resolution carbon‐13 solid‐state “magic‐angle” sam... more We have obtained high‐field (11.7 Tesla), high‐resolution carbon‐13 solid‐state “magic‐angle” sample‐spinning nuclear magnetic resonance (NMR) spectra of a variety of phospholipids, sphingolipids, myelin and white matter samples, resolving and assigning over 40 resonances in the spectra of human and bovine myelin. The NMR results indicated no large spectral changes due to sample preparation, sample freezing, or brain location, and also no changes in myelin structure detectable via light microscopy, electron microscopy, thin layer chromatography, or sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, attributable to the sometimes lengthy NMR data acquisition process. Human myelin and white matter chemical shift assignments were made based on 13C “magic angle” sample spinning (MAS) NMR spectra of individual model lipids, as well as on spectra of lipid mixtures. In all myelin samples there were essentially no features attributable to membrane proteins, with the exception of one ...

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2004

A morphological transformation involving loss of adhesion between myelin lamellae and formation o... more A morphological transformation involving loss of adhesion between myelin lamellae and formation of myelin vesicles has been described as a mechanism for demyelination in multiple sclerosis and marmoset experimental allergic encephalomyelitis (EAE). Although protein interactions are involved in maintaining normal myelin structure, we describe here how lipids contribute to myelin stability and how lipid changes in EAE, including increases in lipid polyunsaturation and negatively charged phosphatidylserine (PS), promote demyelination. Three physico-chemical techniques were used to identify these changes: (1) Langmuir monolayer isotherms indicated that EAE white matter lipids were significantly more 'expanded' (fluid) than controls. (2) NMR spectroscopy indicated that EAE myelin lipids were more polyunsaturated than controls. (3) High-performance liquid chromatography (HPLC) with an evaporative light scattering detector indicated increased PS in EAE compared to controls, while sphingomyelin (SM), sulfatides and phosphatidylcholine (PC) were decreased. We present a physical model considering electrostatic, van der Waals and undulation forces to quantify the effect of these changes on myelin adhesion at the extracellular interface. Taken together, the isotherm, NMR, HPLC and modeling results support a mechanism for autoimmune demyelination whereby the composition of myelin lipids is altered in a manner that increases myelin fluidity, decreases myelin adhesion, increases membrane curvature, and promotes vesiculation.

Annals of Neurology, Aug 1, 1994

The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesi... more The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal-appearing white matter by evaluating the spectral broad component from phosphorus 3 1 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p < : 0.001) in both lesions and in normal-appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times. Husted CA, Matson GB, Adams DA, Goodin DS, Weiner MW. In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging.

Journal of Structural Biology, 2001

Myelin is one of the few biological membranes to contain the lipid galactocerebrosides, although ... more Myelin is one of the few biological membranes to contain the lipid galactocerebrosides, although their role in myelin is unclear. To explore its structural role, we used fluorescence and atomic force microscopy (AFM) to study nonhydroxy galactocerebrosides (NCer) at the air-water interface of a Langmuir-Blodgett trough. Fluorescence microscopy at the air-water interface indicated that NCer forms micrometer scale domains of varying radii with six fractal-like extensions. Atomic force microscopy using TappingMode in water on samples transferred to mica confirmed the fractal-like domain structure in the absence of dye and showed that the domains consisted of many aggregated nanotubes with a diameter of 30 nm. The Hausdorf fractal dimension was estimated to be 1.26 and 1.11 for two domains imaged with AFM. This evidence indicates that NCer forms a bulk phase of nanotubes at the air-water interface, unlike the liquidcondensed phase of a phospholipid monolayer. That NCer forms bilayer nanotubes that aggregate strongly suggests NCer helps maintain the stability of myelin by contributing to the curvature and adhesion of the membrane. We found that NCer appears to be decreased in myelin from multiple sclerosis normal appearing white matter, which could be an important event in the loss of myelin stability.

Proceedings of the National Academy of Sciences, 2006

Current Opinion in Neurology, Jun 1, 1994

Biochimica Et Biophysica Acta: Molecular Basis Of Disease, 2004

A morphological transformation involving loss of adhesion between myelin lamellae and formation o... more A morphological transformation involving loss of adhesion between myelin lamellae and formation of myelin vesicles has been described as a mechanism for demyelination in multiple sclerosis and marmoset experimental allergic encephalomyelitis (EAE). Although protein interactions are involved in maintaining normal myelin structure, we describe here how lipids contribute to myelin stability and how lipid changes in EAE, including increases in lipid polyunsaturation and negatively charged phosphatidylserine (PS), promote demyelination. Three physico-chemical techniques were used to identify these changes: (1) Langmuir monolayer isotherms indicated that EAE white matter lipids were significantly more 'expanded' (fluid) than controls. (2) NMR spectroscopy indicated that EAE myelin lipids were more polyunsaturated than controls. (3) High-performance liquid chromatography (HPLC) with an evaporative light scattering detector indicated increased PS in EAE compared to controls, while sphingomyelin (SM), sulfatides and phosphatidylcholine (PC) were decreased. We present a physical model considering electrostatic, van der Waals and undulation forces to quantify the effect of these changes on myelin adhesion at the extracellular interface. Taken together, the isotherm, NMR, HPLC and modeling results support a mechanism for autoimmune demyelination whereby the composition of myelin lipids is altered in a manner that increases myelin fluidity, decreases myelin adhesion, increases membrane curvature, and promotes vesiculation.

PubMed, Sep 1, 1999

Context: The greatest needs of people with chronic conditions are long-term care, maximized indep... more Context: The greatest needs of people with chronic conditions are long-term care, maximized independence, and improved quality of life. With conventional medicine becoming increasingly expensive, depersonalized, and unable to adequately meet such needs, many with chronic conditions are seeking health promotion strategies to effectively manage their symptoms. Objective: An 8-week t'ai chi program was conducted to explore psychosocial and physical benefits for those with multiple sclerosis. Design: Nonrandomized, noncontrolled pilot study. Setting: American College of Traditional Chinese Medicine, San Francisco, Calif. Patients: 19 patients with multiple sclerosis. Intervention: T'ai chi. Main outcome measures: Walking speed (distance = 25 ft), hamstring flexibility, and psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-form Health Survey. Results: Walking speed increased by 21% and hamstring flexibility increased by 28%. Patients experienced improvements in vitality, social functioning, mental health, and ability to carry out physical and emotional roles. Conclusions: This pilot program was conducted entirely on a volunteer basis and led to the implementation of several additional t'ai chi classes for people with multiple sclerosis across the United States. T'ai chi and other health promotion programs offer help toward achieving the goals of increasing access to services, maximizing independence, and improving quality of life for people with chronic disabling conditions.

Journal of Organic Chemistry, Nov 1, 1983

1-Acetyl-3,4-dihydronaphthalene appears to be the usual reduction product of the reaction without... more 1-Acetyl-3,4-dihydronaphthalene appears to be the usual reduction product of the reaction without mention of any detection of the expected 1,4-dihydro product. However, sodium-ammonia reductions of 1-acetylnaphthalene and its 4-methyl and 4-ethyl derivatives provide the corresponding 1,4-dihydro products in essentially quantitative yields. These products appear to be stable and no facile conversion to the conjugated isomers was noted.

Proceedings of the National Academy of Sciences of the United States of America, Sep 7, 2004

This report describes force measurements and atomic force microscope imaging of lipid-protein int... more This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid ''hole-filler,'' effectively preventing defect holes from developing. From our protein-mediated-adhesion and forcedistance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the ''important ones'' may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.

Journal of the American Chemical Society, Feb 1, 1988

We have obtained proton ('H) "magic-angle" sample-spinning (MASS) nuclear magnetic resonance (NMR... more We have obtained proton ('H) "magic-angle" sample-spinning (MASS) nuclear magnetic resonance (NMR) spectra of a variety of smectic liquid crystalline phases, including sodium decanoate (30.1 wt %)-decanol(38.9 wt %)-water, potassium oleate (72 wt %)-water, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (lecithin)(50 wt %)-water, in addition to investigating the effects of temperature and cholesterol (CHOL) addition on the lecithin spectrum. Our results indicate that even relatively slow (-3 kHz) MASS causes averaging of the dipolar interactions causing line broadening in the static NMR spectra, at least for the non-CHOL species. All of the major proton-containing groups are well resolved, the resolution being at least as good as obtained in previous studies of oriented samples or sonicated systems. The methylene chain protons in each liquid crystalline lipid bilayer system give rise to intense, sharp, spinning sidebands (SSBs) due to the special form of the dipolar Hamiltonian. The methyl groups of the lipids, and the trimethylammonium group in lecithin, do not yield intense SSB patterns. Addition of CHOL causes attenuation of the center-band methylene peak of the lecithin, and a corresponding increase in SSB intensity. All or nearly all of the non-CHOL protons present in the samples appear to contribute to the high-resolution spectra, within our experimental error of-10-20%. Use of a chain-deuterated lecithin allows peaks arising from the side chain of CHOL to be observed. In the gel phase of lecithin, only the trimethylammonium peak is apparent. The high-resolution afforded by MASS of the liquid crystalline phases permits rapid determination of the spin-lattice relaxation times (TI) of all resolved resonances. In addition, the observation of numerous chemically shifted peaks permits the use of two-dimensional (2-D) NMR techniques, which can give information on the spatial proximity of the various groups in the bilayer. Taken together, our results indicate a very promising future for high-field 'H MASS NMR studies of other lipid and membrane systems because of the extremely high sensitivity of the IH nucleus and the unique ability to obtain chemical shift, T I , and 2-D information from a single sample, without recourse to isotopic labeling, macroscopic sample orientation, or ultrasonic irradiation. Nuclear magnetic resonance (NMR) spectroscopy has been used to investigate the structure of model and biological membranes for over 20 years, and studies of molecular motion in simple

Annals of the New York Academy of Sciences, Aug 1, 2009

An overview of the concept of regeneration in Tibetan medicine is presented with descriptions of ... more An overview of the concept of regeneration in Tibetan medicine is presented with descriptions of detoxification and tonification longevity protocols. The body must be fortified before receiving stronger treatments for regeneration. All disease is brought into balance with understanding of the interplay of the five elements, three humors, and their qualities and locations. The example of multiple sclerosis (MS) is given. The macroscopic three-humor interpretation of MS agrees with the microscopic three-humor description of demyelination, providing a new framework for the understanding and treatment of MS. Treatments for MS and other chronic conditions are based on age, season, time of day, and the individual's three-humor and hot (excess) and cold (deficiency) balance. Treatments to promote regeneration include nutrition, gentle exercise, herbal formulas, accessory therapies such as herbal baths and oils, and meditation. It is built into the theory of Tibetan medicine to have predictions about outcome and distinguish different disease patterns in patients with MS and other disorders. Taking into account daily and seasonal variations coupled with the changing nature of MS, it is critical to frequently evaluate people with MS and other chronic conditions for monitoring and adjustment of treatment for regeneration.

Recent Patents on Biomedical Engineering, Aug 1, 2011

Medicinal plant formulations have been used in traditional medicines for thousands of years. Plan... more Medicinal plant formulations have been used in traditional medicines for thousands of years. Plant-based medicine is still a major source of new drug leads and herbal treatments are highly lucrative in the international marketplace. The intellectual property issues for medicinal plant formulas are complicated for numerous reasons. Many of the patents are attempting to emulate the pharmaceutical model of composition patents that as we will discuss, is usually not an appropriate approach for medicinal plants. This paper does not seek to be an exhaustive review but rather provide an overview of the many aspects of medicinal plant patents, a topic of considerable future growth. Our experience has been that the merging of modern and traditional knowledge leads to unexpected correlations, elucidations and insights with tremendous potential for patentable discovery. A continuation of the dialogue on indigenous intellectual property rights will benefit from the inclusion of an increased diversity of voices that have the ability to recognize the mutual and often complementary abilities of traditional and modern sciences. The question is not how to simplify the complexity but rather how to embrace the complexity from the traditional medicine worldview with the tools of science.

Tetrahedron Letters, 1984

... THE 13C NMR CONFORMATIONAL ANALYSIS OF 9,10DIHYDROANTHRACENE MONOANIONSPeter W. Rabideau*, Do... more ... THE 13C NMR CONFORMATIONAL ANALYSIS OF 9,10DIHYDROANTHRACENE MONOANIONSPeter W. Rabideau*, Donna M. Wetze!. Cynthia A. Husted, J. Robert Lawrence Purdue School of Science at Indianapolis Indiana UniversityPurdue University at Indianapolis ...

Magnetic Resonance in Medicine, Feb 1, 1993

We have obtained high-field (11.7 Tesla), high-resolution carbon-13 solid-state "magic-angle" sam... more We have obtained high-field (11.7 Tesla), high-resolution carbon-13 solid-state "magic-angle" sample-spinning nuclear magnetic resonance (NMR) spectra of a variety of phospholipids, sphingolipids, myelin and white matter samples, resolving and assigning over 40 resonances in the spectra of human and bovine myelin. The NMR results indicated no large spectral changes due to sample preparation, sample freezing, or brain location, and also no changes in myelin structure detectable via light microscopy, electron microscopy, thin layer chromatography, or sodium dodecyl sulfate-polyacrylamide gel electrophoresis, attributable to the sometimes lengthy NMR data acquisition process. Human myelin and white matter chemical shift assignments were made based on 13C "magic angle" sample spinning (MAS) NMR spectra of individual model lipids, as well as on spectra of lipid mixtures. In all myelin samples there were essentially no features attributable to membrane proteins, with the exception of one small feature due to C(of Arg residues, primarily in the myelin basic proteins. The general similarity between the model lipid and intact myelin spectra suggested no major effects of protein on lipid mobility. We have also investigated human myelin samples as a function of developmental age (4,15,48 months and adult), and our results showed only small changes in overall lipid composition, although there were significant decreases in lipid hydrocarbon chain unsaturation with age, as determined by computer line-shape simulations of myelin and model compounds. The spectrum of an infant leukoencephalopathy myelin showed marked decreases in galactocerebrosides. Overall, the ability to resolve and assign over 40 resonances in the 13C MAS NMR spectra of myelin, and to detect changes as a function of development and disease, should provide a useful starting point for further more detailed studies of myelin membrane molecular motions, and function.

The Journal of Organic Chemistry, 1990

a small amount of p-toluenesulfonic acid. It was considered to be a linear polysalicylide with p-... more a small amount of p-toluenesulfonic acid. It was considered to be a linear polysalicylide with p-toluenesulfonate as terminal group: IR (

Magnetic Resonance in Medicine, 1993

We have obtained high‐field (11.7 Tesla), high‐resolution carbon‐13 solid‐state “magic‐angle” sam... more We have obtained high‐field (11.7 Tesla), high‐resolution carbon‐13 solid‐state “magic‐angle” sample‐spinning nuclear magnetic resonance (NMR) spectra of a variety of phospholipids, sphingolipids, myelin and white matter samples, resolving and assigning over 40 resonances in the spectra of human and bovine myelin. The NMR results indicated no large spectral changes due to sample preparation, sample freezing, or brain location, and also no changes in myelin structure detectable via light microscopy, electron microscopy, thin layer chromatography, or sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, attributable to the sometimes lengthy NMR data acquisition process. Human myelin and white matter chemical shift assignments were made based on 13C “magic angle” sample spinning (MAS) NMR spectra of individual model lipids, as well as on spectra of lipid mixtures. In all myelin samples there were essentially no features attributable to membrane proteins, with the exception of one ...

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2004

A morphological transformation involving loss of adhesion between myelin lamellae and formation o... more A morphological transformation involving loss of adhesion between myelin lamellae and formation of myelin vesicles has been described as a mechanism for demyelination in multiple sclerosis and marmoset experimental allergic encephalomyelitis (EAE). Although protein interactions are involved in maintaining normal myelin structure, we describe here how lipids contribute to myelin stability and how lipid changes in EAE, including increases in lipid polyunsaturation and negatively charged phosphatidylserine (PS), promote demyelination. Three physico-chemical techniques were used to identify these changes: (1) Langmuir monolayer isotherms indicated that EAE white matter lipids were significantly more 'expanded' (fluid) than controls. (2) NMR spectroscopy indicated that EAE myelin lipids were more polyunsaturated than controls. (3) High-performance liquid chromatography (HPLC) with an evaporative light scattering detector indicated increased PS in EAE compared to controls, while sphingomyelin (SM), sulfatides and phosphatidylcholine (PC) were decreased. We present a physical model considering electrostatic, van der Waals and undulation forces to quantify the effect of these changes on myelin adhesion at the extracellular interface. Taken together, the isotherm, NMR, HPLC and modeling results support a mechanism for autoimmune demyelination whereby the composition of myelin lipids is altered in a manner that increases myelin fluidity, decreases myelin adhesion, increases membrane curvature, and promotes vesiculation.

Annals of Neurology, Aug 1, 1994

The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesi... more The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal-appearing white matter by evaluating the spectral broad component from phosphorus 3 1 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p < : 0.001) in both lesions and in normal-appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times. Husted CA, Matson GB, Adams DA, Goodin DS, Weiner MW. In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging.

Journal of Structural Biology, 2001

Myelin is one of the few biological membranes to contain the lipid galactocerebrosides, although ... more Myelin is one of the few biological membranes to contain the lipid galactocerebrosides, although their role in myelin is unclear. To explore its structural role, we used fluorescence and atomic force microscopy (AFM) to study nonhydroxy galactocerebrosides (NCer) at the air-water interface of a Langmuir-Blodgett trough. Fluorescence microscopy at the air-water interface indicated that NCer forms micrometer scale domains of varying radii with six fractal-like extensions. Atomic force microscopy using TappingMode in water on samples transferred to mica confirmed the fractal-like domain structure in the absence of dye and showed that the domains consisted of many aggregated nanotubes with a diameter of 30 nm. The Hausdorf fractal dimension was estimated to be 1.26 and 1.11 for two domains imaged with AFM. This evidence indicates that NCer forms a bulk phase of nanotubes at the air-water interface, unlike the liquidcondensed phase of a phospholipid monolayer. That NCer forms bilayer nanotubes that aggregate strongly suggests NCer helps maintain the stability of myelin by contributing to the curvature and adhesion of the membrane. We found that NCer appears to be decreased in myelin from multiple sclerosis normal appearing white matter, which could be an important event in the loss of myelin stability.

Proceedings of the National Academy of Sciences, 2006

Current Opinion in Neurology, Jun 1, 1994

Biochimica Et Biophysica Acta: Molecular Basis Of Disease, 2004

A morphological transformation involving loss of adhesion between myelin lamellae and formation o... more A morphological transformation involving loss of adhesion between myelin lamellae and formation of myelin vesicles has been described as a mechanism for demyelination in multiple sclerosis and marmoset experimental allergic encephalomyelitis (EAE). Although protein interactions are involved in maintaining normal myelin structure, we describe here how lipids contribute to myelin stability and how lipid changes in EAE, including increases in lipid polyunsaturation and negatively charged phosphatidylserine (PS), promote demyelination. Three physico-chemical techniques were used to identify these changes: (1) Langmuir monolayer isotherms indicated that EAE white matter lipids were significantly more 'expanded' (fluid) than controls. (2) NMR spectroscopy indicated that EAE myelin lipids were more polyunsaturated than controls. (3) High-performance liquid chromatography (HPLC) with an evaporative light scattering detector indicated increased PS in EAE compared to controls, while sphingomyelin (SM), sulfatides and phosphatidylcholine (PC) were decreased. We present a physical model considering electrostatic, van der Waals and undulation forces to quantify the effect of these changes on myelin adhesion at the extracellular interface. Taken together, the isotherm, NMR, HPLC and modeling results support a mechanism for autoimmune demyelination whereby the composition of myelin lipids is altered in a manner that increases myelin fluidity, decreases myelin adhesion, increases membrane curvature, and promotes vesiculation.

PubMed, Sep 1, 1999

Context: The greatest needs of people with chronic conditions are long-term care, maximized indep... more Context: The greatest needs of people with chronic conditions are long-term care, maximized independence, and improved quality of life. With conventional medicine becoming increasingly expensive, depersonalized, and unable to adequately meet such needs, many with chronic conditions are seeking health promotion strategies to effectively manage their symptoms. Objective: An 8-week t'ai chi program was conducted to explore psychosocial and physical benefits for those with multiple sclerosis. Design: Nonrandomized, noncontrolled pilot study. Setting: American College of Traditional Chinese Medicine, San Francisco, Calif. Patients: 19 patients with multiple sclerosis. Intervention: T'ai chi. Main outcome measures: Walking speed (distance = 25 ft), hamstring flexibility, and psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-form Health Survey. Results: Walking speed increased by 21% and hamstring flexibility increased by 28%. Patients experienced improvements in vitality, social functioning, mental health, and ability to carry out physical and emotional roles. Conclusions: This pilot program was conducted entirely on a volunteer basis and led to the implementation of several additional t'ai chi classes for people with multiple sclerosis across the United States. T'ai chi and other health promotion programs offer help toward achieving the goals of increasing access to services, maximizing independence, and improving quality of life for people with chronic disabling conditions.

Journal of Organic Chemistry, Nov 1, 1983

1-Acetyl-3,4-dihydronaphthalene appears to be the usual reduction product of the reaction without... more 1-Acetyl-3,4-dihydronaphthalene appears to be the usual reduction product of the reaction without mention of any detection of the expected 1,4-dihydro product. However, sodium-ammonia reductions of 1-acetylnaphthalene and its 4-methyl and 4-ethyl derivatives provide the corresponding 1,4-dihydro products in essentially quantitative yields. These products appear to be stable and no facile conversion to the conjugated isomers was noted.

Proceedings of the National Academy of Sciences of the United States of America, Sep 7, 2004

This report describes force measurements and atomic force microscope imaging of lipid-protein int... more This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid ''hole-filler,'' effectively preventing defect holes from developing. From our protein-mediated-adhesion and forcedistance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the ''important ones'' may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.

Journal of the American Chemical Society, Feb 1, 1988

We have obtained proton ('H) "magic-angle" sample-spinning (MASS) nuclear magnetic resonance (NMR... more We have obtained proton ('H) "magic-angle" sample-spinning (MASS) nuclear magnetic resonance (NMR) spectra of a variety of smectic liquid crystalline phases, including sodium decanoate (30.1 wt %)-decanol(38.9 wt %)-water, potassium oleate (72 wt %)-water, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (lecithin)(50 wt %)-water, in addition to investigating the effects of temperature and cholesterol (CHOL) addition on the lecithin spectrum. Our results indicate that even relatively slow (-3 kHz) MASS causes averaging of the dipolar interactions causing line broadening in the static NMR spectra, at least for the non-CHOL species. All of the major proton-containing groups are well resolved, the resolution being at least as good as obtained in previous studies of oriented samples or sonicated systems. The methylene chain protons in each liquid crystalline lipid bilayer system give rise to intense, sharp, spinning sidebands (SSBs) due to the special form of the dipolar Hamiltonian. The methyl groups of the lipids, and the trimethylammonium group in lecithin, do not yield intense SSB patterns. Addition of CHOL causes attenuation of the center-band methylene peak of the lecithin, and a corresponding increase in SSB intensity. All or nearly all of the non-CHOL protons present in the samples appear to contribute to the high-resolution spectra, within our experimental error of-10-20%. Use of a chain-deuterated lecithin allows peaks arising from the side chain of CHOL to be observed. In the gel phase of lecithin, only the trimethylammonium peak is apparent. The high-resolution afforded by MASS of the liquid crystalline phases permits rapid determination of the spin-lattice relaxation times (TI) of all resolved resonances. In addition, the observation of numerous chemically shifted peaks permits the use of two-dimensional (2-D) NMR techniques, which can give information on the spatial proximity of the various groups in the bilayer. Taken together, our results indicate a very promising future for high-field 'H MASS NMR studies of other lipid and membrane systems because of the extremely high sensitivity of the IH nucleus and the unique ability to obtain chemical shift, T I , and 2-D information from a single sample, without recourse to isotopic labeling, macroscopic sample orientation, or ultrasonic irradiation. Nuclear magnetic resonance (NMR) spectroscopy has been used to investigate the structure of model and biological membranes for over 20 years, and studies of molecular motion in simple

Annals of the New York Academy of Sciences, Aug 1, 2009

An overview of the concept of regeneration in Tibetan medicine is presented with descriptions of ... more An overview of the concept of regeneration in Tibetan medicine is presented with descriptions of detoxification and tonification longevity protocols. The body must be fortified before receiving stronger treatments for regeneration. All disease is brought into balance with understanding of the interplay of the five elements, three humors, and their qualities and locations. The example of multiple sclerosis (MS) is given. The macroscopic three-humor interpretation of MS agrees with the microscopic three-humor description of demyelination, providing a new framework for the understanding and treatment of MS. Treatments for MS and other chronic conditions are based on age, season, time of day, and the individual's three-humor and hot (excess) and cold (deficiency) balance. Treatments to promote regeneration include nutrition, gentle exercise, herbal formulas, accessory therapies such as herbal baths and oils, and meditation. It is built into the theory of Tibetan medicine to have predictions about outcome and distinguish different disease patterns in patients with MS and other disorders. Taking into account daily and seasonal variations coupled with the changing nature of MS, it is critical to frequently evaluate people with MS and other chronic conditions for monitoring and adjustment of treatment for regeneration.

Recent Patents on Biomedical Engineering, Aug 1, 2011

Medicinal plant formulations have been used in traditional medicines for thousands of years. Plan... more Medicinal plant formulations have been used in traditional medicines for thousands of years. Plant-based medicine is still a major source of new drug leads and herbal treatments are highly lucrative in the international marketplace. The intellectual property issues for medicinal plant formulas are complicated for numerous reasons. Many of the patents are attempting to emulate the pharmaceutical model of composition patents that as we will discuss, is usually not an appropriate approach for medicinal plants. This paper does not seek to be an exhaustive review but rather provide an overview of the many aspects of medicinal plant patents, a topic of considerable future growth. Our experience has been that the merging of modern and traditional knowledge leads to unexpected correlations, elucidations and insights with tremendous potential for patentable discovery. A continuation of the dialogue on indigenous intellectual property rights will benefit from the inclusion of an increased diversity of voices that have the ability to recognize the mutual and often complementary abilities of traditional and modern sciences. The question is not how to simplify the complexity but rather how to embrace the complexity from the traditional medicine worldview with the tools of science.

Tetrahedron Letters, 1984

... THE 13C NMR CONFORMATIONAL ANALYSIS OF 9,10DIHYDROANTHRACENE MONOANIONSPeter W. Rabideau*, Do... more ... THE 13C NMR CONFORMATIONAL ANALYSIS OF 9,10DIHYDROANTHRACENE MONOANIONSPeter W. Rabideau*, Donna M. Wetze!. Cynthia A. Husted, J. Robert Lawrence Purdue School of Science at Indianapolis Indiana UniversityPurdue University at Indianapolis ...

Magnetic Resonance in Medicine, Feb 1, 1993

We have obtained high-field (11.7 Tesla), high-resolution carbon-13 solid-state "magic-angle" sam... more We have obtained high-field (11.7 Tesla), high-resolution carbon-13 solid-state "magic-angle" sample-spinning nuclear magnetic resonance (NMR) spectra of a variety of phospholipids, sphingolipids, myelin and white matter samples, resolving and assigning over 40 resonances in the spectra of human and bovine myelin. The NMR results indicated no large spectral changes due to sample preparation, sample freezing, or brain location, and also no changes in myelin structure detectable via light microscopy, electron microscopy, thin layer chromatography, or sodium dodecyl sulfate-polyacrylamide gel electrophoresis, attributable to the sometimes lengthy NMR data acquisition process. Human myelin and white matter chemical shift assignments were made based on 13C "magic angle" sample spinning (MAS) NMR spectra of individual model lipids, as well as on spectra of lipid mixtures. In all myelin samples there were essentially no features attributable to membrane proteins, with the exception of one small feature due to C(of Arg residues, primarily in the myelin basic proteins. The general similarity between the model lipid and intact myelin spectra suggested no major effects of protein on lipid mobility. We have also investigated human myelin samples as a function of developmental age (4,15,48 months and adult), and our results showed only small changes in overall lipid composition, although there were significant decreases in lipid hydrocarbon chain unsaturation with age, as determined by computer line-shape simulations of myelin and model compounds. The spectrum of an infant leukoencephalopathy myelin showed marked decreases in galactocerebrosides. Overall, the ability to resolve and assign over 40 resonances in the 13C MAS NMR spectra of myelin, and to detect changes as a function of development and disease, should provide a useful starting point for further more detailed studies of myelin membrane molecular motions, and function.

The Journal of Organic Chemistry, 1990

a small amount of p-toluenesulfonic acid. It was considered to be a linear polysalicylide with p-... more a small amount of p-toluenesulfonic acid. It was considered to be a linear polysalicylide with p-toluenesulfonate as terminal group: IR (