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Biomedical subjects

R B Martin

Publications and source records attributed to R B Martin.

At least 127 records · Page 7Linked to original sources

Studies of skeletal remodeling in aging men.

Senile osteoporosis in the male skeleton was studied in midshaft cross-sections from the femur, humerus, and metacarpal of 42 white male cadavers, aged 37 to 96 years. The cortical area (AC) and polar moment of inertia (J) of each section were measured. Cortical porosity and haversian canal density were also measured as functions of position in the sections, and the sizes of osteons and haversian canals in the femur were studied. In addition, the density and cross-sectional geometry of the neck of the femur were determined in 10 subjects. Age-related increases in porosity at each skeletal site are compensated by concomitant increases in cross-sectional geometry. These increases in J and AC are limited, however, being reversed at age 80 in the femur and humerus, and at age 60 in the metacarpus. Intracortical porosity was found to be localized in each bone in ways consistent with Wolff's law. The number of haversian canals/mm2 increased with age, but the size of haversian canals did not. Osteon size decreased with age. Osteon distribution patterns in the femur were consistent with random rather than directed patterns of osteon placement.

Adult↗

Sphingomyelin multiple phase behavior as revealed by multinuclear magnetic resonance spectroscopy.

31P and 13C nuclear magnetic resonance (NMR) spectra are employed to study the phase behavior of bovine brain sphingomyelin as a function of temperature. The 31P NMR data suggest that, while at low temperatures sphingomyelin can form a lamellar phase, at physiological temperatures and higher the lamellar phase is unstable, and a new phase, best described as a hexagonal phase, is formed. Egg phosphatidylcholine is suggested to play an important role in stabilizing bilayers in natural membranes. Cholesterol also exhibits a sphingomyelin bilayer-stabilizing ability. The 13C NMR spectra suggest a gelling of the hydrocarbon chains of sphingomyelin at low temperature. Thus, bovine brain sphingomyelin undergoes both a gel to liquid-crystalline phase transition and a lamellar to nonlamellar transition.

Animals↗

Location and interactions of phospholipid and cholesterol in human low density lipoprotein from 31P nuclear magnetic resonance.

The major phospholipids, phosphatidylcholine and spingomyelin, of low density lipoprotein (LDL) are accessible to small amounts of Pr3+, suggesting that the head groups of all mobile phospholipids are on the surface of the particle in contact with the aqueous medium. The major source of the nuclear Overhauser effect enhancement of 31P resonances is the N-methyl proton of the choline moiety, indicating close N-methyl phosphate group interactions, probably similar to those found previously in phospholipid vesicles. This behavior of the phospholipid head groups in LDL is similar to that in small vesicles without cholesterol, suggesting that in LDL most of the cholesterol is not associated with mobile, surface phospholipids. In contrast to LDL, where the presence of a large protein immobilizes some phospholipid head groups, immobilization does not occur in high density lipoprotein, consistent with occurrence of smaller peptides in the latter.

Chemical Phenomena↗

The effect of electric fields on osteoporosis of disuse.

An experiment originally done by McElhaney et al. was repeated to obtain additional information about the effects of electrical fields on osteoporosis of disuse. The right femurs of 35 male rats were immobilized in plaster casts. Sixteen rats were treated with transcutaneous electrical fields of 30 Hz and approximately 100 V/cm for periods of 2 or 8 h a day. While the right femurs of the untreated rats were found to be atrophic with respect to the opposite limb, in the treated rats the immobilized femur was made larger than the opposite bone. Longer daily treatments exaggerated this effect. The tumors found in the previous study were not seen in our experiments. Other similarities and differences in the 2 studies are discussed.

Animals↗

Verbal reinforcement combinations in schizophrenics.

Investigated the effects of verbal reinforcement paradigms on hospitalized schizophrenics and staff. Positive reinforcement that involved good was found to be relatively ineffective for all groups; furthermore, associating good with the termination of a white noise did not increase its effectiveness for schizophrenics. Verbal punishment was more effective than verbal positive reinforcement for staff, but for schizophrenics only when explicit problem-solving instructions were given. The results suggest that the reduction of deficit is not more likely via verbal punishment; if anything, deficit is increased because of increased staff performance under verbal punishment.

Behavior Therapy↗

Models for lipid organization in cholesterol-phospholipid bilayers including cholesterol dimer formation.

Three new structural models, which account for abrupt changes in physical properties observed at several molar concentrations of cholesterol in phospholipid bilayers, are described. Cholesterol monomers, each surrounded by its own envelope of unshared acyl hydrocarbon chains of the phospholipid, can accommodate 22% cholesterol. Cholesterol dimers, each surrounded by its envelope of unshared acyl hydrocarbon chains, can accommodate 31% cholesterol. When surrounded by shared acyl hydrocarbon chains, cholesterol dimmers can accommodate about 47% cholesterol. At greater concentrations, cholesterol aggregation occurs, the system is unstable, and cholesterol forms a separate phase.

Chemical Phenomena↗

Phospholipid head-group conformations; intermolecular interactions and cholesterol effects.

The predominant orientation of the phosphorylcholine polar head group in phosphatidylcholine and sphingomyelin bilayers and cholesterol perturbations of that orientation have been identified by exploiting the 31P (1H) nuclear Overhauser effect (NOE) in the 31P NMR spectra of phospholipid bilayers. In pure egg phosphatidylcholine bilayers, a NOE of 40% is observed. The magnitude of the NOE has been measured as a function of continuous-wave proton-decoupler frequency in order to identify the proton source of the NOE. In pure egg phosphatidylcholine bilayers, the maximum NOE occurs at the N-methyl proton resonance position of the choline moiety. In a modified phosphatidylcholine in which all the N-methyl protons were replaced by deuterium, the NOE arose from methylene protons next to the phosphate. In mixed systems of phosphatidylcholine and phosphatidylethanolamine, and phosphatidylcholine and diphosphatidylglycerol, both phospholipid resonances attained maximum NOE at the position of the N-methyl proton resonance of phosphatidylcholine. An analogous result was obtained with pure sphingomyelin. These results are explained by orienting the phosphorylcholine portion of the molecule parallel to the surface of the bilayer so that the positively charged N-methyl moiety is located close to the negatively charged phosphate on a neighboring phospholipid in an intermolecular interaction. Addition of cholesterol is shown to disrupt the intermolecular interaction in phosphatidylcholine bilayers.

Chemical Phenomena↗

Phospholipid-protein interactions in human low density lipoprotein detected by 31P nuclear magnetic resonance.

31P nuclear magnetic resonance (NMR) spectra of human low density lipoprotein (LDL) has been obtained and the major phospholipid components identified. Analysis of the spectra revealed two phospholipid environments: one occupied by 4/5 of the phospholipid with high resolution resonances possessing properties similar to phospholipids in vesicles, and a second occupied by 1/5 of the phospholipid with broad lines indicative of immobilization. Limited trypsin treatment of the particle cleaved all of the B peptide into smaller molecular weight peptides which remained with the particle. Trypsin-treated LDL eluted from a Sepharose CL-6B column similarly to native LDL so that the modified particle remained intact. 31P NMR spectra of trypsin-treated LDL showed little or no immobilized phospholipid. The immobilization in the native LDL particle is attributed to lipid-protein interactions between 1/5 of the phospholipid and the B peptide.

Apolipoproteins↗

Molecular dynamics of the local anesthetic tetracaine in phospholipid vesicles.

Upon introduction into phosphatidylcholine vesicles, the 13C magnetic resonance peaks of the aromatic resonances of tetracaine are broadened while the T1 relaxation times show little change. Addition of tetracaine to vesicles containing 30% cholesterol produces a similar broadening in the 13C NMR spectrum of tetracaine. Nuclear magnetic resonance parameters of phosphatidylcholine in vesicles which are unchanged by the addition of equimolar tetracaine include 13C T1 relaxation time and 31P linewidth, T1 relaxation time, and nuclear Overhauser effect enhancement. These results are interpreted as indicating a hydrophobic interaction between hydrocarbon portions of the anesthetic and phospholipid bilayer. The rotational correlation time of tetracaine about its long axis in the vesicles has been calculated from the 13C NMR spin lattice relaxation times to be about 10(-10.3) s and is unchanged by incorporation into the phospholipid bilayer. The positively charged ammonium group of tetracaine interacts with the negatively charged phosphate group of the vesicle lipids. Using shift reagents and 31P NMR, tetracaine has been shown to displace cations from the bilayer surface, and does not undergo fast flip-flop across the vesicle bilayer.

Anesthetics, Local↗

The structure of vesicular stomatitis virus membrane. A phosphorus nuclear magnetic resonance approach.

The proton decoupled 40.48 M Hz 31P NMR spectrum of intact and unperturbed membrane-enclosed vesicular stomatitis virus (sterotype Indiana) exhibited two distinct maxima. These can be resolved into a narrow, symmetric line and a broad asymmetric line. The 31P NMR spectrum of a multilamellar (unsonicated) preparation of the extracted viral lipids exhibited a line shape similar to that of the intact virus. A sonicated vesicle preparation of the extracted viral lipids exhibited a narrow symmetric line. The narrow component in the intact virus spectrum may be attributed to small membrane fragments. Phospholipase C digestion of the intact virus resulted in substantial reduction in intensity of both components which suggests that much of the contribution to both peaks is due to phosphate in the phospholipid polar head groups. The phospholipid phosphates in both sonicated and unsonicated preparations of the extracted viral lipids exhibited substantially longer relaxation times than did those in the intact virus. The short relaxation time emanating from the intact virus preparation is caused by immobilization of the phospholipid head groups which could be due to lipid-protein interactions. Trypsin treatment of vesicular stomatitis virions, which results in complete removal of the exterior hydrophilic segment of the membrane glycoprotein, increased the 31P relaxation time to a value similar to that observed in the protein-free total lipid extracts; this finding provides supporting evidence for the role of virus glycoprotein in shortened relaxation times. A reversible temperature-dependent change in apparent line width and absence of an effect of cholesterol on the 31P phospholipid spectrum were also demonstrated.

Cell Line↗

The interaction of lanthanide and calcium salts with phospholipid bilayer vesicles: the validity of the nuclear magnetic resonance method for determination of vesicle bilayer phospholipid surface ratios.

Contrary to a recent report (B. Sears et al., Biochemistry 15 (1976) 1635), it has been determined that the ratio of the number of phospholipids on the inner and outer surfaces of phospholipid bilayer vesicles can be accurately determined by NMR paramagnetic ion shift reagent studies of vesicles. It is concluded that the metal interacts with all of the phospholipid on the exposed bilayer surface. A ratio of outer phospholipid to inner surface phospholipid of 2.1 +/- 0.1 is obtained regardless of the nucleus studied, position of the nucleus relative to the metal ion binding site, molar ratio of metal to phospholipid over three orders of magnitude, or location of the metal ion of the inside or outside of the vesicle. Additionally, P-31 NMR studies using LaC13 and CaC12 indicate that Ca2+ weakly interacts with egg PC vesicles and that the lanthanides are adequate substitutes for Ca2+ since neither metal is found to perturb measurably the average polar head group conformation.

Calcium↗

Non-cooperative Ca(II) removal and terbium(III) substitution in carp muscle calcium binding parvalbumin.

Close coorelation of atomic absorption measurements for Ca(II) contents indicates that from pH 5.8-7.4 a twentyfold excess of EGTA1 removes but one of two Ca(II) from carp parvalbumin. Thus binding of the two Ca(II) appears to be noncooperative. The maximum in emission intensity observed at a nonintegral 1.4-1.7 equivs of added Tb(III) is shown to be due to quenching by excess Tb(III). The emission intensity at the maximum increased 40% upon dialysis to remove Tb(III) not bound in the CD or EF sites. Atomic absorption results show that both Ca(CD) and Ca(EF) of native parvalbumin are easily replaced by Tb(III). Emission of Tb(EF) is not quenched by Tb(CD), but by solution Tb(III) bound at a third site, perhaps the single water molecule bound to Tb(EF). Labeling of the single sulfhydryl group with a trifluoroacetonyl gorup yields a protein with ultraviolet circular dichroism, emission, and circularly polarized emission spectra closely similar to those of native parvalbumin.

Animals↗