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Biomedical subjects

M Bloom

Publications and source records attributed to M Bloom.

At least 55 records · Page 3Linked to original sources

The six languages of social work.

This article describes the six languages that scientifically minded and practice-competent social workers need to be fluent in: the lay language of the client, the abstract language of the theorist, the empirical and often quantitative language of the researcher, the categorical language of the information scientist, the technical terminology or jargon used by helping professionals, and the preferential language that conveys values. It is the thesis of this article that social workers need multilingual and translingual proficiency in moving rapidly back and forth among these languages for maximum effectiveness and humane service.

Humans↗

Comparison of the orientational order of lipid chains in the L alpha and HII phases.

The orientational order profile has been determined by using deuterium nuclear magnetic resonance (2H NMR) for POPE in the lamellar liquid-crystalline (L alpha) and the hexagonal (HII) phases and is shown to be sensitive to the symmetry of the lipid phase. In the HII phase, as compared to the L alpha phase, the acyl chains are characterized by a greater motional freedom, and the orientational order is distributed more uniformly along the lipid acyl chain. This is consistent with a change from a cylindrical to a wedge-shaped space available for the lipid chain. 2H NMR studies of POPE dispersions containing tetradecanol or decane, both of which can induce HII phase structure, show very different behavior. Tetradecanol appears to align with the phospholipid chains and experience the L alpha to HII phase transition with a similar change in motional averaging as observed for the phospholipid chains themselves. In contrast, decane is apparently deeply embedded in the lipid structure and exhibits only a small degree of orientation. The L alpha to HII phase transition for systems containing decane leads to a dramatic increase of the motional freedom of decane which is more pronounced than that observed for the lipid chains. This is consistent with a preferential partition of the decane molecules into a disordered environment such as the intercylinder spaces in the HII phase. The presence of decane in the HII phase structure does not modify the order of the lipid chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkanes↗

Ca2+, Mg2+, Li+, Na+, and K+ distributions in the headgroup region of binary membranes of phosphatidylcholine and phosphatidylserine as seen by deuterium NMR.

The binding of calcium, magnesium, lithium, potassium, and sodium to membrane bilayers of 5 to 1 (M/M) 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1-palmitoyl- 2-oleoylphosphatidylserine (POPS) was investigated by using deuterium nuclear magnetic resonance (2H NMR). Both lipids were deuteriated on their polar headgroups, and spectra were obtained at 25 degrees C in the liquid-crystalline phase as a function of salt concentration. The spectra obtained with calcium were correlated with 45CaCl2 binding studies to determine the effective membrane-bound calcium at low calcium binding, up to 0.78 calcium per POPS. Deuterium quadrupolar splittings of both POPC and POPS headgroups were shown to be very sensitive to calcium binding. The behavior of these two headgroups over a wide range of CaCl2 concentrations suggests that Ca2+ binding occurs in at least two steps, the first step being achieved with 0.5 M CaCl2, with a stoichiometry of 0.5 Ca2+ per POPS. Correlations of the deuterium Ca2+ binding data with related data obtained after incorporation of a cationic integral peptide showed that the effects of these two cationic molecules of the POPS headgroup are qualitatively similar, and provided further support for two-step Ca2+ binding to the POPC/POPS 5:1 membranes. The corresponding data obtained with magnesium, lithium, and potassium indicate that these cations interact with both the choline and serine headgroups. The amplitudes of headgroup perturbations could be partly correlated to the relative affinities of the metallic cations for the lipid membrane. The two-step binding described with Ca2+ appears to be relevant to the Mg2+ data, and in certain limits to the Li+ data. The data were interpreted in terms of conformational changes of the lipid headgroups induced by an electric field due to the charges of the membrane-bound metallic cations. A conformational change of the serine headgroup induced by the membrane-bound charges is proposed. We propose that the metallic cations can be differentiated on the basis of their respective spatial distribution functions relative to the choline and serine headgroups. According to this interpretation, the divalent cations Ca2+ and Mg2+ are more deeply buried in the membrane than monovalent Na+ and K+, the case of Li+ being intermediate of the latter two. This conclusion is discussed in relation to fundamental theories of the spatial distribution of ions near the interface between water and smooth charged solid surfaces.

Binding Sites↗

Modulation of the orientational order profile of the lipid acyl chain in the L alpha phase.

The orientational order profile along the lipid acyl chain has been characterized under several different conditions of polar headgroup composition, temperature, and cholesterol content. Despite the different nature of these factors, the variation of the order is governed by two common trends. First, the relative change of order induced by the variation of these factors is always more pronounced towards the end of the chain than for the methylene groups near the interface. Second, there is, to a first approximation, a distinct correlation between the magnitude of the order parameters and the shape of the order profile. For example when the chain is highly ordered, the relative width of the order distribution is narrow indicating that the plateau region is longer. These conclusions suggest that the orientational order profile depends on only a small number of parameters and demonstrate clearly that the correlation length for changes in orientational order is much greater than one C-C bond length. Our results also show that the reduced temperature is not related in simple terms to orientational order and probably has little theoretical significance. The orientational order profiles of POPC and POPE bilayers are significantly different even when expressed in terms of reduced temperature. The behavior of POPC/cholesterol systems also indicates that the orientational order of the lipid chain and the gel-to-liquid crystalline phase transition temperature are not related in a straightforward manner.

Cell Membrane↗

Physical properties of single phospholipid bilayers adsorbed to micro glass beads. A new vesicular model system studied by 2H-nuclear magnetic resonance.

Spherical supported vesicles (SSVs), a new model system consisting of single dimyristoyl phosphatidylcholine (DMPC) bilayers adsorbed to spherical glass beads with a narrow size distribution, were prepared at two different sizes (0.5 and 1.5 microns) and their physical properties were studied by deuterium nuclear magnetic resonance (2H-NMR). Such SSV samples can be prepared at any desired size between 0.3 and 10 microns. The 2H-NMR measurements provide evidence for a strong dependence of the spectra and the transverse relaxation times on the curvature of the SSVs in a diameter range between 0.5 and 1.5 microns. For larger SSVs (1.5 microns diameter) their powder spectra and their calculated oriented spectra are similar to those obtained for multilamellar dispersions of DMPC-d54. The lineshape of the smaller SSVs exhibits a temperature dependence which is not found in multilamellar samples. The SSVs are stable in the liquid crystalline phase over days but irreversibly change to multilamellar vesicles in the gel state. The average thickness of the water layer between the single bilayer and the glass bead surface was estimated by 1H-NMR to e 17 +/- 5 A.

Adsorption↗

Relationships between lipid membrane area, hydrophobic thickness, and acyl-chain orientational order. The effects of cholesterol.

A microscopic interaction model for a fully hydrated lipid bilayer membrane containing cholesterol is used to calculate, as a function of temperature and composition, the membrane area, the membrane hydrophobic thickness, and the average acyl-chain orientational order parameter, S. The order parameter, S, is related to the first moment, M1, of the quadrupolar magnetic resonance spectrum which can be measured for lipids with perdeuterated chains. On the basis of these model calculations as well as recent experimental measurements of M1 using magnetic resonance and of membrane area using micromechanical measurements, a discussion of the possible relationships between membrane area, hydrophobic thickness, and moments of nuclear magnetic resonance spectra is presented. It is pointed out that S under certain circumstances may be useful for estimating the hydrophobic membrane thickness. This is particularly advantageous for multicomponent membranes where structural data are difficult to obtain by using diffraction techniques. The usefulness of the suggested relationships is demonstrated for cholesterol-containing bilayers.

Cholesterol↗

Lipid polymorphism and hydrocarbon order.

The use of 2H nuclear magnetic resonance for the characterization of the polymorphic behavior of lipids is illustrated. Different lipid phase preferences may be expected to influence the orientational order and its variation along the acyl chains. Several results are presented to support that view. An increase of motional freedom and a redistribution of the order along the acyl chains are observed during the lamellar-to-hexagonal phase transition, showing that the order profile is sensitive to the lipid phase symmetry. In addition, if the preferences for nonlamellar phases are not expressed explicitly, the presence of "nonbilayer" lipids constrained in bilayer environment induces increased hydrocarbon order. This suggests that order parameters of the acyl chains and lipid polymorphic tendencies are intimately related.

Chemical Phenomena↗

Conformational changes of phospholipid headgroups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance.

Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction of a cationic amphiphilic peptide with pure DMPC membranes and with mixed bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS). The choline and serine headgroups were selectively deuteriated at the alpha and beta positions. The amphiphilic peptide, with 20 leucine residues in the hydrophobic core and two cationic hydrophilic lysine residues at each end, spanned the lipid bilayer. Although 2H NMR experiments using DMPC with perdeuteriated fatty acyl chains showed that the average order parameter of the hydrophobic region was not significantly modified by the incorporation of the amphiphilic peptide, for either DMPC or DMPC/DMPS (5:1) bilayers, large perturbations of the quadrupolar splittings of the choline and serine headgroups were observed. The results obtained with the DMPC headgroup suggest that the incorporation of the cationic peptide in both DMPC and DMPC/DMPS (5:1) bilayers leads to a structural perturbation directly related to the net charge on the membrane surface. The magnitude of the observed effect seems to be similar to those observed previously with other cationic molecules [Seelig, J., MacDonald, P.M., & Scherer, P.G. (1987) Biochemistry 26, 7535-7541]. Two of the three quadrupolar splittings of the PS headgroup exhibited large variations in the presence of the amphiphilic peptide, while the third one remained unchanged. Our data have led us to propose a model describing the influence of membrane surface charges on headgroup conformation. In this model, the surface charge is represented as a uniform charge distribution. The electric field due to the charges produces a torque which rotates the polar headgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Transsternal radical thymectomy for myasthenia gravis: a 15-year review.

Thymectomy is an accepted therapeutic modality for patients with myasthenia gravis. The selection of patients for operation and the surgical approach are controversial. We reviewed 52 patients (aged 18 months to 82 years; mean age, 34 years) treated with transsternal radical thymectomy between 1972 and 1987. Patients were symptomatically staged according to the modified Osserman classification. There was one hospital death and postoperative follow-up was obtained on 51 patients. Improvement after thymectomy was observed in 3 of 11 patients (27%) in Osserman stage I, 16 of 25 patients (64%) in Osserman stage IIA, and 13 of 15 patients (86%) in combined Osserman stages IIB, III, and IV. Preoperative Osserman stage, patient sex, and thymic histology correlated with postoperative clinical response. Transsternal radical thymectomy is effective therapy for myasthenia gravis. Sustained improvement is obtained in patients with moderate and advanced disease. The majority of patients with ocular disease do not benefit from operation.

Adult↗

Smoothed orientational order profile of lipid bilayers by 2H-nuclear magnetic resonance.

A new method has been developed to determine the complete orientational order profile of lipid bilayers using 2H-NMR. The profile is obtained from a single powder spectrum of a lipid which has a saturated chain fully deuteriated. The smoothed order profile is determined directly from the normalized dePaked spectrum assuming a monotonic decrease of the order along the acyl chain. The oscillatory variations of the order at the beginning of the chain are not described by this method. However the smoothed order profile reveals in a straightforward way the crucial features of the anisotropic order of the bilayer.

Deuterium↗

Affinity labeling of the allosteric activator site(s) of spinach leaf ADP-glucose pyrophosphorylase.

Pyridoxal-P has been shown to be an activator of the spinach leaf ADP-glucose pyrophosphorylase. It has a higher apparent affinity than the physiological activator 3-phosphoglycerate but only activates the enzyme activity 6-fold whereas 3-phosphoglycerate gives a 25-fold activation. Reductive phosphopyridoxylation of the spinach leaf enzyme results in enzyme having less dependence on the presence of activator for activity. Labeled pyridoxal-P is incorporated into both the 54- and 51-kilodalton subunits of the spinach leaf enzyme. The incorporation is inhibited by the presence of either 3-phosphoglycerate or the allosteric inhibitor, inorganic phosphate, thus suggesting that pyridoxal phosphate is covalently bound to the allosteric activator site. The pyridoxal phosphate is bound to an epsilon-amino group of a lysine residue. The phosphopyridoxylated enzyme is more resistant to phosphate inhibition than the unmodified form. The modified 51-kDa subunit has been digested with trypsin, and the peptide containing the labeled pyridoxal phosphate has been purified via high performance liquid chromatography and sequenced. Comparison of this sequence with the deduced amino acid sequence of a rice endosperm cDNA clone indicates that the putative allosteric site of the 51-kDa subunit is close to the carboxyl-terminal. This is in contrast to what had been demonstrated for the position of the activator site of the Escherichia coli ADP-glucose pyrophosphorylase which was shown to be close to the amino-terminal of the subunit.

Affinity Labels↗

2H and 31P NMR study of pentalysine interaction with headgroup deuterated phosphatidylcholine and phosphatidylserine.

The interaction of cationic pentalysine with phospholipid membranes was studied by using phosphorus and deuterium Nuclear Magnetic Resonance (NMR) of headgroup deuterated dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS). In the absence of pentalysine, some of the deuterium and phosphorus spectra of DMPC/DMPS 5:1 (m:m) membranes gave lineshapes similar to those of partially-oriented bilayers with the planes of the bilayers being parallel to the magnetic field. The deuterium NMR data show that the quadrupolar splittings of the deuterated methylenes of the DMPC headgroup are not affected by adsorption of pentalysine on the PC/PS membranes. By contrast, the pentalysine produces significant changes in the quadrupolar splittings of the negatively charged DMPS headgroup. The results are discussed in relation to previous 2H NMR investigations of phospholipid headgroup perturbations arising from bilayer interaction with cationic molecules.

Deuterium↗

Comparison of the central and peripheral effects of cetirizine and terfenadine.

The peripheral and central effects of 10 mg cetirizine 2 HCl and 60 mg terfenadine have been compared with placebo in 9 healthy male volunteers. The peripheral effect, in terms of cutaneous reactivity to 1 microgram histamine i.d., was measured by planimetry of the wheal and erythemas. Central effects were assessed with a self-evaluation visual scale and from the results of electroencephalographic spectrum analysis. Peripheral inhibition of histamine reactivity was more intense and quicker for cetirizine than for terfenadine. On the self-evaluation scale, no significant difference between terfenadine, cetirizine and placebo was noted. The quantified EEG did not show any variation in spectral parameters at any time after cetirizine. By contrast, at 6 h terfenadine had increased slow waves and had inhibited the alpha band. Thus, 10 mg cetirizine 2 HCl had less effect on the central nervous system than terfenadine 60 mg, whilst its peripheral action appeared more quickly and was more intense.

Adult↗