Search PubMed⌕ Search

Biomedical subjects

D Marsh

Publications and source records attributed to D Marsh.

At least 289 records · Page 16Linked to original sources
PubMed1980

Clinical significance of tolerant strains of Staphylococcus aureus in patients with endocarditis.

We have studied 50 cases of endocarditis and 54 cases of bacteremia due to Staphylococcus aureus to ascertain the clinical significance of the newly described phenomenon of tolerance. In 32 of the patients with endocarditis and 35 of those with bacteremia strains were classified as tolerant (minimum bactericidal concentration/minimum inhibitory concentration greater than or equal to 16). Patients with endocarditis due to a tolerant strain responded less favorably than did patients with a sensitive strain. A larger number of patients with a tolerant strain had prolonged fever (58% versus 19%), a higher mean number of complications (1.6 versus 0.73), a greater number of intensive-care unit admissions (66% versus 33%), and a higher mortality (25% versus 11%). In contrast there was no difference in response to therapy in bacteremic patients without endocarditis having sensitive and tolerant strains. We conclude that infection with a tolerant organism adversely influences the outcome of staphylococcal endocarditis.

Adult↗
PubMed1979

Transurethral resection of large prostates.

A total of 102 men (mean age 70) underwent transurethral resection of the prostate. The weight of the resected prostate ranged from 40 to 152 g. Two deaths occurred in patients aged 85 and 92 years, both of whom were generally unfit. The average postoperative stay in hospital was 8.3 days. The proportions of patients with incontinence, infection, and stricture were similar to those in other series of resections and open prostatectomies, suggesting that resection of the larger prostate is safe and an acceptable alternative to an open operation.

Aged↗
PubMed1978

Morphology of egg phosphatidylcholine-cholesterole single-bilayer vesicles, studied by freeze-etch electron microscopy.

Homogeneous, small, single-bilayer vesicles were prepared from egg phosphatidylcholine with various concentrations of cholesterol by ultrasonic dispersion in 0.1 M KCl, 0.01 M Tris, pH 8.0, buffer, followed by gel chromatography. The shape and size distributions of the fractionated vesicles were investigated for preparations with cholesterol compositions from 0 to 50 moles/100 moles, using freeze-etch electron microscopy. The size distribution was estimated from the shadow width of vesicles which were exposed by etching and the vesicle shape was checked by comparing the images obtained by tilting the replicas. The widths of the vesicle diameter distributions were relatively broad, corresponding to standard deviations in the range 60--90 A, but showing no systematic variation with cholesterol composition. In all cases it was found that 70% of the vesicle diameters lay within 150 A of the modal value. The apparent vesicle diameters remained constant for cholesterol compositions up to 20 moles/100 moles (modal diameter = 330 +/- 20 A, mean diameter = 350 +/- 3 A), but there was a sharp net increase in diameter at 30 moles cholesterol/100 moles reaching a model diameter of 430 +/- 20 A (mean diameter = 430 +/- 3 A) at 50 moles cholesterol/100 moles. Using the tilted microscope stage it was found that all vesicles were spherical at all cholesterol compositions studied, including those above 30 moles cholesterol/100 moles. The molecular mechanism by which cholesterol controls the vesicle size is discussed in terms of the asymmetric distribution of cholesterol across the vesicle bilayer.

Cholesterol↗
PubMed1978

Mechanisms by which proteolytic enzymes prolong the golden period of antibiotic action.

These experimental studies provide an explanation for the therapeutic value of proteolytic enzymes as adjuncts to antibiotic treatment of contaminated wounds. After wounding, a fibrinous coagulum develops on the wound surface. This coagulum surrounds the bacteria and protects them from contact with sustemically or topically administered antibiotics. Treatment of the wound surface with proteolytic enzymes disrupts the coagulum and exposes the bacteria to the action of the antibiotic. The topical use of enzymes is also associated with significant increases in the concentration of antibiotic at the wound and thus a decrease in the rate of infection.

Administration, Topical↗
PubMed1978

Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata.

The lipid environment of acetylcholine receptor-rich membranes from Torpedo marmorata has been studied with spin labels. The electron spin resonance spectra of both stearic acid and steroid probes in the membranes revealed an immobilized lipid component, in addition to the fluid component which is found in aqueous bilayer dispersions of the extracted lipids. The spin labels also cause a differential paramagnetic quenching of the intrinsic protein fluorescence of the membranes, which is sensitive to the action of cholinergic ligands and follows a modified Stern-Volmer law. Electron spin resonance difference spectroscopy shows that the protein-associated lipid is immobilized with respect to rotation both around and perpendicular to the long molecular axis, with correlation times : formula: (see text) approximately 50-70 ns. The proportion of lipid in the immobilized component is greater than calculated for a single boundary layer around the protein and corresponds more closely to the total interstitial lipid occupying the area between densely packed protein units in acetylcholine receptor-rich membranes.

Acetylcholine↗
PubMed1977

The gross architecture of an antibody-combining site as determined by spin-label mapping.

1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall ;tumbling' time of the antibody-hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1-1.2nm and has lateral dimensions at the entrance to the site >/=0.6nmx0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95(L) (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody-hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol.41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made.

Binding Sites, Antibody↗
PubMed1977

Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping.

The mouse immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 all possess dinitrophenyl (Dnp)-binding activity. Differences in specificities were shown by measuring the affinities of a variety of haptens. By using a series of Dnp-spin-labelled haptens, the dimensions of the binding sites of the three myeloma proteins were compared by the method described for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177-197]. The dinitrophenyl ring is rigidly held in all three sites. The depths of the sites are all 1.1-1.2nm, but there are differences in the lateral dimensions at the entrance to the sites. For protein XRPC 25 these dimensions are 0.75nmx0.8nm, which may be compared with 0.85nmx1.1nm for protein MOPC 315 and >/=1.0nmx1.1nm for protein MOPC 460. The site in protein MOPC 460 is more symmetrical with respect to the plane of the dinitrophenyl ring than in either of the other two myeloma proteins and also allows greater penetration of solvent. In protein XRPC 25 a positively charged residue was located at the entrance to the site, similarly positioned to that reported for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem.J.165, 177-197]. All three proteins possess lanthanide-binding sites, but only in protein MOPC 315 is there antagonism between lanthanide and hapten binding. However, the effects of the diamagnetic La(III) on the electron-spin-resonance spectra of bound Dnp spin labels in both proteins MOPC 460 and XRPC 25 suggest an interaction between the two sites. Comparison of this effect with that caused by the addition of the paramagnetic Gd(III) enables the distance between the lanthanide- and hapten-binding sites to be calculated. In both proteins MOPC 460 and MOPC 315 the metal site is approx. 1.0nm from the nitroxide moiety of the spin-labelled hapten, but in protein XRPC 25 this distance is at least 2.0nm.

Antibody Specificity↗
PubMed1977

Echo-detecting characteristics of neurons in inferior colliculus of unanesthetized bats.

Neurons in the inferior colliculus of echolocating bats responded well to two stimuli presented in close temporal sequence. Favorable recovery of responsiveness was seen with stimuli having durations, intensities, and interpulse intervals similar to the natural biosonar signals reaching the ears during the various phases of echolocation. Some units responded to a subthreshold simulated echo but only when preceded by a loud initial pulse. These units appear to be specialized for echo-detection.

Action Potentials↗
PubMed1977

Cooperativity of the phase transition in single- and multibilayer lipid vesicles.

The effect of membrane morphology on the cooperativity of the ordered-fluid, lipid phase transition has been investigated by comparing the transition widths in extended, multibilayer dispersons of dimyristoyl phosphatidyl-choline, and also of dipalmitoyl phosphatidylcholine, with those in the small, single-bilayer vesicles obtained by sonication. The electron spin resonance spectra of three different spin-labelled probes, 2,2,6,6-tetramethylpiperdine-N-oxyl, phosphatidylcholine and stearic acid, and also 90 degrees light scattering and optical turbidity measurements were used as indicators of the phase transition. In all cases the transition was broader in the single-bilayer vesicles than in the multibilayer dispersions, corresponding to a decreased cooperativity on going to the small vesicles. Comparison of the light scattering properties of centrifuged and uncentrifuged, sonicated vesicles suggests that these are particularly sensitive to the presence of intermediate-size particles, and thus the spin label measurements are likely to give a more reliable measure of the degree of cooperativity of the small, single-bilayer vesicles. Application of the Zimm and Bragg theory ((1959) J. Chem. Phys. 31, 526-535) of cooperative transitions to the two-dimensional bilayer system shows that the size of the cooperative unit, 1/square root sigma, is a measure of the mean number of molecules per perimeter molecule, in a given region of ordered or fluid lipid at the centre of the transition. From this result it is found that it is the vesicle size which limits the cooperativity of the transition in the small, single-bilayer vesicles. The implications for the effect of membrane structure and morphology on the cooperativity of phase transitions in biological membranes, and for the possibility of achieving lateral communication in the plane of the membrane, are discussed.

Chemical Phenomena↗