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Biomedical subjects

K F Smith

Publications and source records attributed to K F Smith.

At least 37 records · Page 2Linked to original sources
PubMed1990

Structural comparisons of the native and reactive-centre-cleaved forms of alpha 1-antitrypsin by neutron- and X-ray-scattering in solution.

alpha 1-Antitrypsin is the best-characterized member of the serpin (serine-proteinase inhibitor) superfamily. Its solution structure was studied by high-flux neutron-scattering and synchrotron X-ray-scattering. Neutron data show that its absorption coefficient A1% 280,1cm is 5.4. The neutron radius of gyration RG at infinite contrast for native alpha 1-antitrypsin is 2.61 nm, characteristic of a moderately elongated structure, and its cross-sectional RG is 1.34 nm. The internal inhomogeneity of scattering densities within alpha 1-antitrypsin is high at 29 x 10(-5). The X-ray RG is 2.91 nm, in good agreement with the neutron RG of 2.82 nm in 1H2O. This RG is unchanged in reactive-centre-cleaved alpha 1-antitrypsin. These parameters are also unchanged at pH 8 in sodium/potassium phosphate buffers up to 0.6 M. The neutron and X-ray curves for native alpha 1-antitrypsin were compared with Debye simulation based on the crystal structure of reactive-centre-cleaved (papain) alpha 1-antitrypsin. After allowance for residues not visible in the crystallographic electron-density map, and rejoining the proteolysed site between Met-358 and Ser-359 by means of a relatively minor conformational re-arrangement, good agreement to a structural resolution of 4 nm is obtained with the neutron data in two contrasts and with the X-ray data. The structures of the native and cleaved forms of alpha 1-antitrypsin are thus similar within the resolution of solution scattering. This places an upper limit on the magnitude of the presumed conformational changes that occur in alpha 1-antitrypsin on reactive-centre cleavage, as indicated in earlier spectroscopic investigations of the Met-358-Ser-359 peptide-bond cleavage. Methods for scattering-curve simulations from crystal structures are critically assessed. The RG data lead to dimensions of 7.8 nm x 4.9 nm x 2.2 nm for native alpha 1-antitrypsin. The high internal inhomogeneity and the asymmetric shorter semi-axes of 4.9 nm and 2.2 nm suggest that the three oligosaccharide chains of alpha 1-antitrypsin are essentially freely extended into solvent in physiological conditions. This conclusion is also supported by the Debye simulations, and by modelling based on hydrodynamic parameters.

Binding Sites↗
PubMed1990

Conformational transition between native and reactive center cleaved forms of alpha 1-antitrypsin by Fourier transform infrared spectroscopy and small-angle neutron scattering.

alpha 1-Antitrypsin (alpha 1-AT) is the best-characterized member of the serpin superfamily of plasma proteins. Protease inhibitor members of this family undergo a characteristic reactive-center cleavage during expression of their inhibitory activity. The physical basis of this transition in alpha 1-AT from the stressed native conformation to the more stable reactive center cleaved (split) form was studied by Fourier transform infrared (FT-IR) spectroscopy and neutron scattering. The FT-IR spectra show that, while split alpha 1-AT has three intense well-resolved components associated with the presence of antiparallel beta-sheet and alpha-helix conformations, the amide I band of native alpha 1-AT has only one intense component, associated with the presence of beta-sheet structure. 1H-2H exchange within the polypeptide backbone, studied by FT-IR and NMR spectroscopy, shows that the native form undergoes greater exchange than the split form. Under the same conditions, neutron scattering shows no differences in the radius of gyration RG of the native and the split forms. In contrast, in high concentrations of phosphate approaching those used for crystallization, the native form (unlike the split form) undergoes dimerization. These data indicate that the conformational transition largely involves localized secondary and tertiary structure rearrangements. We propose that the energetically stressed native alpha 1-AT structure is the consequence of a significantly reduced number of hydrogen bonds in secondary structure components and that reactive-site cleavage between Met358 and Ser359 is the key for the development of the fully hydrogen bonded more stable serpin structure.

Fourier Analysis↗
PubMed1990

Structural homologies of component C5 of human complement with components C3 and C4 by neutron scattering.

The complement component C5 is one of a family of structurally related plasma proteins that includes components C3 and C4. Activation of C5 is the initial step in the formation of the membrane attack complex of complement. Analysis of the solution structure of C5 and comparisons with similar analyses of the structures of C3 and C4 are reported here. Neutron solution scattering gave an Mr for C5 of 201,000, which demonstrates that C5 is monomeric in solution. The radius of gyration RG of C5 at infinite contrast is 4.87 nm and corresponds to an elongated structure. The longest length of C5 was determined to be at least 15-16 nm from three calculations on the basis of the RG, the scattering intensity at zero angle I(0), and the indirect transformation of the scattering curve into real space. Comparison of the RG and contrast variation data and indirect transformations of the scattering curves for C3, C4, and C5 show that these have very similar structures. Comparisons of the C5 scattering curve with Debye small-sphere models previously employed for C4 and C3 show that good curve fits could be obtained. Unlike previous studies that have suggested significant differences, these experiments indicate that, while C5 differs from C3 and C4 in its activation and inactivation pathways, significant structural homology exists between the native proteins, as might be predicted from their high (and similar) sequence homology.

Complement C3↗
PubMed1989

Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy.

Myocardial perfusion in ten normal volunteers and 20 patients with coronary artery disease documented by recent coronary arteriography was studied with 99mTc-labeled SQ30217 and 201TI. Plantar 201TI imaging followed standard treadmill exercise and planar SQ30217 imaging followed upright bicycle exercise, performed to angina, or the same double product achieved on the treadmill test. Upright anterior, 30 degrees left anterior oblique, and 60 degrees left anterior oblique images were obtained for 3, 6, and 9 min, respectively, starting 2 min after injection of 15 mCi of 99mTc SQ30217. A second 15-mCi dose was injected at rest approximately 2 hr later, and the same imaging protocol was followed. No adverse reactions or laboratory abnormalities attributable to SQ30217 were observed. All scans on the normal volunteers were interpreted as normal. Qualitative readings of both tests were equally sensitive for detecting patients with coronary disease (SQ30217 - 16/20, TI - 17/20, p = NS) and identifying abnormal vessels (SQ30217 - 19/45, TI - 21/45, p = NS). Both agents were falsely positive in 1/15 vessels. Ten vascular regions showed persistent abnormalities on resting SQ30217 scans; eight of these were distal to stenoses of at least 90% and three were also abnormal on thallium redistribution images. Hepatic uptake of SQ30217 obscured inferoapical segments in some views in 14/20 patients but did not interfere with abnormal vessel identification.

Adult↗
PubMed1985

Comparative risks and costs of male and female sterilization.

Couples who are considering elective sterilization should compare the risks and costs of male and female sterilization procedures as part of the decision process. Morbidity, mortality, failure rates, and short-term costs associated with male and female sterilization procedures were estimated from data available in previous case series. Male sterilization procedures were found to have zero attributable deaths and significantly less major complications when compared to female sterilization procedures. No less than 14 deaths a year can be attributed to female sterilization procedures in the US. Male and female sterilization procedures have efficacy rates that are not significantly different from each other. The short-term costs of female sterilization are 3.0 to 4.1 times that of vasectomy.

Adolescent↗
PubMed1983

Hepatic sinusoidal endothelium in sheep: an ultrastructural reinvestigation.

Following perfusion fixation of livers from fetal, neonatal, and adult sheep, the ultrastructure of the fenestrated sinusoidal endothelium was examined. In contrast to an earlier report which utilized immersion fixation, we found the fenestrae to be unoccluded by diaphragms or basal lamina, thus offering only a discontinuous barrier between the blood and the space of Disse and hepatocytes. This observation was confirmed by perfusing the liver with marker particles. The fenestrae appear, therefore, to have a sieving function, regulating the metabolism of particulate matter such as lipoproteins in sheep in a similar manner to that which has been shown to occur in rats.

Animals↗
PubMed1983

Hepatic sinusoidal endothelium in goats.

The ultrastructure of the hepatic sinusoids of the goat was examined. Contrary to current belief concerning this and other ruminant species, we found the sinusoids to be lined by a smooth, continuous layer of endothelium, broken only by the presence of numerous, unoccluded fenestrae which provide a direct path of communication between the sinusoidal lumen and the space of Disse. Therefore, we suggest that a sieving function similar to that which has been shown to occur in rats may be attributed to the sinusoidal endothelium of the goat.

Animals↗
PubMed1982

Intraoral insertion of grafts to project the nasal tip.

Certain tip-projecting techniques require insertion of grafts and/or implants into the premaxillary region. These grafts may extend anteriorly into the columella or may have to reach all the way to the tip to exert the projecting forces exactly where the surgeon wishes to have them applied. The most direct technique for insertion of these long grafts is one of the columella-splitting maneuvers, but some patients will not accept the external scarline necessitated. An intraoral approach can be used in these patients or in any others in whom the surgeon wishes to have no external scar. It allows good exposure, easy insertion of the grafts and/or implants, and secure closure for stabilization and fixation of the grafts.

Humans↗
PubMed1981

Blunt dissection in augmentation mammaplasty-an instrumental aid.

The iconoclast is an instrument that facilitates blunt dissection in areas where this basic technique is difficult because of anatomical or postsurgical adherence. Medical and inferior undermining in augmentation mammaplasty in primary and revisional cases is described. The instrument capitalizes on the gripping rather than the spreading strength of the surgeon's hand, allows easy penetration of tissues to be spread apart, and diminished severance of blood vessels. We have used the iconoclast for almost two years in selected cases and have had no problems or complications attributable to it.

Breast↗