Biomedical subjects
Publications and source records attributed to A Salmon.
After a Fontan operation pulmonary blood flow is heavily dependent on respiration. Two patients with a Fontan and normal sinus rhythm developed episodes of collapse with loss of cardiac output secondary to the tonic phase of an epileptic fit. The forced expiratory effort during the tonic phase severely compromised systemic venous return and led to collapse due to loss of cardiac output.
Rotational resonance (RR) NMR methods are explored for determining intramolecular and intermolecular distances between 13C-labeled sites in membrane bilayers. Specific 13C labels have been incorporated into dipalmitoylphosphatidylcholine (DPPC) and a hydrophobic peptide corresponding to the transmembrane domain of human glycophorin A. The exchange of magnetization between these labels in the RR NMR experiment can be related to their internuclear separation. Intramolecular magnetization exchange rates have been measured between 13C labels incorporated at the 1-position of the sn-1 acyl chain (1-[1-13C]) and the 2-position of the sn-2 acyl chain (2-[2-13C]) of DPPC. These positions are 5.3-5.5 A apart in the crystal structure of dimyristoylphosphatidylcholine (DMPC), but are estimated to be 4.5-5.0 A apart in DPPC below the subphase transition temperature. These results are consistent with a smaller axial displacement between the sn-1 and sn-2 acyl chains than the approximately 3.6-A displacement observed in the DMPC crystal structure. Intermolecular magnetization transfer rates have been measured between 1,2-[2-13C]DPPC and 2-[1,13C]DPPC and between 1,2-[1-13C]DPPC and 2-[2-13C]DPPC. In addition, intermolecular magnetization exchange rates have been measured between 1,2-[2-13C]DPPC and the 13C-OH position of Y93 in the glycophorin transmembrane domain. These intermolecular distance measurements demonstrate that the relative orientation and location of membrane lipids and peptides can be established using RR NMR methods.
The phase relation of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) has been determined by measurement of the endothermic transitions of mixtures of DPPC and POPG in 100 mM NaCl, 50 mM PIPES (pH 7.0). With the use of differential scanning calorimetry, the gel-liquid crystalline phase transitions of pure POPG and DPPC were estimated to be 274 K and 315.8 K, respectively. With mixtures, there was considerable broadening of the endotherms, but there was no evidence of immiscibility. At high and low mole fractions of DPPC, the observed transition regions are not different from that calculated assuming ideal behavior. However in the central region of the phase diagram, there were deviations from both the ideal liquidus and solidus curves. The chemical shift anisotropy of the 13C-labelled carbonyl carbon of pure DPPC was determined as a function of temperature. At 298 K, a broad peak characteristic of axially symmetric motional averaging of the shielding tensor was observed. At a temperature of 300 K, a narrow peak at 173 ppm was superimposed upon the broad peak. The magnitude of the narrow resonance increased with temperature over the range of 300 to 315 K with the spectrum obtained at the latter point almost completely devoid of any broad features. Spectra obtained with a 9:1 mole ratio of DPPC/POPG was very similar to that obtained with pure DPPC. However, with increasing amounts of POPG, both the temperature at which the narrow resonance appeared and the temperature at which only a narrow resonance was observed were reduced. Over the range of 0 to 50 mol % POPG, there was no major change in the width or shape of the spectra which contained only a broad or narrow resonance. Also for mol % of POPG of 20% and less, there was agreement between the temperature at which only the narrow component was observed and the completion of the main phase transition based on the DSC scans. However, at the two higher mol % of 33 and 50%, the temperature at which only the narrow component was observed was lower than the temperature established for the completion of the main phase transition.
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Diacylglycerols are minor constituents of membrane lipids, yet are essential in the activation and membrane association of protein kinase C. Solid-state 13C NMR experiments have been used to characterize the orientation of the glycerol backbone of dipalmitoylglycerol (DPG) and dipalmitoylphosphatidylcholine (DPPC) in egg phosphatidylcholine (PC) bilayers. The 13C NMR spectra of both DPG and DPPC specifically 13C-labeled at the sn-2 chain carbonyl exhibit a single narrow resonance (approximately 2 ppm) in liquid-crystalline egg PC bilayers. In contrast, specific 13C-labeling of both the sn-1 and sn-2 chain carbonyls results in an additional broad component (24-32 ppm) with an axially symmetric line shape. These data reveal that DPG has a distinct motionally-averaged structure in PC bilayers that is similar to that of DPPC and is not significantly affected by the absence of the large polar PC headgroup. The NMR line shapes are roughly consistent with the results of previous FTIR and NMR studies that indicate the sn-1 chain extends from the C1 carbon of the glycerol backbone into the hydrophobic interior of the bilayer, while the sn-2 chain first extends parallel to the bilayer surface and incorporates a bend at the ester linkage in order to keep the sn-1 and sn-2 chains parallel. However, the data suggest that the time-averaged orientation of the glycerol backbone is tilted from the bilayer normal, in contrast to the nearly parallel orientation observed in the crystal structures of phosphatidylcholines and phosphatidylethanolamines or the perpendicular orientation observed in the crystal structures of diacylglycerols.
Polyunsaturated fatty acids are widely distributed components of biological membranes and are believed to be involved in many biological functions. However, the mechanisms by which they act on a molecular level are not understood. To further investigate the unique properties of omega 3 polyunsaturated phospholipid bilayers, deuterium nuclear magnetic resonance (2H NMR) studies have been made of the liquid-crystalline (L alpha) and gel phases of a homologous series of mixed-chain phosphatidylcholines containing docosahexaenoic acid: (per-2H-n:0)(22:6)PC, where n = 12, 14, 16, and 18. The moments of the 2H NMR lineshapes have been evaluated, and from these the warming and cooling main phase transition temperatures were determined. The transition temperatures of the mixed-chain series were found to be significantly lower than those of the corresponding lipids in the disaturated series, di(per-2H-n:0)PC, with hystereses ranging from 2 to 14 degrees C. Distinct effects of the docosahexaenoyl chain on bilayer order were found, though these effects varied across the mixed-chain series. In evaluating the moment data, an empirical method for normalizing the moments with respect to differences in temperature was applied, in addition to using the reduced temperature method. For the systems studied here, the method of normalization had no significant effect on the interpretation of the moment data.
The interaction of cholesterol with ceramides containing alpha-hydroxy fatty acyl chains (hydroxyceramides) has been studied as a foundation for characterizing the lipid bilayers of the stratum corneum. A relatively large quantity of cerebrosides was obtained from bovine brain and converted to ceramides through removal of the carbohydrate side chain. The ceramides were separated based on the absence or presence of hydroxy fatty acyl chains. The lyophilized hydroxyceramides showed a broad melting region at 92 degrees C. Hydroxyceramides dispersed in water produced a relatively narrow, thermotropic transition at 75 degrees C. The effect of cholesterol on this thermotropic phase transition of hydroxyceramides was determined by differential scanning calorimetry. With respect to the main transition, cholesterol caused a broadening of the phase transition at relatively low levels as well as a decrease in the peak transition temperature. The presence of cholesterol at levels in excess of 7 wt% gave rise to an additional low-temperature transition at 55 degrees C. Upon immediate rescanning, this transition was exothermic, but with increasing incubation time the area under the excess heat capacity curve as a function of temperature became smaller. After two days or more, the transition observed was endothermic. At cholesterol levels between 40 and 50 wt%, multiple peaks were observed. From comparisons with related systems, the cooperative thermal transitions of hydroxyceramides with cholesterol are suggested to result from changes in hydrogen bonding or be due to phase separation. The composition of isolated brain ceramides is being compared with that reported for the stratum corneum.
Uvulopalatopharyngoplaty was performed in 18 consecutive patients (15 men and three women; mean +/- standard deviation [SD] age, 46.3 +/- 7.5 years) who presented for the treatment of heavy habitual snoring. No attempt was made to select patients who were ideal anatomically for palatal modification. The loudness of snoring was measured during sleep by integrating the output of a calibrated microphone. An assessment before operation showed that nine patients had obstructive sleep apnoea; four patients had an apnoea index of greater than or equal to 25 apnoeas per hour. The patients were overweight and consumed, on average, 38 g of alcohol per day, but these variables did not change after the operation. The postoperative assessment was performed 138 +/- 44 days after uvulopalatopharyngoplasty. Fourteen patients showed a reduction in the loudness of their snoring, although snoring was abolished in one patient only (average snoring loudness in arbitrary units/min of sleep, 2.8 +/- 2.1 before operation compared with 1.4 +/- 1.5 units/min of sleep after the operation; P less than 0.05. The loudest snore in arbitrary units measured 7.1 +/- 3.3 units compared with 4.8 +/- 3.3 units, respectively; P less than 0.05). The percentage of the sleep time that was spent at an arterial oxygen saturation of less than 90% was reduced after uvulopalatopharyngoplasty (28% +/- 32% of total sleep time compared with 17% +/- 24% of total sleep time, respectively; P less than 0.05). There was no change in the apnoea index. The diastolic blood pressure was lower at the postoperative assessment (94 +/- 11 mmHg compared with 87 +/- 8 mmHg; P less than 0.05); six of 10 subjects whose diastolic blood pressures were greater than or equal to 95 mmHg before the operation had a diastolic blood pressure of less than 95 mmHg after uvulopalatopharyngoplasty (P less than 0.02). Computed tomographic scans showed an increase in the upper airway cross-sectional area at 3 cm and 4 cm above the hyoid bone after uvulopalatopharyngoplasty (P less than 0.05). We conclude that uvulopalatopharyngoplasty is an effective treatment for habitual, heavy snoring in many patients, but it is not the treatment of choice for patients with clinically-significant obstructive sleep apnoea.
We have investigated the molecular features of recombinant membranes that are necessary for the photochemical function of rhodopsin. The magnitude of the metarhodopsin I to metarhodopsin II phototransient following a 25% +/- 3% bleaching flash was used as a criterion of photochemical activity at 28 degrees C and pH 7.0. Nativelike activity of rhodopsin can be reconstituted with an extract of total lipids from rod outer segment membranes, demonstrating that the protein is minimally perturbed by the reconstitution protocol. Rhodopsin photochemical activity is enhanced by phosphatidylethanolamine head groups and docosahexaenoyl (22:6 omega 3) acyl chains. An equimolar mixture of phosphatidylethanolamine and phosphatidylcholine containing 50 mol% docosahexaenoyl chains results in optimal photochemical function. These results suggest the importance of both the head-group and acyl chain composition of the rod outer segment lipids in the visual process. The extracted rod lipids and those lipid mixtures favoring the conformational change from metarhodopsin I to II can undergo lamellar (L alpha) to inverted hexagonal (HII) phase transitions near physiological temperature. Interaction of rhodopsin with membrane lipids close to a L alpha to HII (or cubic) phase boundary may thus lead to properties which influence the energetics of conformational states of the protein linked to visual function.
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Sonography was able to suggest a diagnosis of uterine rupture by demonstrating intra- or extraperitoneal hematoma in the correct clinical setting. A pelvic abscess complicating a uterine rupture was seen in one case. Previous uterine scar, use of prostaglandins for induction of labor, trauma with a currette, and cornual pregnancy were the implicated etiologic factors. Although the rupture site was never directly visualized by sonography, the combination of sonographic and clinical findings was strongly suggestive of the correct diagnosis.
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Magnetic circular dichroism spectra are reported for the visible and near ultraviolet spectral regions of liver microsomes from dimethylbenzanthracene-treated rats. The sequential addition of NADH, dithionite, and carbon monoxide enables us to determine contributions to the magnetic circular dichroism by cytochromes b-5 and P-450, which dominate the spectra. The magnetic circular dichroism of the microsomal preparation is compared with that of purified oxidized and reduced cytochrome -b-5 from pig liver and with the camphor-complexed and camphor-free oxidized, reduced, and reduced carbonmonoxy cytochrome P-450-cam from Pseudomonas putida. The magnetic circular dichroism spectra of the membrane bound cytochrome -b-5 are similar to those of the purified protein, indicating that little or no alteration in the environment of the heme occurs during the isolation procedure. The soluble bacterial cytochrome P-450 also appears to be a suitable model for microsomal P-450, although differences in the magnetic circular dichroism intensity are observed for the two enzymes. No effect of dimethylbenzanthracene on the magnetic circular dichroism spectra of induced compared to control rat microsomes could be observed.
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