A B S T R A C T 95 individual human atherosclerotic lesions from 26 persons were classified into three groups under the dissecting microscope: fatty streaks, fibrous plaques, and gruel (atheromatous) plaques. Each lesion was isolated by microdissection, its lipid composition determined by chromatography, and the physical states of the lipids identified by polarizing microscopy and in some cases by X-ray diffraction. The composition of each lesion was plotted on the in vitro phase diagram of the major lipids of plaques: cholesterol, cholesterol ester, and phospholipid. The observed physical states were compared with those predicted by the location of the lipid composition on the phase diagram.The most severe lesions (gruel plaques) had an average lipid composition of cholesterol 31.5±1.9%, cholesterol ester 47.2±2.3%, and phospholipid 15.3±0.5%.Their compositions fell within the three-phase zone of the phase diagram, predicting the lipids to be separated into a cholesterol crystal phase, a cholesterol ester oily phase and a phospholipid liquid crystalline phase. In addition to the phospholipid liquid crystalline phase of membranes and myelin-like figures demonstrable by electron microscopy, polarizing microscopy revealed the other two predicted phases, isotropic cholesterol esterrich droplets and cholesterol crystals. X-ray diffraction studies verified the identity of the crystals as cholesterol monohydrate.Fibrous plaques also had an average lipid composition within the three-phase zone of the phase diagram. Polarizing microscopy revealed the presence of cholesterol monohydrate crystals and lipid droplets in all of these lesions; the droplets were predominately isotropic in 28 of the 31 fibrous plaques. Although these lesions had less free cholesterol and more cholesterol ester than gruel plaques, they were otherwise similar.Fatty streaks had compositions within both the twoand three-phase zones of the phase diagram. Compared with gruel plaques, the fatty streaks within the twophase zone, defined as "ordinary," had more cholesterol ester, less free cholesterol, a higher cholesteryl oleate/ cholesteryl linoleate ratio, a lower sphingomyelin/lecithin ratio, more anisotropic lipid droplets, and rare or no cholesterol crystals. Those lesions within the three-phase zone had many chemical and physical features intermediate between ordinary fatty streaks and gruel plaques. Moreover, 68% of these "intermediate" lesions had no cholesterol crystals by polarizing microscopy in spite of their compositions being within the three-phase zone, indicating the cholesterol ester oily phase or the phospholipid phase or both were supersaturated with cho-
These findings suggest that strategies aimed at improving social support can have a favorable impact on psychological distress and, ultimately, can improve health outcomes in patients with IBD.
Increased physician awareness that psychologically distressed patients have difficulty processing of clinically relevant information may lead to improved doctor-patient communication during an office visit.
Sunmmary1. A method for measuring the rate of production of "IC-labelled adenine nucleotides, including cyclic adenosine 3',5'monophosphate (cyclic AMP), from ["IC]-adenosinetriphosphate (ATP) was developed and used to study the effects of ATP, adenosine diphosphate (ADP) and adenosine 5'-monophosphate (AMP) on the rate of accumulation of cyclic AMP in cell-free preparations of adenyl cyclase from rat brain. 2. The mechanism by which NaF increases cyclic AMP accumulation was studied by comparing its effect on adenine nucleotide metabolism with that of an ATP regenerating system.3. ADP and ATP are potent inhibitors of phosphodiesterase (PDE) and it is the sum of the concentrations of these two nucleotides which controlled the rate of destruction of cyclic AMP. The effect of these nucleotides was significant even in the presence of 6-7 mm theophylline; theophylline itself inhibited PDE only 50-60%. 4. Fluoride ion had no direct effect on PDE but it inhibited the rate of hydrolysis of ADP and ATP and thus indirectly inhibited PDE. The effect of fluoride ion on cyclic AMP accumulation can be explained, at least in part, by this indirect inhibition of PDE.5. Studies on a more purified preparation of adenyl cyclase clearly demonstrated a direct action of NaF on adenyl cyclase.
A B S T R A C T The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53°C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37°C. X-ray diffraction studies of splenic tissue at 37°C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52°C, with a maximum mean transition temperature at 42°C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86+0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition.Lipid compositions of spleen and liver were de-
Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.
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