Biomedical subjects
S G Wolf
Publications and source records attributed to S G Wolf.
Plasma fibrinogen patterns in patients with coronary atherosclerosis.
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The goal of medical education: achievement or approval.
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Tubulin conformation in zinc-induced sheets and macrotubes.
The protein tubulin is the main constituent of microtubules. Previous studies have shown that zinc ions induce the formation of crystalline sheets and macrotubes of tubulin. Both crystal types are suitable for structural studies by electron crystallography. However, crystallographic structural analysis of tubulin has been hampered by limited crystal size and quality and the inability to control crystal polymorphism. We can obtain well-ordered crystals which are grown upon prolonged incubations (up to 24 hr). The presence of NaCl delays the degradation of the crystals, and addition of the protease inhibitor pepstatin improves crystal quality. The crystal form (sheet or macrotube) can be controlled with incubation conditions. The size of the crystals can reach up to 2 microns in width for the sheets and up to 0.5 microns in diameter for the macrotubes. Both crystal types can reach several micrometers in length. Comparison of the projection maps of the two crystal structures shows that adjacent protofilaments in the macrotubes are shifted by about 6 A relative to their positions in the sheets. Observable changes of monomer shape appear to allow close interprotofilament contacts to be maintained in both crystal forms. Images of glucose-embedded specimens obtained under these conditions give structural information beyond 4 A resolution. Merging of high- and low-resolution data allows for unambiguous assignment of monomer boundaries to high-resolution features.
Preservation of 2-D crystals of tubulin for electron crystallography.
Zinc-induced sheets of tubulin are two-dimensional crystalline polymers that constitute an ideal sample for high resolution studies of tubulin by electron crystallography. We show that these 2-dimensional tubulin crystals can be stabilized by taxol against low-temperature depolymerization and degradation with time, easing the way for the preparation of electron microscopy samples. The preservation of the crystals to high resolution has been tested with different embedding media. While glucose-embedded samples diffract poorly, samples embedded in tannin consistently diffract to a resolution of at least 3.5 A. Even better results are obtained by embedding with a combination of tannin and glucose, which improves the flatness of the crystals and allows the collection of isotropic high-resolution data from tilted specimens.
Brain mechanisms in fatal cardiac arrhythmia.
Intravenous injection of histamine to rabbits was used as a prototype in an investigation of the mechanism of sudden death due to anaphylaxis and other causes. The "dive" reflex, bradycardia due to activation of the ophthalmic branch of the fifth cranial nerve, was induced in thirty-seven of the animals while they inhaled a very small amount of cigarette smoke. Associated with the resulting bradycardia were lowered blood pH and increased serum content of lactic acid and potassium and increased peripheral arterial constriction with elevation of diastolic blood pressure. Intravenous injection of 1 ml of histamine in the presence of the dive reflex induced potentially fatal ventricular arrhythmia, but no cardiac disturbance when administered while the dive reflex was inactive, thereby strongly suggesting that sudden death in anaphylaxis may involve an overzealous response to a normally protective neural reflex.
Effects of transient coronary artery occlusion on canine intrinsic cardiac neuronal activity.
In order to further elucidate the regulatory function of canine epicardial neurons, the effects of transient coronary artery occlusion on their spontaneous activity was studied. Fifty-eight individual, spontaneously active units were identified by means of their action potential configurations in specific loci of atrial and ventricular epicardial fat of 10 anesthetized dogs. The activity of 49 of the units was modified by one minute of coronary artery occlusion. Twenty-four of the 49 responding units exhibited increased activity and 37 decreased activity during coronary artery occlusions. Activity changes were sometimes, but not always, associated with decreased left ventricular intramyocardial systolic pressure. During reperfusion, the activity of 6 units was increased compared to control levels, even though ventricular pressures remained the same. Following acute decentralization, 48% of previously active units generated spontaneous activity; the activity of 89% of these was altered during coronary artery occlusion despite the fact that overall cardiodynamics were unchanged. Following hexamethonium administration, the activity generated by 9 of 10 spontaneously active units was modified by coronary artery occlusion. It is concluded that transient coronary artery occlusion can modify the activity generated by intrinsic cardiac neurons, such modification involving central and peripheral neuronal interactions.
Federal funding of medical research.
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Diaphragmatic spasm: a neglected cause of dyspnoea and chest pain.
The study included 17 patients, 12 women and 5 men, with a recurrent symptom complex involving chest pain and dyspnoea characterized by inability to get a full breath. Some attacks had subsided spontaneously. Others had lasted hours or days. When examined by fluoroscopy during an attack, each subject was found to have a nearly maximally contracted (flat) diaphragm. In some of them the attack was promptly interrupted by a small intravenous injection of sodium amytal. In others it could be aborted by a conscious effort at full expiration. The syndrome associated with diaphragmatic spasm is discussed in comparison with other noncardiac sources of chest pain and dyspnoea.
Shortening of the QT interval of the EKG is associated primarily with increased ventricular contractility rather than heart rate.
The objective of this study was to gather direct evidence on whether the duration of the QT interval relates primarily to heart rate or to ventricular contractility. The electrocardiographic and cardiodynamic consequences of electrical stimulation (15 V, 5 ms, 10Hz) of various intrathoracic sympathetic efferent neuronal structures were studied in 10 anesthetized mongrel dogs. Stimulation of efferent sympathetic axons in the right intraganglionic nerve, which innervates the sinoatrial node, induced tachycardia (110 +/- 5 - 133 +/- 6 bpm; p < 0.01) without significantly altering right or left ventricular intramyocardial ventricular chamber pressures. The QT interval, as determined by leads I, II and III of the EKG and a transthoracic lead, was not affected by this intervention 310 +/- 8 - 302 +/- ms). Increasing heart rate to a similar degree (111 +/- 3 - 131 +/- 3 bpm) by right atrial pacing did not induce changes in the QT interval. When right (23 +/- 3 - 49 +/- 8 mm Hg; p < 0.01) and left (81 +/- 10 - 127 +/- 19 mm Hg; p < 0.01) ventricular forces were augmented without concomitant increases in heart rate by stimulating efferent sympathetic axons in the left caudal pole cardiopulmonary nerve the QT interval shortened (322 +/- 11 - 290 +/- 12 ms; p < 0.01). Only when an efferent sympathetic nerve, that contains fibers destined for both the sinoatrial node and the ventricles was stimulated did both heart rate and ventricular contractility augment and QT shorten (318 +/- 10 - 290 +/- 11 ms; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Application of chaos theory to a model biological system: evidence of self-organization in the intrinsic cardiac nervous system.
The neutral organization that determines the specific beat-to-beat pattern of cardiac behavior is expected to be demonstrated in the independent regulation of the RR intervals (chronotropy) and the corresponding QT subintervals (inotropy), as the former defines the rate of contraction and the latter has a linear negative correlation with the peak pressure inside the contracting ventricular muscles. The neurons of the isolated cardiac nervous system, many of which are located in the fat-pads of the heart, exhibit the same types of mechanical and chemical receptors and the same types of cholinergic and noradrenergic effectors as those found in the neural superstructure. In the surgically isolated and perfused rabbit heart we studied the responses of the QT and RR intervals evoked by block of coronary blood flow. We found that if we separated each RR cycle into QT and RR-QT components, then the dynamics of variation for each subinterval series often had the same fractional number of degrees of freedom (i.e., chaotic dimensions), a finding which suggests they are both regulated by the same underlying system. The ischemia/anoxia evoked transient dimensional increases and separations between the two subinterval series that, after the temporary divergence, reconverged to having the same lower value. The dimensional fluctuations occurred repeatedly and preceded or coincided with alterations in the magnitude and sign of the slope of QT vs RR-QT. We interpret the dimensional fluctuations of the two subinterval series as correlates of adaptation-dependent self-organization and reorganization in the underlying intrinsic cardiac nervous system during accumulating ischemia/anoxia. Such attempts at functional reorganization in this simple neurocardiac system may explain the transient dimensional changes in the RR intervals that precedes by 24 hrs the occurrences of fatal ventricular fibrillation in high-risk cardiac patients.