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Biomedical subjects

W J Atkinson

Publications and source records attributed to W J Atkinson.

17 recordsLinked to original sources
PubMed1985

Hyperthermia induction with thermally self-regulated ferromagnetic implants.

We have developed a self-regulating thermoseed for interstitial hyperthermia treatment of tumors. The seeds are made of a 70.4% nickel-29.6% copper alloy, and they have a Curie point at 50 degrees C. When exposed to an oscillating magnetic field (90 kHz, 50 Oersted amplitude), these seeds show a sharp drop in the rate of heat production at temperatures above the Curie point. In a simulated treatment of a small visceral mass that had negligible blood flow, the tissue temperature stabilized at the Curie point of the alloy with good temperature homogeneity throughout the volume heated by an array of thermoseeds.

Alloys↗
PubMed1985

Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction.

Atherosclerotic arteries have enhanced reactivity to vasoconstrictors, which suggests that features of the atherosclerotic process itself may result in this abnormal responsiveness. Since vascular smooth muscle proliferation is a prominent feature of atherosclerosis, we postulated that vasoactive agonists and smooth muscle mitogens may share certain common cellular mechanisms of action which potentially contribute to this hyperreactivity. To test this hypothesis, we studied the effects of epidermal growth factor (EGF), a well-characterized mitogen, on rat aortic vascular smooth muscle, both in intact aortic strips and in culture. EGF caused contraction (EC50 = 19 nM) of rat aortic strips which maximally was equivalent to 40% of that induced by angiotensin II, a potent vasoconstrictor. EGF increased 45Ca efflux (EC50 = 3 nM) from cultured rat aortic smooth muscle cells, which was an effect shared by angiotensin II and thought to reflect increased cytosolic-free calcium concentration. EGF (7.5 nM) also stimulated growth of these cultured cells to the same extent as 10% calf serum. These results demonstrate that EGF is both a vasoconstrictor and mitogen for rat aortic smooth muscle cells. The similarities in the effects of EGF and angiotensin II suggest that certain common intracellular mechanisms of action may exist for vasoactive agonists and growth factors which may contribute to the altered vasoreactivity of atherosclerotic vessels.

Animals↗
PubMed1985

Cultured vascular smooth muscle cells: an in vitro system for study of alpha-adrenergic receptor coupling and regulation.

Cultured vascular smooth muscle cells derived by enzymatic dissociation of rabbit aortic media were used for study of alpha 1-adrenergic receptors (AAR) and receptor-coupled calcium flux. AAR were characterized by binding of the alpha 1-selective radioligand [3H]prazosin, and norepinephrine-stimulated 45calcium efflux was measured as an index of AAR-mediated calcium flux. The binding of [3H]prazosin to a crude cellular homogenate was to a single, saturable site of high affinity (Kd = 0.15 nM, Bmax = 75-125 fmol/mg protein), which was stereo-specific and exhibited the appropriate potency order for competition by agonists. Prazosin (Kd = 0.07 nM) was approximately 3000-fold more potent than the alpha 2-selective antagonist yohimbine (Kd = 222 nM), both of which exhibited Hill coefficients of one, indicative of binding to a single receptor type. In intact cells, norepinephrine caused a concentration-related (EC50 = 100 nM) increase in 45calcium efflux which was blocked by low concentrations of prazosin (IC50 approximately equal to 0.1 nM), but not yohimbine (IC50 greater than 100 nM). An alpha 1-selective concentration of prazosin (100 nM) fully blocked norepinephrine-stimulated 45calcium efflux, and therefore, it appears that this effect does not involve alpha 2-adrenergic receptors. Treatment of cultured cells with 1-norepinephrine for 48 h caused a concentration-related decrease in both AAR density and maximum norepinephrine-stimulated 45calcium efflux. This cultured vascular smooth muscle cell system provides several advantages for the study of alpha-adrenergic receptor coupling and regulation.

Animals↗
PubMed1984

Local hyperthermia with interstitial techniques.

The heating of deep visceral tumors with implanted electrodes and with self-regulating ferromagnetic thermoseeds was investigated. Clinical trials on six patients heated with implanted electrodes indicate that good local tumor control can be obtained by application of hyperthermia during a normal course of radiotherapy. The heating method was found practical, and neither toxicity nor severe patient discomfort was encountered. However, temperature inhomogeneity within the tumor volume remains a problem. Theoretical studies and an animal experiment indicate that temperature homogeneity can be largely improved by heating the tumor with thermoseeds made of an alloy of 70.4% nickel and 29.6% copper. The highly temperature-dependent rate of heat production in the vicinity of the Curie point, about 50 degrees for this material, provides automatic temperature regulation.

Body Temperature↗
PubMed1982

Functional angiotensin II receptors in cultured vascular smooth muscle cells.

To study cellular mechanisms influencing vascular reactivity, vascular smooth muscle cells (VSMC) were obtained by enzymatic dissociation of the rat mesenteric artery, a highly reactive, resistance-type blood vessel, and established in primary culture. Cellular binding sites for the vasoconstrictor hormone angiotensin II (AII) were identified and characterized using the radioligand 125I-angiotensin II. Freshly isolated VSMC, and VSMC maintained in primary culture for up to 3 wk, exhibited rapid, saturable, and specific 125I-AII binding similar to that seen with homogenates of the intact rat mesenteric artery. In 7-d primary cultures, Scatchard analysis indicated a single class of high-affinity binding sites with an equilibrium dissociation constant (Kd) of 2.8 +/- 0.2 nM and a total binding capacity of 81.5 +/- 5.0 fmol/mg protein (equivalent to 4.5 x 10(4) sites per cell). Angiotensin analogues and antagonists inhibited 125I-AII binding to cultured VSMC in a potency series similar to that observed for the vascular AII receptor in vivo. Nanomolar concentrations of native AII elicited a rapid, reversible, contractile response, in a variable proportion of cells, that was inhibited by pretreatment with the competitive antagonist Sar1,Ile8-AII. Transmission electron microscopy showed an apparent loss of thick (12-18 nm Diam) myofilaments and increased synthetic activity, but these manifestations of phenotypic modulation were not correlated with loss of 125I-AII binding sites or hormonal responsiveness. Primary cultures of enzymatically dissociated rat mesenteric artery VSMC thus may provide a useful in vitro system to study cellular mechanisms involved in receptor activation-response coupling, receptor regulation, and the maintenance of differentiation in vascular smooth muscle.

Angiotensin II↗
PubMed1978

De subitaneis mortibus. XXX. Observations on the pathophysiology of the long QT syndromes with special reference to the neuropathology of the heart.

Eight patients (different families) with syncopal attacks and a long QT interval in the ECG died suddenly. Five heard normally and three were born deaf. At postmortem examination of all eight hearts the single consistent abnormality was focal neuritis and neural degeneration within the sinus node, A-V node, His bundle and ventricular myocardium. Although the etiology of this intracardiac neural disease is uncertain, a chronic viral infection or some noninfectious degenerative process are among the plausible causes discussed. If intracardiac neuritis and neural degeneration prove to be a prevalent finding among other victims dying from the long QT syndromes, further consideration should be given to whether there is any genuine hereditary component in the pathogenesis. Because of the asymmetrical and focal distribution of the cardioneural lesions, the response to present forms of medical or surgical treatment of the lung QT syndromes may vary from benefit to harm. Until more is known of the true etiology of the neural disease, treatment will probably remain empirical in nature and should be conducted with cautious clinical observation.

Adolescent↗
PubMed1975

New approach to management of intracranial aneurysms.

In six cases an attempt was made to relieve the tension on intracranial aneurysms by temporarily clamping the internal carotid artery in the neck, so as to increase the expansibility of the artery. This approach was based on the concept (or "A principle") that haemorrhage is caused by the aneurysm having to bear the full force of systolic pulse pressure when atherosclerosis prevents this pressure being taken up by the normally expansile arterial wall. Follow-up has been fairly short, but the preliminary findings in four of the six patients are encouraging. More attention must be paid in the future to the significance of atherosclerosis in the onset of bleeding from intracranial aneurysms and the incidence of postoperative problems. The argument that atherosclerosis permits the transmission of the systolic pulse directly to the aneurysm wall requires further investigation. The earlier pathological signs of atherosclerosis must receive greater attention, and post-mortem study of the walls of arteries in immediate juxtaposition to aneurysms with high-powered magnification is required.

Adult↗
PubMedDate not supplied

Temperature distributions in tumor models heated by self-regulating nickel-copper alloy thermoseeds.

Needle-shaped thermoseeds have been manufactured from an alloy consisting of 70.4% nickel and 29.6% copper. The magnetic properties of the alloy were measured at various temperatures and from this the heating power produced by a thermoseed exposed to an electromagnetic induction field was computed as a function of the seed temperature. Calorimetric measurements were also performed. From these data, temperature distributions in simple tumor models assumed to be heated by an array of nickel-copper implants were computed. It was found that the nickel-copper implants produce substantially better temperature homogeneity than readily available constant power seeds, especially in tumors with unpredictable rates of blood perfusion or when the implant arrangement is not perfectly regular. Since such conditions are likely to be present in actual patients, the nickel-copper implants should be very useful in clinical hyperthermia.

Alloys↗
PubMedDate not supplied

Angiotensin increases cytosolic free calcium in cultured vascular smooth muscle cells.

We used the calcium-sensitive fluorescent indicator quin 2 to monitor changes in cytosolic free calcium concentration ([Ca2+]i) associated with angiotensin II receptor activation in cultured vascular smooth muscle cells isolated from rat aorta. Resting [Ca2+]i in unstimulated vascular smooth muscle cells was 198 +/- 7 nM. Angiotensin II induced concentration-dependent rapid increases in [Ca2+]i (threshold congruent to 10(-11) M; effective concentration, 50% congruent to 5 X 10(-10) M; maximum congruent to 10(-8) M); the rate of increase in [Ca2+]i also appeared to be concentration dependent. The angiotensin II-induced changes were completely blocked by the angiotensin II receptor antagonist [Sar1, Ile8]-angiotensin II. In the presence of extracellular calcium, 10(-8) M angiotensin II induced an increase in [Ca2+]i that reached peak values of five to six times the resting levels within 15 seconds, followed by a gradual decline to a plateau at two to three times the resting level. When EGTA was added to chelate external calcium, the angiotensin II-induced increases in peak [Ca2+]i were attenuated and the plateau phase was abolished. These data show that (1) quin 2 can be used in cultured vascular smooth muscle cells to study changes in calcium homeostasis induced by angiotensin II, and (2) angiotensin II acts on cultured vascular smooth muscle cells to cause a rapid increase in [Ca2+]i that appears to depend on both the mobilization of intracellular calcium and the influx of extracellular calcium.

Aminoquinolines↗