The genetic epidemiology of hypertension: a review of past studies and current results for 948 persons in 48 Utah pedigrees.
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Adolescent↗
Biomedical subjects
J B Smith
Publications and source records attributed to J B Smith.
Benign ureteral tumors: report of a case and review of the literature.
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Fibroma↗
Determination of SRS-A release from guinea-pig lungs by a radioimmunoassay.
A sensitive radioimmunoassay for leukotrienes (LTs) has been developed. Rabbits were immunized with a conjugate of LTD4 and bovine serum albumin, prepared by using 1,5-difluoro-2,4-dinitrobenzene as the coupling agent. The assay can detect 0.045 pmol LTD4 at a final plasma dilution of 1:72. 50% displacement of bound 3H-LTD4 was obtained with 0.43 +/- 0.03 pmol LTD4. LTC4, LTE4 and LTF4 cross-react 159%, 57% and 85%, respectively, whereas LTB4, 5-HETE and prostaglandins did not. The assay was validated by measuring the antigen-induced release of LTs from sensitized guinea-pig chopped lungs. High correlation (0.9434, p less than 0.05) was found when LTs were simultaneously determined by this assay and a bioassay on guinea pig ileum.
Animals↗
Role of thromboxanes and prostaglandin endoperoxides in the pathogenesis of eicosanoid induced sudden death.
Arachidonic acid (1 mg/kg) or 9,11-azo PGH2 (35 micrograms/kg) injected intravenously into anesthetized rabbits results in sudden death characterized by a marked loss of circulating platelets, a dramatic rise in circulating thromboxane B2 concentrations and a precipitous drop in blood pressure. Death ensues in 3 to 5 minutes from pulmonary thrombosis and pulmonary artery constriction. Administration of dazoxiben (2 mg/kg) prior to arachidonic acid, prevents all of these changes. However, dazoxiben failed to prevent any of these effects after injection of azo-PGH2, a synthetic agonist of the endoperoxide and thromboxane receptor. These results demonstrate the importance of endoperoxide-thromboxane accumulation in eicosanoid induced sudden death and suggests that there is no significant functional difference between the actions of these agents in the rabbit.
Animals↗
Functional aspects of T-cells from patients with non-Hodgkin's lymphoma. Responses to self, TNP-modified self, and alloantigens.
Peripheral blood T-cell proliferative responses to autologous non-T cells, Trinitrophenyl-modified autologous non-T cells, and allogeneic lymphocytes were measured in 27 patients with non-Hodgkin's lymphoma (NHL) and 22 age- and sex-matched healthy controls. The NHL patients were not receiving chemotherapy or immunosuppressive drugs at the time of the study and had not received such agents for at least 3 weeks prior to the study. Responses to autologous non-T cells (the autologous mixed lymphocyte reaction [AMLR] ) and to TNP-modified non-T cells were significantly lower in NHL patients than in controls (P less than 0.00002 and P less than 0.0001, respectively), but responses to alloantigens were not significantly different between the NHL patients and the controls (P greater than 0.85). There was no definite correlation of low AMLR responses with disease activity, and normal AMLR responses did not define a subgroup of patients relative to histopathologic findings. The deficiency of AMLR in NHL patients appears to be due to a disturbance in the T-cell compartment.
Humans↗
Human and rabbit platelets form platelet-activating factor in response to calcium ionophore.
Homogenous preparations of human and rabbit platelets synthesized platelet-activating factor (PAF) when stimulated by calcium ionophore A23187. PAF was isolated by high performance liquid chromatography (HPLC) on a Lichrosorb Si60 column. PAF was well separated from other phospholipids especially sphingomyelin and lysolecithin. The retention times of PAF derived from human or rabbit platelets were identical to the commercially available semisynthetic PAF and radiolabeled PAF. The amount of PAF was determined by the extent to which it induced the aggregation of washed rabbit platelets.
Animals↗
Beneficial effects of ibuprofen in pacing-induced myocardial ischemia.
Lysosomal membrane instability and platelet activation are both associated with acute myocardial ischemia. The effect of ibuprofen on cathepsin D as a marker of lysosomal membrane "leakiness" and thromboxane B2 as a marker of platelet activation was evaluated in 44 patients with angina pectoris. Samples of blood analyzed for cathepsin D, thromboxane B2, and lactate were withdrawn from the coronary sinus and brachial artery before and after pacing to 140 beats/min for 4 minutes. Myocardial ischemia was assessed by determination of transmyocardial lactate extraction or production. Ibuprofen (800 mg) or placebo was administered orally 2 hours before cardiac catheterization. Patients were classified into 4 groups on the basis of administration of placebo or ibuprofen and the presence or absence of myocardial ischemia as determined by demonstration of lactate extraction or production after atrial pacing. In patients with lactate extraction, no significant efflux of cathepsin D or thromboxane B2 occurred after pacing. In patients with lactate production given placebo, a 64 +/- 25% increase in the thromboxane B2 level and a 113 +/- 37% increase in cathepsin D activities occurred in the coronary sinus effluent sampled after pacing. In contrast, in patients with comparable coronary artery disease and comparable lactate production who were given ibuprofen, no release of thromboxane B2 (p = 0.05 compared with patients given placebo) or cathepsin D (p less than 0.01 compared with patients given placebo) occurred after pacing-induced ischemia. These findings suggest that ibuprofen stabilizes membranes and prevents platelet-activated release of thromboxane A2 in pacing-induced myocardial ischemia.
Angina Pectoris↗
Effect of des-amino-D-arginine vasopressin (DDAVP) on plasma levels of platelet and endothelial cell release products.
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6-Ketoprostaglandin F1 alpha↗
Analysis of angiotensin-stimulated sodium transport in cultured smooth muscle cells from rat aorta.
Angiotensin peptides (AI, AII, AIII) increased the rate of Na+ accumulation by smooth muscle cells (SMC) cultured from rat aorta. The stimulatory effect of AII on Na+ uptake was observed when Na+ exodus via the Na+/K+ pump was blocked either by ouabain or by the removal of extracellular K+. AII was at least ten times more potent than AIII and about 100 times more potent than AI in stimulating Na+ uptake. Saralasin had little effect on Na+ uptake by itself but almost completely blocked the increase caused by AII. The stimulation of net Na+ entry by AI, but not AII, was prevented by protease inhibitors. The stimulation of Na+ uptake was almost completely blocked by amiloride. Tetrodotoxin, which prevented veratridine from increasing Na+ uptake, had no effect on the response to AII. Angiotensin increased the rate of ouabain-sensitive 86Rb+ uptake (Na+/K+ pump activity) but had no effect on ouabain-sensitive ATPase activity in frozen-thawed SMC or in microsomal membranes isolated from cultured SMC. The stimulation of ouabain-sensitive 86Rb+ uptake by AII was blocked by saralasin. Omitting Na+ from the external medium prevented AII from increasing 86Rb+ uptake. AII had no effect on cell volume or cyclic AMP levels in the cultured SMC. These results suggest that angiotensin peptides activate an amiloride-sensitive Na+ transporter which supplies the Na+/K+ pump with more Na+, its rate-limiting substrate.
Amiloride↗
1-O-alkyl-linked phosphoglycerides of human platelets: distribution of arachidonate and other acyl residues in the ether-linked and diacyl species.
In this study, the 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine content of human platelets was determined. The distribution of arachidonate among the 1,2-diacyl, 1-O-alkyl-2-acyl, and 1-O-alk-l'-enyl-2-acyl classes of choline- and ethanolamine-containing phosphoglycerides was also assessed. The major platelet phospholipids were choline-containing phosphoglycerides (38%), ethanolamine-containing phosphoglycerides (25%) and sphingomyelin (18%), with smaller amounts of phosphatidylserine (11%) and phosphatidylinositol (4%). In addition to the diacyl class, the choline-linked fraction was found to contain both 1-O-alkyl-2-acyl (10%) and 1-O-alk-l'-enyl-2-acyl (9%) species. The ethanolamine-linked fraction, on the other hand, had an elevated level of the 1-O-alk-1'-enyl-2-acyl (60%) species and a small amount of the 1-O-alkyl-2-acyl component (4%). The major fatty acyl residues found in all classes of the choline and ethanolamine phospholipids were 16:0, 18:0, 18:1 (delta 9), 18:2(n-6) and 20:4(n-6). The 1-O-alkyl and 1-O-alk-1'-enyl fraction of the ethanolamine-linked phospholipids also contained substantial amounts of 22:5(n-3) and 22:6(n-3) acyl chains. Arachidonate comprised 44% of the acyl residues in the sn-2 position of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine. Corresponding values for the diacyl and 1-O-alk-1'-enyl-2-acyl species were 23% and 25%, respectively, based on all 20:4(n-6) being linked to the sn-2 position of all classes.(ABSTRACT TRUNCATED AT 250 WORDS)
Arachidonic Acid↗
Metabolism of platelet-activating factor by blood platelets and plasma.
High performance liquid chromatography in combination with a radioactivity detector was used to study the metabolism of platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by washed platelets, platelet-free plasma and platelet-rich plasma obtained from rabbits and humans. Degradation of platelet-activating factor to its 2-lyso derivative was observed in rabbit and human plasma. This degradation of platelet-activating factor in plasma was completely inhibited by diisopropylfluorophosphate and was partially inhibited by ethylenediamine tetraacetic acid. Washed platelets metabolized platelet-activating factor not only to the 2-lyso compound but also, by reacylation of this lyso intermediate, to an analogue of platelet-activating factor probably containing a long-chain acyl group at the sn-2 position. These transformations occurred, but to a lesser extent, in platelet-rich plasma.
Animals↗
Penile calibration for nocturnal penile tumescence studies.
Artificial penile erections were created in 23 impotent patients by infusion of heparinized saline solution into the corpora cavernosa. Penile circumference as related to rigidity was accurately assessed. The increase in circumference necessary to produce erection adequate for vaginal penetration varied from 7.5 to 35 mm, whereas for maximum rigidity the penile circumference increase varied between 10 mm and 40 mm. These were then compared with the changes during nocturnal penile tumescence studies. Even though 5 patients in the series had erection greater than 15 mm, 40 per cent of them did not achieve rigidity adequate for vaginal penetration. One patient had nocturnal tumescence of only 12 mm; this, however, was an erection adequate for vaginal penetration. The approach discussed in this article may allow the rational use of portable home tumescence monitoring.
Adult↗
Urinary excretion of prostacyclin and thromboxane A2 metabolites after angiotensin converting enzyme inhibition in hypertensive patients.
The contribution, if any, of various prostaglandins to the antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) is controversial. We studied the effect of the ACEI captopril (CAP) on the urinary excretion of 6-keto-PGF2 alpha (6-KF), the major metabolite of the vasodilatory prostaglandin, prostacyclin, and thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor TxA2, in 8 patients with essential hypertension after placebo, two weeks of CAP 25 mg t.i.d. alone, and the same dose of CAP in combination with hydrochlorothiazide (HCTZ) 50 mg/day. Mean 6-KF and TxB2 (nmol/8 hr post-dosing, respectively) did not differ significantly with any treatment; the mean ratio of 6-KF/TxB2 was also unchanged. Likewise, the excretion of these prostaglandins was also evaluated after placebo, the ACEI enalapril (ENA) (5 or 10 mg/day), and the combination of ENA and HCTZ in another group of 8 patients with essential hypertension. Mean 6-KF and TxB2 (nmol/24 hr post-dosing, respectively) showed no significant treatment-related differences; the mean ratio was again unchanged. No correlation existed between the magnitude of blood pressure responses with any treatment and either 6-KF or TxB2 excretion. Thus, the antihypertensive action of ACEI, alone or in combination with HCTZ, does not appear to involve alterations in these vasoactive prostaglandins.
6-Ketoprostaglandin F1 alpha↗
Vanadium ions stimulate DNA synthesis in Swiss mouse 3T3 and 3T6 cells.
Vanadyl sulfate and sodium orthovanadate in the concentration range between 5 and 50 microM are shown to be mitogenic for quiescent cultures of Swiss mouse 3T3 and 3T6 cells. The compounds caused a striking shift in the dose-response for the effect of serum on [3H]thymidine incorporation and DNA synthesis. In the absence of serum the effect of vanadium was greatly potentiated by insulin. Vanadium ions produced no more than additive increases in [3H]thymidine incorporation when combined with epidermal growth factor, cholera toxin, or phorbol 12-myristate 13-acetate. Both vanadium compounds stimulated ouabain-inhibitable 86Rb+ uptake, indicating that the vanadium ions increase, rather than inhibit, Na+/K+ pump activity in the intact cell. Neither vanadium compound had any effect on cellular cAMP under a variety of different conditions. The mitogenic effect of the vanadium compounds was similar to that of colchicine. Taxol, which stabilizes cytoplasmic microtubules, prevented the stimulation of DNA synthesis by vanadium.
Animals↗
Sodium-lithium countertransport in erythrocytes of hypertension prone families in Utah.
Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.
Adolescent↗
Prevention of extension of ischaemic damage following acute myocardial ischaemia by dazoxiben, a new thromboxane synthetase inhibitor.
1 Dazoxiben, a new thromboxane synthetase inhibitor, at an infusion rate of 5 mg/kg/h inhibited the ischaemia-induced increase in circulating thromboxane B2 in cats. 2 Dazoxiben also restored the S-T segment of the electrocardiogram toward normal values after the onset of ischaemia, and prevented the rise in plasma creatine kinase activity usually observed during myocardial ischaemia. 3 Associated with the above changes were reduced loss of myocardial creatine kinase activity and amino-nitrogen concentration in the ischaemic region of those cats treated with dazoxiben. 4 No significant effects of dazoxiben were observed on heart rate, mean arterial blood pressure or the product of the two, the pressure-rate index. Therefore, dazoxiben does not protect by reducing myocardial oxygen demand. 5 The mechanism of the protective action of dazoxiben in acute myocardial ischaemia seems to be either due to prevention of the constrictor and cytolytic actions of thromboxane A2 or to metabolic and cellular actions of dazoxiben unrelated to thromboxane synthetase inhibition.
Animals↗
Responsiveness of platelets and coronary arteries from different species to synthetic thromboxane and prostaglandin endoperoxide analogues.
1--Platelet-rich plasma (PRP) from humans, cats, dogs (after addition of 10 microM adrenaline), rabbits and guinea-pigs aggregated in response to sodium arachidonate or 9,11-azo-prostaglandin H2, while PRP obtained from sheep was unresponsive to either agent. 2--The stable thromboxane (Tx) analogues, carbocyclic TxA2 (CTA2) and pinane TxA2 (PTA2) significantly inhibited these aggregatory responses in platelets from humans, dogs and guinea-pigs, while PTA2 but not CTA2 produced significant inhibition in cat platelets. The aggregatory response of PRP from rabbits was not significantly blocked by either analogue. 3--CTA2 and the endoperoxide analogue 9,11-methanoepoxy PGH2 (U-46619) constricted coronary arteries from cats, dogs, rabbits and guinea-pigs, while sheep vessels were unresponsive to either analogue. 4--Vasoconstrictor responses to U-46619 were significantly attenuated by PTA2 in vessels from all species. However, constriction produced by CTA2 was blocked significantly only in vessels from cats, dogs and guinea-pigs. 5--These results demonstrate the species differences which exist in the responsiveness of platelets and coronary arteries to thromboxane and endoperoxide analogues. Furthermore, the results illustrate the importance of species selection in the study of thromboxane antagonists for potential therapeutic use.
Animals↗
Animal welfare and the Australian veterinarian.
This paper discusses the moral and philosophical arguments related to animal welfare. The veterinary profession in Australia has, to date, addressed this matter on a superficial and unsatisfactory level. In my view, the Australian Veterinary Association has not yet considered sound philosophical and moral positions in any area of animal welfare. This paper provides some examples of arguments concerning animal rights. It is suggested that the veterinary profession in Australia needs to take heed of these arguments and to develop a philosophy of its own. The profession is not seen to be having sufficient influence on the development of community standards in animal welfare. For example, public statements on the stray cat and dog problem concern the nuisance to human society and little is said of the welfare or rights of the animals themselves. The Australian Veterinary Association has not looked thoroughly at problems of animal welfare in the livestock industries, where the need for attention is urgent. Few veterinarians in Australia have the knowledge and experience to tackle problems in the area of animal experimentation. These include questions of laboratory animal production and disease, as well as those of a moral and philosophical nature. A discussion of ethical problems in studies on animal behaviour points to the lack of experience of veterinarians in this area. Possible mechanisms for statutory control of animal experimentation are explored. Antivivisectionist ideas and the significance of their political influence are outlined.
Animals↗