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Biomedical subjects

J Burton

Publications and source records attributed to J Burton.

At least 127 records · Page 7Linked to original sources
PubMed1978

Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis.

To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1977

Pityriasis lichenoides--an immune complex disease.

Circulating immune complexes have been detected in patients with pityriasis lichenoides during disease activity when IgM and C3 have been observed in dermal vessels on direct immunofluorescence of fresh lesions. This implies that pityriasis lichenoides is an immune complex disorder and that deposited complexes play a part in the pathogenesis of the condition. There is a characteristic pattern of immunofluorescence which may be a diagnostic aid.

Adolescent↗
PubMed1976

On the specificity of human renin. Studies with peptide inhibitors.

The amino acid sequence around the renin substrate site is known to be identical to the N-terminal tetradecapeptide: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser. Renin (EC 3.4.99.19) from both primates and non-primates cleaves this peptide at the leucylleucine bond. Several analogs of the octapeptide segment: His-Pro-Phe-His-Leu-Leu-Val-Tyr of this tetradecapeptide act as competitive inhibitors for human renin with inhibition constants down to 1 muM. The same peptides were shown, however, to have no or only slight affinity for non-primate renin. The substrate site has been preserved throughout evolution whereas the enzyme site for human renin is different from that of non-primate renins. The findings suggest that species-specific peptides must be developed for both studies of renin inhibition and for renin purification.

Animals↗
PubMed1976

The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.

Adult↗
PubMed1976

Fibrinopeptide A in plasma of normal subjects and patients with disseminated intravascular coagulation and systemic lupus erythematosus.

A radioimmunoassay for fibrinopeptide A (FPA) has been developed. This assay uses rabbit antibodies induced by injection of native FPA-human serum albumin conjugates and 125I introduced into tyrosine-FPA synthesized in out laboratory. Plasma FPA is separated from fibrinogen by TCA extraction. The assay is capable of detecting as little as 50 pg/ml of FPA. In 20 normal donors this assay revealed a mean concentration of 0.9 ng/ml (0.3 SD). In five patients with disseminated intravascular coagulation, FPA concentrations ranged from 13.0 to 346 ng/ml. Two groups of patients with systemic lupus erythematosus (SLE) whose disease had achieved complete remission were studied; one consisted of four patients with no history of lupus nephritis and another with a history of nephritis. Mean FPA concentrations of 1.5 ng/ml (range, 0.7-1.8 ng/ml) and 2.7 ng/ml (range, 1.1-5.6 ng/ml) were found in these two groups, respectively. Another group of nine patients with active SLE, but without evidence of lupus nephritis, had a mean FPA concentration of 4.5 ng/ml (range, 2.4-7.8 ng/ml). Finally, a group of seven patients with active SLE, including active nephritis, had a mean FPA concentration of 10.2 ng/ml (range, 5.3-17.0 ng/ml). A positive correlation was found between the concentration of plasma FPA and serum DNA-binding activity and an inverse correlation was found between plasma FPA and the concentration of serum C3. No correlation existed between plasma FPA and concentration of serum creatinine. Several possibilities for the origin of plasma FPA in patients with SLE were considered; at present it seems most likely that FPA arises through the action of thrombin on fibrinogen.

Adolescent↗
PubMed1976

Competitive inhibitors of renin. A review.

This review describes some of the characteristics for renin's substrate specificity and also some features of its species specificity. It describes how competitive inhibitors were synthesized and how the solubility was increased in order to make them effective at physiological pH. Their use for in vitro and in vivo inhibition of renin is discussed and their use for purification of renin demonstrated.

Animals↗
PubMed1975

Competitive inhibitors of renin. Inhibitors effective at physiological pH.

Previously we reported the development of competitive inhibitors of renin effective at pH 5.5 (Poulsen, K., Burton, J., and Haber, E. (1973), Biochemistry 12, 3877). At physiologic pH (7.5), the inhibitory constants (Ki) increased and solubility decreased to the point that inhibition could not be demonstrated with these peptides. Modification of the octapeptide sequence, His-Pro-Phe-His-Leu-Leu-Val-Tyr, either by addition of serinol to the carboxyl terminus or by replacement of valine-7 with an isosteric threonyl residue failed to yield peptides active at pH 7.5. Attachment of polyproline sequences to the amino terminus increased solubility from threefold to tenfold and decreased Ki so that competitive inhibition was demonstrable at physiologic pH. In addition, if leucine-6 was replaced in these peptides with a phenylalanyl or tyrosyl residue, Ki decreased (3-12 muM) to give effective competitive inhibitors at physiologic pH in both buffer and in plasma.

Binding Sites↗
PubMed1975

Purification of hog renin by affinity chromatography using the synthetic competitive inhibitor (D-Leu6)octapeptide.

The renin substrate analog His-Pro-Phe-His-Leu-D-Leu-Val-Tyr ([D-Leu6]-octapeptide) acts as a potent inhibitor of renin because of the D-amino acid substitution at the cleavage site. This inhibitor was coupled to CNBr-activated Sepharose 4B to yield a support for affinity chromatography. Hog renin with a specific activity of 1.2 Goldblatt units/mg was in one step purified 195-fold to a final specific activity of 234 Goldblatt units/mg. Application of a pH gradient from 5.0 to 7.5 to the support was found to be the most successful elution program, probably because the [D-Leu6]-octapeptide is not an inhibitor for renin at neutral pH.

Animals↗
PubMed1975

The role of the renin--angiotensin--aldosterone system in cardiovascular homeostasis in normal man.

1. To examine the role of angiotensin II in the maintenance of blood pressure and control of aldosterone secretion, eight normal human subjects were studied on a tilt table in sodium-replete and sodium-depleted states, before and after the administration of an angiotensin converting-enzyme inhibitor (CEI). 2. Administration of CEI was followed by a marked fall in blood pressure on tilting in sodium-depleted, but not in sodium-replete, subjects. CEI administration also resulted in a rise in plasma renin activity in the supine position, in the absence of haemodynamic change. The rise in plasma aldosterone observed both in response to tilting and sodium depletion did not occur after CEI, even though plasma renin activities were higher. 3. These results indicate that: (a) angiotensin II is essential for blood pressure control in the sodium-depleted individual; (b) angiotensin II exerts direct feedback control on renin secretion; (c) angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and posture.

Adult↗
PubMed1974

Sodium-calcium sites in smooth muscle and their accessibility to lanthanum.

1. The Na, K, Ca, and Mg contents were determined in longitudinal smooth muscles of the guinea-pig ileum incubated in various physiological solutions with or without ouabain or in a solution containing LaCl(3) 10 mM instead of CaCl(2).2. The Na and K contents were dependent upon the K concentration of the physiological solution. A decrease in [K](o) below 6 m-mole/l. increased tissue Na.3. A rise in [Na](i) was followed by an increase of total cell Ca preceding a secondary decrease of total Ca, as well as by an increased (45)Ca content occurring even when total Ca was decreased.4. Muscles washed in the lanthanum solution contained less Ca and Na than those incubated in the physiological solution. The Mg content was not significantly modified in the presence of La.5. In the La solution, the (45)Ca diffusion space was not different from the [(14)C]inulin diffusion space, indicating that there was no Ca entry within the cell nor Ca binding at superficial sites. (45)Ca content of preloaded muscles decreased; this decrease was blocked after 30 min washout in the La solution: this arrest lasted a further 45 min.6. The cell Ca fraction displaced by increased [Na](i) originated from a Ca compartment which was not blocked by La.

Animals↗