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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 271 records · Page 15Linked to original sources

The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate.

The cellular distribution of certain enzymes associated with the metabolic compartmentation of glutamate was estimated in ultrastructurally preserved and metabolically competent perikarya fractions that were enriched in astrocytes, granule cells and Purkinje cells and derived from 8-day-old rat cerebellum, and in monolayer cultures (14 days in vitro) composed principally of interneurones or astrocytes. The neuronal activities of glutamine synthetase and glutamate dehydrogenase were respectively about 4- to 8-fold and 2- to 5-fold lower than in astrocytes, depending upon the class of neurone and the type of preparation used for comparison. By contrast glutaminase activity was about 3- to 12-fold higher in neuronal than in astroglial preparations. Estimations of the specific activity of succinate dehydrogenase differed less between cell types, indicating that the differences in glutamate dehydrogenase and glutaminase were not simply related to variations in the concentration of mitochondria relative to the other cellular constituents. The findings presented provide direct evidence in support of our model assigning the 'small' glutamate compartment, where most of the labelled glutamine is synthesized, to glial cells, and the 'large' compartment to neurones, and also underline the metabolic interaction between these two cell types in the brain.

Animals↗

Aldosterone-producing-adenoma (A-P-A): effect of pregnancy.

Serial measurements of plasma renin activity, plasma progesterone and urinary aldosterone were made before, during and after pregnancy in a patient from whom an A-P-A was later removed with cure of hypertension and hypokalemia. Despite 16-fold increases in urinary aldosterone during pregnancy, plasma renin activity levels became unsuppressed, and hypertension and hypokalemia were reversed. Increases in plasma progesterone or other steroids, competitively inhibiting the effects of aldosterone on its receptor, may explain remission of A-P-A and reversal of renin suppression during pregnancy. In a second patient, the features of primary aldosteronism appeared immediately after a pregnancy, and removal of an A-P-A cured hypertension and hypokalemia. A-P-A is more common in females and may appear following pregnancy. Urinary aldosterone was 6-fold higher after pregnancy than before. Thus, sex steroids may not only protect from hyperaldosteronism but may also stimulate growth of A-P-A's.

Adenoma↗

Once daily beta-blocker in hypertension--oxprenolol slow-release.

In a within-patient comparison of conventional oxprenolol administered twice daily with slow-release oxprenolol administered once daily in the treatment of hypertension, twenty patients previously responsive to beta-blockers took each formulation for 4 weeks, after wash-out periods off beta-blocker of 2 weeks' duration. The order of administration of the two forms was randomized, and sixteen patients continued medication with cyclopenthiazide 0.5 mg daily. Blood pressure levels at the end of the 4-week treatment periods were compared with levels at the end of the preceding 2-week wash-out periods. Both formulations lowered blood pressure and pulse rate significantly. There was no difference in their effects on pulse rate or on blood pressure, whether measured by the doctors using standard sphygmomanometers or by the hypertension sister using a random-zero sphygmomanometer. In four patients who measured their own blood pressures at home each morning (before medications), afternoon and night, mean levels were similar with the two formulations. Both formulations were very well tolerated.

Adult↗

Radioenzymic measurement of norepinephrine, epinephrine, and dopamine: stability, enzymic activity, and sensitivity.

We investigated factors affecting sensitivity and reproducibility of radioenzymic (catechol-O-methyltransferase) measurement of plasma catecholamines. There was no apparent deterioration of catecholamine during storage at -20 degrees C for 240 days. Accuracy and sensitivity of the assay depended mostly on the method of transferase preparation; its preparation by adjusting the pH to 6.8 before fractionation with ammonium sulfate resulted in an unsuitable enzyme with a relatively high background-radioactivity count, particularly for neorepinephrine and dopamine.

Catechol O-Methyltransferase↗

Influence of sodium balance on ACTH/adrenal corticosteroid dose-response curves in the dog.

In order to define short-term ACTH/corticosteroid dose-respone characteristics, we infused ACTH for 1 h at each of five incremental rates into pedigreed male beagle dogs in four different states of sodium balance. Progressive sodium depletion was associated with progressive increased in basal (pre-ACTH) plasma levels of renin, angiotensin II, aldosterone, 18-hydroxycorticosterone (18-OH-B), and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Administration of dexamethasone significantly reduced the preinfusion levels of cortisol, aldosterone, 18-OH-B, and 18-OH-DOC. The threshold dose of ACTH required to elicit an aldosterone response during low-sodium intake was similar to that for cortisol, but was higher during normal or high-sodium intake. Steepest portions of the dose-response curves were at lower rates of ACTH infusion for cortisol than for aldosterone, and maximum increment was much greater for cortisol (60-fold) than for aldosterone (12-fold). Whereas the slopes of ACTH/aldosterone and ACTH/18-OH-B dose-response curves were steepened by lower sodium diets, the ACTH/cortisol response was significantly flattened by severe sodium depletion. We conclude that ACTH is a potent and direct-acting short-term regulator of aldosterone secretion, subject to modification by altered sodium balance.

Adrenal Cortex Hormones↗

The endocrine effects of vasectomy: a prospective five-year study.

A prospective study of plasma luteinizing hormone (LH) and testosterone in 54 men for 5 years following vasectomy revealed no significant continuing alteration in either testosterone or LH. Plasma LH levels 1 year after operation were higher than preoperative levels but did not increase further. Stimulation studies (4 years postvasectomy) using human chorionic gonadotropin confirmed acceptable Leydig cell functional reserve.

Adult↗

Variability of plasma catecholamine levels: age, duration of posture and time of day.

1. In order to define factors which influence plasma catecholamine levels, and which might be controlled in the interests of reproducability and comparability, plasma noradrenaline plus adrenaline (NA + A) was measured repeatedly in normal subjects by a double isotope technique. 2. Age and posture were important determinants for plasma NA + A levels, whereas time of day was less important. 3. Levels were higher in old men aged 70--92 years than in young men aged 19--28 years, measured after 30 min or 9 h (overnight) recumbency, or after 5 min standing. 4. Duration of recumbency and of upright posture were both important. Recumbent levels were lower after 9 h (overnight) than after 30 min (mid-morning). Upright posture caused an increase in levels within 2 min. Levels peaked between 5 and 20 min, were lower after 12 h than after 20 min, but upright levels were always higher than levels after 9 h recumbency. 5. During continuous recumbency, levels were lowest at 24.00 h, and increased thereafter. During a second hospitalisation, levels at 09.00 h were again higher than levels at 06.00 h after overnight recumbency. 6. Variability of levels obtained by repeated sampling was lower while sitting, during a normal upright day, than after 30 min recumbency. Upright legels may be a better index of cardiovascular sympathetic activity.

Adult↗

Anti-H-Y responses of H-2b mutant mice.

Two strains of H-2b mutant mice, H-2ba and H-2bf, in which the mutational event took place at H-2K, make anti-H-Y cytotoxic T cell responses which are H-2-restricted, Db-associated and indistinguishable in target cell specificity from those of H-2b mice. Thus, alteration of the H-2K molecule affects neither the Ir gene controlling the response, nor the associative antigen. On the other hand, one H-2Db mutant strain, H-2bo, although it makes a good anti-H-Y cytotoxic response, shows target cell specificity restricted to its own Dbo antigen(s), and neither H-2b, H-2ba or H-2bf anti-H-Y cytotoxic cells kill H-2bo male target cells. Thus, the alteration of the H-2Db molecule does not affect the Ir gene of H-2b mice, but it does alter the H-2Db-associative antigen.

Animals↗

Early diagnosis of Addison's disease; pigmentation as sole symptom.

A diagnosis of primary adrenocortical insufficiency was made in a shapely, suntanned girl whose sole complaint was increasing pigmentation. Plasma cortisol was low in spite of markedly elevated levels of ACTH. Plasma cortisol, urinary 17-oxogenic steroids and urinary aldosterone did not respond to three days of ACTH stimulation. Addison's disease can be diagnosed and treated before development of anorexia, weight loss, weakness and other classical symptoms.

Addison Disease↗

Failure of methyclothiazide to lower home blood pressure level in "essential" hypertensive and normotensive young men, despite significant plasma volume contraction.

Home blood pressure measurements were used to assess the effect of methyclothiazide in young essential hypertensive and normotensive males. Although plasma volume was reduced by approximately 10 percent, blood pressure was not reduced in either group. The lack of effect on blood pressure was probably not attributable to dosage employed, as doubling the dose (5 to 10 mg) in the normal subjects (who were equilibrated on constant diet) did not significantly increase changes in plasma volume, plasma renin activity, aldosterone excretion, urine sodium or blood pressure. The higher dose did result in greater changes in plasma potassium and uric acid. Homeostatic mechanisms which limit the volume mediated and other antihypertensive effects of methyclothiazide apparently achieved complete compensation in these young males. This suggests that thiazide diuretics may not be the drug of first choice in the treatment of hypertension in young adults. Further studies with other diuretics are clearly necessary before the significance of these findings can be fully assessed.

Adolescent↗

Selective response to H-Y antigen by F1 female mice sensitized to F1 male cells.

T-cell mediated cytotoxic responses to H-Y antigen require co-recognition of H-Y and H-2 gene products. F1 mael stimulating cells and target cells express H-Y antigen in association with both parental H-2 haplotypes. However, F1 females primed in vivo and challenged in vitro with F1 male cells lyse male target cells of F1 and only one parental H-2 haplotype. Thus, (CBA X B10)F1 females sensitized to (CBA X B10)F1 male cells lyse (CBA X B10)F1 and CBA but not B10 male target cells, and (BALB/c X B10)F1 females sensitized to (BALB/c X B10)F1 male cells will lyse (BALB/c X B10)F1 and B10 but not BALB/c male target cells. It is suggested that this may represent an effect of immune response or suppressor genes mapping in the major histocompatibility gene complex which regulate responsiveness to H-Y antigen.

Animals↗

Bilateral renal artery aneurysms: in-situ and extracorporeal repair.

Renal artery aneurysms are uncommon, but when they do occur they are frequently associated with hypertension which may be amenable to surgery. Complex arterial abnormalities which formerly would have been treated by nephrectomy may now be reconstructed with preservation of the kidney. This is illustrated by a patient with renovascular hypertension and bilateral renal artery aneurysms, in whom arteriography and renal vein renin ratios were used as a guide to surgery performed in two stages. An in-situ repair was performed on one side. On the other side, where the aneurysm involved the three main branches of the renal artery, an extracorporeal repair was performed using continuous cold perfusion, substitution of the pathological segment with the patient's internal iliac artery, and autotransplantation to the iliac fossa. Both kidneys were retained and the hypertension was cured.

Adult↗

Responsiveness to HY antigen Ir gene complementation and target cell specificity.

The H-2 restricted nature of the cytotoxic T cell responses to the HY antigen in mice has been reviewed, together with mapping data for the H-2 K and/or D association of responses to male cells of the following haplotypes: H-2b, H-2d, H-2k, H-2s. Ir gene complementation is implicated in the HY response of a number of F1 mice derived from non-responder parental haplotypes, and in one recombinant strain. Thus, at least two and possibly more Ir genes are involved in the anti-HY response, in addition to the K and/or D gene products with which HY is obligatorily associated, certainly at the target cell level.

Animals↗