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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 559 records · Page 31Linked to original sources

Urea handling by the renal countercurrent system: insights from computer simulation.

The renal handling of urea has been investigated with the aid of a computer model of the countercurrent system in which active electrolyte reabsorption occurs along the entire ascending limb of Henle's loop. In this model, summarized in Fig.9, the buildup of a corticopapillary gradient for urea is optimized if there is net addition of urea to loops of Henle only in the outer medulla. This added urea remains within the tubular system until it is reabsorbed from collecting ducts in the inner medulla. Thus, a net transfer of urea from outer to inner medulla is accomplished (via distal tubule and cortical collecting duct). There is no net addition of urea to loops of Henle within the inner medulla; in this region, the loops act simply as countercurrent exchangers for urea. Computer simulation of systematic variation in the urea permeabilities of each nephron segment shows that interference with any element of the above schema results in impairment of the medullary accumulation of urea relative to plasma. Simulation of varying rates of urinary urea excretion demonstrates that this model can account for the ability of the kidney to excrete substantial amounts of urea without an accompanying osmotic loss of water. The major insight gained from this study is that net addition of urea to loops of Henle in the outer medulla greatly enhances the medullary accumulation of urea, whereas, net addition of urea to loops within the inner medulla tends to defeat such accumulation and hence the urinary concentrating process. This general principle applies also to an alternate model of the countercurrent system, in which electrolyte reabsorption from thin ascending limbs of Henle is passive.

Computers↗

Evaluation of cellular substrates for antinuclear antibody determinations.

The immunofluorescent technique was employed to evaluate the sensitivity of 10 human and animal cell monolayers and tissue sections as substrates for titering the antinuclear antibody content of serum samples. The highest mean ranks of sensitivity, the relative ability of each substrate to maintain its sensitivity rank when 21 selected positive sera were tested, were achieved by two fibroblast cell lines, baby hamster kidney (BHK 21/C13) and human lung (WI-38), respectively. The least sensitive substrates were commercial rat kidney and liver tissue sections.

Animals↗

The apical A wave versus the fourth heart sound in assessing the severity of aortic stenosis.

The height of the "a" wave of the apexcardiogram was evaluated as a marker for critical aortic stenosis in patients over 40. Critical aoritc stenosis was defined as an aortic valve area less than .75 cm-2 with no more than mild aortic insufficiency. Phonocardiograms and apexcardiograms were performed on 72 patients with catheterization proven aortic stenosis and on 14 normal controls, all over age 40. The height of the "a" wave of the apexcardiogram was measured as a percentage of the e to o excursion (a/e-o). Fourth heart sound gallops ( S4G) were recorded in 71% (11 of 14) of normal controls, 86% (6 of 7) of patients with less than critical aortic stenosis, and 85% ( 55 of 65) of patients with critical aortic stenosis. The a/e-o was less than 16% in all normals or patients with less than critical aortic stenosis. The a/e-o exceeded 16% in 45% (29 of 65) with critical aortic stenosis. Audibility of the S4G bore no relationship to recordability, apical "a" wave geight, or the severity of the aortic stenosis. In conclusion, therefore, we believe that when one is confronted with findings suggestive of aortic stenosis, the finding of a palpable apical "a" wave (or an "a" wave height of greater than 16% of the total complex on the apexcardiogram) is an important positive feature, suggesting severe aortic stenosis. Its absence, however, does not exclude severe valvar obstruction. Probably because of auscultatory inaccuracy in this condition, the apparent presence or absence of an S4G has not been of much aid in this evaluation. This sound, however, might be more useful in a carefully performed prospective study.

Adult↗

Genetic studies on the mechanism of action of aldosterone in mice.

Aldosterone reduced the urinary sodium:creatinine ratio and increased the potassium:creatinine ratio in a CBA strain of mice. In the Peru strain, under the same conditions, aldosterone had no detectable effect on the sodium:creatinine ratio but had an even more marked effect on the potassium:creatinine ratio. Thus, the effect of aldosterone on potassium excretion is separable from and is not simply a secondary consequence of the effect on sodium retention. Specific binding of 3H-aldosterone to kidney was reduced in Peru mice compared to CBA. However the correlation between 3H-aldosterone binding and physiological effect of the hormone on sodium excretion disappeared totally in a second generation cross between the strains. A possible explanation is that the nuclear binding of 3H-aldosterone as measured here was heterogeneous. In this same second generation cross, the ratio of bound nuclear 3H-aldosterone extracted by low-ionic strength Tris, to the residue of nuclear 3H-aldosterone resistant to extraction by 0.4M KCl, was strongly correlated to the ratio of the effect of aldosterone on potassium excretion to that on sodium excretion. Thus in these experiments the type of nuclear binding was correlated to the type of physiological effect. These results imply that the specific binding of aldosterone to renal tissue was, in some way at least, related to the mechanism of action of the hormone; and that the heterogeneity of this binding had functional significance in terms of the separable effects of aldosterone on renal sodium retention and potassium excretion in these two strains of mice.

Aldosterone↗

Usefulness and limitations of precordial phonocardiography and external pulse recordings.

Phonocardiography provides one of a growing list of valuable intermediary studies between physical examination and cardiac catheterization. It not only provides a medium for instruction in physical examination, but also allows one to make certain diagnoses and assess severity of numerous cardiovascular lesions. It is especially valuable in the evaluation of all valvular stenoses, especially aortic stenosis. One can also use phonocardiography for screening and diagnosis of idiopathic hypertrophic subaortic stenosis. It is a helpful adjunct in the study of several congenital abnormalities as well as in the assessment of myocardial function in cardiomyopathies and ischemic heart disease, and may often be decisive in confirming the diagnosis of pericardial constriction.

Adolescent↗

Renal aldosterone receptors: studies with (3H)aldosterone and the anti-mineralocorticoid (3H)spirolactone (SC-26304).

In vivo, a spirolactone (SC-26304) inhibited the effects of aldosterone on urinary K(+):Na(+) ratios and the binding of [(3)H]aldosterone to renal cytoplasmic and nuclear receptors. Cytoplasmic binding of [(3)H]aldosterone and [(3)H]spirolactone (SC-26304) was similar in magnitude and involved the same set of sites. Under three sets of conditions-(i) in the intact rat, (ii) in kidney slices, and (iii) in reconstitution studies (mixing prelabeled cytoplasm with either purified renal nuclei or chromatin), [(3)H]spirolactone (SC-26304) did not yield specific nuclear complexes in contrast to the reproducible generation of these complexes with [(3)H]aldosterone. In glycerol density gradients, cytoplasmic [(3)H]aldosterone receptor complexes sedimented at 8.5 S and 4 S in low concentrations of salt and at 4.5 S in high concentrations of salt. Cytoplasmic [(3)H]spirolactone (SC-26304) receptor complexes sedimented at 3 S in low concentrations of salt and 4 S in high concentrations of salt. These results are discussed in terms of an allosteric model of the receptor system.

Adrenalectomy↗