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Biomedical subjects

A Licht

Publications and source records attributed to A Licht.

At least 37 records · Page 2Linked to original sources

Low affinity of kappa chain bearing (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibodies in the primary antibody repertoire of C57BL/6 mice may explain lambda chain dominance in primary anti-NP responses.

The primary anti-(4-hydroxy-3-nitrophenyl)acetyl (anti-NP) antibody response of C57BL/6 mice was analyzed by several methods. Serum analyses by solid-phase radioimmunoassay (RIA) showed that stimulation with the thymus-independent (TI) type 1 antigen NP-LPS results in an anti-NP antibody response dominated by kappa (kappa) light chain bearing antibodies, whilst responses to NP-Ficoll (a TI-2 antigen) and NP-KLH (a thymus dependent antigen) are dominated by lambda (lambda) 1 light chain bearing antibodies. However, in all these responses NP-specific plaque-forming cells (PFCs) were predominantly heteroclitic, and inhibitable by anti-lambda antiserum. In addition, kappa-bearing IgM-producing hybridomas obtained by fusion of spleen cells from NP-LPS-immunized mice, although producing NP-specific antibodies detectable by RIA, were unable to produce NP-specific plaques. Direct determination of the affinity of 5 of those hybridomas by fluorometric titrations showed that their affinity is indeed lower than 10(-5) M. These results suggest that most NP-specific antibodies stimulated by NP-LPS are of too low affinity to be detected in a direct PFC assay, with the exception of a population of lambda-bearing antibodies. Therefore, the differential expression of kappa- or lambda-bearing antibodies in primary responses to the hapten NP presented on different carriers may be due to different affinity requirements for B-cell triggering via different activation pathways.

Animals↗

Progress in isolation and purification of an inhibitor of sodium transport obtained from dog urine.

Among the potential modulators of transtubular sodium transport is the putative natriuretic hormone. Widespread efforts are underway to isolate this substance in pure form. The present studies describe a series of experiments directed to this goal. Urine samples in the amount of 150 liters were taken from normal, mineralocorticoid hormone "escape" dogs and were chromatographed through Sephadex G-25. The active fraction of the eluate (that is, the fraction containing the inhibitor of sodium transport) was then subjected to high pressure liquid chromatography (HPLC) in four consecutive steps using three different resins. Approximately 5% of the each column eluate was diverted by use of a stream-splitting apparatus, and the fluorescent pattern was measured and recorded, in most instances following the addition of fluorescamine. Based on the respective fluorescent patterns obtained from the eluates of the successive chromatographic steps, the residual portion (95%) of each eluate was divided into fractions, and each fraction was bioassayed. In each instance only the biologically active fraction was subjected to further purification. In the first step involving HPLC and a cation exchange resin, six fractions were obtained. Only one was active. When this fraction was subjected to reverse-phase chromatography, seven new fractions emerged. Again only one was active. When it was chromatographed using a second cation exchange resin, two fluorometrically detectable peaks, termed N ad H, were identifiable. N exhibited spontaneous fluorescence; H exhibited fluorescamine-dependent fluorescence. In the final step, N and H were separated and bio-assayed individually. N was inactive; H proved to be a potent inhibitor of sodium transport. Accumulation of H in sufficient quantity will determine whether it is a single compound and will permit analysis of its chemical nature.

Animals↗

The effect of prostaglandin synthetase inhibitors on renal function: studies in normal rats during sodium or water diuresis and in rats with chronic renal insufficiency.

The effect of acute infusion of the prostaglandin synthetase inhibitors - meclofenamate or indomethacin - was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups. Absolute urinary excretion rates for sodium and potassium decreased only in the normal, salt-replete rats. In contrast, prostaglandin synthetase inhibitors consistently decreased urinary flow and osmolar clearance under all experimental conditions studied. In the normal, salt-replete rats the fall in urine flow was preceded by an increase in urinary excretion of cyclic AMP. These results show that inhibitors of prostaglandin synthesis enhance the ability of the kidney to reabsorb water. This effect may be secondary to increased cyclic AMP generation and to increased urea recirculation resulting in higher urea accumulation in the renal medulla.

Animals↗

Absence of renal sodium adaptation in chronic renal failure.

A patient with advanced chronic renal failure secondary to polycystic kidney disease suffered an episode of volume contraction during which his urinary sodium concentration fell to less than 5 mEq daily. Urine sodium excretion remained at this level when later in his course he became clinically volume expanded. The patient also suffered from Crohn's disease and had an ileostomy from which he excreted from 100 to 150 mEq sodium daily. We propose that this patient's capacity to produce urine virtually free of sodium despite advanced renal failure was a result of the persistent loss of sodium from his ileostomy. This sodium loss obviated the development of the adaptive natriuresis that usually occurs in the functioning nephrons of the diseased kidney and prevented the development of a 'salt-losing' tendency.

Adult↗

Effect of interchain disulfide bond on hapten binding properties of light chain dimer of protein 315.

The hapten binding characteristics of the covalent light chain dimer, derived from the murine IgA secreted by plasmacytoma MOPC-315, to two nitroaromatic compounds, epsilon-N-(2,4-dinitrophenyl)-L-lysine and 4-(alpha-N-alanine)-m-nitrobenz-2-oxa-1,3-diazole, were investigated by differential spectroscopic titrations. The binding curves for both haptens were found to display sigmoidity similar to that reported earlier for the reduced and alkylated dimer held together by noncovalent bonds only. However, the presence of the interchain disulfide bond in the covalent dimer was found to cause marked changes in its binding properties. The data, like those obtained for the noncovalent dimer, fit the allosteric model of Monod, Wyman, and Changeux in which binding of the first hapten to the dimer causes a conversion of both sites of the protein molecule from a lower to a higher affinity conformation. However, the binding parameters show that both the affinity and the positive cooperativity in the interaction between haptens and the covalent dimer are significantly enhanced. The differences in the parameters of the binding and of the allosteric transition caused by the presence of the interchain disulfide bond demonstrate the existence of longitudinal interactions in immunoglobulin derivatives. These properties of the light chain dimer make it a potential model for the receptors present on thymus-derived lymphocytes.

Allosteric Regulation↗

Transient hypoaldosteronism after renal allotransplantation.

Studies were performed to investigate the nature of the hyperkalemia and hypokaliuria observed in two patients after renal allotransplantation in both of whom the graft was functioning and urinary output was adequate. In the first patient, examinations in the upright position revealed low values for plasma renin activity and plasma aldosterone. The second patient showed similar findings, and, in addition, an angiotensin II (Hypertensin) infusion was ineffective in stimulating aldosterone secretion during the hyperkalemic state. In both patients, short-term administration of 9 alpha-fluorohydrocortisone caused kaliuresis with a definite decrease in serum potassium. There was a spontaneous correction of the biochemical and hormonal abnormalities six weeks after transplantation and the response to an angiotensin II infusion normalized. We suggest that the hyperkalemia in both of these patients was due primarily to the transient failure of the renin-angiotensin system of the transplanted kidney.

Adult↗

Natriuretic factor, a lasting enigma.

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Animals↗

Paroxysmal choreoathetosis as a presenting symptom in idiopathic hypoparathyroidism.

A patient with idiopathic hypoparathyroidism presenting with spells of paroxysmal choreoathetosis is described. The possible mechanisms by which hypoparathyroidism induces choreoathetosis and other extrapyramidal motor dyfunctions are discussed. The need for screening patients with extrapyramidal disease for hypoparathyroidism is stressed.

Adolescent↗

Post partum renal failure due to progressive systemic sclerosis treated with chronic hemodialysis.

An unusual case of progressive systemic sclerosis with rapidly progressing renal failure after a successful delivery is described. The presenting syndrome was malignant hypertension. The blood pressure was refractory to the various therapeutic measures which were instituted, including hemodialysis. The patient, therefore, underwent bilateral nephrectomy, following which the blood pressure returned to normal, and she survived on hemodialysis for 17 months. To the best of our knowledge, the patient presented herein is the only reported case of this kind of fetal and maternal salvage.

Adult↗

Steroid-induced glaucoma and cataract in renal transplant recipients.

Fifteen kidney transplant recipients were studied ophthalmologically for periods of one to five years following the transplantation. All subjects received maintenance immunosuppressive therapy which included azathioprine (IMURAN) and corticosteroids. Two patients developed posterior subcapsular cataracts. Seven patients (47%) developed increased intraocular pressure and one of these had glaucomatous field loss and disk cupping. The increased intraocular pressure responded favorably to topical treatment while the patients were under continuous treatment with systemic steroids and immunosuppressive drugs.

Administration, Oral↗