Light Chain Distribution in Immune Deposits on Glomeruli of Kidneys in Human Renal Disease

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Abstract

The γG-immunoglobulin (IgG) deposited on glomeruli of 32 percutaneous renal biopsies from 30 patients with various forms of renal disease was examined by fluorescent techniques to determine its light chain composition. Serum kappa: lambda light chain ratios were determined on 17 serum samples from 16 of the 30 patients.

Authors

Roger C. Herdman, Richard Hong, Alfred F. Michael, Robert A. Good

The Immunologic Character of Acquired Inhibitors of Antihemophilic Globulin (Factor VIII) and the Kinetics of Their Interaction with Factor VIII

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Abstract

Investigations were undertaken of the chemical nature and kinetics of interaction of three acquired inhibitors of Factor VIII. The inhibition was stoichiometric, one molecule of inhibitor (or one site on a molecule) being required to inactivate one molecule of Factor VIII. All three inhibitors were found to be monotypic antibodies of class IgG, Type K (γ2 κ2). This appears to be the second syndrome due to the production of monotypic antibody, and the first instance involving IgG immunoglobulins.

Authors

Sandor S. Shapiro

Glucose Titration Studies in Patients with Chronic Progressive Renal Disease

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Abstract

Glucose titration studies were performed on 17 patients with either chronic pyelonephritis or chronic glomerulonephritis. Glomerular filtration rates for the group ranged from 4.3 to 58.1 ml per minute. In none of the patients in whom the glomerular filtration rate was over 15 ml per minute was there appreciable splay, and the mean titration curve for these patients resembled that obtained by Smith and associates in normal man (1). In half of this group of eight patients, GFR ranged from 16.6 to 22.7 ml per minute; in the other half values ranged from 42.3 to 58.1 ml per minute. Yet, the mean titration curves were identical for the two groups. In addition, no difference was observed in the titration curves for patients with pyelonephritis and those with glomerulonephritis. In patients with GFR values below 15 ml per minute, increased splay was observed, and below a GFR of 10 ml per minute, the splay was very marked. Both the absence of exaggerated splay in patients with reduction of glomerular filtration rate by as much as 85%, and the emergence of exaggerated splay in patients with more marked reduction of GFR, require explanation. Theoretical considerations are presented in the text.

Authors

Richard E. Rieselbach, Steward W. Shankel, Eduardo Slatopolsky, Herbert Lubowitz, Neal S. Bricker

On the Mechanism of the Splay in the Glucose Titration Curve in Advanced Experimental Renal Disease in the Rat

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Abstract

Glucose titration studies were performed in rats with unilateral chronic pyelonephritis before and after removal of the contralateral control kidneys. Identical studies were performed in animals with unilateral partial renal infarction in which the experimental kidneys had a marked reduction in nephron population but no anatomic deformation in the surviving nephrons. In the initial studies, both groups of animals were free of clinical and chemical abnormalities of uremia. In the follow-up studies uremic abnormalities were present. Minimal splay was observed in the titration curves in the initial studies; marked splay was present in the group data from the same kidneys in the subsequent studies. Thus a marked reduction in the nephron population was associated with the evolution of splay in both groups of animals. In association with the increase in splay, the mean values for maximal glucose transport increased; thus a defect in glucose transport can be excluded as the basis of the splay. Glomerular filtration rate increased proportionately more than the maximal transport of glucose; hence the ratios of glomerular filtration rate to maximal glucose transport increased consistently. The possibility of asymmetric hypertrophy of glomerular and tubular functions among the nephron population imposed by scar tissue or other anatomic deformities was considered, but the results in the animals with partially infarcted kidneys militate against this explanation. The splay also could reflect an asymmetric alteration in the distribution of glomerulotubular balance among the residual units initiated by functional adaptations. Finally, the splay could relate to an alteration in the kinetics of glucose transport without any change in the level of functional homogeneity. The possible nature of these has been considered in the text.

Authors

Stewart W. Shankel, Alan M. Robson, Neal S. Bricker

Concomitant Alterations of Sodium Flux and Membrane Phospholipid Metabolism in Red Blood Cells: Studies in Hereditary Spherocytosis

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Abstract

The role of membrane phosphatides in transport processes has been investigated in red cells from splenectomized patients with hereditary spherocytosis (HS).

Authors

Harry S. Jacob, Manfred L. Karnovsky

Effect of Diet upon Intestinal Disaccharidases and Disaccharide Absorption

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Abstract

The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding.

Authors

J. J. Deren, S. A. Broitman, N. Zamcheck

ACTH Antibodies in Patients Receiving Depot Porcine ACTH to Hasten Recovery from Pituitary-Adrenal Suppression

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Abstract

Six patients who had experienced prolonged steroid-induced pituitary-adrenal suppression were treated with 100 U of depot procine ACTH every 2 to 4 days for several months. Such treatment did not hasten the recovery of normal pituitary-adrenal function compared with the rate of recovery of a group of similarly suppressed patients who received no depot ACTH. Eight of nine patients who received prolonged courses of depot porcine ACTH developed antibodies to ACTH that cross-reacted with endogenous ACTH, binding it in the circulation in inactive form and retarding its removal from the circulation. The presence of such antibodies did not in itself grossly alter pituitary-adrenal interrelationships.

Authors

Norman Fleischer, Kaoru Abe, Grant W. Liddle, David N. Orth, Wendell E. Nicholson

Atrial Fibrillation in the Intact Unanesthetized Dog: Hemodynamic Effects during Rest, Exercise, and Beta-Adrenergic Blockade

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Abstract

The effects of atrial fibrillation were studied in 12 healthy unanesthetized dogs, 9 to 49 days after surgical implantation of transducers for measurement of aortic flow and left ventricular diameter. Atrial fibrillation and pacing at comparable ventricular rates were induced by electrical stimulation of the right atrial appendage, and their effects were compared with observations made during sinus rhythm in each dog. At rest, cardiac output and mean arterial pressure were not significantly different during sinus rhythm, atrial fibrillation, and atrial pacing. After beta-adrenergic blockade with propranolol, cardiac output during fibrillation was significantly less than that during pacing at comparable ventricular rates. Arterial pressure was not detectably altered. During moderately severe treadmill exercise by six dogs, cardiac output fell significantly upon induction of fibrillation. After pentobarbital anesthesia fibrillation caused decrements in cardiac output and arterial pressure that were accentuated after thoracotomy.

Authors

Richard H. Martin, Samuel T. Lim, Robert L. Van Citters

Collagen Degradation and the Response to Parathyroid Extract in the Intact Rhesus Monkey

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Abstract

Proline-14C was administered to five adult rhesus monkeys, and the degradation of collagen was followed by the excretion of hydroxyproline-14C. The results suggested the presence of at least three separate pools of collagen with half-lives of 1 to 2, 2 to 3, and 50 to 70 days. The monkeys were killed after 44 days; at that time the specific activity of the hydroxyproline-14C in urine was found to be four to five times that of the hydroxyproline in soluble collagen and 81 to 93% that of hydroxyproline in insoluble collagen. The relationships between urinary hydroxyproline and the degradation of collagen were similar to those previously demonstrated in rats.

Authors

Louis V. Avioli, Darwin J. Prockop

Regulation of Renal Citrate Metabolism by Bicarbonate Ion and pH: Observations in Tissue Slices and Mitochondria

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Abstract

The effect of acid-base balance on the oxidation and utilization of citrate and other organic acids has been studied in tissue slices and isolated kidney mitochondria. The results show that: 1) With bicarbonate-buffered media, citrate oxidation and utilization are inhibited in slices of renal cortex and in kidney mitochondria when [HCO3-] and pH are increased within the physiologic range (pH 7.0 to 7.8; 10 to 60 μmoles HCO3- per ml). When phosphate or Tris buffers are used, no comparable effect on citrate oxidation occurs when pH is varied. 2) This effect is not demonstrable in heart or liver slices when a physiologic buffer is used. 3) α-Ketoglutarate utilization is inhibited in slices of renal cortex under similar conditions. Pyruvate and L-malate utilization are not inhibited in slices or mitochondria. 4) Citrate content in slices of renal cortex incubated with a high [HCO3-] is considerably greater than the concentration found with a low [HCO3-] in the medium. This effect is not duplicated by pH change in a nonbicarbonate buffer system. In mitochondria citrate content is also increased markedly at high bicarbonate concentrations. 5) The kinetic characteristics of the inhibition of citrate oxidation are those of a competitive type of inhibition. 6) When pH was varied with a constant [HCO3-] in the media, citrate oxidation was inhibited by increasing pH in slices of renal cortex but not in mitochondria. On the other hand, when [HCO3-] was increased without change in pH, no decrease in citrate oxidation occurred in slices, but a marked inhibitory effect was found when mitochondria were used.

Authors

David P. Simpson

Tissue Lipoprotein Lipase in Normal Individuals and in Individuals with Exogenous Hypertriglyceridemia and the Relationship of this Enzyme to Assimilation of Fat

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Abstract

Lipoprotein lipase activity (LLA) was measured in the adipose tissue of six healthy subjects and five members of a family in whom the trait for familial exogenous hypertriglyceridemia was segregating. The lipase activity measured was characteristic of lipoprotein lipase: increased by feeding, dependent on the presence of serum, and inhibited by sodium chloride and protamine sulfate. When compared with lipase activity in healthy individuals, LLA was grossly deficient in two siblings with postabsorptive chylomicronemia and was intermediate in both parents and one sibling, who had normal postabsorptive triglycerides. These findings are compatible with autosomal recessive inheritance. The hormone-sensitive lipolytic enzyme responsible for mobilization of free fatty acids from adipose storage was normal in the hyperlipemic subjects.

Authors

William R. Harlan Jr., Preston S. Winesett, Albert J. Wasserman

Radioimmunoassay for Luteinizing Hormone in Human plasma Or Serum: Physiological Studies

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Abstract

It is not practical to quantitate gonadotropin in the blood of normal men and women by utilizing bioassays. We have developed a method for sensitive, precise, and specific radioimmunoassay of luteinizing hormone (LH) in human serum or plasma. Antisera were developed against human chorionic gonadotropin, and one of these was selected for extensive cross-reaction with human LH. Highly purified LH was radioiodinated by the method of Greenwood, Hunter, and Glover. Separation of antibody-bound from free LH-131I was accomplished by a double antibody technique. Dose-response curves for the purifed LH, an impure urinary LH preparation, pituitary powder, and LH in plasma were all identical. Immunoassay and bioassay of impure urinary and pituitary gonadotropin preparations in terms of a common standard resulted in an index of discrimination of close to unity. LH levels in plasma from 32 adult men and 30 women outside the midcycle ranged from 0.6 to 3.2 mμg per ml (1 mμg of our laboratory LH standard is equivalent to 8 mU of the Second International Reference Preparation of Human Menopausal Gonadotropin). Levels were remarkably constant in men from day to day and in women except at midcycle, when a sharp peak occurred lasting less than 24 hours. In all women studied who had a midcycle LH peak, mean plasma LH levels during the follicular phase of the menstrual cycle were higher than mean values obtained during the luteal phase. Prepubertal children had detectable plasma LH, and mean values were only slightly less than in adults. Plasma from castrate men or women or postmenopausal women contained 4.5 to 10.5 mμg per ml. Clomiphene treatment of four men resulted in a doubling of plasma LH in 5 days.

Authors

W. D. Odell, G. T. Ross, P. L. Rayford

Evidence That an Acute Increase in Glomerular Filtration Has Little Effect on Sodium Excretion in the Dog unless Extracellular Volume is Expanded

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Abstract

The concept that acute increases in glomerular filtration rate (GFR) will cause large concomitant increases in sodium excretion has been re-examined. In previous work, GFR was elevated by volume expansion, usually with saline infusions. Recent evidence shows that tubular reabsorption is depressed during saline loading; hence, the independent effect of increased GFR on sodium excretion cannot be assessed.

Authors

Marshall D. Lindheimer, Richard C. Lalone, Norman G. Levinsky

Light and Heavy Chain Components of Gamma Globulins in Urines of Normal Persons and Patients with Agammaglobulinemia

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Abstract

A heavy chain component of γG-globulins in normal urines has the characteristics of the proteolytic digestion product, Fc-fragment. This fragment is estimated to compose up to 15% of the gamma globulins present in urines. In contrast to urinary light chains, the urinary Fc-like fragment probably represents a catabolic component in normal γG-globulin metabolism.

Authors

John H. Vaughan, Ralph F. Jacox, Barry A. Gray

The Effect of Treatment of Acidosis on Calcium Balance in Patients with Chronic Azotemic Renal Disease

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Abstract

Small but statistically significant negative calcium balances were found in each of eight studies in seven patients with chronic azotemic renal disease when stable metabolic acidosis was present. Only small quantities of calcium were excreted in the urine, but fecal calcium excretion equaled or exceeded dietary intake. Complete and continuous correction of acidosis by NaHCO3 therapy reduced both urinary and fecal calcium excretion and produced a daily calcium balance indistinguishable from zero.

Authors

John R. Litzow, Jacob Lemann Jr., Edward J. Lennon