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Issue published August 1, 1968 Previous issue | Next issue

  • Volume 47, Issue 8
Go to section:
  • Research Articles
Research Articles
Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia
John F. Bertles, Paul F. A. Milner
John F. Bertles, Paul F. A. Milner
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1731-1741. https://doi.org/10.1172/JCI105863.
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Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia

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Abstract

The amount of fetal hemoglobin (Hb F) in erythrocytes of patients with sickle cell anemia (Hb SS disease) was measured by two methods: (a) photometry of individual cells stained for Hb F by the Kleihauer-Betke technique; and (b) chemical assay of alkali-resistant hemoglobin in cells distributed according to specific gravity by ultracentrifugation. Irreversibly sickled cells (ISC), which could be identified directly during photometry and which were found to gather in high concentration at the bottom of ultracentrifuged cell columns, contained significantly less Hb F than non-ISC. Cell content of total Hb was constant regardless of cell size, shape, or ultracentrifugal behavior: thus absolute amounts of Hb F and S varied reciprocally from cell to cell.

Authors

John F. Bertles, Paul F. A. Milner

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Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia
Frederic C. Bartter, … , Robert I. Henkin, George T. Bryan
Frederic C. Bartter, … , Robert I. Henkin, George T. Bryan
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1742-1752. https://doi.org/10.1172/JCI105864.
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Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

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Abstract

Patients with the “non-salt-losing” form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well.

Authors

Frederic C. Bartter, Robert I. Henkin, George T. Bryan

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Leukocyte degranulation and vacuole formation in patients with chronic granulomatous disease of childhood
Emanuel Kauder, … , Hernan Moreno, John C. Partin
Emanuel Kauder, … , Hernan Moreno, John C. Partin
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1753-1762. https://doi.org/10.1172/JCI105865.
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Leukocyte degranulation and vacuole formation in patients with chronic granulomatous disease of childhood

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Abstract

A cellular defect associated with decreased bactericidal activity of the polymorphonuclear leukocyte has been found in a 2½ yr old Negro boy with the typical clinical and pathological findings of chronic granulomatous disease. Unlike previously described patients his polymorphonuclear leukocytes were shown to undergo apparently normal degranulation and vacuole formation after phagocytosis. Metabolic studies of the leukocytes indicated a failure to increase oxygen consumption with phagocytosis or to reduce Nitroblue tetrazolium dye. These metabolic abnormalities are identical with those previously reported in patients with chronic granulomatous disease. Two additional patients with chronic granulomatous disease have also been found to have apparently adequate degranulation of polymorphonuclear leukocytes after phagocytosis. Our studies suggest that failure of degranulation may not be a necessary part of this functional leukocyte abnormality.

Authors

Emanuel Kauder, Louis L. Kahle, Hernan Moreno, John C. Partin

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The influence of bacteriocins on resistance to infection by gram-negative bacteria: II. Colicin action, transfer of colicinogeny, and transfer of antibiotic resistance in urinary infections
Abraham I. Braude, J. S. Siemienski
Abraham I. Braude, J. S. Siemienski
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1763-1773. https://doi.org/10.1172/JCI105866.
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The influence of bacteriocins on resistance to infection by gram-negative bacteria: II. Colicin action, transfer of colicinogeny, and transfer of antibiotic resistance in urinary infections

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Abstract

Dual urinary infections were produced in rats with colicinogenic Escherichia coli CF1, elaborating colicin V in the urine, and colicine-sensitive E. coli 9224 by injecting each organism into the medulla of opposite kidneys. The colicin-sensitive organism was eradicated from the urine of 24.3% of rats and the degree of infection by E. coli 9224 reduced to less than half of the control group. Colicin-resistant mutants of E. coli 9224 were not inhibited in mixed infections with colicin producing E. coli CF1. No evidence of inhibitory activity by colicin V was found in the kidneys. The bladder urine, but not the kidney, was also the site for transfer of colicinogeny between homologous (E. coli) and heterologous (E. coli and Aerobacter aerogenes) species. Episomes controlling colicin V and J + I were transferred within 24 hr after establishing the mixed infection. Since E. coli 9224 was resistant to streptomycin and tetracycline, observations were also made on transmission of multiple drug resistance. Streptomycin and tetracycline resistance was readily transferred to E. coli CF1 within 48 hr in the bladder. These results demonstrate that in urinary infections colicins can kill susceptible bacteria and that bacterial genetic elements are transferred.

Authors

Abraham I. Braude, J. S. Siemienski

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Hemodynamic effects after conversion of arrhythmias
Robert J. Corliss, … , Charles W. Crumpton, George G. Rowe
Robert J. Corliss, … , Charles W. Crumpton, George G. Rowe
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1774-1786. https://doi.org/10.1172/JCI105867.
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Hemodynamic effects after conversion of arrhythmias

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Abstract

Systemic and coronary hemodynamic parameters were determined during an arrhythmia and immediately after a direct current transthoracic shock given in an attempt to convert the arrhythmia to a sinus mechanism. No anesthesia or drugs were administered between the two studies. 16 patients with atrial fibrillation converted to sinus rhythm and five did not. In two patients with atrial flutter and one with supraventricular tachycardia, the arrhythmia was corrected. The arrhythmia persisted in a single patient with ventricular tachycardia. Utilizing each patient as his own control, we compared statistically various hemodynamic parameters before and after the shock. In addition, the group of patients whose atrial fibrillation terminated was compared to the group treated in the same manner but in which the atrial fibrillation persisted. Pressures in the right side of the heart decreased in both groups so that the changes appeared to be caused by factors associated with the transthoracic direct current shock or the catheterization procedure. The differences between those with atrial fibrillation who converted to sinus rhythm as compared to those who did not were a decrease in heart rate, an increase in stroke volume, and an increase in cardiac efficiency. There was no immediate effect on the cardiac output or coronary blood flow.

Authors

Robert J. Corliss, David H. McKenna, Charles W. Crumpton, George G. Rowe

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Defective lipid metabolism in the failing heart
Benjamin Wittel, James F. Spann Jr.
Benjamin Wittel, James F. Spann Jr.
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1787-1794. https://doi.org/10.1172/JCI105868.
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Defective lipid metabolism in the failing heart

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Abstract

The metabolism of long chain fatty acids was investigated in the failing heart of guinea pigs with chronic constriction of the ascending aorta. Homogenates prepared form failing hearts exhibited (a) a decreased capacity to oxidize palmitic acid (failure = 0.50 ± 0.06 μmole/g of protein per 20 min; control = 1.09 ± 0.10); (b) a reduced level of carnitine, a myocardial constituent which serves to control the oxidation rate of long chain fatty acids in the heart (failure = 0.91 ± 0.10 μmole/g wet weight; control = 1.69 ± 0.10); and (c) an increased rate of palmitate incorporation into triglycerides and lecithin. Exogenous carnitine effected a restoration of the defective palmitate metabolism of the homogenates towards normal. In contrast to long chain fatty acid oxidation, glucose oxidation by the failing heart was not impaired. As a consequence of this selective lesion in energy substrate utilization, the failing heart might be forced to rely on substrates other than long chain fatty acids for its major energy supply.

Authors

Benjamin Wittel, James F. Spann Jr.

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Plasma lipids and urinary excretion of catecholamines in man during experimentally induced emotional stress, and their modification by nicotinic acid
Lars A. Carlson, … , Lennart Levi, Lars Orö
Lars A. Carlson, … , Lennart Levi, Lars Orö
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1795-1805. https://doi.org/10.1172/JCI105869.
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Plasma lipids and urinary excretion of catecholamines in man during experimentally induced emotional stress, and their modification by nicotinic acid

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Abstract

33 male volunteers were studied in the morning after fasting overnight. 11 (the control group) were allowed to sit comfortably for three consecutive 2-hr periods, no stressors or treatment being introduced. The remaining 22 were divided into two groups, each being exposed to standardized, emotional stressors during the second of the three 2-hr periods. The subjects in one of these groups were each given a total dose of 3 g of nicotinic acid during the first 3 hr of the experiment, whereas the other group received no treatment.

Authors

Lars A. Carlson, Lennart Levi, Lars Orö

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Effect of neomycin on exchangeable pools of cholesterol in the steady state
Paul Samuel, … , Edward Meilman, William Perl
Paul Samuel, … , Edward Meilman, William Perl
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1806-1818. https://doi.org/10.1172/JCI105870.
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Effect of neomycin on exchangeable pools of cholesterol in the steady state

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Abstract

Five patients received cholesterol-7α-3H intravenously during control periods. Specific activity of total serum cholesterol was determined serially during the 1st wk and weekly thereafter. 28-59 wk after the injection of the tracer, when no further radioactivity could be detected in serum cholesterol, 2 g of oral neomycin was given daily to four patients for the remainder of the experiment. Average total serum cholesterol concentrations were reduced by 20, 21, 26, and 29%, respectively, in these subjects. The fifth patient, given placebo, had no change in serum cholesterol. After a period of 12-26 wk of medication the intravenous injection of cholesterol-7α-3H was repeated, and while neomycin or placebo administration was continued, serum cholesterol specific activity was again determined serially during the 1st wk and weekly thereafter for 23-42 wk. The data were subjected to a two-compartment analysis. During the administration of neomycin, half-times of the cholesterol radio-activity decay curves were decreased in two patients and remained unchanged in two subjects. The size of the “intermediate” pool of cholesterol decreased in each patient during the administration of neomycin by 33, 36, 40, and 44%, respectively. The absolute decrease was much larger in each case than the concomitant reduction of serum cholesterol. There was no significant change in the data during the administration of placebo in one patient. The size of the “intermediate” pool can be calculated by compartmental analysis from the cholesterol decay curves. For the “slow” pool size and the other kinetic parameters only ranges of values can be deduced from the present experiment.

Authors

Paul Samuel, Charles M. Holtzman, Edward Meilman, William Perl

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Malabsorption of hemoglobin iron in pernicious anemia: correction with intrinsic factor—containing substances
Samuel Waxman, … , Peter Pratt, Victor Herbert
Samuel Waxman, … , Peter Pratt, Victor Herbert
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1819-1825. https://doi.org/10.1172/JCI105871.
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Malabsorption of hemoglobin iron in pernicious anemia: correction with intrinsic factor—containing substances

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Abstract

Hemoglobin iron absorption in patients with treated prenicious anemia (PA) and concomitant iron deficiency was low compared to absorption in patients with iron deficiency alone. Crude and purified hog intrinsic factor (IF) concentrates doubled the absorption of hemoglobin iron in these patients as did normal (neutralized depepsinized) human gastric juice. Hemoglobin iron absorption was not significantly enhanced by PA gastric juice. Absorption of heme iron, like that of hemoglobin iron, was enhanced by normal neutralized depepsinized gastric juice. No enhancement of hemoglobin iron absorption by these substances was obtained in the normal or iron-deficient non-PA control subjects. Preincubation of the hog IF concentrate with antisera to IF significantly reduced the enhancement of hemoglobin iron absorption due to the concentrate.

Authors

Samuel Waxman, Peter Pratt, Victor Herbert

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Enzymes of fructose metabolism in human liver
Fritz Heinz, … , Walther Lamprecht, Joachim Kirsch
Fritz Heinz, … , Walther Lamprecht, Joachim Kirsch
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1826-1832. https://doi.org/10.1172/JCI105872.
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Enzymes of fructose metabolism in human liver

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Abstract

The enzyme activities involved in fructose metabolism were measured in samples of human liver. On the basis of U/g of wet-weight the following results were found: ketohexokinase, 1.23; aldolase (substrate, fructose-1-phosphate), 2.08; aldolase (substrate, fructose-1,6-diphosphate), 3.46; triokinase, 2.07; aldehyde dehydrogenase (substrate, D-glyceraldehyde), 1.04; D-glycerate kinase, 0.13; alcohol dehydrogenase (nicotinamide adenine dinucleotide [NAD]) substrate, D-glyceraldehyde), 3.1; alcohol dehydrogenase (nicotinamide adenine dinucleotide phosphate [NADP]) (substrate, D-glyceraldehyde), 3.6; and glycerol kinase, 0.62. Sorbitol dehydrogenases (25.0 U/g), hexosediphosphatase (4.06 U/g), hexokinase (0.23 U/g), and glucokinase (0.08 U/g) were also measured. Comparing these results with those of the rat liver it becomes clear that the activities of alcohol dehydrogenases (NAD and NADP) in rat liver are higher than those in human liver, and that the values of ketohexokinase, sorbitol dehydrogenases, and hexosediphosphatase in human liver are lower than those values found in rat liver. Human liver contains only traces of glycerate kinase.

Authors

Fritz Heinz, Walther Lamprecht, Joachim Kirsch

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Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants
L. Luzzatto, A. Afolayan
L. Luzzatto, A. Afolayan
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1833-1842. https://doi.org/10.1172/JCI105873.
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Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants

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Abstract

Enzymic properties have been compared in the following five genetic variants of glucose-6-phosphate dehydrogenase from human erythrocytes: the two common variants with normal activity, A and B; the common variant associated with enzyme deficiency, A-; and two new rare variants, “Ijebu-Ode” and “Ita-Bale.”

Authors

L. Luzzatto, A. Afolayan

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Effect of dibutyryl cyclic adenosine 3′,5′-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism
Howard Rasmussen, … , Maurice Pechet, Danuta Fast
Howard Rasmussen, … , Maurice Pechet, Danuta Fast
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1843-1850. https://doi.org/10.1172/JCI105874.
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Effect of dibutyryl cyclic adenosine 3′,5′-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism

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Abstract

The effect of dibutyryl cyclic adenosine 3′,5′-monophosphate upon calcium and phosphate metabolism in thyroparathyroidectomized rats was undertaken in an effort to clarify the possible role of adenosine 3′,5′-monophosphate (3′,5′ AMP) in parathyroid hormone action. The infusion of dibutyryl cyclic 3′,5′ AMP at a rate of 3 mg/hr into thyroparathyroidectomized rats leads to changes in calcium, phosphate, and hydroxyproline excretion, and calcium and phosphate concentrations in plasma that are qualitatively similar to those induced by parathyroid hormone given at a rate of 5 μg/hr. The effect of dibutyryl cyclic 3′,5′ AMP upon calcium and hydroxyproline mobilization from bone is blocked by thyrocalcitonin administration in the same way that thyrocalcitonin blocks PTH effects. Other closely related nucleotides do not act in the same way.

Authors

Howard Rasmussen, Maurice Pechet, Danuta Fast

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Improved oxygen release: an adaptation of mature red cells to hypoxia
Miles J. Edwards, … , Carrie-Lou Walters, James Metcalfe
Miles J. Edwards, … , Carrie-Lou Walters, James Metcalfe
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1851-1857. https://doi.org/10.1172/JCI105875.
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Improved oxygen release: an adaptation of mature red cells to hypoxia

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Abstract

Blood from patients with erythrocytosis secondary to arterial hypoxemia due either to congenital heart disease or to chronic obstructive pulmonary disease was shown to have a decreased affinity for oxygen; the average oxygen pressure required to produce 50% saturation of hemoglobin with oxygen was 29.8 mm Hg (average normal, 26.3 mm Hg). Such a displacement of the blood oxygen equilibrium curve promotes the release of oxygen from blood to the tissues.

Authors

Miles J. Edwards, Miles J. Novy, Carrie-Lou Walters, James Metcalfe

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Studies of red cell stromal proteins in Tay-Sachs disease
John A. Balint, Emilios C. Kyriakides
John A. Balint, Emilios C. Kyriakides
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1858-1864. https://doi.org/10.1172/JCI105876.
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Studies of red cell stromal proteins in Tay-Sachs disease

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Abstract

Hemoglobin-free red blood cell ghosts of nine patients with Tay-Sachs disease and 14 normal control subjects have been analyzed for content of total protein, hexosamines, individual amino acids, and sialic acid. Red cell ghosts from Tay-Sachs' children have been shown to contain significantly increased amounts of protein, hexosamine, threonine, and serine, and probably sialic acid, each of which was increased by approximately 25% over control values. These observations suggest that the red cell membrane in patients with Tay-Sachs disease contains a significant excess of a glycoprotein or proteins, as compared with normal, and that the metabolic defect in this disease, therefore, affects glycoproteins as well as complex lipids.

Authors

John A. Balint, Emilios C. Kyriakides

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Control of phosphate excretion in uremic man
E. Slatopolsky, … , I. Elkan, N. S. Bricker
E. Slatopolsky, … , I. Elkan, N. S. Bricker
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1865-1874. https://doi.org/10.1172/JCI105877.
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Control of phosphate excretion in uremic man

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Abstract

The present studies were performed in an effort to examine the characteristics of the control system governing phosphate excretion in uremic man. In a group of patients with glomerular filtration rates (GFR) ranging from normal to 2 ml/min, it was found that the lower the GFR the lower the fraction of filtered phosphate reabsorbed (TRP). On a fixed phosphate intake, phosphate excretion rate was the same in patients with GFRs ranging from 60 to 3 ml/min. When plasma phosphate concentrations were diminished to subnormal levels in hyperphosphatemic, hypocalcemic uremic patients, TRP values increased but did not return to normal. TRP failed to rise substantially when GFR, as well as plasma phosphate concentrations, were diminished. In patients with unilateral renal disease, TRP values were equal bilaterally, and values were substantially higher in the diseased kidneys than in patients with bilateral involvement. When plasma calcium concentrations were raised to normal for 2-3 wk in uremic patients in whom plasma phosphate concentrations had previously been lowered to subnormal levels, TRP values rose to an average value of 86%. Values remained in the normal range when phosphate concentrations were allowed to increase while normocalcemia was maintained. The data are interpreted to indicate that in advancing renal disease, the changing patterns of phosphate excretion are mediated by a control system in which parathyroid hormone serves as a major effector element. An increase in GFR per nephron, hyperphosphatemia, and intrinsic inability of the surviving nephrons to transport phosphate do not appear to be of primary importance in the progressive reduction in TRP.

Authors

E. Slatopolsky, A. M. Robson, I. Elkan, N. S. Bricker

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Human monoclonal γG-cryoglobulins with anti—γ-globulin activity
Howard M. Grey, … , William D. Terry, Edward C. Franklin
Howard M. Grey, … , William D. Terry, Edward C. Franklin
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1875-1884. https://doi.org/10.1172/JCI105878.
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Human monoclonal γG-cryoglobulins with anti—γ-globulin activity

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Abstract

Seven human γG-myeloma proteins which were also cryoglobulins were studied with respect to their reactivity with γG-globulins as well as with regard to their antigenic classification within the γG—heavy chain subclasses. Five of the seven cryoglobulins studied were positive in at least two of the three tests used to assay for anti—γ-globulin activity. One protein was only weakly positive in one test system and another was negative in all test systems. The structures which were recognized by the cryoglobulins were localized to the Fc-fragment. Only primate γG-globulins contained these antigenic determinants and in some cases the cryoglobulin appeared to show specificity for one human heavy chain subclass over the others. Antigenic analysis revealed that four of the five cryoglobulins with definite antibody activity belonged to the γG3-subclass, the fifth belonged to the γG1-subclass. The two cryoglobulins which reacted only weakly or failed to combine with γG-globulins were both of the γG1-subclass. These findings taken together with the localization of the combining site to the Fab-fragment suggests that many of these cryoglobulins may represent antibodies to γG-globulin, and that the cryoprecipitate in these cases represents antigen-antibody complexes of such a nature that they precipitate only in the cold.

Authors

Howard M. Grey, Peter F. Kohler, William D. Terry, Edward C. Franklin

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Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias
John F. Williams Jr., … , Daniel L. Boyd, John F. Border
John F. Williams Jr., … , Daniel L. Boyd, John F. Border
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1885-1894. https://doi.org/10.1172/JCI105879.
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Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias

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Abstract

The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 μg/kg per min.

Authors

John F. Williams Jr., Daniel L. Boyd, John F. Border

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Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype
Thomas G. Gabuzda, … , Ruth K. Silver, Hugh B. Lewis
Thomas G. Gabuzda, … , Ruth K. Silver, Hugh B. Lewis
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1895-1904. https://doi.org/10.1172/JCI105880.
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Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype

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Abstract

This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with 59Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days.

Authors

Thomas G. Gabuzda, Marc A. Schuman, Ruth K. Silver, Hugh B. Lewis

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Immunoglobulin metabolism in ataxia telangiectasia
Warren Strober, … , Dale E. McFarlin, Thomas A. Waldmann
Warren Strober, … , Dale E. McFarlin, Thomas A. Waldmann
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1905-1915. https://doi.org/10.1172/JCI105881.
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Immunoglobulin metabolism in ataxia telangiectasia

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Abstract

Immunoglobulin metabolism has been studied in five patients with ataxia telangiectasia and in control subjects. Serum IgG levels were normal, increased, or decreased, reflecting normal, increased, or decreased synthetic rates, respectively. Serum IgM concentration was normal in three cases and slightly elevated in two cases. IgM turnover studies in the three cases with normal serum IgM levels showed normal IgM synthetic and catabolic rates. None of the five patients with ataxia telangiectasia had detectable serum IgA, and the maximum IgA synthetic rates possible for these patients were 0.3-10% of the normal mean synthetic rate (24 ± 15 mg/kg per day) of 12 control individuals. Three of the patients had normal IgA fractional catabolic rates: 22% of the intravascular pool per day vs. 25 ± 4% in controls. In two patients, fractional catabolic rates 4 and 20 times normal were found. In these cases, metabolic turnover, in vitro precipitation, radioimmunoelectrophoresis, and (or) the C′la fixation and transfer test provided evidence for the presence of a circulating antibody directed against IgA causing immune elimination of the molecule. These studies suggest that therapy with exogenous IgA may not be possible in some patients with ataxia telangiectasia or in other subjects with dysgammaglobulinemia.

Authors

Warren Strober, R. Dean Wochner, Mahlon H. Barlow, Dale E. McFarlin, Thomas A. Waldmann

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Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia
Malcolm A. Holliday, … , M. N. Kalayci, Jean Harrah
Malcolm A. Holliday, … , M. N. Kalayci, Jean Harrah
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1916-1928. https://doi.org/10.1172/JCI105882.
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Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

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Abstract

Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (NaE and ClE). The following observations are noted: Brain Cl content varies directly with ClE and brain Na content in the Cl space (Nae) varies directly with NaE, indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (Vi) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in Vi in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) NaE is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) Vi is osmotically active; and (d) there is no net gain or loss of solute from Vi. The validity of these assumptions is considered. When changes in osmolality are sustained, Vi is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in Vi observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon NaE describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in NaE by the freedom for Na and Cl to move from the Cl space, by Vi not changing acutely to the degree predicted from osmotic properties of cells in general, and by significant quantities of Na + K in Vi being osmotically inactive. With sustained changes in osmolality, Vi approaches normal values and brain K changes to account for part of this later adjustment.

Authors

Malcolm A. Holliday, M. N. Kalayci, Jean Harrah

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An inherited molecular lesion of erythrocyte pyruvate kinase: Identification of a kinetically aberrant isozyme associated with premature hemolysis
Donald E. Paglia, … , Claude F. Reed, O. Ross McIntyre
Donald E. Paglia, … , Claude F. Reed, O. Ross McIntyre
Published August 1, 1968
Citation Information: J Clin Invest. 1968;47(8):1929-1946. https://doi.org/10.1172/JCI105883.
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An inherited molecular lesion of erythrocyte pyruvate kinase: Identification of a kinetically aberrant isozyme associated with premature hemolysis

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Abstract

Atypical cases of heritable hemolytic anemia have been noted that conform clinically and biochemically to anemias of the pyruvatekinase (PK)-deficient type, except for the presence of apparently adequate quantities of erythrocyte-PK activity by the usual assay procedure. Investigations of four such anomalous cases, occurring in two unrelated families, are presented. Erythrocytes contained a kinetically aberrant isozyme of pyruvate kinase (PK2). Michaelis constants for the pathologic isozyme relative to phosphoenolpyruvate were over 10-fold greater than control values, but no kinetic abnormality was evident for the second substrate, adenosine diphosphate. PK2 exhibited a pH optimum almost 1 U lower than the wild enzyme form (PK1). Significant differences were also evident in the functional stabilities of the isozymes. Leukocytes were unaffected.

Authors

Donald E. Paglia, William N. Valentine, Marjorie A. Baughan, Denis R. Miller, Claude F. Reed, O. Ross McIntyre

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