Receptors for complement and immunoglobulin on human leukemic cells and human lymphoblastoid cell lines

• Text
• PDF

Abstract

The bone marrow-derived (B) lymphocyte can be identified by the presence of easily detectable surface immunoglobulin and a receptor for antigen-antibody-complement complexes (EAC′). Monocytes and macrophages also bear a receptor for EAC′ and in addition possess a receptor for red cell-IgG complexes (EA). Thymus-derived (T) lymphocytes bear neither of these receptors. The cells of 15 patients with leukemia and 19 human lymphoblastoid cell lines were examined for the presence of the EAC′ and EA receptors. Of the human leukemias studied, only the cells from the patients with chronic lymphatic leukemia (CLL) possess the EAC′ receptor. The EA receptor could not be demonstrated on CLL cells; hence, CLL cells bear the lymphocyte EAC′ receptor and by this criteria represent B lymphocytes. 12/19 of the cell lines studied could be classified as B lymphocytes by the presence of the EAC′ receptor and absence of the EA receptor. 2/19 cell lines possessed both the EAC′ and EA receptors and thus resemble the monocyte. 5/19 cell lines had no detectable receptor for EAC′ or EA. The approach presented in this study for the classification of leukemias and cell lines as to their B lymphocyte, T lymphocyte, or monocyte origin may have useful diagnostic and therapeutic implications.

Authors

Ethan M. Shevach, Ronald Herberman, Michael M. Frank, Ira Green

Direct immunoassay of triiodothyronine in human serum

• Text
• PDF

Abstract

A sensitive and precise radioimmunoassay for the direct measurement of triiodothyronine (T3) in human serum has been designed using sodium salicylate to block T3-TBG binding. This assay is sufficiently sensitive to quantitate T3 accurately in 50-100 μl of normal serum and to measure quantities as small as 12.5 pg in 0.2 ml of hypothyroid serum. The T3 values observed in euthyroid subjects and in patients with various thyroid diseases are as follows: euthyroid (38) 1.10±0.25 (SD) ng/ml, hypothyroid (25) 0.39±0.21 (SD) ng/ml, and hyperthyroid (24) 5.46±4.42 (SD) ng/ml. The levels of T3 parallel the thyroxine (T4) concentration in the sera of these subjects. In eight pregnant women at the time of delivery, T3 concentrations were in the upper normal range (mean 1.33 ng/ml). The levels of T3 in cord serum obtained at the time of delivery of these patients (mean 0.53 ng/ml) are distinctly lower and close to the hypothyroid mean.

Authors

P. R. Larsen

Studies of the control of plasma aldosterone concentration in normal man: II. Effect of dietary potassium and acute potassium infusion

• Text
• PDF

Abstract

The responses of plasma aldosterone, cortisol, and corticosterone to an infusion of 75 mEq of potassium chloride over 120 min were studied in 10 normal subjects. Five subjects were fed a 10 mEq and five a 200 mEq sodium diet, while all subjects ingested 40 mEq and 200 mEq potassium sequentially. Two potassium infusions were performed in each subject when in balance on a fixed sodium intake and low and then high potassium diets.

Authors

Robert G. Dluhy, Lloyd Axelrod, Richard H. Underwood, Gordon H. Williams

Pathogenesis of congenital alkalosis with diarrhea: Implications for the physiology of normal ileal electrolyte absorption and secretion

• Text
• PDF

Abstract

Using a triple-lumen constant perfusion system, we have studied ileal electrolyte transport in a patient with congenital alkalosis with diarrhea and made the following observations. First, chloride cannot be transported against electrochemical gradients, but can be readily absorbed or secreted down electrochemical gradients. Second, chloride secretion down an electrochemical gradient can be increased by raising lumen bicarbonate concentration. Third, sodium absorption does occur against electrochemical gradients and is associated with hydrogen ion secretion. Fourth, electrical potential difference (PD) between lumen and blood is near zero when lumen sodium concentration is 140 mEq/liter. Fifth, a normal sodium diffusion potential is present. Sixth, potassium is transported passively in response to electrochemical gradients.

Authors

Frederick A. Bieberdorf, Phillip Gorden, John S. Fordtran

Pathways of glutamine and organic acid metabolism in renal cortex in chronic metabolic acidosis

• Text
• PDF

Abstract

The metabolism of labeled glutamine and of several labeled organic acid anions was compared in tissue slices of renal cortex from chronically acidotic and alkalotic littermate dogs. 15NH3 formation and 15N-amideglutamine utilization were significantly increased by slices from acidotic animals providing further evidence for the similarity of the metabolic responses seen in the tissue slice system and the physiologic effects produced by chronic metabolic acidosis on renal metabolism in the intact animal. Slices from acidotic dogs formed more 14CO2 and glucose-14C than did slices from alkalotic animals when labeled glutamine, citrate, or malate was used as substrate but 14CO2 production from pyruvate-1-14C was slightly reduced in acidotic tissue. With most of the substrates used glucose-14C formation was small compared with 14CO2 formation. Using the amount of glucose-14C formed, the expected 14CO2 production was calculated based on the hypothesis that the primary site of action of metabolic acidosis is on a cytoplasmic step in gluconeogenesis. The actual difference in 14CO2 production between slices from acidotic and alkalotic animals always greatly exceeded this predicted amount, indicating that stimulation of gluconeogenesis represents a minor metabolic response to chronic metabolic acidosis. Evidence from experiments with citrate labeled in various positions showed that metabolic acidosis has its principal effect on an early step in substrate metabolism which must be intramitochondrial in location.

Authors

David P. Simpson

Liquid crystalline lipid in the plasma of humans with biliary obstruction

• Text
• PDF

Abstract

Plasma lipoprotein characteristics were evaluated in a group of patients with obstructed biliary tracts. A 1:1 molar lecithin-free cholesterol liquid crystal phase was observed in the low density flotation region of these patients. The smectic nature of this mesophase was confirmed by electron microscopy, polarized microscopy, and low angle X-ray scattering. A small amount of protein was associated with these liquid crystals, some of which appeared to be components of normal very low and high density lipoproteins. The composition and physical properties of the very low and high density lipoproteins from these obstructed patients differed from normal as well. Aberrant apoprotein patterns were observed for both obstructed very low and high density lipoproteins. A β-electrophoretic migration was observed for a component of these two lipoprotein groups.

Authors

Steven H. Quarfordt, Harald Oelschlaeger, William R. Krigbaum

The effect of Sendai virus infection on bactericidal and transport mechanisms of the murine lung

• Text
• PDF

Abstract

Pulmonary virus infections predispose to bacterial infections in the lung. The mechanism of this effect was studied by quantitative comparison of the effects of airborne acute viral infection on pulmonary transport vs. in situ bactericidal mechanisms in mice. Animals infected by aerosol with 104 TCID50 of Sendai virus developed pathologic pulmonary changes of interstitial pneumonitis, bronchial epithelial desquamation, and peribronchial mononuclear cell infiltration 7 days later. At that time, the mice were challenged with an aerosol of viable 32P-labeled Staphylococcus aureus. Pulmonary bactericidal activity and physical transport by the lung were determined by the determination of viable staphylococcal and 32P radiotracer counts respectively at 4, 24, 48, and 72 hr after bacterial challenge. Infected mice showed a significant decrease from normal in the rate of reduction of viable bacterial counts in the first 4 hr after challenge followed by a proliferation of the staphylococci. By contrast, radiotracer removal rates at 4 and 24 hr were similar in infected and noninfected mice. There was a small but significant retention of 32P in the lungs of the infected animals at the later periods. These data demonstrate that bacterial multiplication associated with virus infection of lungs is related to defects in in situ bactericidal (phagocytic) mechanisms rather than transport mechanisms of the lung, despite histologic evidence of extensive destruction of bronchial-ciliated epithelium.

Authors

George J. Jakab, Gareth M. Green

Urea transport in the proximal tubule and the descending limb of Henle

• Text
• PDF

Abstract

Urea transport in proximal convoluted tubule (PCT) and descending limb of Henle (DLH) was studied in perfused segments of rabbit nephrons in vitro.

Authors

Juha P. Kokko

The neutrophilic leukocyte in wound repair: A study with antineutrophil serum

• Text
• PDF

Abstract

The role of the neutrophilic leukocyte in wound healing was investigated by observing the progress of repair in the absence of these cells. Circulating neutrophils were eliminated in guinea pigs by the administration of antineutrophil serum (ANS) 24 hr before wounding and by daily injections throughout a 10 day period of healing. Control animals received normal rabbit serum at the same dose levels and times. The wounds consisted of six linear incisions in the dorsal skin of the animals.

Authors

David M. Simpson, Russell Ross

Glycosyltransferases in human blood: I. Galactosyltransferase in human serum and erythrocyte membranes

• Text
• PDF

Abstract

Human serum and hemoglobin-free erythrocyte membranes were found to contain a galactosyltransferase which catalyzes the transfer of galactose from UDP-galactose to specific large and small molecular weight acceptors. The requirements for enzyme activity were found to be similar for the enzymes from both sources. However, the membrane-bound enzyme depended on a detergent for maximal activity. Mn++ was an absolute requirement for transfer and uridine nucleoside phosphates were inhibitors. The most effective acceptor for galactose was a glycoprotein containing N-acetylglucosamine residues in the terminal position of its oligosaccharide side chains, N-acetylglucosamine was also an acceptor. While the presence of α-lactalbumin in the incubation medium resulted in a significant decrease in the transfer of galactose to N-acetylglucosamine, glucose, which was not an acceptor for galactose in the absence of α-lactalbumin, became an excellent acceptor. The serum enzyme catalyzed the transfer of 54 nmoles of galactose per milliliter of serum per hour and its apparent Km for UDP-galactose was 7.5 × 10-6M. The membrane enzyme had a similar apparent Km. Using a quantitative assay system the enzyme was found to be present in all individuals studied, regardless of their blood type, secretor status, or sex.

Authors

Young S. Kim, Jose Perdomo, James S. Whitehead

Glycosyltransferases in human blood: II. Study of serum galactosyltransferase and N-acetylgalactosaminyltransferase in patients with liver diseases

• Text
• PDF

Abstract

Serum galactosyltransferase activity was found to be elevated in patients with alcoholic and other liver disorders but remained at a normal level in patients with a variety of nonhepatic diseases. The properties of the galactosyltransferase in patients with liver disease were compared with those of the enzyme in the serum of normal subjects. The possible presence of inhibitors or activators in the serum was examined. Results indicated that in patients with liver disease, the rise in the serum galactosyltransferase was due to an increase in the level of the enzyme present in normal serum and not due to the appearance of a new enzyme. In the cases examined, the level of the enzyme increased with the deterioration of liver function and declined in a patient recovering from acute alcoholic hepatitis. Another glycosyltransferase, an N-acetylgalactosaminyltransferase, was not elevated in the serum of liver disease patients and, unlike the galactosyltransferase, was not detected in normal liver. The results suggest that the serum galactosyltransferase originates from the liver and that an abnormal rise in the level of this enzyme in serum is due to hepatocellular damage.

Authors

Y. S. Kim, J. Perdomo, J. S. Whitehead, K. J. Curtis

Circadian rhythm in serum parathyroid hormone concentration in human subjects: correlation with serum calcium, phosphate, albumin, and growth hormone levels

• Text
• PDF

Abstract

A circadian variation in serum calcium, albumin and PTH concentration in normal subjects has been demonstrated. The levels of the three blood constituents were remarkably constant during the day, but striking night and early morning changes occurred. Serum calcium levels were highest at 8:00 p.m. and reached a nadir between 2:00 and 4:00 a.m. Serum albumin levels were parallel to those of serum calcium. PTH levels began to rise after 8:00 p.m., reached the highest levels between 2:00 and 4:00 a.m., and fell to baseline values by 8:00 a.m. The nocturnal fall in serum calcium levels appears to be secondary to dilution of serum proteins by increasing blood volume. The nocturnal rise in PTH levels appears to be independent of serum calcium levels within the normal range but it can be abolished by induced hypercalcemia.

Authors

William Jubiz, Janet M. Canterbury, Eric Reiss, Frank H. Tyler

A threshold distribution hypothesis for packet storage of insulin and its mathematical modeling

• Text
• PDF

Abstract

Phases of insulin release were studied in the perfused pancreas during a variety of glucose stimulation patterns. Patterns included staircase stimulations, constant prolonged single steps, restimulations, and ramp functions. Except at low concentrations, prolonged single steps of glucose elicited early spikes of insulin and a slowly rising second phase. Total insulin in the initial spikes increased with higher glucose concentrations. However, the time-related pattern of these spikes was similar in all cases; ratios of initial secretion rate to total insulin released were constant. Total insulin released in this early phase approximated a sigmoidal function of glucose concentration; mathematical differentiation of this function gave a skewed bell-shaped distribution curve. Staircase stimulations caused insulin to be released as a series of transient spikes which did not correlate with the increment of glucose but rather to the available insulin for a given glucose concentration minus that released in previous steps. The sum of total insulin released as spikes in a staircase series leading to a given glucose concentration was the same as when that concentration was used as a single step. Interrupted prolonged glucose infusions indicated the second phase of insulin release could prime the pancreas and that the first and second phases were interrelated. When glucose was perfused as ramp functions of slow, increasing, concentration, phasic response disappeared.

Authors

Gerold M. Grodsky

Excretion of sterols from the skin of normal and hypercholesterolemic humans: Implications for sterol balance studies

• Text
• PDF

Abstract

The 24 hr sterol excretion from the entire skin surface was determined in six normal and five hypercholesterolemic (Type II) patients fed a controlled, eucaloric diet containing 400 mg of plant sterols. All subjects received radiolabeled cholesterol intravenously in order to measure cholesterol turnover and exchange. The 24 hr skin surface lipids were collected subsequently at intervals of 7-10 days. Sterols were quantified and identified by a combination of thin-layer and gas-liquid chromatographic methods. The mean 24 hr excretion of cholesterol in milligrams was 82.6 in the normal subjects and 82.7 in the hypercholesterolemic patients. Cholesterol constituted 89% of the total sterol excretion through the skin surface in both groups.

Authors

Ashim K. Bhattacharyya, William E. Connor, Arthur A. Spector

Free fatty acid oxidation and carnitine levels in diphtheritic guinea pig myocardium

• Text
• PDF

Abstract

Previous studies from this laboratory and by Wittels and Bressler have suggested that myocardial carnitine depletion and an accompanying decrease in fatty acid oxidation may contribute to the myocardial disease associated with diphtheria. In addition, administration of carnitine was found to prolong survival of diphtheritic guinea pigs and improve ventricular function in diphtheritic dogs.

Authors

David R. Challoner, Hans G. Prols

Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones

• Text
• PDF

Abstract

Inhibition of thyrotropin (TSH) release by chronic treatment with small quantities of triiodothyronine (T3) and thyroxine (T4) was evaluated by determining the serum TSH response to thyrotropin-releasing hormone (TRH) in normal subjects and hypothyroid patients. Response to TRH was determined before treatment and after each dosage of a synthetic combination of T3 + T4 had been given for 3-4 wk.

Authors

Peter J. Snyder, Robert D. Utiger

Mitochondrial lesions in reversible erythropoietic depression due to chloramphenicol

• Text
• PDF

Abstract

The mechanism underlying the reversible depression of erythropoiesis by chloramphenicol has been investigated in rabbits in which hemolytic anemia had been induced by phenylhydrazine so that the compensatory erythroid hyperplasia would provide a situation where abnormalities in the bone marrow cells reflected predominantly those of erythroid precursors.

Authors

Frank C. Firkin

The effect of carbohydrates on ammonium and ketoacid excretion during starvation

• Text
• PDF

Abstract

The metabolic effects of oral ingestion of minute quantities of carbohydrate during prolonged starvation were studied in nine obese subjects. Measurements were made during a control period of total starvation, during the ingestion of 7.5 g carbohydrate daily, and finally during the ingestion of 15.0 g carbohydrate daily. Daily ketoacid excretion fell after carbohydrate ingestion and was significantly correlated (r = 0.62, P < 0.01) with the amount of carbohydrate administered. Despite this fall in ketoacids, the concentration of blood ketoacids, plasma free fatty acids, and serum insulin remained constant throughout the study. Urinary ammonium excretion, closely correlated with ketoacid output (r = 0.95, P < 0.001), also fell significantly after carbohydrate ingestion. No significant changes were present in extracellular or urinary pH. Urea nitrogen excretion did not change when urinary ammonium output fell. These results indicate that: the excretion of ketoacids and ammonium in starving man is exquisitely sensitive to minute amounts of ingested carbohydrate; the change in ketonuria appears to be due to increased renal ketoacid reabsorption after carbohydrate ingestion; and the nitrogen-sparing effect of reducing renal ammonium output in starvation can be dissociated from nitrogen sparing occurring because of changes in urine urea excretion.

Authors

D. G. Sapir, O. E. Owen, J. T. Cheng, R. Ginsberg, G. Boden, W. G. Walker

Plasma triglyceride metabolism in thyroid disease

• Text
• PDF

Abstract

Plasma endogenous triglyceride transport kinetics were determined in 16 hyperthyroid and in 12 hypothyroid patients and the results compared with those of euthyroid control subjects. In addition, the removal of exogenous particulate fat (Intralipid; Vitrum, Sweden) from the circulation and the postheparin plasma lipolytic activity (PHLA) were studied in these patients for further characterization of the alterations of plasma triglyceride metabolism in thyroid disease.

Authors

Esko A. Nikkilä, Matti Kekki

Hepatic fructose-1,6-diphosphatase deficiency: A cause of lactic acidosis and hypoglycemia in infancy

• Text
• PDF

Abstract

An 8-month-old female, maintained on breast feeding for 6 months, experienced numerous attacks of hyperventilation when weaned to baby food and was admitted with severe lactic acidosis (20 mM) and hypoglycemia. Physical examination was negative except for hepatomegaly. Fasting (18 hr) after stabilization on a high carbohydrate diet resulted in hypoglycemia (plasma glucose 40 mg/100 ml), lactic acidosis (6-10 mM), and a rise in plasma alanine. Glucagon produced a glycemic response after 6 hr, but not after 18 hr fasting. Intravenous galactose increased plasma glucose (Δ 45 mg/100 ml) but intravenous fructose, glycerol, and alanine caused a 40-50% fall in plasma glucose and a significant rise in lactate (Δ 3-4 mM).

Authors

Anthony S. Pagliara, Irene E. Karl, James P. Keating, Barbara I. Brown, David M. Kipnis

Effects of catecholamines and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man

• Text
• PDF

Abstract

Studies were performed in healthy volunteers to determine the effects of catecholamines and adrenergic-blocking agents on plasma and urinary levels of adenosine 3′,5′-monophosphate (cyclic AMP) and guanosine 3′,5′-monophosphate (cyclic GMP).

Authors

John H. Ball, Neil I. Kaminsky, Joel G. Hardman, Arthur E. Broadus, Earl W. Sutherland, Grant W. Liddle

Transport of dibasic amino acids, cystine, and tryptophan by cultured human fibroblasts: absence of a defect in cystinuria and Hartnup disease

• Text
• PDF

Abstract

Transport of lysine, arginine, cystine, and tryptophan was studied in cultured skin fibroblasts from normal controls and from patients with cystinuria and Hartnup disease. Each of these amino acids was accumulated against concentration gradients by energy-dependent, saturable mechanisms. Lysine and arginine were each transported by two distinct processes which they shared with each other and with ornithine. In contrast, cystine was taken up by a different transport system with no demonstrable affinity for the dibasic amino acids. The time course and Michaelis-Menten kinetics of lysine and cystine uptake by cells from three cystinuric patients differed in no way from those found in control cells. Similarly, the characteristics of tryptophan uptake by cells from a child with Hartnup disease were identical to those noted in control cells. These findings indicate that the specific transport defects observed in gut and kidney in cystinuria and Hartnup disease are not expressed in cultured human fibroblasts, thus providing additional evidence of the important role that cellular differentiation plays in the regulation of expression of the human genome.

Authors

Ulrich Groth, Leon E. Rosenberg

Human prolactin and thyrotropin concentrations in the serums of normal and hypopituitary children before and after the administration of synthetic thyrotropin-releasing hormone

• Text
• PDF

Abstract

Synthetic thyrotropin-releasing hormone (TRH) was administered to normal children and hypopituitary patients in a dose of 7 μg/kg i.v. over 30-60 sec. Serum thyrotropin (TSH) and prolactin (HPr) concentrations were measured by radioimmunoassay before and at 15-min intervals for 2 hr after TRH. In 20 normal children HPr rose from a mean baseline value of 7.0±1.2 (SEM) ng/ml to a mean peak value of 39.5±5 ng/ml.

Authors

Thomas P. Foley Jr., Laurence S. Jacobs, William Hoffman, William H. Daughaday, Robert M. Blizzard

Studies on the purification and characterization of human factor VIII

• Text
• PDF

Abstract

Factor VIII (antihemophilic globulin) has been prepared from Hyland method IV AHG and cryoprecipitate using limited chymotryptic digestion followed by Sepharose gel filtration. The activity of factor VIII is unaffected by the digestion procedure, while fibrinogen in converted to large noncoagulable fragments.

Authors

Sally L. Marchesi, N. Raphael Shulman, Harvey R. Gralnick

The renal handling of low molecular weight proteins: II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia

• Text
• PDF

Abstract

The present study was directed toward determining the role of the kidney in the metabolism of various classes of serum proteins and to define the urinary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with proteinuria. To this end, the metabolic fates of a small protein, λ-L chain (mol wt 44,000), and a protein of intermediate size, IgG (mol wt 160,000), were studied in controls and patients with renal disease. Controls metabolized 0.28%/hr of circulating IgG and 22.3%/hr of circulating λ-L chain. All the IgG and 99% of the λ-L chain was catabolized with the remaining λ-L chain lost intact into the urine. The kidney was shown to be the major site of catabolism for small serum proteins. Three distinct disorders of protein metabolism were noted in patients with renal tubular disease and tubular proteinuria, glomerular disease (the nephrotic syndrome), and disease involving the entire nephrons (uremia), respectively. Patients with renal tubular disease had a 50-fold increase in the daily urinary excretion of 15-40,000 molecular weight proteins such as lysozyme and λ-L chains. Serum IgG and λ-L chain survivals were normal; however, the fraction of the over-all λ-L chain metabolism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly decreased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small proteins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight increase in λ-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine was markedly increased. Here, abnormal glomerular permeability to proteins of intermediate size is the basic abnormality. Patients with uremia had a normal IgG survival but a four to 10-fold prolongation of λ-L chain survival due to loss of entire nephrons, the major site of metabolism of these proteins. This results in an increase (up to 10-fold) in the serum concentration of λ-L chain, lysozyme, and other small biologically active proteins, a phenomenon that may be of importance in causing some of the manifestations of the uremic syndrome.

Authors

Thomas A. Waldmann, Warren Strober, R. Peter Mogielnicki

Brain response to protein undernutrition: Mechanism of preferential protein retention

• Text
• PDF

Abstract

This study was designed to determine how the brain, in contrast to most other tissues, maintains an almost normal protein content during a period of dietary protein deficiency. Administration of leucine-3H to rats was started during a period of early development (6-18 days) which is characterized by disproportionately rapid brain growth; later (24-33 days) leucine-14C was administered, when brain growth diminishes but total body weight gain continues to be rapid. At 35 days of age the ratio of 3H:14C in cerebrum, cerebellum, and brain stem protein averaged between 1.63 and 1.82. In skeletal muscle, liver, myocardium, and intestinal mucosa the mean 3H:14C was 1.07 or less. Then, a diet containing either 26% or 3.4% protein was administered. In animals fed the 26% protein diet, 3H:14C in the three brain segments remained essentially unchanged over a 42 day period. In contrast, in the 3.4% protein group 3H:14C in brain decreased to values approaching those of other tissues in the body: cerebrum, 1.18; cerebellum, 1.20; and brain stem, 1.16. The results suggest that conservation of brain protein is not due entirely to the long life-span of its cellular components or to efficient reutilization of the products of protein catabolism but through utilization of amino acids from degradation of protein elsewhere in the body.

Authors

Peter R. Dallman, Robert A. Spirito

Alpha-aminoisobutyric acid transport in human leukemic lymphocytes: in vitro characteristics and inhibition by cortisol and cycloheximide

• Text
• PDF

Abstract

We have studied the transport of alpha-aminoisobutyric acid (AIB)-3-14C and its response to cortisol and cycloheximide in vitro in blood lymphocytes from untreated patients with chronic lymphocytic leukemia. The accumulation of AIB-3-14C increased in a linear fashion for 60 min, and reached an apparent steady state in 120 min. The initial rate of AIB accumulation (Vo) varied from 1.1 to 10.2 μmoles/kg cell H2O per min in cells from 16 different patients; however, Vo was reproducible in cells from five of six patients which were studied repeatedly over 1-9 months, and correlated positively with the lymphocyte count (r = 0.51, P = < 0.01).

Authors

Daniel T. Baran, Marshall A. Lichtman, William A. Peck

Studies of neutrophil production and turnover in grey collie dogs with cyclic neutropenia

• Text
• PDF

Abstract

12 grey collie dogs had cyclic neutropenia with the neutropenia recurring at 11.8±0.1-day intervals. The recovery from neutropenia was accompanied by a single wave of myeloid proliferation, an increase in marrow myeloid-labeling indices, and an increase in serum muramidase levels. After recovery from neutropenia during the period when blood neutrophils (PMN) were normal or increased, marrow myeloid precursors became scarce. The decline in marrow precursors and marrow PMN reserves heralded the recurrence of neutropenia. Neither diisopropyl fluorophosphate (DF32P) leukokinetic studies nor the rate of development of neutropenia suggested shortened PMN survival as a mechanism for the neutropenia. These studies indicate that the cyclic neutropenia is due to a regularly recurring failure in PMN production.

Authors

D. C. Dale, S. B. Ward, H. R. Kimball, S. M. Wolff

Cyclic hematopoiesis: the mechanism of cyclic neutropenia in grey collie dogs

• Text
• PDF

Abstract

Two grey collie dogs had regular cyclic fluctuations in the number of all formed elements of the blood. The period lengths for all elements for an individual dog were the same, but the pattern of fluctuation for each element was distinctive. Normal dogs lacked periodic fluctuations.

Authors

David C. Dale, David W. Alling, Sheldon M. Wolff

Studies of secretin-stimulated insulin responses in man

• Text
• PDF

Abstract

Recent studies have suggested that secretin, like glucose, stimulates a rapid insulin response from a small storage pool. In order to evaluate the mechanism of the secretin-stimulated insulin response, small (15 U) rapidly administered intravenous injections (pulses) of secretin were given before, during, and after a 20 hr 300 mg/min glucose infusion. Contrary to previous studies demonstrating that the acute insulin response to a small (5 g) pulse of glucose given 45 min after the start of the glucose infusion was significantly diminished compared to the response to the preinfusion pulse, the acute insulin response (2-5 min Δimmuno-reactive insulin μU/ml) to 15-U secretin pulses exhibited a greater than twofold increase (before: 31.1±15.4; during: 71.2±40.4, μU/ml, mean ±SD, P < 0.02). The increased response to secretin was also found after 20 hr of continuous glucose infusion, but was not observed 1 hr after cessation of the infusion when plasma glucose levels returned to control values. Thus, this increased response to secretin was glucose dependent.

Authors

Roger L. Lerner, Daniel Porte Jr.

In vivo formation of H₂O₂ in red cells during exposure to hyperoxia

• Text
• PDF

Abstract

Chow-fed and tocopherol-deficient mice were given aminotriazole (AT), exposed to 100% O2 at 60 pounds per square inch absolute for 1 hr (OHP), and red blood cells were assayed for catalase activity and lipid peroxide levels. A decrease of catalase activity (CA) in the presence of AT can be taken as evidence of excess formation or accumulation of H2O2. No differences of CA were observed among chow-fed mice, with or without AT and/or OHP. Tocopherol-deficient mice with AT had lower CA (0.174±0.040) than chow-fed mice with AT (0.225±0.028) P < 0.01. Tocopherol-deficient mice with AT exposed to OHP had even lower CA, 0.137±0.024, P < 0.01.

Authors

William P. Johnson, Devenia Jefferson, Charles E. Mengel