A method is described for the measurement of soluble thrombin-altered fibrinogen (circulating fibrin) in human plasma. This method is dependent upon the enzymatic incorporation of glycine ethyl ester-14C (GEE-14C) into circulating fibrin by the action of the fibrin-stabilizing enzyme, factor XIII. The mean incorporation of GEE-14C into the fibrinogen of normal human plasma controls was 167 ±47 dpm/mg fibrinogen. The addition of 0.03 NIH U/ml of thrombin to normal human plasma resulted in a two to threefold increase in the incorporation of GEE-14C into the fibrinogen. The addition of plasmin split products of fibrinogen to normal plasma did not increase the incorporation of GEE-14C unless these products were also exposed to thrombin. The addition of plasmin split products of a fibrin clot resulted in only minimal increase in the incorporation of GEE-14C (57 dpm/mg fibrinogen) at 37.5% concentration. The method was therefore sensitive to thrombin alterations of fibrinogen but insensitive to plasmin alterations of fibrinogen and fibrin.
C. Thomas Kisker, Ruth Rush
The process by which various anions, including bilirubin and several dyes, drugs, hormones and their metabolites, are transferred from plasma into the liver cell is poorly understood. Two hepatic cytoplasmic proteins, Y and Z, that bind various organic anions in vivo and in vitro have been postulated to be involved in this process.
Humberto Reyes, A. Jonathan Levi, Zenaida Gatmaitan, Irwin M. Arias
We have documented the presence of abnormal sodium transport in Liddle's syndrome by measuring sodium concentration, sodium influx, and fractional sodium outflux in vitro in erythrocytes from normal subjects, two patients with Liddle's syndrome, and one patient with primary hyperaldosteronism. Sodium influx and fractional sodium outflux, but not sodium concentration, were significantly increased in patients with Liddle's syndrome. Sodium outflux in a patient with primary hyperaldosteronism did not differ significantly from normal. These alterations of sodium transport in erythrocytes from patients with Liddle's syndrome were not attributable to circulating levels of aldosterone, renin, angiotensin, or serum potassium. Furthermore, changes in aldosterone secretory rate and levels of circulating renin produced by varying dietary sodium intake, did not alter sodium influx or fractional sodium outflux in either patients with Liddle's syndrome or normal subjects. The response of fractional sodium outflux and sodium influx to ouabain, ethacrynic acid, and to changes in the cation composition of the incubation medium suggests that the increased sodium fluxes in Liddle's syndrome do not result solely from a quantitative increase in those components of sodium transport which occur in normal human erythrocytes. Instead, at least a portion of the increased erythrocyte sodium transport in Liddle's syndrome represents a component of sodium transport which does not occur in normal human erythrocytes.
Jerry D. Gardner, Allen Lapey, Artemis P. Simopoulos, Emmanuel L. Bravo
A new method for the direct measurement in vivo of the synthetic rate of bilirubin from hepatic hemes is proposed. This method depends on the application of the labeled precursor-product relationship to the hepatic pool of porphobilinogen, which is a common precursor of both urinary porphobilinogen and hepatic-synthesized bilirubin. The hepatic pool of porphobilinogen is labeled by means of an intravenous injection of δ-aminolevulinic acid-4-14C. The proportion of total bilirubin production which is derived from hepatic hemes is calculated from the ratio of the mean 14C specific activities of stercobilin and porphobilinogen estimated in pooled specimens of feces and urine, respectively. The method can be most readily applied to patients with acute intermittent porphyria, as the appreciable quantities of prophobilinogen in the urine of these patients greatly facilitate the measurement of porphobilinogen-14C specific activity. In three patients with acute intermittent porphyria, values obtained for the synthetic rate of bilirubin from hepatic hemes were 20.7, 15.8, and 13.3% of total bilirubin production.
E. A. Jones, J. R. Bloomer, N. I. Berlin
A 30 cm segment of the duodenum, jejunum, or ileum of normal human volunteers was perfused, on separate occasions, with test solutions containing either glycylglycine, free glycine, glycylleucine, or equimolar amounts of free glycine and free leucine. Luminal fluid contained no hydrolytic activity against glycylglycine and minimal activity against glycylleucine. In each intestinal segment, amino acid absorption rates were significantly greater from the test solutions containing the same amount of amino acids in dipeptide than in free form(as high as 185% increase). Perfusion of each intestinal segment with a test solution containing the equimolar mixture of free glycine and free leucine always resulted in a greater leucine than glycine absorption rate. This preferential absorption of leucine, however, was either diminished (jejunum) or almost abolished (duodenum and ileum) when the glycylleucine solution instead of the equimolar mixture was presented to the intestinal mucosa. Among the three segments, the duodenum exhibited the least potential for the disappearance of dipeptides. The jejunal and ileal dipeptide disappearance rates were either similar for glycylleucine (94% vs. 92%) or slightly different for glycylglycine (92% vs. 79%). Despite lack of a remarkable difference in the disappearance rates, absorption rates of constituent amino acids were markedly greater in the jejunum than in the ileum. This reduced amino acid absorption was brought about by a greater accumulation of free amino acids in the lumen of the ileal segment (3 to 10-fold difference). Inhibition of free glycine absorption by leucine during the perfusion of the intestine with a test solution containing glycylglycine and leucine did not result in any greater concentration of free glycine in the lumen than when the glycylglycine test solution did not contain free leucine. Similarly, inhibition of free glycine and free leucine absorption by isoleucine was not accompanied by any remarkable alteration of absorption rates of the constituent amino acids of glycylleucine. The results of these studies suggest that: (a) dipeptide disappearance in the gut lumen is principally accomplished by intact absorption and not by hydrolysis; (b) intracellular hydrolysis of dipeptides is markedly greater in the ileum than in the jejunum, while dipeptide absorption rates are either similar or only slightly different in these two segments; (c) there is no appreciable hydrolysis of glycylglycine by the membrane-bound enzymes and only a small fraction of glycylleucine is hydrolyzed by these enzymes.
Siamak A. Adibi, Emile L. Morse
We report the effects of methylmalonic acid (MMA) on the mitochondrial transport systems for malate, α-oxoglutarate, and isocitrate. MMA is shown to be a substrate for all three carrier systems, and an inhibitor of the malate-phosphate exchange carrier. The effects of MMA on the metabolism of malate, oxoglutarate, and isocitrate by rat liver mitochondria are demonstrated to be mediated by the influence of MMA on the transport step. A hypothesis regarding the metabolic impairments responsible for hypoglycemia and ketonemia in methylmalonic aciduria is formulated in relation to these findings.
M. L. Halperin, C. M. Schiller, I. B. Fritz
A study was performed in five normal men in whom left ventricular volume was measured by thermodilution in the supine and 60° head-up postures, in the control state, and then during steady-state response to isoproterenol. The mean rate of circumferential shortening of the left ventricle was calculated for each of the postures in both inotropic states and was found to remain constant in the control state at 12.5 ±0.6 cm/sec in the supine posture and 13.3 ±0.5 cm/sec in the tilted posture. Similarly, mean rate of circumferential shortening remained constant in response to the positive inotropic effect of isoproterenol at 20.9 ±0.5 cm/sec in the supine position and 20.7 ±0.5 cm/sec in the tilted posture. It is concluded that the constancy of mean rate of circumferential shortening over the relatively broad physiologic range of left ventricular end-diastolic volume and mean force of ejection during a given state of myocardial contractility represents the coupled reciprocal influences of ventricular wall tension and myocardial fiber length on the velocity of ventricular wall shortening. Unlike stroke work, stroke power, and mean rate of left ventricular ejection, which are volume-dependent parameters of myocardial performance, the mean rate of circumferential shortening appears to be a reasonable index of left ventricular contractility, which in steady-state conditions is independent of left ventricular end-diastolic volume and mean ventricular wall force of ejection. In this study, changes in mean rate of circumferential shortening associated with changes of heart rate were small and variable.
H. W. Paley, Ian G. McDonald, Joseph Blumenthal, James Mailhot, Gunnard W. Modin
Patients with chronic uremia develop neurologic defects which are similar to the demyelinating lesions seen in thiamine deficiency. The present study describes inhibitory effects of uremic material on nervous tissue transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway which has been reported to have functional importance in the metabolism of myelinated nervous structures.
R. B. Sterzel, M. Semar, E. T. Lonergan, G. Treser, K. Lange
The mechanism of cholestasis (decreased bile flow) induced by taurolithocholate in the isolated perfused hamster liver was investigated. Taurocholate was infused to maintain bile acid output, and sulfobromophthalein (BSP) was administered to establish a BSP transport maximum in bile. The effects of taurolithocholate on bile flow and on the biliary secretion of BSP and bile acid anions were determined.
John E. King, Leslie J. Schoenfield
An adolescent male proband with hypersarcosinemia was discovered incidentally in a French-Canadian family; no specific disease was associated with the trait. The hypersarcosinemia is not diminished by dietary folic acid even in pharmacologic doses (30 mg/day). The normal absence of sarcosine dehydrogenase in cultured human skin fibroblasts and in leukocytes was confirmed, thus eliminating these tissues as useful sources for further investigation of mutant sarcosinemic phenotypes and genotypes.
Francis H. Glorieux, Charles R. Scriver, Edgard Delvin, Fazl Mohyuddin
The capacity of gastrocnemius and quadriceps muscles to oxidize palmitate, oleate, linoleate, palmityl CoA, and palmityl carnitine doubled in rats subjected to a program of treadmill running. The rate of palmitate oxdation by whole homogenates of, or the mitochondrial fraction from, leg muscles was twice as great per gram wet weight of muscle in the trained as in the sedentary animals over a wide range (0.125-1.5 mM) of palmitate concentrations.
P. A. Molé, L. B. Oscai, J. O. Holloszy
The Wiskott-Aldrich syndrome is an immune deficiency disorder with an impairment of both humoral and cellular immune responses. Metabolic turnover studies of IgG, IgA, IgM, and albumin were conducted in seven patients with the Wiskott-Aldrich syndrome using purified radioiodinated proteins. The survival of each of the proteins studied was significantly shortened with a half-time of 7.5 days for IgG (normal 22.9 ±4 SD), 3.0 days for IgA (normal 5.8 ±1), 5.0 days for IgM (normal 10.1 ±2.1), and 8.6 days for albumin (normal 17, range 13-20); the fractional catabolic rates were correspondingly elevated and the distribution of protein among the body compartments was normal. For three of the four proteins. IgG, IgA, and albumin, the steady-state synthetic rates were generally elevated leading to normal or even elevated serum proteins levels. Thus, in the case of IgA, the synthetic rate averaged five times normal while the fractional degradative rate was twice normal. The resulting serum concentration was, therefore, significantly elevated, IgM represented an exception to this pattern in that the increased rate of degradation was not counterbalanced by an increased synthetic rate and, therefore, the serum levels were low.
R. Michael Blaese, Warren Strober, Arthur L. Levy, Thomas A. Waldmann
The effect of clofibrate (CPIB) on hepatic glycerolipid formation has been studied in vivo and in vitro in the rat. Feeding 0.25% CPIB in laboratory chow significantly reduced serum triglyceride levels by 6 hr and concomitantly decreased the rate of glycerol-14C incorporation into hepatic and serum glycerides, in vivo. These changes persisted for at least 14 days. A similar decrease in serum triglyceride and glycerol incorporation into hepatic glycerides was observed in rats fed high glucose diets containing 0.25% CPIB. Serum glycerol was reduced by feeding CPIB for 14 days. The formation of diglyceride and triglyceride from 14C-sn-glycerol-3-P by rat liver homogenates was inhibited by addition of 1-40 mM CPIB to the reaction mixture. These results suggest that CPIB reduces hepatic glycerolipid synthesis, possibly by inhibition of one or more reactions in the esterification of sn-glycerol-3-P. This change may account for the early fall in serum triglyceride. At later time periods, serum glycerol levels fall and in some experiments, hepatic triglyceride content increases. Therefore, it is likely that additional metabolic alterations may contribute to the sustained hypotriglyceridemic effects of CPIB.
Larry L. Adams, William W. Webb, Harold J. Fallon
The renal handling of phosphorus was evaluated in rats with acute renal failure (ARF) induced by injection of mercuric chloride (HgCl2). Clearances of endogenous creatinine (Ccr) and of phosphorus (Cp) were measured in the following groups: 1. Intact animals (control); 2. Parathyroidectomized rats (PTX) with normal kidney function (PTX control); 3. Animals with mercury-induced acute renal failure (Hg-ARF); 4. PTX rats with Hg-ARF; 5. Rats with Hg-ARF maintained normophosphatemic with dietary phosphate restriction; 6. Animals with oliguric ARF following renal artery constriction; 7. Rats with unilateral Hg-ARF. In addition, radioinulin clearances were measured in 6 normal and in 14 azotemic animals and correlated with simultaneously recorded endogenous Ccr. Radioinulin clearance was also used as an estimate of GFR (glomerular filtration rate) in the animals of group 7.
Mordecai M. Popovtzer, Shaul G. Massry, Mario Villamil, Charles R. Kleeman
Studies were performed in rat small intestine in vivo to determine the effect of saline infusion on intestinal transport of Na+ and H2O. Saline infusion decreased net Na+ flux (JnNa) from 12.7 ±0.8 to 6.4 ±1.5 μEq/hr per cm in the jejunum when the intestinal perfusate contained both Na+ and glucose. A similar fall in JnNa occurred in ileum. When mannitol was substituted for glucose in the perfusate, control absorption decreased 29% in jejunum and 18% in ileum, but saline infusion still caused a decrease in JnNa quantitatively similar to that seen when glucose was present. When choline was substituted for Na+ in the perfusate, there was net movement of Na+ from blood to lumen during control and this net secretion was increased further after saline infusion. These observations suggest that saline infusion has a similar effect to decrease intestinal JnNa under three widely different conditions of basal sodium transport. Permeability of intestinal mucosa to inulin was very low under basal conditions but increased fivefold after saline infusion, and the unidirectional flux of Na+ from blood to lumen doubled. This increase in unidirectional flux of Na+ was greater than the observed decrease in JnNa.
Michael H. Humphreys, Laurence E. Earley
The distribution of peripheral blood lymphocytes that contain surface Ig has been studied by means of immunofluorescence in humans. Normal individuals, individuals with sex-linked and acquired agammaglobulinemia, selective IgA deficiency, cellular immune deficiencies, and individuals with chronic lymphatic leukemia (CLL) were studied. Approximately 28% of the peripheral blood lymphocytes from normal individuals contained surface Ig. On an average 15% contained IgG, 6%, IgA, and 8%, IgM; and the kappa: lambda ratio was 2:1. Lymphocytes from patients with CLL appeared to be “monoclonal” in that the cells from a given individual had a single Ig associated with them (e.g., kappa IgM). In three-quarters of the cases the H chain class was IgM; in the remaining one-quarter no H chain could be detected on the cell surface. The L chain class was kappa in 12 cases and lambda in 8. Four patients with sex-linked agammaglobulinemia and one with “acquired” agammaglobulinemia had markedly decreased numbers of cells with surface Ig (0-4%). In contrast, the three patients with selective IgA deficiency and no detectable serum IgA contained normal numbers of cells (6-8%) with surface IgA. Five patients with cellular deficiency states, including two with Wiskott-Aldrich syndrome, contained a normal or low percentage of cells with surface Ig.
Howard M. Grey, Enrique Rabellino, Bernard Pirofsky
The alpha-2 macroglobulins from human serum and plasma were isolated by Bio-Gel P-300 and A5m gel filtration. The material showed a single peak on sedimentation velocity ultracentrifugation, a mol wt of 650,000 by sedimentation equilibrium ultracentrifugation, and a major precipitin arc in the alpha-2 macroglobulin region by immunoelectrophoresis against whole human serum. Two bands were observed in the alpha-2 macroglobulin region when acrylamide gel electrophoresis was performed with a pH 8.9 running gel. When a pH 7.8 gel was used, five electrophoretic species were observed. In both cases, the preaddition of stoichiometric amounts of trypsin or chymotrypsin added to alpha-2 macroglobulin resulted in disappearance of slower bands leaving only one band on acrylamide gel electrophoresis patterns.
Russell Saunders, Barbara J. Dyce, Wilton E. Vannier, Bernard J. Haverback
Dose- and time-response studies were performed in iron-loaded and iron-deficient rats in order to define, (a) the kinetics of absorption of cobalt and iron, (b) the nature of the inhibitory effect of one metal on the absorption of the other, and (c) the effect of variations in body iron stores on these processes. The duodenum was perfused for 5-90 min with labeled solutions containing 5.0 mM iron or 5.0 mM cobalt. In iron-loaded rats, the rate of cobalt absorption was constant for 90 min whereas the rate of iron absorption fell after 30 min. In comparison to these results, the rate of absorption of both metals was increased in iron deficiency, and was more rapid in the first 30 min than in the 30-90 min period.
A. B. R. Thomson, L. S. Valberg, D. G. Sinclair
An unstable hemoglobin variant termed Hb Louisville, was found in four members of a Caucasian family, who were suffering from a mild hemolytic anemia. The variant showed a decreased stability upon warming at 65°C and an increased tendency to dissociate in the presence of sulfhydryl group-blocking agents. The structural abnormality was identified as a replacement of phenylalanyl residue in position 42 (CD1) by a leucyl residue. Substitution of this phenylalanyl residue, which participates in the contact with heme, by a nonpolar leucyl residue has apparently less severe consequences than a replacement of the same residue by a polar seryl residue as in Hb Hammersmith.
Marie M. Keeling, Lynn L. Ogden, Ruth N. Wrightstone, J. B. Wilson, Cecelia A. Reynolds, Janice L. Kitchens, T. H. J. Huisman
The lung volume at which the dependent lung zones begin to trap gas as a result of airway closure (i.e., the “closing volume”) was measured with 133Xe in 10 seated patients with hepatic cirrhosis. In all of them the closing volume was increased above normal, and in eight it was greater than the functional residual capacity, indicating the presence of airway closure and gas trapping during resting tidal volume breathing. Direct measurements made with 133Xe in five cirrhotic patients (a) confirmed the presence of increased gas trapping in the lower lung zones both at residual volume and at functional residual capacity, and (b) indicated that in liver cirrhosis the ventilation-perfusion ratio of the dependent lung zones may be very low, primarily as a result of decreased ventilation due to airway closure. It is concluded that in hepatic cirrhosis, gas trapping in the dependent lung zones may be an important cause of impaired gas exchange within the lungs. It is suggested that the premature airway closure observed in this disease may be due to mechanical compression of small airways by dilated blood vessels and/or interstitial pulmonary edema.
F. Ruff, J. M. B. Hughes, N. Stanley, D. McCarthy, R. Greene, A. Aronoff, L. Clayton, J. Milic-Emili
Extracellular fluid volume expansion with isotonic saline (7.5% of body weight) decreased maximum glucose reabsorption rate by rat kidneys at plasma glucose concentrations greater than 30 mM. Glucose reabsorption rate was 30.2 ±1.6 (SE) μmoles/min·g kidney in nonexpanded rats; it was 18.4 ±1.5 μmoles/min·g in volume-expanded rats. Glucose reabsorption determined by micropuncture was 92% complete at the end of accessible superficial proximal convolutions. Volume expansion resulted in a slight but statistically insignificant reduction of maximal glucose reabsorption rate in superficial nephrons from 786 ±35 μμmoles/min·g kidney in nonexpanded rats to 720 ±30 μμmoles/min·g in volume-expanded rats. Superficial nephron filtration rate was increased by volume expansion from 28.8 ±1.2 nl/min·g to 36.6 ±1.5 nl/min·g kidney. In nonexpanded rats, the ratio of glucose reabsorption to glomerular filtration (tmg/sgfr) was similar in superficial and juxtamedullary nephrons. In volume-expanded rats superficial nephron tmg/sgfr was greater than juxtamedullary nephron tmg/sgfr. Juxtamedullary nephron function was measured by puncturing loops of Henle in the exposed papillae of small rats.
Andrew D. Baines, John H. V. Bishop
The effects of diseases of the liver, the thyroid, and the kidneys on the retinol-binding protein (RBP)-prealbumin (PA) system responsible for the transport of vitamin A in plasma were examined, using a radial gel diffusion immunoassay for PA and the previously described radioimmunoassay for RBP. Measurements were made on plasma samples from 118 normal subjects, 31 patients with cirrhosis, 5 with chronic active hepatitis, 27 with acute viral hepatitis, 14 patients with hyperthyroidism, 7 with hypothyroidism, and 26 patients with chronic renal disease of varying etiologies. In the patients with liver disease, the levels of vitamin A, RBP, and PA were all markedly decreased and were highly significantly correlated over a wide range of concentrations. Serial samples were available in 19 patients with acute hepatitis; as the disease improved the plasma concentrations of vitamin A, RBP, and PA all increased. In patients with acute hepatitis RBP concentrations correlated negatively with the levels of plasma bilirubin, glutamic-oxaloacetic transaminase, and alkaline phosphatase. In the hyperthyroid patients both RBP and PA concentrations were significantly lower than normal; in hypothyroidism, neither protein showed levels significantly different from normal. In both hyper- and hypothyroidism and in liver disease, the molar ratios of RBP:PA and of RBP:vitamin A were not significantly different from normal.
Frank Rees Smith, DeWitt S. Goodman
The present study was carried out to determine if antidiuretic hormone (ADH) altered the solute handling characteristics of the peritoneal membrane. Lightly anesthetized dogs primed with urea-14C (60 mol wt) and inulin (5200 mol wt) were volume expanded with hypotonic saline solution to suppress endogenous ADH as assessed by urine/plasma osmolality. With ADH suppressed, two to three control peritoneal dialysis exchanges were carried out. A constant infusion of ADH in a physiologic dose of 150 mU/hr in saline was begun and the urine/plasma osmolality followed until it was significantly greater than one. Two to three experimental dialysis exchanges were then carried out. Dialysance across the peritoneal membrane was calculated for inulin (DI) and urea (DU). In 16 such studies DU fell in all but three (the mean value for the fall was 2.8 ±2.6 ml/min; P < 0.001). DI varied randomly and showed no significant change. In all 16 studies DI/DU rose (DI/DU = 0.054 ± 0.054; P < 0.005). Seven dogs were studied with an identical protocol but saline was infused without ADH. DU and the dialysance ratio varied randomly. DU fell in one and did not change or rose in four and DI/DU rose in two and fell in three. The data are interpreted to show a fall in area but an increase in mean pore radius of the “peritoneal membrane” in response to physiologic amounts of intravenous ADH. The fall in area is consistent with a decreasing splanchnic blood flow.
Lee W. Henderson, James E. Kintzel
The reabsorption of water and solute by the papillary collecting duct was studied during water diuresis and vasopressin-induced antidiuresis in young rats with hereditary hypothalamic diabetes insipidus. The tip of the left renal papilla was exposed and fluid was obtained by micropuncture from loops of Henle and from collecting ducts at the papillary tip, and at an average of 1 mm proximal to the tip. In water diuresis the ratio of tubule fluid to plasma (TF/P) osmolality (osm) of loop fluid was 1.73 ±0.058 (SE); of fluid from the proximal collecting duct, 0.63 ±0.027; and from the tip, 0.55 ±0.024; indicating a substantial osmotic pressure difference across the collecting duct epithelium. The fraction of filtered water reabsorbed (× 100) by the terminal collecting duct was 1.58% ±0.32. In antidiuresis the TF/P osm of loop fluid was 2.65 ±0.109; of fluid from the proximal collecting duct, 2.20 ±0.093; and from the tip, 2.71 ±0.111; indicating a marked decrease in the driving force for water reabsorption. The fraction of filtered water reabsorbed (× 100) by the terminal collecting duct was reduced to 0.58% ±0.08, while the delivery of solute to the same segment was unchanged from that in water diuresis. The glomerular filtration rate (GFR) of the right kidney declined from 327 ±24.4 μl/min in water diuresis to 274 ±24.4 μl/min in antidiuresis (P < 0.005); similar results were obtained in a study comparing right and left GFRs in five additional rats. Thus, fractional reabsorption (and very likely the absolute volume) of water reabsorbed by the terminal collecting duct was less in antidiuresis than in water diuresis (mean difference, 1.01% ±0.29, P < 0.005).
Rex L. Jamison, John Buerkert, Frank Lacy, Dan Marcus, Betty Henton
An epinephrine infusion of 6 μg/min decreased the rapid insulin response to a 5 g glucose pulse by 96% (P < 0.001) compared with the preinfusion control. In contrast when an identical epinephrine infusion was superimposed on a prolonged glucose infusion, elevated steady-state insulin levels did not decrease, but increased from 26.9 ±6 (mean ±SD, μU/ml) to 56.8 ±15 μU/ml (P < 0.05) in parallel with the epinephrine-induced hyperglycemia. Thus epinephrine inhibition of insulin secretion was observed during acute but not chronic glucose stimulation. To evaluate further the insulin responses during a prolonged glucose infusion, a 5 g glucose pulse was given before and 60 min later during a concomitant epinephrine infusion. Although the acute insulin response to the first glucose pulse was observed during the elevated steady-state glucose and insulin levels associated with the glucose infusion, epinephrine again inhibited the acute insulin response to the subsequent 5 g glucose pulse by 91% (P < 0.01). Thus epinephrine appears to inhibit selectively the rapid insulin response to glucose but not to influence insulin output stimulated by prolonged hyperglycemia. These observations provide further evidence for a model of insulin secretion which includes a small storage pool available for immediate release to a glucose challenge and a more slowly responding pool regulating insulin secretion in the basal and steady state.
Roger L. Lerner, Daniel Porte Jr.
Human hemoglobin messenger RNA was isolated by sucrose gradient centrifugation from reticulocytes of patients having various hemolytic anemias. Using a messenger RNA-dependent cell-free system derived entirely from rabbit reticulocytes, the human hemoglobin messenger RNA has been translated and the products analyzed by carboxymethylcellulose column chromatography. Normal messenger RNA directs synthesis of normal human α- and β-globin chains in nearly equal amounts. Sickle cell anemia messenger RNA directs the synthesis of normal α- and sickle β-chains, β-thalassemia messenger RNA directs the synthesis of normal α- and β-chains, but the amount of β-globin synthesized is markedly reduced. Thus the inability of the thalassemia reticulocyte to produce β-globin is clearly attributable to the β-globin messenger RNA.
Arthur W. Nienhuis, W. French Anderson