ERRATA

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ERRATA

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Abstract

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Studies on the absorption and metabolism of folic acid: I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths

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Folic acid absorption was studied in anesthetized dogs by determining the amount and chemical nature of folate in venous blood emerging from isolated intestinal segments containing free folic acid and/or pteroylpolyglutamates of a known chain length. Chromatographically pure test materials placed in the lumen were prepared by unambiguous solid phase synthetic methods. This synthetic procedure not only yields compounds of known structure, it also provides a means by which glutamic acid residues at any given position in the gamma glutamyl chain can be made radioactive. For example, teropterin (pteroyltriglutamate) was synthesized in such a way that 14C was present only in the middle glutamic acid unit. Suitable placement of label permitted assessment of the extent of peptide cleavage. The action of plasma conjugase was inhibited by copper chloride. Plasma samples were analyzed by Lactobacillus casei and Streptococcus faecalis assay, by column chromatography, and by quantitative measurement of pteridine-bound radioactivity.

Authors

C. M. Baugh, C. L. Krumdieck, H. J. Baker, C. E. Butterworth Jr.

Relationship between plasma sodium concentration and vascular reactivity in man

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Experiments were done to study the effects of acute changes in plasma sodium concentration [Na] on vasoconstrictor responses to norepinephrine and to reflex sympathetic stimulation in man. [Na] in the venous return from the forearm of each of 21 normal subjects was reduced (to an average of 118 mEq/liter), increased (147 mEq/liter), and maintained within the normal range (140 mEq/liter) by means of infusions into the brachial artery of three solutions containing different [Na]. Mannitol or sucrose and disodium sulfate were substituted for sodium chloride to produce the desired changes in [Na] without changing blood osmolarity.

Authors

Donald D. Heistad, Francois M. Abboud, Dennis R. Ballard

Radioimmunassay for measurement of triiodothyronine in human serum

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A convenient, specific, precise, and reproducible radioimmunoassay system for measurement of triiodothyronine (T3) in human serum has been developed. The procedure compares the ability of standards and unknowns to compete with radioactive T3 for binding sites on a T3-binding antiserum produced in rabbits by immunization with human thyroglobulin. The assay is set up in the presence of 250 ng thyroxine (T4) in all tubes, to mobilize T3 from its binding with the thyronine-binding globulin (TBG), and athyreotic sheep serum in standards to correct for the TBG in the unknowns. The method regularly detected 0.4 ng T3, which would correspond to a T3 concentration of 100 ng/100 ml when 400 μl of serum is analyzed. The mean recovery of unlabeled T3 added to normal serum pools was 106%. Serial dilution of hyperthyroid sera containing high concentrations of T3 with athyreotic sheep serum yielded expected values.

Authors

Inder J. Chopra, David H. Solomon, Gildon N. Beall

Inducible heme oxygenase in the kidney: a model for the homeostatic control of hemoglobin catabolism

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We have recently identified and characterized NADPH-dependent microsomal heme oxygenase as the major enzymatic mechanism for the conversion of hemoglobin-heme to bilirubin-IXα in vivo. Enzyme activity is highest in tissues normally involved in red cell breakdown, that is, spleen, liver, and bone marrow, but it usually is negligible in the kidney. However, renal heme oxygenase activity may be transiently increased 30- to 100-fold following hemoglobinemia that exceeded the plasma haptoglobin-binding capacity and consequently resulted in hemoglobinuria. Maximal stimulation of enzyme activity in rats is reached 6-16 hr following a single intravenous injection of 30 mg of hemoglobin per 100 g body weight; activity returns to basal levels after about 48 hr. At peak level, total enzyme activity in the kidneys exceeds that of the spleen or liver. Cyclohexamide, puromycin, or actinomycin D, given just before, or within a few hours after, a single intravenous injection of hemoglobin minimizes or prevents the rise in renal enzyme activity; this suggests that the increase in enzyme activity is dependent on continued synthesis of ribonucleic acid and protein. The apparent biological half-life of renal heme oxygenase is about 6 hr. These observations indicate that functional adaptation of renal heme oxygenase activity reflects enzyme induction either directly or indirectly by the substrate, hemoglobin.

Authors

Neville R. Pimstone, Peter Engel, Raimo Tenhunen, Paul T. Seitz, Harvey S. Marver, Rudi Schmid

The formation and metabolism of 3α,7α-dihydroxy-5β-cholestan-26-oic acid in man

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The formation and metabolism of a naturally occurring C27 bile acid, 3α,7α-dihydroxy-5β-cholestan-26-oic acid, was studied in patients with T-tube bile fistulas. C-26-cholesterol-14C was shown to be converted to this C27 bile acid. After synthesis and labeling with tritium, 3α,7α-dihydroxy-5β-cholestan-26-oic acid was efficiently metabolized to chenodeoxycholic acid. After oral and i.v. administration there was conversion of about 80% of the administered amount to chenodeoxycholic acid. A small amount, less than 2% of the administered radioactivity, was converted to cholic acid. The remainder of the radioactivity was excreted in two unidentified peaks of radioactivity.

Authors

Russell F. Hanson

Studies on purified rheumatoid synovial collagenase in vitro and in vivo

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Rheumatoid synovial collagenase obtained from culture medium can be separated by Sephadex gel filtration into two peaks of enzyme activity. These have been designated as fast-moving and slow-moving rheumatoid synovial collagenases on the basis of their electrophoretic mobility on polyacrylamide gels. The slow-moving rheumatoid synovial collagenase has been highly purified by affinity chromatography on collagen conjugated to Sepharose and used to prepare a monospecific anti-synovial collagenase antiserum.

Authors

Eugene A. Bauer, Arthur Z. Eisen, John J. Jeffrey

Synthesis and transport of lipoprotein particles by intestinal absorptive cells in man

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The site of synthesis and some new details of lipoprotein particle transport have been demonstrated within the jejunal mucosa of man. In normal fasting volunteers, lipoprotein particles (88%, 150-650 A diameter) were visualized within the smooth endoplasmic reticulum and Golgi cisternae of absorptive cells covering the tips of jejunal villi. Electron microscopic observations suggested that these particles exited through the sides and bases of absorptive cells by reverse pinocytosis and then passed through the extracellular matrix of the lamina propria to enter lacteal lumina.

Authors

Guido N. Tytgat, Cyrus E. Rubin, David R. Saunders

Immunologic differentiation of primary hyperparathyroidism from hyperparathyroidism due to nonparathyroid cancer

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Serum immunoreactive parathyroid hormone (IPTH) was measured by radioimmunoassay in 54 patients with primary hyperparathyroidism and in 18 consecutive patients with ectopic hyperparathyroidism due to nonparathyroid cancer without apparent skeletal metastasis. Although serum calcium concentration was higher in the group with ectopic hyperparathyroidism, serum IPTH was lower (rank sum test, P < 0.001) and was undetectable in eight. A second anti-PTH antiserum also differentiated between IPTH in the two groups, although IPTH was undetectable in only 1 of 14 sera. When IPTH values in serial dilutions were plotted, slopes for the two patients with ectopic hyperparathyroidism who had relatively high IPTH were less (P < 0.001) than slopes for standard hyperparathyroid sera. By using differences in either IPTH rank or slope of the dilutional curve of sera, primary hyperparathyroidism could be excluded as a cause of the hypercalcemia in 16 of the 18 patients with ectopic hyperparathyroidism. The data are interpreted as indicating that PTH-like material in the serum of these patients with ectopic hyperparathyroidism is immunologically different from the PTH in the serum of patients with primary hyperparathyroidism.

Authors

B. Lawrence Riggs, Claude D. Arnaud, James C. Reynolds, Lynwood H. Smith

Separation of Plasma Thromboplastin Antecedent from Kallikrein by the Plasma α₂-Macroglobulin, Kallikrein Inhibitor

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Plasma thromboplastin antecedent (PTA, factor XI) is an important intermediate in the intrinsic coagulation system, and plasma kallikrein has been implicated as a mediator of the inflammatory process. Whereas their biologic activities are functionally distinct, their identity as separate entities in plasma has not been fully established, and the nature of their plasma inhibitors has not been completely characterized. A partially purified preparation containing the clotting, tosyl arginine methyl ester (TAMe) esterase and kinin-producing activities of these substances has been prepared by DEAE-cellulose chromatography of a Celite eluate obtained from acid-treated human plasma. These activities were not separable by acrylamide gel electrophoresis nor by isoelectric focusing, their pI being approximately 8.7. Human plasma α2-macroglobulin has been shown to inhibit the proteolytic activity of kallikrein and to inhibit partially its TAMe esterase activity. An α2-macroglobulin, PTA, kallikrein incubation mixture was separated by gel filtration chromatography. The α2-macroglobulin formed a high molecular weight complex with kallikrein and appeared in early chromatographic fractions. The PTA-clotting activity was not inhibited by the α2-macroglobulin; 64% of the initial PTA activity was isolated in later fractions free of kallikrein-induced kinin-like activity. In contrast, clotting, TAMe esterase, and kinin-forming activities were inhibited after gel filtration chromatography of an incubation mixture of these activities and partially purified C1̄ inactivator (C1 esterase inhibitor). Electrofocusing of an incubation mixture of an activated PTA, kallikrein preparation, and α2-macroglobulin resulted in the isolation of a PTA fraction free of kallikrein proteolytic activity, and with 4% of the original TAMe esterase activity. In this manner, activated PTA and plasma kallikrein have been shown to be distinct substances, and methods have been introduced for the further purification of active coagulation factor XI.

Authors

Peter C. Harpel

Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita

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In isolated fiber bundles of external intercostal muscle from each of 13 normal volunteers and each of 6 patients with myotonia congenita, some or all of the following were measured: concentrations of Na+, K+, and Cl-, extracellular volume, water content, K+ efflux, fiber size, fiber cable parameters, and fiber resting potentials.

Authors

R. J. Lipicky, S. H. Bryant, J. H. Salmon

Metabolic alterations in the human erythrocyte produced by increases in glucose concentration: The role of the polyol pathway

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Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [14C]O2 production from glucose-1-14C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide—adenine dinucleotide phosphate/reduced form of nicotinamide—adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism.

Authors

Susan F. Travis, Anthony D. Morrison, Rex S. Clements Jr., Albert I. Winegrad, Frank A. Oski

Proinsulin-like component of circulating insulin in the basal state and in patients and hamsters with islet cell tumors

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The proinsulin-like component comprised approximately 20% of total circulating basal immunoreactive insulin in 15 patients without islet cell tumors. 15 min after oral glucose, the concentration of the proinsulin-like component was unchanged and its percentage of the total immunoreactive insulin decreased with the acute release of the insulin component. By 2 hr after oral glucose, the concentration of the proinsulin-like component increased and the insulin component concentration decreased so that the percentage of the proinsulin-like component was essentially the same as in the basal state.

Authors

Phillip Gorden, Barry Sherman, Jesse Roth

Secretion of glucagon from the isolated, perfused canine pancreas

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Using the isolated, perfused canine pancreas preparation, previously described, the interrelationship of the secretion of pancreatic glucagon and insulin was studied after stimulation with glucose, gastrointestinal hormones, and the amino acid arginine.

Authors

Johan Iversen

Serum alkaline phosphatase in hypophosphatasia

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It is recognized that serum alkaline phosphatase may reflect enzyme contributions from bone, liver, and intestine. We have investigated serum alkaline phosphatases in two siblings with hypophosphatasia. After administration of long-chain triglycerides, the major alkaline phosphatase component of their sera was shown to be of intestinal origin on the basis of inhibition by l-phenylalanine. Starch block electrophoresis suggested that there were other regions of l-phenylalanine-sensitive alkaline phosphatase in addition to the major slow-moving intestinal band. Medium-chain triglycerides which are absorbed by the portal route did not cause a similar augmentation of intestinal alkaline phosphatase activity. These studies indicate that serum levels of intestinal alkaline phosphatase are increased normally after long-chain fat feeding in hypophosphatasia and may be the major component of total serum alkaline phosphatase activity.

Authors

Joseph B. Warshaw, John W. Littlefield, William H. Fishman, Norma R. Inglis, Leo L. Stolbach

Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema

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Normal human serum contains 18 ±5 mg/100 ml of C1 esterase inhibitor (alpha-2 neuraminoglycoprotein) as estimated by immunochemical means. Of 118 patients with hereditary angioneurotic edema, the sera of 80, from 42 kindred, contained a mean concentration of 3.15 mg/100 ml or 17.5% of normal. The mean serum concentration in 35 patients in 7 other kindred was 20 mg/100 ml or 111% of normal, and 3 patients in another kindred contained over 80 mg/100 ml or greater than 400% of normal. The nonfunctional inhibitors in patients' sera of these eight kindred were identical with normal C1 esterase inhibitor by Ouchterlony analysis, but they were different from normal and from each other with respect to their electrophoretic mobility, their capacity to bind C1 esterase, and their ability to inhibit esterolysis of N-acetyl-tyrosine-ethylester.

Authors

Fred S. Rosen, Chester A. Alper, Jack Pensky, Martin R. Klemperer, Virginia H. Donaldson

Proximal tubular function in dogs with thoracic caval constriction

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The effect of saline infusion on proximal sodium reabsorption was compared in normal dogs and in dogs with acute or chronic partial thoracic vena cava obstruction. After acute vena cava obstruction, proximal fractional sodium reabsorption rose by 74%. During continued caval obstruction, saline loading strikingly reduced proximal reabsorption but sodium excretion remained minimal. In chronic caval dogs, saline loading reduced proximal fractional sodium reabsorption by 31% but sodium excretion in the micropunctured kidney was only 41 μEq/min. After saline infusion in normal dogs, proximal fractional sodium reabsorption fell 39% while unilateral sodium excretion rose to 584 μEq/min.

Authors

R. Brewer Auld, Edward A. Alexander, Norman G. Levinsky

The turnover and transport of vitamin D and of a polar metabolite with the properties of 25-hydroxycholecalciferol in human plasma

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Four normal men were injected intravenously with physiological doses (6 μg) of vitamin D3-1,2-3H. Serial samples of plasma were collected for 50 days. Total lipid extracts were chromatographed on silicic acid columns or thin-layer plates in order to characterize the radioactive components. Labeled vitamin D3 disappeared rapidly from plasma (initial half-life approximately 12 hr); after 7 days unchanged vitamin D3 represented less than 1% of circulating radioactivity. Coincident with vitamin D3 disappearance a more polar labeled metabolite appeared with chromatographic and other properties identical with those of 25-hydroxycholecalciferol. The disappearance of the more polar metabolite was relatively slow with a half-life of 19.6 ±0.6 days. A similar half-life was seen in a fifth subject, injected with 80 μg of vitamin D3-3H. Most (approximately 92%) of the plasma total radioactivity was represented by this component throughout the study. Plasma samples collected at various times were adjusted to density (d) 1.21 and were ultracentrifuged to separate plasma lipoproteins from proteins with d > 1.21. In all samples, almost all (mean 94%) of the radioactivity was found in association with proteins of d > 1.21. This observation was confirmed by bioassay, measuring uptake of 45Ca by intestinal slices. All plasma bioassayable vitamin D was found in association with proteins of d > 1.21; 55% of bioactivity was found in the chromatographic fraction corresponding to 25-hydroxycholecalciferol and 44% in the fractions representing vitamin D3. Since both vitamin D3 and its 25-hydroxy metabolite are lipid-soluble sterol derivatives, the finding that these compounds do not circulate in association with the known plasma lipoproteins provides presumptive evidence for the existence of a specific transport protein of d > 1.21. The transport protein for the polar metabolite has been partly characterized by gel filtration on Sephadex G-200 and by electrophoresis on polyacrylamide gel. The protein has an apparent size slightly smaller than plasma albumin (approximate mol wt 50,000-60,000) and an electrophoretic mobility very slightly greater than that of albumin. Studies are in progress to fractionate further and to characterize the transport protein.

Authors

John Edgar Smith, DeWitt S. Goodman

Inhibition of collagen-induced platelet aggregation by normal plasma

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Normal plasma has been found to inhibit the platelet aggregation-inducing effect of collagen in a time consuming reaction independent of temperature. Collagen treated with serum and washed has reduced reactivity which can be restored to normal by treatment with 1.5 M sodium chloride. On the basis of this result, it is suggested that inhibition results from adsorption to collagen of a plasma component. The inhibitory plasma component is destroyed at 56°C, is unstable below pH 7, and migrates with the alpha globulins on starch block electrophoresis at pH 8.6. On the basis of ultrafiltration and sucrose density gradient ultracentrifugation studies, a molecular weight in the range of 330,000 is suggested and there may be an additional component of considerably greater size. Partial purification can be achieved by ion exchange chromatography. The purified fraction was completely inactivated by incubation with trypsin. Partially purified fractions inhibit cationic platelet aggregators such as collagen, polylysine, and hexadimethrine but do not affect anionic aggregators such as succinylated collagen and sodium stearate. Normal plasma and serum inhibit succinylated collagen and stearate. Stearate is inhibited by crystalline albumin and Cohn fraction IV-4. It is suggested that plasma proteins may regulate platelet adhesion to collagen and other vessel wall materials.

Authors

H. L. Nossel, G. D. Wilner, M. Drillings

Performance of the right ventricle under stress: relation to right coronary flow

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Right ventricular performance was studied relative to right coronary artery flow in the chloralose-anesthetized, open chest dog. The right coronary artery was cannulated for measurement and control of flow and pressure. Under control conditions, right coronary artery occlusion caused no change in cardiac output, or right and left ventricular pressures, although right ventricular contractile force fell markedly. With right coronary artery flow intact, incremental pulmonary artery obstruction caused a corresponding decline in cardiac output and elevation of right ventricular end-diastolic pressure with eventual total right ventricular failure and systemic shock. With right coronary artery occlusion, identical degrees of pulmonary artery obstruction resulted in more pronounced changes in cardiac output and right ventricular end-diastolic pressure with right ventricular failure occurring at a much lower level of right ventricular stress.

Authors

Harold Brooks, Edward S. Kirk, Pantel S. Vokonas, Charles W. Urschel, Edmund H. Sonnenblick

A decreased metabolic clearance rate of aldosterone in benign essential hypertension

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Aldosterone secretion rate, metabolic clearance rate, and/or plasma concentration were determined in 16 patients with benign, uncomplicated essential hypertension and compared with those of control subjects. The mean metabolic clearance rate of aldosterone in 10 patients was significantly (P < 0.001) lower (mean 867 liters of plasma/day per m2 ±270 SD) than in a group of 7 healthy subjects (mean 1480 liters/day per m2 ±265 SD). Secretion rates in 13 patients (including the 10 already mentioned) tended to be low (83 ±43 vs. 109 ±54 μg/day) and plasma concentrations tended to be high (13.6 ±4.6 vs. 7.5 ±4.8 ng/100 ml), but neither of these differences was statistically significant.

Authors

W. Nowaczynski, O. Kuchel, J. Genest

The relative contributions of reabsorptive rate and redistributed nephron filtration rate to changes in proximal tubular fractional reabsorption during acute saline infusion and aortic constriction in the rat

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The absolute rate of reabsorption by superficial rat proximal tubules was measured by the in situ microperfusion technique under conditions of hydropenia, infusion of saline, and infusion of saline plus aortic constriction sufficient to decrease whole kidney filtration rate below hydropenic levels. Fractional reabsorption was measured in adjacent filtering nephrons by collecting and recollecting tubular fluid from late proximal convolutions during each experimental condition. During hydropenia, the absolute rate of proximal tubular reabsorption averaged 3.56 ±0.60 nl/min per mm and late proximal tubular fractional reabsorption averaged 0.56 ±0.10. From these two measurements and measurements of tubule length to the site of micropuncture, a value for filtration rate was calculated for filtering nephrons. During hydropenia this value averaged 32.9 ±7.1 nl/min. Saline infusion increased sodium excretion to 5.5% of the filtered load as the absolute rate of proximal tubular reabsorption decreased 38% and fractional reabsorption decreased 45%. Calculated superficial nephron filtration rate increased 21% which on the average was identical with the simultaneously measured increase in whole kidney filtration rate. Similar results were obtained in a separate group of animals by the technique of total collection of late proximal tubular fluid. Aortic constriction during saline infusion decreased whole kidney and calculated nephron filtration rate to the same degree and to values lower than those during hydropenia. Fractional reabsorption increased but not to hydropenic values. The persistent natriuresis during aortic constriction was associated with a continued depression of the absolute rate of proximal tubular reabsorption which was sufficient to maintain an increased delivery of filtrate out of the proximal tubule despite the fall in nephron filtration rate. These results indicate that depressed fractional reabsorption in the proximal tubule during acute saline infusion is due predominantly to a decrease in absolute reabsorptive rate and to a lesser extent to an increase in superficial nephron filtration rate which is proportional to the increase in whole kidney filtration. Continued natriuresis when filtration rate is decreased during saline infusion can be accounted for entirely by the persistent large reduction in the absolute rate of proximal tubular reabsorption.

Authors

Ettore Bartoli, Laurence E. Earley

Synchronization and recruitment in acute leukemia

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The in vivo effects of several chemotherapeutic agents on the mitotic cycle of leukemic blasts in the bone marrow were evaluated by serial measurements of cells in mitosis and in deoxyribonucleic acid (DNA) synthesis as indicated by ability to incorporate tritiated thymidine or tritiated deoxyuridine. 28 studies were done in 23 children and 1 adult. The changes in the marrow after a single injection of L-asparaginase, hydrocortisone, cyclophosphamide, cytosine arabinoside, methotrexate, and an exchange transfusion (62% of the total blood volume) were evaluated. L-asparaginase and hydrocortisone were found to arrest the entry of cells into the S period. Cyclophosphamide appeared to inhibit DNA synthesis, arrest cells in mitosis, and inhibit the entry of cells into the S period. Cytosine arabinoside, and methotrexate inhibited DNA synthesis. During the period of time the cells were inhibited in the S phase by these two drugs, cells continued to enter the S period. Thus partial synchronization was achieved after these two drugs. An exchange transfusion had no consistent effect on the mitotic cycle, but partial synchronization in the S period was seen in one patient.

Authors

Beatrice C. Lampkin, Takeshi Nagao, Alvin M. Mauer

The effect of alanine on glucagon secretion

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If glucagon plays a hormonal role in the regulation of gluconeogenesis from endogenous amino acids, its secretion might be stimulated by an increase in the concentration of alanine, which has recently been identified as a principal gluconeogenic precursor. To determine if this is the case, 0.75 mmole of alanine per kilo was infused into conscious dogs immediately after a priming injection of 0.25 mmole per kg for 15 min. A uniform rise in the plasma level of pancreatic glucagon, as determined by a relatively specific radioimmunoassay for pancreatic glucagon, was observed. The rise, which averaged 90 pg per ml, was highly significant at 7½ and 15 min after the start of the infusion. Insulin rose an average of only 8 μU per ml, while glucose rose an average of 10 mg per 100 ml. A lower dose of alanine, 1 mmole per kg, infused over a 1 hr period without an initial priming injection, also elicited a significant rise in glucagon measured in the pancreaticoduodenal venous plasma; glucagon rose from 350 pg per ml to 1066 pg per ml at the end of the infusion. The insulin response was modest and inconsistent, and glucose, again, rose 10 mg per 100 ml.

Authors

Walter A. Müller, Gerald R. Faloona, Roger H. Unger

Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone: An approach to distinguishing hypothalamic from pituitary forms of idiopathic hypopituitary dwarfism

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To test the hypothesis that the primary defect in some patients with idiopathic hypopituitary dwarfism is failure to secrete hypothalamic hypophysiotropic-releasing factors, synthetic thyrotropin-releasing factor (TRF), 500 μg, wa given intravenously, and timed venous samples obtained for determination of the concentration of plasma TSH by radioimmunoassay in three groups of subjects: (a) 11 patients without evidence of endocrine or systemic disease, (group I) (b) 8 with isolated growth hormone deficiency and normal thyroid function, (group II) and (c) 9 patients with idiopathic hypopituitary dwarfism and thyroid-stimulating hormone (TSH) deficiency (group III). The mean fasting plasma TSH value was 4.1 μU/ml in group I, and 3.9 μU/ml in group II; in both groups there was a brisk rise in plasma TSH to peak levels of 12-45 μU/ml at 30-45 min, and a fall toward base line levels at 120 min. All children in group III had basal TSH levels of < 1.5 μU/ml; one failed to respond to TRF; eight exhibited a rise in plasma TSH with peak values comparable with those in groups I and II. In four of eight children in group III who responded to TRF, the TSH response was delayed and the initial rise in plasma TSH was not detectable until 10-60 min. In these four patients, plasma TSH levels continued to rise at 120 min.

Authors

Bruce H. Costom, Melvin M. Grumbach, Selna L. Kaplan

Hydrogen peroxide utilization in myeloperoxidase-deficient leukocytes: a possible microbicidal control mechanism

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Phagocytosis-induced formate and glucose C-1 oxidation by the polymorphonuclear leukocytes of a patient with hereditary myeloperoxidase deficiency was considerably greater than normal. The addition of catalase to the leukocyte suspension was required for optimum formate oxidation. Azide and cyanide increased glucose C-1 oxidation by normal leukocytes but had little or no effect on myeloperoxidase-deficient leukocytes suggesting that these agents normally stimulate glucose C-1 oxidation, in part, by inhibition of myeloperoxidase. It is suggested that the inhibition or absence of myeloperoxidase results in an increased utilization of H2O2 in nonmyeloperoxidase-mediated H2O2-dependent reactions such as formate oxidation and hexose monophosphate pathway activation. The possibility of a microbicidal control mechanism in which a decrease in the microbicidal activity of myeloperoxidase is offset, in part, by an increase in the nonenzymatic microbicidal activity of H2O2 is considered.

Authors

Seymour J. Klebanoff, Stephanie H. Pincus

Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline

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Free-flow and stop-flow intratubular pressures were measured in rats with an improved Gertz technique using Landis micropipets or a Kulite microtransducer. In hydropenia, average single nephron glomerular filtration rate was 29.3 nl/min, glomerular hydrostatic pressure (stop-flow pressure + plasma colloid osmotic pressure) was 70 cm H2O and mean glomerular effective filtration pressure was 12.7-14.3 cm H2O, approaching zero at the efferent end of the glomerulus. Thus, the glomerulus is extremely permeable, having a filtration coefficient four to five times greater than previously estimated. Mean effective filtration pressure and single nephron glomerular filtartion rate fell with elevated ureteral pressure and rose with volume expansion, more or less proportionately. Changes in effective filtration pressure were due primarily to increased intratubular pressure in ureteral obstruction and to reduced plasma colloid osmotic pressure in volume expansion; glomerular hydrostatic pressure remained constant in both conditions and thus played no role in regulation of filtration rate.

Authors

Vittorio E. Andreucci, Jaime Herrera-Acosta, Floyd C. Rector Jr., Donald W. Seldin