Serum cholesterol esterifying and cholesteryl ester hydrolyzing activities in liver diseases: relationships to cholesterol, bilirubin, and bile salt concentrations

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Abstract

Patients with acute hepatitis and chronic alcoholic liver disease had decreased net serum cholesterol esterifying activity (CEA) which correlated positively with the percentages and concentrations of cholesteryl esters in their serum. These cholesterol parameters also correlated negatively with serum bilirubin concentrations, but bilirubin added to sera in vitro failed to influence CEA. The decreased net CEA in the patients was not due to its inhibition by serum bile salts. The sera from five patients catalyzed a net hydrolysis of cholesteryl esters rather than a net esterification of free cholesterol. Since serum cholesteryl ester hydrolase activity may also have been present in the patients with decreased CEA, net CEA cannot be equated with the activity of lecithin-cholesterol acyl transferase (LCAT) in patients with liver disease. The relative contributions of LCAT and cholesteryl ester hydrolase activities to CEA in disease states remain to be evaluated by mutually independent assays. Nevertheless, the correlations found between net CEA and the concentrations and percentages of cholesteryl esters support the concepts that serum cholesterol esterifying activity is physiologically important in the formation of serum cholesteryl esters and that decreased CEA is one mechanism for the decreased level of cholesteryl esters seen in patients with liver diseases.

Authors

Don P. Jones, Freddy R. Sosa, Jack Shartsis, Praful T. Shah, Eileen Skromak, William T. Beher

Response of the rheumatoid synovial membrane to exogenous immunization

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Abstract

The secondary immune response to tetanus toxoid in 14 patients with rheumatoid arthritis (RA) has been studied in suspension cultures of peripheral blood lymphocytes (PBL) and synovial membrane obtained at synovectomy. Sequential cultures of PBL from three normal subjects established the optimal time of antibody response at 5 days. At this time, the antitetanus antibody produced was predominantly IgG, comprising half of this immunoglobulin fraction. Rheumatoid synovium synthesized 5-9 times more IgG than PBL, expressed as per cent of total protein synthesis, but only negligible amounts of tetanus antibody. The same results were observed in synovial cultures following repeated immunization and after the additional intra-articular injection of tetanus antigen. This marked limitation of the synovium to respond to exogenous antigen in spite of its large immunoglobulin production was considered consistent with a prior commitment of the synovial lymphoid infiltrate to other antigen.

Authors

Jerome H. Herman, John Bradley, Morris Ziff, J. Donald Smiley

Comparison of the HL-A phenotypes of lymphocytes and kidney cells determined by the fluorochromasia cytotoxicity assay

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Abstract

Correlation of leukocyte typing with homograft survival suggests that HL-A typing of white blood cells reflects the histocompatibility factors of the kidney, yet some apparently well-matched kidneys are rejected. The latter results may, in part, reflect inadequacies of typing techniques, incomplete expression of HL-A factors on white blood cells as compared with the cells of the rejected organ, or isoantigens not shared with leukocytes.

Authors

Kathryn S. Douglas, Herbert A. Perkins, Kent Cochrum, Samuel L. Kountz

The occurrence of cryoproteins in synovial fluid; the association of a complement-fixing activity in rheumatoid synovial fluid with cold-precipitable protein

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Abstract

A significant portion of a complement-fixing activity found in the synovial fluid of patients with rheumatoid arthritis, and previously implicated as a possible cause of the low synovial fluid complement levels in these patients behaves as a high solubility cryoprotein. Analysis of rheumatoid synovial fluid cryoproteins has revealed mixed immunoglobulins, bound complement components, fibrinogen, DNA, and rheumatoid factor.

Authors

Robert L. Marcus, Alexander S. Townes

A microperfusion study of sucrose movement across the rat proximal tubule during renal vein constriction

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Abstract

Constriction of the renal vein has been shown to inhibit net sodium and water reabsorption by the rat proximal tubule. The mechanism is unknown but might be the result of inhibition of the active sodium pump induced by changes in the interstitial fluid compartment of the kidney, or to enhanced passive backflux of sodium and water into the cell or directly into the tubular lumen. Since passive movement of solutes across epithelial membranes is determined in part by the permeability characteristics of the epithelium, an increase in the permeability of the proximal tubule during venous constriction would suggest that enhanced passive flux is involved in the inhibition of reabsorption. In the present experiments, isolated segments of rat proximal convoluted tubules were microperfused in vivo with saline while the animals were receiving 14C-labeled sucrose intravenously. In normal control animals, no sucrose was detected in the majority of the collected tubular perfusates. In rats with renal vein constriction (RVC), however, sucrose consistently appeared in the tubular perfusates. The rate of inflow of sucrose correlated with the length of the perfused segment, estimated by fractional water reabsorption. In another group of animals with renal vein constriction, inulin-14C was given intravenously and the proximal tubules similarly microperfused. Inulin did not appear in the majority of collected perfusates in these animals.

Authors

Norman Bank, William E. Yarger, Hagop S. Aynedjian

Inhibition of transepithelial sodium transport in the frog skin by a low molecular weight fraction of uremic serum

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Abstract

An inhibitor of transepithelial sodium transport was found in a low molecular weight fraction obtained from serum of patients with far advanced chronic renal disease. In 18 nondialyzed patients, the mean inhibition of short circuit current (SCC) was 24.9 ±2.2% (SE). With a comparable fraction from 11 normal subjects. SCC decreased by only 5.3 ±1.5%. There was significantly greater inhibition with the serum fractions of patients with end stage renal disease being maintained on chronic hemodialysis than in the normal control group; but the degree of inhibition in the dialyzed population was significantly less than that observed in the nondialyzed chronically uremic patients. The inhibition of SCC produced by the serum fractions of a group of seven patients with acute renal failure was not significantly different from the control group despite the presence of high grade uremia in the former. The inhibitory fraction has characteristics identical with the uremic serum fraction which previously has been shown to inhibit p-aminohippurate (PAH) uptake by rabbit kidney cortical slices. With gel filtration through Sephadex G-25, the active fraction appears after the major peaks of substances as small as urea and sodium; hence it may have been retarded on the column. But its ultrafiltration characteristics suggest that its molecular weight may be less than 1000. The inhibitory capability was not destroyed by boiling, freezing, or digestion with chymotrypsin or pronase. Neither methylguanidine nor guanidinosuccinic acid in concentrations well above those present in the serum of uremic patients inhibited sodium transport in the frog skin. The data suggest that there is an inhibitor of sodium transport in the serum of patients with chronic uremia. The role of this material in the regulation of sodium excretion in uremia as well as its possible role as a uremic toxin are subjects of both theoretical and practical interest.

Authors

Jacques Bourgoignie, Saulo Klahr, Neal S. Bricker

Ion transport during cholera-induced ileal secretion in the dog

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Abstract

To assess the ion transport mechanism by which cholera causes the small bowel to secrete, ion transport rates and electrical potential difference (PD) were determined simultaneously in the normal and choleragen-treated dog ileum in vivo. The results indicate that, during cholera, HCO3 is actively secreted (i.e., against both an electrical and a concentration gradient); Cl is also actively secreted, against a modest electrochemical gradient. Electrogenic pumping of one or both of these anions is probably responsible for an observed PD change of approximately 13 mv (lumen negative). Na secretion can be accounted for entirely by passive ion movement. K secretion can be partly explained by passive diffusion secondary to the negative intraluminal PD; however, its concentration in the secreted fluid is two to three times higher than expected on the basis of passive forces, suggesting a component of active K secretion. The PD response of the choleragen-treated ileum is normal in response to glucose, but there was no PD response to saline-free mannitol perfusion. This suggests that the normal differential permeability of the ileum to anions and cations may be altered by choleragen, although other explanations of this finding are also possible.

Authors

William L. Moore Jr., Fred A. Bieberdorf, Stephen G. Morawski, Richard A. Finkelstein, John S. Fordtran

Action of neomycin on the intraluminal phase of lipid absorption

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Abstract

Administration of a single 1 g dose of neomycin sulfate to five healthy subjects simultaneously with a test meal caused a marked increase in the proportion of fatty acid and bile acid in the ultracentrifuged deposit of aspirated intestinal contents. Labeled cholesterol was precipitated in a similar manner in two hypercholesterolemic patients. Neomycin had no effect on the pancreatic lipase concentration or on the pH of intestinal contents. These results confirm that the ability of neomycin to precipitate micellar lipids is due to interaction between the polybasic neomycin molecule and ionized fatty acids and bile acids. This mechanism provides an explanation for both the steatorrhea and hypocholesterolemia induced by this compound.

Authors

Gilbert R. Thompson, James Barrowman, Louis Gutierrez, R. Hermon Dowling

Studies of a hypomorphic variant of human C3

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A hypomorphic electrophoretic variant of C3 with the mobility of C3 F was found in the serum of a healthy man, his mother, and one of his two sons. Serum C3 concentrations were normal in these subjects as were hemolytic complement levels. Metabolic studies with radiolabeled purified C3 FF and C3 SS in the propositus suggested, but did not prove, that the variant C3 F gene was hyposynthetic. The designation C3 f was therefore proposed for this allele.

Authors

Chester A. Alper, Fred S. Rosen

Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

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Abstract

Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO3/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO3/Ca increased 3.1% and bone Na/Ca increased 3.0%.

Authors

James M. Burnell

Serum level of erythropoietin in anemias associated with chronic infection, malignancy, and primary hematopoietic disease

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Abstract

The serum level of erythropoietin was measured in 31 patients with anemia secondary to chronic infection or malignancy and compared with erythropoietin levels in 23 patients with iron-deficiency anemia and 14 patients with primary hematopoietic diseases. Erythropoietin levels varied directly with the degree of anemia in patients with iron deficiency or primary hematopoietic disorders. There was no correlation of erythropoietin and the degree of anemia in patients with chronic infection or malignancy and the erythropoietin levels were significantly lower than in patients with iron deficiency or primary hematopoietic disease and the same degree of anemia. A major factor in the anemia of chronic disorders is a decrease in levels of erythropoietin.

Authors

Harry P. Ward, John E. Kurnick, Michael J. Pisarczyk

Postglomerular vascular protein concentration: evidence for a causal role in governing fluid reabsorption and glomerulotubular balance by the renal proximal tubule

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Abstract

We tested the relationship between postglomerular microvascular protein concentration and rates of sodium and water transfer by rat proximal tubules. Using recently described microperfusion techniques, efferent arterioles and branch peritubular capillaries of normal hydropenic rats were perfused with colloid-free Ringer's solution, and isoncotic (9.0-10.0 g/100 ml) and hyperoncotic (15 g/100 ml) albumin-Ringer's solutions. Reabsorption in adjacent proximal tubules was studied using free-flow techniques, with initial collections obtained during normal blood perfusion, recollections during experimental microperfusion, and in some tubules, repeat recollections after microperfusion and spontaneous resumption of blood perfusion. Colloid-free perfusion resulted in a uniform inhibition of proximal reabsorption (absolute and fractional). Despite identical techniques, substitution of isoncotic and hyperoncotic perfusates resulted, on average, in unchanged and increased rates of reabsorption, respectively. These findings of direct linear changes in reabsorption in response to changes in postglomerular protein concentrations usually occurred in the absence of significant changes in filtered load, and were nearly always found to be reversible within minutes of cessation of experimental perfusion.

Authors

Barry M. Brenner, Julia L. Troy

Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy

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Abstract

Using a hemagglutination test which can detect antibodies to (a) native and denatured deoxyribonucleic acid (DNA) and (b) an extractable nuclear antigen (ENA), a comparative study of patterns of autoantibody formation has been done in systemic lupus erythematosus (SLE) and related rheumatic diseases. Antibody to native DNA was present in the serum in 96% of patients with active SLE and disappeared during remissions. Antibody to ENA was found in 86% of those patients with SLE nephritis who responded to treatment but in only 8% of those who did not. The highest titers of antibody to ENA were found in patients having a mixed connective tissue disease syndrome with features of SLE, scleroderma, and myositis. The latter syndrome was notable for the absence of renal disease and for a striking responsiveness to corticosteroid therapy. Hemagglutination testing of 277 sera from normal persons and patients with a wide variety of acute diseases other than SLE revealed the presence of antibody to native DNA in only 1.4% and antibody to ENA in only 0.4%.

Authors

Gordon C. Sharp, William S. Irvin, Robert L. LaRoque, Carmen Velez, Virginia Daly, A. D. Kaiser, Halsted R. Holman

Immunologic and cellular changes accompanying the therapy of pollen allergy

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Abstract

We had found previously that children with ragweed hay fever were somewhat less symptomatic after preseasonal immunization with large doses of ragweed pollen extract than were placebo-treated children. To study further the immunologic changes which accompany immunotherapy, these children were treated again the following year. Each patient served as his own control.

Authors

D. A. Levy, L. M. Lichtenstein, E. O. Goldstein, K. Ishizaka

Platelet storage at 22°C; metabolic, morphologic, and functional studies

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Abstract

Platelets stored at 22°C for transfusion purpose have been examined with metabolic, morphologic, and functional studies. Evaluations were made of platelet-rich plasma (PRP) stored for 3-4 days and platelet concentrates (PC) stored for 24 hr. During these periods, lactate accumulated continuously without significant change in platelet count, pH, or plasma glucose. Platelet glycogen fell dramatically both chemically and by electron microscopy, but adenosine triphosphate (ATP), adenosine diphosphate (ADP), and intracellular potassium did not change. After storage, the cell's capacity for glucose utilization through glycolysis, the hexose monophosphate shunt, and the tricarboxylic acid cycle appeared to be intact. Although platelet volume during storage did not change, disc to sphere transformation was observed by phase microscopy. Platelet aggregration with ADP was reduced even after 1 day of storage. After transfusion of stored platelets to thrombocytopenic recipients, recovery of platelet glycogen and capacity for aggregation occurred within 24 hr. In summary, the platelet remains surprisingly intact during the intervals studied; those defects which do develop are reversible in the circulation of a thrombocytopenic recipient if viability has been maintained. A “storage lesion” responsible for loss of viability has not been defined.

Authors

Scott Murphy, Frank H. Gardner

Alterations in thyroid hormone economy during acute infection with Diplococcus pneumoniae in the rhesus monkey

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Abstract

In order to study the alterations in thyroid hormone economy that accompany an acute bacterial infection, rhesus monkeys were inoculated i.v. with a virulent Diplococcus pneumoniae culture containing approximately 108 organisms per dose. This was found to produce a well-defined febrile illness followed in most instances by spontaneous recovery, thereby permitting sequential observations to be made during progression from the healthy state through acute infection into convalescence. During the acute febrile period of the infection, the clearance of both exogenously labeled L-thyroxine (T4) and 3,3′,5-triiodo-L-thyronine (T3) from their peripheral pools was accelerated. This alteration was often evident by 8 hr after inoculation with the virulent culture and could not be ascribed to a decrease in extracellular binding. Despite the accelerated hormonal clearance, the concentrations of both endogenously labeled thyroid hormone and stable T4 in the sera of the surviving monkeys remained essentially unchanged or increased, indicating that hormonal secretion must have increased during this period. During the convalescent period, hormonal clearance was similar to preinfection control values. Leukocytes isolated from blood obtained 6 hr after inoculation with the virulent culture displayed enhanced T4-deiodinative activity.

Authors

Kenneth A. Woeber, William A. Harrison

Synthesis of hemoglobin Gun Hill: increased synthesis of the heme-free β^GH globin chain and subunit exchange with a free α-chain pool

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Abstract

Hemoglobin Gun Hill is an unstable mutant hemoglobin associated with mild compensated hemolysis. This abnormal protein has a deletion of five amino acids in the β-chains. The deletion includes the heme-binding proximal histidine at position 92. The β-chains of hemoglobin Gun Hill lack heme groups. Approximately 32% of the circulating hemoglobin in heterozygous subjects consists of the mutant hemoglobin. When reticulocytes were incubated with radioactive amino acid the specific activity of hemoglobin Gun Hill was three to six times that of hemoglobin A. Total incorporation of radioactivity into hemoglobin Gun Hill was two to three times that into hemoglobin A. There were 20-50% more total counts in β-Gun Hill (βGH) than in βA. These results indicate that in reticulocytes there was greater synthesis of the abnormal β-chains than βA-chains. The ratio of the specific activities of the α-chains of hemoglobin Gun Hill to the α-chains of hemoglobin A was 20: 1. There was evidence of a free pool of α-chains in the reticulocytes containing hemoglobin Gun Hill. After 10 min of incubation approximately 40% of the total α-chain radioactivity was in the free pool. When protein synthesis was blocked by incubation of reticulocytes with puromycin, the specific activity of the α-chains of hemoglobin Gun Hill continued to increase due to direct exchange of α-subunits between the free pool and preformed hemoglobin Gun Hill. Studies of the assembly of βA and βGH revealed that the rates of translation of the two polypeptide chains were equal and uniform. No evidence was obtained for the existence of “slow points” in the process of globin chain assembly. The studies also suggest that lack of strong heme-globin binding does not hinder the synthesis of globin chains.

Authors

Ronald F. Rieder

Glutathione-dependent peroxidative metabolism in the alveolar macrophage

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Abstract

Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in O2 consumption, glucose oxidation, and H2O2 formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied.

Authors

Molly T. Vogt, Catherine Thomas, Charles L. Vassallo, R. E. Basford, J. Bernard L. Gee

Metabolic response to human growth hormone during prolonged starvation

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Abstract

The metabolic response to human growth hormone (HGH) was studied in five obese subjects in the fed state and during prolonged (5-6 wk) starvation. In the fed state (three subjects), HGH induced an elevation in basal serum insulin concentration, a minimal increase in blood and urine ketone levels, and a marked reduction in urinary nitrogen and potassium excretion resulting in positive nitrogen and potassium balance.

Authors

Philip Felig, Errol B. Marliss, George F. Cahill Jr.

Disproportionate inhibition of sodium reabsorption in the unilaterally diseased kidney of dog and man after an acute saline load

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Abstract

Clearance studies were performed on 49 split-bladder dogs with a unilateral pyelonephritic or remnant kidney and three patients with unilateral kidney disease to examine the effects of an acute saline load on the diseased kidney (DK) as opposed to a simultaneously studied, contralateral control kidney (CK), which also served to maintain a nonuremic environment.

Authors

Frank D. Gutmann, Richard E. Rieselbach

Cyclic adenosine 3′,5′-monophosphate in human lymphocytes. Alterations after phytohemagglutinin stimulation

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Abstract

We have studied cyclic adenosine 3′,5′-monophosphate (cyclic AMP) concentrations in human peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA), isoproterenol, prostaglandins, and aminophylline. Purified lymphocytes were obtained by nylon fiber chromatography, and low speed centrifugation to remove platelets. Cyclic AMP levels were determined by a highly sensitive radioimmunoassay. At concentrations of 0.1-1.0 mmoles/liter isoproterenol and aminophylline produced moderate increases in cyclic AMP concentrations, whereas prostaglandins produced marked elevations. High concentrations of PHA produced 25-300% increases in cyclic AMP levels, alterations being demonstrated within 1-2 min. The early changes in cyclic AMP concentration appear to precede previously reported metabolic changes in PHA-stimulated cells. After 6 hr cyclic AMP levels in PHA-stimulated cells had usually fallen to the levels of control cells. After 24 hr the level in PHA-stimulated cells was characteristically below that of the control cells.

Authors

Jay W. Smith, Alton L. Steiner, W. Marcus Newberry Jr., Charles W. Parker

Human lymphocyte metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin

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Abstract

The effects of extracellular nucleotides and agents which elevate intracellular cyclic adenosine 3′,5′-monophosphate (cyclic AMP) concentrations on human lymphocyte metabolism have been studied. Aminophylline, isoproterenol, and prostaglandins, all of which elevate lymphocyte cyclic AMP levels, inhibited incorporation of 3H-labeled thymidine, uridine, and leucine into the DNA, RNA, and protein of phytohemagglutinin (PHA)-stimulated lymphocytes. Aminophylline inhibition was maximal only when the inhibitor was added within 1 hr after exposure of cells to PHA, suggesting that a relatively early step in the lymphocyte transformation process may be affected.

Authors

Jay W. Smith, Alton L. Steiner, Charles W. Parker

Hormonal regulation of human lower esophageal sphincter competence: interaction of gastrin and secretin

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Abstract

The interaction of gastrin and secretin, in the regulation of human lower esophageal sphincter competence, was studied in 54 normal subjects. A dose-response curve, for the lower esophageal sphincter, was constructed from the rapid intravenous injections of synthetic gastrin I (amino acid sequence 2-17). This curve was sigmoid shaped and showed a peak response that was 460.0 ±24.0% (mean ±2 SE) of the initial sphincter pressure, at a dose of 0.7 μg/kg of gastrin I. Secretin, either endogenously released by duodenal acidification, or exogenously administered as a single intravenous injection, markedly reduced the peak response of the sphincter to gastrin I. To ascertain the character of this inhibition, a gastrin I dose-response curve was obtained during a continuous intravenous secretin infusion. This curve showed a parallel shift to the right, with the maximal sphincter response to gastrin I still attainable at higher doses. A sphincter, endogenously stimulated by gastrin, showed a dose-related reduction in pressure with rapid intravenous injections of secretin. At the level of resting sphincter pressure, response to secretin diminished, and larger doses were required for comparable reduction in pressure. These studies indicate; (a) Secretin interacts with gastrin in the physiological regulation of human lower esophageal sphincter competence; (b) Secretin is a sensitive inhibitor to gastrin stimulation of the lower esophageal sphincter; (c) This inhibitory effect of secretin is competitive in character.

Authors

Sidney Cohen, William Lipshutz

Folates in plasma and bile of man after feeding folic acid—³H and 5-formyltetrahydrofolate (folinic acid)

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Abstract

During the 1st hr after feeding folic acid—3H (3H-PteGlu) to fasting human volunteers, plasma S. faecalis and 3H activity were elevated to an equivalent degree, whereas after this, the 3H activity exceeded S. faecalis activity, which suggests gradual conversion of folic acid—3H to methyltetrahydrofolate-3H (5-CH3H4 PteGlu). The increase of L. casei activity exceeded the increase of S. faecalis and 3H activity, which is consistent with flushing of endogenous methyltetrahydrofolate from the tissues by the administered folic acid—3H. Feeding of 5-formyltetrahydrofolate (±5CHOH4PteGlu) produced a large increase of plasma L. casei activity and only a slight increase of S. faecalis and P. cerevisiae activity, which is consistent with very rapid conversion of folinic acid to methyltetrahydrofolate.

Authors

Roy F. Pratt, Bernard A. Cooper