Carbohydrate metabolism in pregnancy. VI. Plasma fuels, insulin, liver composition, gluconeogenesis, and nitrogen metabolism during late gestation in the fed and fasted rat

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

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Sounds from a different drum.

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Halsted R. Holman

Abstracts

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A physiological approach to the assessment of disease activity in rheumatoid arthritis

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A method is described for assessing the in vivo oxygen consumption and lactate production rates of human knee joints. It is based on the rate of fall of Po2 and the rate of rise in lactate concentration in an intra-articular saline pool after interruption of the circulation to the joint with an arterial tourniquet. Studies in 5 control patients with degenerative joint disease and 29 patients with rheumatoid arthritis showed a 2- to 3-fold higher mean oxygen uptake rate and a 10- to 12-fold higher mean lactate appearance rate in the saline in the rheumatoid joints with severe disease compared to the control joints. These metabolic variables correlated with tissue metabolic demand as estimated in synovial biopsies. 133Xe washout from the intra-articular space, which reflects joint circulatory flow, showed a 3-fold greater mean washout rate from the rheumatoid joints (48 studies) than control joints (7 studies) with extensive overlap between the two groups. 133Xe washout rate correlated with knee joint inflammation estimated both clinically and histologically. After synovectomy in four patients, the operated knee showed a greater fall in lactate production than the opposite knee in three of these patients. Neither knee joint oxygen uptake nor 133Xe washout rate changed significantly. Intra-articular corticosteroid injection (eight patients) resulted in decreased lactate production and a decreased 133Xe washout rate in the injected knee and variable results in the untreated knee. Oxygen uptake again was unchanged after therapy.

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E. J. Goetzi, K. H. Falchuk, L. S. Zeiger, A. L. Sullivan, C. L. Hebert, J. P. Adams, J. L. Decker

Redox state of free nicotinamide-adenine nucleotides in the cytoplasm and mitochondria of alveolar macrophages

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Cytoplasmic free NAD+/NADH ratios have been calculated from lactate to pyruvate ratios, and mitochondrial NAD+/NADH ratios, have been calculated from β-hydroxybutyrate to acetoacetate ratios in isolated rabbit alveolar macrophages. In freshly harvested cells, assuming a pH of 7 for the two compartments, cytoplasmic NAD+/NADH averaged 709 ±293 (SD), and mitochondrial NAD+/NADH averaged 33.2 ±30.2, values which are significantly different. 30 min of air incubation in a relatively poorly buffered medium showed a significant reduction in calculated mitochondrial NAD+/NADH to 10.1 ±4.8. 30 min of exposure of cells to a hypoxic environment (equivalent to a nonventilated, perfused alveolus) caused significant reductions of NAD+/NADH in both compartments. Re-exposure of hypoxic cells to air produced a change toward normal in cytoplasmic NAD+/NADH but did not reverse mitochondrial abnormality. Uncertainties concerning the value of cytoplasmic and mitochondrial pH under control conditions and during experimental pertubations, limit absolute interpretation of NAD+/NADH ratios calculated from redox pairs, but the data suggest the following: (a) separate cytoplasmic and mitochondrial compartments for NAD+ and NADH exist in the alveolar macrophage; (b) brief periods of exposure to moderate hypoxia of the degree seen in clinical lung disease produce decreases in both cytoplasmic and mitochondrial NAD+/NADH; (c) the mitochondrial changes are less easily reversed than the cytoplasmic changes; (d) measurements of NAD+/NADH provide an early sensitive indication of biochemical abnormality; and (e) careful control of extracellular pH is required in studies involving experimental modifications of alveolar macrophage function.

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Sheldon Mintz, Eugene D. Robin

The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man

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Eight normal subjects were administered tracer amounts of a 14C-labeled thyroxine, L-[tyrosyl-14C] T4, by multiple injections. Then serial blood samples were collected for isolation of the thyroxine, triiodothyronine, and tetraiodothyroacetic acid fractions by a combination of column and paper chromatographies. The chromatographic artifacts were corrected by adding to the sera a purified 3H-labeled thyroxine, D,L-[α,β-3H] T4 immediately after the separation of sera from blood. 1-2% of the serum 14C radioactivity was observed in the triiodothyronine fraction and 2-4% of the serum 14C radioactivity was observed in the tetraiodothyroacetic acid fraction. Complete kinetic studies of thyroxine and triiodothyronine were compared in the same individual in four of the subjects. The extrathyroidal conversion rates of thyroxine to triiodothyronine were calculated from data obtained during both the injection and the postinjection periods as functions of the 14C-labeled thyroxine and triiodothyronine remaining in the body at time t and their fractional turnover rates. The average daily rate of the extrathyroidal conversion of thyroxine to triiodothyronine was 4% of the extrathyroidal thyroxine pool or 33% of the total thyroxine production. The amount of triiodothyronine generated by this pathway (22 μg/day) was found to contribute 31% of the extrathyroidal triiodothyronine pool or 41% of the daily triiodothyronine production. This pathway is a major source of triiodothyronine production. The extrathyroidal conversions of thyroxine to triiodothyronine and tetraiodothyroacetic acid are major metabolic pathways of thyroxine in normal man.

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Constance S. Pittman, Joseph B. Chambers Jr., Virginia H. Read

Changing types of nephritogenic streptococci in Trinidad

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The relation of seven different M types of streptococci to acute glomerulonephritis associated with skin lesions in South Trinidad has been studied by means of type-specific antibody assays as well as by isolation and identification of the strains. The data indicate that, one after another, five of these strains have prevailed among patients with acute glomerulonephritis during the past five years. At least three of the strains (M-types 55, 49, 57, and/or 60) were associated with epidemic increases in nephritis cases. The appearance of five consecutively predominant types of nephritogenic streptococci during a relatively short period of time is in contrast to the continuing prevalence of M-type 12 strains among nephritogenic streptococci primarily associated with respiratory infections in temperate zones. These observations suggest that the skin sores commonly found on children in tropical Trinidad, provide a particularly suitable environment for development of nephritogenic types. It remains to be seen whether these types will recur or whether new types will continue to emerge in Trinidad.

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Elizabeth V. Potter, Jesse S. Ortiz, A. Richey Sharrett, Emma G. Burt, Juanita P. Bray, John F. Finklea, Theo Poon-King, David P. Earle

The effect of epsilon amino caproic acid and other inhibitors of proteolysis upon the response of human peripheral blood lymphocytes to phytohemagglutinin

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Previous work has suggested that intracellular proteolysis may play a role in lymphocyte stimulation. An inhibitor of proteolysis, epsilon amino caproic acid (EACA) was studied for its effect on the lymphocyte response to phytohemagglutinin (PHA). EACA was found to inhibit several parameters of lymphocyte stimulation (e.g. DNA, RNA, and protein synthesis as well as alterations in morphology) This inhibition was not due to diminished cellular viability and did not permanently impair the capacity of the lymphocyte to subsequently respond to PHA. Additionally, there was no evidence that this inhibition was due to other possible effects of EACA, such as alterations in Na+ — K+ transport, competitive amino acid deprivation or interference with PHA binding. Moreover, the inhibitors of proteolysis, tosyl arginine methyl ester (TAME), tosyl lysine chloromethyl ketone (TLCK), and tosyl phenyl-alanine chloromethyl ketone (TPCK), were also shown to inhibit lymphocyte stimulation.

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Rochelle Hirschhorn, Judith Grossman, Walter Troll, Gerald Weissmann

Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins

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The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3′,5′-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE1 (maximal effect at 0.03 mM) and PGE2. The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE1 and PGE2 again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE1 and vice versa. It was concluded, therefore, that the SCC response to PGE1, like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE1 and NaF were the same in CT-treated and control mucosa. Cyclic 3′,5′-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE1. A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is concluded that CT and certain prostaglandins produce small intestinal fluid secretion by increasing mucosal adenyl cyclase activity, thereby stimulating an active secretory process.

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Daniel V. Kimberg, Michael Field, Judith Johnson, Antonia Henderson, Elaine Gershon

Renal effects of adenosine 3′,5′-cyclic monophosphate and dibutyryl adenosine 3′,5′-cyclic monophosphate: Evidence for a role for adenosine 3′,5′-cyclic monophosphate in the regulation of proximal tubular sodium reabsorption

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Stable water diuresis was produced in anesthetized, hydrocortisone-treated hypophysectomized dogs by infusion of 2.5% dextrose. Infusion of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) in the left renal artery decreased ipsilaterally glomerular filtration rate (GFR), cortical and non-cortical renal plasma flow, and tended to increase urine flow (V) and free-water clearance (CH2O) despite a decrease in mean arterial pressure. Infusion of dibutyryl adenosine 3′,5′-cyclic monophosphate (dibutyryl cyclic AMP) in the left renal artery increased V and CH2O significantly (P<0.01) bilaterally with essentially no change in GFR, in total renal plasma flow or its cortical and non-cortical components. For each kidney the magnitude of the change in V was similar to the magnitude of the change in CH2O and the change in sodium excretion was trivial. Cyclic AMP probably produced its effects on renal hemodynamics and mean arterial pressure wholly or in part through the action of metabolites such as 5′-AMP and adenosine on the renal and systemic vasculature. The absence of an effect of dibutyryl cyclic AMP on renal hemodynamics and its bilateral effect may be explained by the resistance of this nucleotide derivative to metabolism.

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John R. Gill Jr., Alfred G. T. Casper

Role of gastrin supersensitivity in the pathogenesis of lower esophageal sphincter hypertension in achalasia

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Intraluminal manometric studies were carried out in 19 patients with untreated achalasia and in 20 normals. Lower esophageal sphincter (LES) pressure was 50.5 ±4.6 mm Hg in patients with achalasia as compared with 19.4 ±1.3 mm Hg in the normal group. In both groups, the LES pressure was lowered when exogenous 0.1 N HCl was placed into the stomach. Although the nadir of pressure attained with acid suppression was the same, the per cent inhibition was significantly greater in patients with achalasia. Serum gastrin levels were the same in the two groups studied. The patients with achalasia, pre- and postpneumatic dilatation, showed a supersensitivity to exogenous intravenous gastrin I, as compared with normals. These data suggest that high, acid-suppressible levels of LES pressure, in patients with achalasia, are due to supersensitivity to endogenous gastrin.

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Sidney Cohen, William Lipshutz, William Hughes

Inhibition of antibodies binding polyinosinic polycytidylic acid in human and mouse lupus sera by viral and synthetic ribonucleic acids

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The specificities of anti-RNA antibodies of diverse origin were studied by inhibition of the binding of radioative polyinosinic polycytidylic acid. The antibodies were from human patients with systemic lupus erythematosus (SLE), older NZB/NZW F1 mice who have SLE, and young NZB/NZW F1 mice immunized with either synthetic or viral double-stranded (ds) RNA. The inhibitors were two viral ds and two synthetic ds RNAs, ribosomal RNA and transfer RNA. The human sera were more heterogeneous than the mouse lupus sera, and had greatest specificity for reovirus RNA. The mouse lupus sera were more homogeneous and, in general, were inhibited efficiently by all four ds RNAs. Sera from mice immunized with synthetic RNA reacted poorly with viral RNA, whereas sera from mice immunized with viral RNA reacted with all four ds RNAs and resembled the lupus sera. These results suggest a role for viruses in the induction of anti-RNA antibodies, and are compatible with the concept that virus infection as well as excessive antibody responses are involved in the pathogenesis of SLE.

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Norman Talal, Alfred D. Steinberg, Gerald G. Daley

Genetic diversity of the “Mediterranean” glucose-6-phosphate dehydrogenase deficiency phenotype

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Genetic diversity of the “Mediterranean” phenotype of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency was revealed when detailed studies were performed on blood specimens from 79 Greek males with G-6-PD levels 0-10% of normal. Four different mutants were found to be responsible for the severely deficient phenotypes: two mutants. G-6-PD U-M (Union-Markham) and G-6-PD Orchomenos, were distinguishable by electrophoresis, while the other two. G-6-PD Athens-like and G-6-PD Mediterranean, were distinguishable on the basis of their kinetic characteristics. Of the kinetic tests applied, the most useful for differentiating the variants were those measuring utilization rates of the analogue substrates deamino-NADP, 2-deoxyglucose-6-phosphate, and galactose-6-phosphate. Among unrelated males with severe G-6-PD deficiency, the relative frequencies of the four variants were: G-6-PD U-M. 5%; G-6-PD Orchomenos, 7%; G-6-PD Athens-like, 16%; G-6-PD Mediterranean, 72%. Genetic, biochemical, and clinical implications of the findings are discussed.

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George Stamatoyannopoulos, Volker Voigtlander, Panayotis Kotsakis, Angelos Akrivakis

Defective cellular immunity in renal failure: depression of reactivity of lymphocytes to phytohemagglutinin by renal failure serum

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In defining host resistance factors in uremia, experiments were designed to assess the effect of renal failure serum upon the reactivity of normal human lymphocytes to phytohemagglutinin in vitro. Normal buffy coat cells were resuspended in sera obtained from normal subjects and from 14 patients with renal failure, then stimulated with phytohemagglutinin M and the cellular response measured by the increase in thymidine or uridine uptake. The mean thymidine uptake by stimulated cells in normal sera was 14,389 ±1695 (SEM) cpm per 2 × 106 lymphocytes. Uridine uptake under the same conditions was 12,540 ±1887 cpm. Compared to these are a mean thymidine uptake of 2740 ±457 cpm and uridine uptake of 3928 ±667 cpm in renal failure sera. Both differences are significant at P<0.01 level.

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W. Marcus Newberry, Jay P. Sanford

Marrow grafts between canine siblings matched by serotyping and mixed leukocyte culture

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Marrow grafts were carried out between 16 canine sibling donor-recipient pairs. The pairs were matched by serological histocompatibility testing and were nonreactive in a one-way mixed leukocyte culture. Recipients were prepared for transplantation by 1500-1580 R of total body irradiation. Donor marrow was infused within 4 hr of irradiation. Recipients were not given immunosuppressive drug therapy after grafting. All 16 recipients showed evidence of prompt and sustained allogeneic marrow engraftment. Six died between 30 and 128 days after grafting with graft-versus-host disease, and three died between days 72 and 230 with pneumonia but no evidence of graft-versus-host disease with the exception of lymphoid atrophy. Seven recipients survived without graft-versus-host disease and are in excellent health between 200 and 684 after grafting.

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Rainer Storb, Robert H. Rudolph, E. Donnall Thomas

Estimation of Vmax in auxotonic systoles from the rate of relative increase of isovolumic pressure: (dP/dt)kP

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High speed oscilloscopic recordings (4000 mm/sec) of left ventricular pressure (micromanometer) and its first derivative were used to calculate contractile element velocity (Vce) during the isovolumic period of auxotonic beats in anesthetized dogs. At 0.5-2.0 msec intervals of isovolumic systole, Vce was derived as (dP/dt)/kP, where k = 24 cm-1. Plots of Vce and P yielded inverse curves from peak Vce to aortic valve opening pressure which averaged 27 msec in controls, and 11 msec during norepinephrine administration. Extrapolated Vmax, in muscle lengths/second, averaged 3.6 (controls), 3.6 (volume load), and 6.6 (norepinephrine). In each experimental state, Vmax was also determined from force-velocity relations of isovolumic beats (abrupt aortic occlusion) analyzed at 10 msec intervals from conventional pressure recordings. Vmax by both methods correlated well (r = 0.88). While good correlations were also noted between Vmax and maximum dP/dt, (max dP/dt)/integrated isovolumic pressure, (max dP/dt)/peak isovolumic pressure, and (max dP/dt)/kP, only the last two of these successfully distinguished changes between volume load and inotropic stimulation. Thus, assuming an unchanged series elasticity, the contractile state of the auxotonic ventricle may be determined utilizing a single high-fidelity catheter system and high speed recordings of isovolumic pressure.

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Michael J. Wolk, John F. Keefe, Oscar H. L. Bing, Lawrence J. Finkelstein, Herbert J. Levine

Fetal bile salt metabolism: I. The metabolism of sodium cholate-¹⁴C in the fetal dog

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Cholate metabolism was studied in fetal dogs 1 wk before term and was compared with cholate metabolism in adult dogs. Tracer amounts of sodium cholate-14C were administered to the fetus in utero by intravenous infusion over 6 hr. Fetal plasma disappearance, biliary excretion, tissue distribution, and placental transfer of cholate were measured over 10 hr.

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B. T. Jackson, R. A. Smallwood, G. J. Piasecki, A. S. Brown, H. F. J. Rauschecker, R. Lester

Abnormal hormone responses of an adrenocortical cancer adenyl cyclase

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Properties of adenyl cyclase of normal adrenals and of a corticosterone-producing adrenal cancer of the rat have been compared. Enzyme activity was found in all particulate fractions of both tissues. The cyclase of the tumor as well as of the adrenals was stimulated by adrenocorticotropic hormone (ACTH) over similar concentration ranges. Unexpectedly, the tumor enzyme was also stimulated by epinephrine, norepinephrine, and thyroid-stimulating hormone (TSH). These hormones produced a dose-related effect over a concentration span that was comparable with that for ACTH. The tumor cyclase was not responsive to angiotensin Il, vasopressin, glucagon, insulin, growth hormone, parathyroid hormone, and thyrocalcitonin. ACTH was the only hormonal preparation that stimulated normal adrenal cyclase. These findings are compatible either with the possibility that the adenyl cyclase receptor of the tumor has undergone structural alteration with a consequent loss of specificity for ACTH or with the possibility that the tumor possesses several cyclase regulatory receptors.

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Immanuel Schorr, Robert L. Ney

Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate

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Serum disappearance curves in dogs after the intravenous injection of radioactive methotrexate, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid followed first-order kinetics with half-disappearance times ranging from 1.3 to 9 hr respectively. Equilibration of spinal fluid tritium levels with those in serum was rapid (3.0 hr) for both of the reduced folates but was not observed at any time after folic acid and methotrexate. The only radioactive folate identified in the spinal fluid after intravenous injection of either 5-formyltetrahydrofolate or folic acid, as well as 5-methyltetrahydrofolate was 5-methyltetrahydrofolate. These findings indicated that 5-methyltetrahydrofolate was taken up preferentially into the spinal fluid and that the other folate congeners were converted to this compound before uptake. Diphenylhydantoin administration did not alter the uptake of 5-methyltetrahydrofolate into the spinal fluid but was associated with reduced renal excretion of this compound.

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M. Levitt, P. F. Nixon, J. H. Pincus, J. R. Bertino

Effect of cortisone treatment on the active transport of calcium by the small intestine

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It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis.

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Daniel V. Kimberg, Richard D. Baerg, Elaine Gershon, Ruta T. Graudusius

Modification of the cardiovascular effects of l-dopa by decarboxylase inhibitors

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Intravenously infused L-dopa (0.3 mg/kg per min) produced hypertension and cardiac arrhythmias in halothane anesthetized dogs. Biochemical studies showed that the heart, kidney, and brain of these animals accumulated significant amounts of catecholamines formed from the administered precursor.

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August M. Watanabe, Leon C. Parks, Irwin J. Kopin

The distribution of sodium-potassium-activated adenosine triphosphatase in medulla and cortex of the kidney

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The activity of sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) is considerably higher in homogenates of outer medulla than in the cortex or papilla of the kidney. The enzyme has similar kinetic characteristics in both cortex and medulla, and binds ouabain in the same proportion. The discrepancy in enzymatic activity is not paralleled by similar change in the activity of adenyl cyclase, 5′nucleotidase, glucose-6-phosphatase, or succinic dehydrogenase. Na-K-ATPase is also higher in distal convoluted tubules (ventral slices) than in the proximal tubules (dorsal slices) of the kidney of Amphiuma. The high concentration of Na-K-ATPase in the red medulla of the kidney is probably related to the presence here of the thick ascending limb of the loop of Henle, and this has important implications with regard to the mechanism of sodium reabsorption by different portions of the nephron.

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Ernesto D. Hendler, Jorge Torretti, Franklin H. Epstein

The metabolic clearance rate and origin of plasma dihydrotestosterone in man and its conversion to the 5α-androstanediols

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Dihydrotestosterone metabolism was studied with a constant infusion technique in three men, three women, five hirsute women, and four estrogen-treated hirsute women. The mean dihydrotestosterone metabolic clearance rate was higher in men (336 liters/24 hr per m2 [range, 239-448]) than in women (153 liters/24 hr per m2 [range, 108-184]). The metabolic clearance rates in hirsute patients were intermediate between those men and women and were decreased by estrogen treatment. These observations demonstrate similarities in the metabolic rates of testosterone and dihydrotestosterone.

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Jacques A. Mahoudeau, C. Wayne Bardin, Mortimer B. Lipsett

Alterations in thyroid hormone economy in patients with hydatidiform mole

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Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal 131I uptake, absolute iodine uptake, and serum protein-bound-131I. Values for serum PBI and serum thyroxine (T4) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T4-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T4 in serum were, on the average, only moderately elevated, since the proportion of free T4 was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was associated with the disappearance from serum of the thyroid stimulator.

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Valerie Anne Galton, Sidney H. Ingbar, Jesus Jimenez-Fonseca, Jerome M. Hershman

A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia

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On a high carbohydrate, fat-free diet, control and hypertriglyceridemic subject had a three-fold increase in d < 1.006, very low density lipoprotein (VLDL) triglyceride, and somewhat lesser increases in VLDL cholesterol and protein. Cholesterol and protein in 1.006 < d < 1.21 lipoprotein decreased in a reciprocal fashion, suggesting that these components might have been utilized in VLDL production. Electron microscope studies demonstrated a significant increase in the size of lipoprotein particles of the VLDL class and, in three of four subjects, an apparent increase in particle number. The change in particle size correlated with an increase in the triglyceride/protein ratio of the d < 1.006 lipoprotein. Hypertriglyceridemic individuals differed from the control subjects in that they had greater absolute increases in VLDL triglyceride, cholesterol, and protein, and greater decreases in 1.006 < d < 1.21 cholesterol and protein. In addition, they had larger VLDL particles with a higher triglyceride/protein ratio, both before the study and at the peak of the carbohydrate effect. The data suggest that the increase in plasma triglycerides induced by a high carbohydrate diet is usually due to the appearance in plasma of both greater numbers of VLDL particles and larger particles that are relatively richer in triglyceride content than those isolated during the basal state.

Authors

Neil B. Ruderman, Albert L. Jones, Ronald M. Krauss, Eleazar Shafrir