Effect of cholestyramine on bile acid metabolism in normal man

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Abstract

The effect of cholestyramine administration on the enterohepatic circulation of bile acids was studied in eight normal volunteers. In six subjects the metabolism of sodium taurocholate-14C was determined after its intravenous injection before and during the 6th wk of cholestyramine administration, 16 g/day. In two subjects, the metabolism of cholic acid-14C was observed before and during the 2nd wk of cholestyramine, 16 g/day. Bile acid sequestration resulted in a more rapid disappearance of the injected primary bile acid and its metabolic products. The composition of fasting bile acids was promptly altered by cholestyramine to predominantly glycine-conjugated trihydroxy bile acid. In four subjects, unconjugated bile acid-14C was administered during cholestyramine administration; the relative proportion of glycine-conjugated bile acid-14C before enterohepatic circulation was similar to the relative proportion of unlabeled glycine-conjugated bile acid present in duodenal contents after an overnight fast, indicating that a hepatic mechanism was responsible for the elevated ratios of glycine- to taurine-conjugated bile acid (G: T ratios) observed. The relative proportions of both dihydroxy bile acids, chenodeoxycholic and deoxycholic, were significantly reduced. Steatorrhea did not occur, and the total bile acid pool size determined after an overnight fast was unaltered by cholestyramine. These findings suggest that in normal man bile acid sequestered from the enterohepatic circulation by cholestyramine is replaced by an increase in hepatic synthesis primarily via the pathway leading to production of glycocholic acid.

Authors

J. T. Garbutt, T. J. Kenney

Effect of variation in dietary NaCl intake on the intrarenal distribution of plasma flow in the rat

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Abstract

The effect of dietary variation in sodium chloride intake on the intrarenal distribution of plasma flow was investigated in rats using the antiglomerular basement membrane antibody technique. Rats were placed on a liquid diet containing either 9.86 (n = 9) or 0 (n = 9) mEq NaCl/daily portion for 2 wk. Labeled antibody was injected and the diets were reversed. After an additional 2 wk period, antibody labeled with a different radionuclide was injected and the animals were sacrificed. Fractional plasma flow distribution was then calculated for each dietary period. No change in flow to any cortical region could be detected. In six additional awake rats on identical dietary regimen, total plasma flow was estimated by the clearance of hippuran-131I. No change in this parameter occurred with changes in NaCl intake. We conclude, therefore, that no change in either total renal plasma flow or intracortical distribution of plasma flow occurs with wide variations in dietary sodium chloride intake in the rat. The implications of this constancy of regional plasma flow are discussed with reference to presumed concomitant alterations in the intrarenal distribution of nephron filtration rate.

Authors

Roland C. Blantz, John D. Wallin, Floyd C. Rector Jr., Donald W. Seldin

Slow fractional removal of nonextractable iodine from rat tissue after injection of labeled l-thyroxine and 3,5,3′-triiodo-l-thyronine: A possible clue to the mechanism of initiation and persistence of hormonal action

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Previous studies have shown that a small but significant proportion of radioiodine from labeled L-thyroxine (T4) and 3,5,3′-triiodo-L-thyronine (T3) is incorporated into plasma and tissue proteins and is not, therefore, extractable with ethanol or other organic solvents. Other studies have shown that the complex consists, at least in part, of the iodothyronine in apparent covalent linkage with protein. In the present series of experiments the disappearance rate of nonextractable iodine (NEI) was determined in plasma, liver, and kidney after the injection of rats with a single dose of T4 and T3 labeled with radioiodine in the phenolic ring. The t½ of NEI decay was substantially longer than the t½ of the initial metabolic removal of T4 (16 hr) and T3 (4-6 hr). Thus, between days 3 and 11 the average t½ of plasma NEI derived from T4 was 2.2 days, from T3, 1.9 days; kidney NEI from T4, 7.4 days, from T3, 6.1 days; hepatic NEI from T4, 4.3 days, from T3, 5.2 days.

Authors

Jack H. Oppenheimer, Martin I. Surks, Harold L. Schwartz

Stimulatory effects of induced phagocytosis on the function of isolated thyroid cells

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Stimulation of endocytosis is a very early effect of thyrotropin on thyroid. However, the relationship of the endocytotic process to the many other thyrotropin effects on thyroid is not clearly defined. Since phagocytosis in isolated thyroid cells is a presumed model for in vivo endocytosis of colloid, we induced phagocytosis in isolated thyroid cells by incubating them at 37°C with 0.109-μ diameter polystyrene microbeads; phagocytosis was confirmed in each experiment by electron microscopy and/or spectrophotometric analysis of dioxane cell extracts. Cells incubated with 50-100-μ diameter polystyrene macrobeads (too large to ingest) served as controls. Microbead-induced phagocytosis in isolated thyroid cells was consistently accompanied by increases in: (a) cyclic 3′,5′-adenosine monophosphate-14C formation from adenine-8-14C (66%); (b) iodide-131I trapping (40%); (c) protein and RNA synthesis (30%); (d) phospholipogenesis (50%); (e) α-aminoisobutyric acid-1-14C uptake (15%). 50- to 100-μ diameter polystyrene macrobeads did not influence cell function in any of these experiments. Aminotriazole, 5 × 10-3M, a peroxidase inhibitor, blocked the stimulatory effect of microbead-induced phagocytosis on phospholipogenesis only. These studies indicate that in isolated thyroid cells the phagocytotic process, per se, may alter activity of the membrane-bound adenyl cyclase enzyme. The resultant increase in cyclic 3′,5′-adenosine monophosphate may be a triggering mechanism for (some) subsequent metabolic changes occuring during phagocytosis. Since these changes mimic those induced by thyrotropin, it is suggested that a variety of thyrotropin effects on thyroid may be secondary to stimulation of colloid resorption and hormone secretion.

Authors

K. Kowalski, D. Babiarz, S. Sato, G. Burke

Ethanol, acetaldehyde, and myocardial protein synthesis

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The cause of alcoholic myocardiopathy is unknown. The effects of acute exposure to ethanol or its metabolite acetaldehyde on protein synthesis in working, intact, guinea pig hearts in vitro were studied utilizing lysine-14C perfusion. Ethanol at 250 mg/100 ml, a level sufficient to markedly inhibit hepatic production of albumin, did not alter cardiac function, the equilibration of the intracellular free lysine pool in either ventricle, or the incorporation of lysine-14C into protein. Thus, in controls and ethanol-perfused hearts, the incorporation of lysine in 3 hr was 44.1±1.5 and 42.8±1.2 μmoles lysine/g protein N for the right ventricles and 25.6±1.0 and 24.3±0.8 for the left ventricles, respectively. Only at lethal levels, 1500 mg/100 ml ethanol, was protein synthesis depressed. Acetaldehyde 3.5 mg/100 ml (0.8 mM) effected a markedly positive chronotropic and inotropic effect on the perfused heart and slightly depressed equilibration of the intracellular free lysine pool. However, determinations of protein incorporation of lysine-14C based on intracellular lysine-14C specific activities showed a significant decrease from control right and left ventricle values, to 27.1±2.8 and 14.9±1.9. Propanalol, which abolished the chronotropic effect, did not prevent the inhibition of protein synthesis. The studies suggest that acetaldehyde, which inhibits cardiac protein synthesis in vitro, may play a role in alcoholic myocardiopathy by interfering with normal myocardial protein synthesis.

Authors

Sidney S. Schreiber, Kay Briden, Murray Oratz, Marcus A. Rothschild

Uterine blood flow and uterine renin secretion

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Experiments were carried out in pregnant nephrectomized rabbits to determine the relationship between uterine blood flow and uterine renin secretion. Uterine blood flow was measured by the percentage distribution of radioactive microspheres injected into the left ventricle which lodged in uterus and placenta, and cardiac output was measured by dye dilution. In 40 animals, 24 hr after nephrectomy, uterine blood flow was 4.7±0.4% of cardiac output and absolute flow 32.4±3 ml/100 g per min. Plasma renin activity (PRA) in uterine vein, 994±182 ng/100 ml per hr, was higher than in carotid artery, 832±143 (P < 0.025). With reduction of uterine blood flow from 4.7±0.5 to 1.95±0.3% of cardiac output and absolute flow from 30.8±4.6 to 8.8±2 ml/100 g per min, uterine vein PRA rose from 1434±234 to 4430±300 (P < 0.001), and carotid artery PRA from 1009±200 to 2300±350 (P < 0.01). Hemorrhagic hypotension caused uterine vein PRA to increase from 913±293 to 3638±1276 (P < 0.001) and carotid artery PRA from 774±252 to 1730±433 (P < 0.01). Uterine blood flow expressed as a percentage of cardiac output remained constant after hemorrhage, 5.5±0.9 and 6.3±0.8%, although absolute flow fell from 37±7.7 to 29±3.6 ml/100 g per min because of the large fall in cardiac output which occurred.

Authors

Thomas F. Ferris, Jay H. Stein, Jeffrey Kauffman

Bone and soft tissue changes with oral phosphate supplements

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Oral phosphate supplements in divided doses were given to adult dogs for a period of 10 months. Bone density, bone turnover, serum chemistry values, and the calcium content of soft tissues were determined initially and at the end of the experimental period. Serum calcium remained the same; serum phosphate decreased slightly but significantly. The decrease in phosphate was related to an increase, compared with pre-experimental values, in bone resorption which was seen in the terminal ulna and iliac crest bone samples from all dogs. Serum immunoreactive parathyroid hormone was increased (compared with pre-experimental values) after 5 and 10 months of phosphate supplementation; this increase was related to the bone loss and the decrease in serum phosphate. Soft-tissue calcification could be demonstrated histologically in the kidney and in the lens of the eye where it resulted in cataracts. Calcium content increased in the thoracic aorta, kidney, heart, and tendon but not in skeletal muscle. Phosphate supplements in adult dogs appear to produce secondary hyperparathyroidism, bone loss, and calcification of soft tissues.

Authors

Georges H. Laflamme, Jenifer Jowsey

Mechanism of ancrod anticoagulation: A direct proteolytic effect on fibrin

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Fibrin formed in response to ancrod, reptilase, or thrombin was reduced by β-mercaptoethanol and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was found that ancrod progressively and totally digested the α-chains of fibrin monomers at sites different than plasmin; however, further digestion of fibrin monomers by either reptilase or thrombin was not observed. Highly purified ancrod did not activate fibrin-stabilizing factor (FSF); however, the reptilase preparation used in these experiments, like thrombin, activated FSF and thereby promoted cross-link formation. Fibrin, formed by clotting purified human fibrinogen with ancrod, reptilase, or thrombin for increasing periods of time in the presence of plasminogen, was incubated with urokinase and observed for complete lysis. Fibrin formed by ancrod was strikingly more vulnerable to plasmin digestion than was fibrin formed by reptilase or thrombin. The lysis times for fibrin formed for 2 hr by ancrod, reptilase, or thrombin were 18, 89, and 120 min, respectively. Evidence was also obtained that neither ancrod nor reptilase activated human plasminogen. These results indicate that fibrin formed by ancrod is not cross-linked and has significantly degraded α-chains: as expected, ancrod-formed fibrin is markedly susceptible to digestion by plasmin.

Authors

Salvatore V. Pizzo, Martin L. Schwartz, Robert L. Hill, Patrick A. McKee

Natural history of impetigo: I. Site sequence of acquisition and familial patterns of spread of cutaneous streptococci

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The appearance on and spread of Group A streptococci among different body sites in relationship to the development of impetigo were studied prospectively in 31 children in five families. During July and August 1969 intensive clinical, bacteriological, and serological observations were made, including cultures taken at least every other day.

Authors

Patricia Ferrieri, Adnan S. Dajani, Lewis W. Wannamaker, S. Stephen Chapman

Natural history of impetigo: II. Etiologic agents and bacterial interactions

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Abstract

Intensive observations on 37 children in a population with endemic skin infections provided an opportunity to study the interrelationships between and the significance of the bacterial genera commonly associated with impetigo. Cultures of the respiratory tract, three normal skin sites, and lesions, when present, were taken three times weekly from July to October 1969. Impetigo developed in all 37 children. Group A streptococci alone were recovered from 21% of 361 lesions, Staphylococcus aureus alone from 8%, Staphylococcus epidermidis alone from 5% and mixtures of streptococci and staphylococci from 61%.

Authors

Adnan S. Dajani, Patricia Ferrieri, Lewis W. Wannamaker

Direct and reflex effects of nitroglycerin on coronary and left ventricular dynamics in conscious dogs

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The effects of intravenous and sublingual glyceryl trinitrate (nitroglycerin), 40 μg/kg, were studied on coronary blood flow and resistance, left ventricular (LV) pressures (P) and diameters (D), rate of change of pressure (dP/dt), (dP/dt)/P, and on the velocity (V) of myocardial fiber shortening in conscious dogs. Nitroglycerin i.v. caused substantial coronary vasodilatation prior to any changes in systemic hemodynamics. Mean coronary flow increased by a maximum of 47 ml/min and coronary sinus Po2 rose from 16 to 26 mm Hg while pressure and diameter began to fall, and heart rate began to rise. After the maximal fall in mean arterial pressure (—26 mm Hg), a secondary peak in coronary flow occurred which was associated with increases in heart rate (100 beats/min), (dP/dt)/P (22%), and isolength V (12%). Beta blockade prevented the reflex increases in contractility but only a part of the reflex tachycardia; the remainder was prevented by cholinergic blockade. Maintaining heart rate constant minimized the decreases in LV D and increases in contractility. When the reflex inotropic and chronotropic effects were prevented by a combination of atrial pacing and beta blockade the early coronary vasodilatation was unaltered, but the later coronary vasodilatation was minimized.

Authors

Stephen F. Vatner, Charles B. Higgins, Ronald W. Millard, Dean Franklin

Erythrocyte function and marrow regulation in hemoglobin Bethesda (β145 histidine)

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Hemoglobin Bethesda (β145 histidine) is one of the two mutants known to affect the penultimate hemoglobin tyrosines. The result of this substitution is extreme disorganization of the oxygenation function of the molecule. Red cells containing 45% Hb Bethesda and 55% Hb A have increased oxygen affinity but, paradoxically, a normal Bohr effect. As is usually seen with other hemoglobins with increased oxygen affinity, Hb Bethesda clinically is manifest in heterozygotes by erythrocytosis. Red cell production in affected individuals is erythropoietin dependent. The reciprocal interdependence of oxygen delivery and effective erythropoiesis was documented by alterations in erythropoietin excretion, quantitative iron kinetics, and reticulocyte production in response to phlebotomy-induced reduction in the oxygen-carrying capacity.

Authors

John W. Adamson, Akira Hayashi, George Stamatoyannopoulos, Wilbur F. Burger

Effect of insulin on muscle glutamate uptake: Whole blood versus plasma glutamate analysis

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For decades, investigators concerned with protein metabolism in man have performed detailed amino acid analyses of human plasma obtained under a wide range of experimental situations. A large body of information has been used to calculated rates of protein synthesis and proteolysis. During the course of an investigation of the effect of intrabrachial artery infusion of insulin (70 μU/min per kg body weight) on glutamate uptake by human forearm muscle, it was discovered that plasma arterio-deep venous glutamate difference analysis failed to document any increase in the uptake of this amino acid, suggesting that insulin had little influence on glutamate uptake by muscle. However, whole blood glutamate analyses, performed on the same blood samples, revealed that (a) the resting muscle uptake of glutamate is smaller than previously reported and (b) insulin is capable of markedly increasing glutamate uptake by muscle from whole blood. Since the hematocrit was obtained on all samples, detailed analyses of the various compartments in which glutamate could be found were performed. It was determined that circulating blood cells have a dynamic role in glutamate transport. These data underscore the need for both whole blood and plasma amino acid analysis in investigations concerned with protein synthesis and/or amino acid flux, for analysis of plasma samples alone could be misleading as illustrated in the present study.

Authors

T. T. Aoki, M. F. Brennan, W. A. Müller, F. D. Moore, G. F. Cahill Jr.

Coproporphyrin I and III excretion in bile and urine

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The excretion of coproporphyrin isomers I and III was studied in the rat. Both isomers were found to bind equally to rat plasma and liver cytosol in vitro and to disappear from plasma at equal rates after single injections in vivo. During equimolar infusions of isomers into bile fistula animals, both the I and III isomers were excreted in bile in a concentration ratio of 2:1, respectively. Pretreatment of animals with ethinylestradiol or simultaneous infusions of phenoldibromophthalein disulfonate caused a reduction in total hepatic excretion with no change in the 2:1 ratio in bile. As hepatic excretion fell, excretion of both isomers in urine rose, with an increase in the proportion of the I isomer. The findings mimic those reported to occur in man and can be explained by inhibition of a common carrier which requires a stereospecific configuration that statistically favors the hepatic transport of the symmetrical coproporphyrin I isomer.

Authors

Neil Kaplowitz, Norman Javitt, Attallah Kappas

Metabolism of 1,25-dihydroxycholecalciferol in the rat

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Administration of 60 pmoles of 1,25-dihydroxycholecalciferol to vitamin D-deficient rats on a low calcium diet gives a maximal intestinal calcium transport response in 7 hr and a maximal bone calcium mobilization response in 12 hr. During the 48 hr after injection of radioactive 1,25-dihydroxycholecalciferol, unchanged 1,25-dihydroxycholecalciferol accounts for 71-98% of the radioactivity found in the intestine with minor amounts appearing in more polar metabolites. In the bone, for the 1st 12 hr, 1,25-dihydroxycholecalciferol is the major form (75-82%) present while at 24 hr, the amount of 1,25-dihydroxycholecalciferol decreases with a corresponding rise in the amounts of metabolites both less polar and more polar than the 1,25-dihydroxycholecalciferol. Since these metabolies are at their highest concentration when bone calcium mobilization is decreasing, they are most likely not responsible for the calcium mobilization observed during the 1st 12 hr. The appearance of water-soluble radioactivity in the kidney, plasma, liver, and muscle 24 hr after 1,25-dihydroxycholecalciferol injection has been demonstrated. The present results suggest that, although 1,25-dihydroxycholecalciferol is converted to further metabolites in the rat, it is probably the form of vitamin D responsible for initiating intestinal calcium transport and bone calcium mobilization.

Authors

Charles A. Frolik, Hector F. DeLuga

Effect of age, sex, and site on the cellularity of the adipose tissue in mice and rats rendered obese by a high-fat diet

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Cell size and number of parametrial fat pads were determined in Swiss mice made obese by means of a high-fat diet (40% lard w/w) given ad lib. This diet and a control were introduced to two groups of mothers during gestation and lactation, and sucklings were given the same diets as their mothers at weaning and throughout life.

Authors

Daniel Lemonnier

The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat

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The transport of immunoglobulins across the intestinal mucosa of neonatal rats provides an excellent model for the study of transcellular protein transport. The mechanism of intestinal uptake and transcellular transport of plasma proteins has been studied in 12-14-day old rats using intraduodenally administered radioiodinated proteins. Appreciable quantities of rat IgG, mouse IgG, rabbit IgG, and all four subclasses of human IgG were taken up by the intestinal wall (19-54% of administered dose at 4 hr) and transported to the animal (10-35% of administered dose at 4 hr). In contrast there was little or no uptake of human IgM, IgA, and IgE and little or no transport of human IgM, IgA, IgD, IgE, albumin, transferrin, and ceruloplasmin. Both the uptake and transport of labeled IgG were significantly inhibited by unlabeled IgG. Further insight into the transport process was obtained from the observation that an appreciable proportion of the label of IgG in intestinal wall homogenates, but not in plasma or intestinal washings, migrated in a sucrose ultracentrifugation gradient much more rapidly than did the administered 7S molecules. This pattern was not observed with other proteins studied. This apparent binding of labeled IgG was also markedly inhibited by unlabeled IgG. In subcellular fractionation studies of intestinal homogenates the complexed labeled IgG was shown to be associated predominantly with cell membrane rather than cell sap fractions. In addition IgG could be shown to bind to purified enterocyte microvillous membranes in vitro.

Authors

E. Anthony Jones, Thomas A. Waldmann

The effect of chronic hypotonic volume expansion on the renal regulation of acid-base equilibrium

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Balance studies have been carried out to evaluate the influence of vasopressin-induced volume expansion on acid-base equilibrium in normal dogs and in dogs with steady-state metabolic acidosis induced by the administration of 5-7 mmoles/kg per day of hydrochloric acid.

Authors

David C. Lowance, Howard B. Garfinkel, William D. Mattern, William B. Schwartz

Histamine release from human leukocytes: studies with deuterium oxide, colchicine, and cytochalasin B

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Agents known to interact with either microtubules or microfilaments influenced the antigen-induced release of histamine from the leukocytes of allergic individuals. Deuterium oxide (D2O) which stabilizes microtubules and thereby favors their formation enhanced histamine release markedly. Concentrations as low as 5% increased antigen-induced release somewhat while concentrations as high as 75% had no effect on release in the absence of antigen. Enhancement occurred over a wide range of antigen concentrations and was also seen when release was initiated by antibody to IgE or IgG. When the release process was divided into two stages a D2O activity could be demonstrated only in the second stage. However, when D2O was present in the first stage together with agents which raise cyclic AMP levels and thereby inhibit release it partially reversed this inhibition. Colchicine, demecolcine, and vinblastine, compounds known to disaggregate microtubules, i.e., have an effect opposite to that of D2O, inhibited the release of histamine and counteracted the effects of D2O. The inhibitory action of colchicine was greater if cells were treated with colchicine before rather than after activation with antigen. Cytochalasin B, a compound which causes the disappearance of microfilaments, had variable effects on histamine release. The most frequently seen response was slight enhancement. Neither D2O nor cytochalasin B altered cyclic AMP levels in leukocytes. These observations support and strengthen the view that an intact and functioning microtubule system is directly important for the secretion of histamine from leukocytes and suggest that microfilaments might have multiple indirect effects.

Authors

Elizabeth Gillespie, Lawrence M. Lichtenstein

Effect of transfer factor on lymphocyte function in anergic patients

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Dialyzable transfer factor, obtained from frozen-thawed peripheral blood leukocytes from a single donor, was given to five anergic patients with chronic mucocutaneous candidiasis. Studies of immunological responses including delayed cutaneous hypersensitivity, in vitro antigen-induced thymidine incorporation, and production of macrophage migration inhibition factor (MIF) were conducted both before and after injection of transfer factor.

Authors

Charles H. Kirkpatrick, Robert R. Rich, Terrill K. Smith

The influence of pyrogen-induced fever on salicylamide metabolism in man

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Salicylamide is metabolized in man by biotransformation to salicylamide glucuronide, salicylamide sulfate, and gentisamide glucuronide. The metabolites are quantitatively and rapidly excreted in urine. Study of the metabolism of this drug in volunteers during episodes of pyrogen-induced fever shows a significant reduction in the half-life (t½) of the excretion of the drug metabolites. The proportion of the drug transformed to its major metabolite, salicylamide glucuronide, is significantly reduced by fever, with concomitant increase in the proportion of one or both of the other metabolites. Thus, the pattern of urinary metabolites of salicylamide is altered. The shortened t½ of the metabolite excretion is probably due to increased hepatic and renal blood flow known to accompany pyrogen-induced fever. This concept was supported by the observation that when two subjects were placed in a high-temperature environmental chamber, a condition in which hepatic and renal blood flows are known to diminish, the t½ of salicylamide metabolite excretion actually increased. No simple explanation exists to explain the changed metabolite pattern noted during febrile periods. It is most likely to be due to complex interactions between the direct or indirect effects of the pyrogens and the factors affecting the hepatic biotransformation of drugs.

Authors

Chull S. Song, Nancy A. Gelb, Sheldon M. Wolff

The role of low pressure baroreceptors in reflex vasoconstrictor responses in man

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Studies were performed on 11 healthy men to evaluate the role of low pressure baroreceptors in the reflex forearm vasoconstrictor responses (plethysmography) to venous pooling produced by lower body negative pressure. Lower body negative pressure (LBNP) at - 5, - 10, - 20, and - 40 mm Hg lowered central venous pressure by 42, 59, 74, and 93%, respectively, and decreased forearm vascular conductance by 24, 29, 34, and 40%, respectively. The decreases in forearm blood flow and conductance during the low levels of venous pooling (LBNP - 5 and - 10 mm Hg) occurred without significant changes in arterial pressure, arterial dP/dt. and heart rate. These results with the low levels indicate that maneuvers which decrease venous return and central venous pressure in man can influence forearm vascular tone without significant changes in the determinants of carotid and aortic baroreceptor activity. During high levels of venous pooling (LBNP - 20 and - 40 mm Hg), significant decreases in arterial pressure and dP/dt and significant increases in heart rate accompanied the further reductions in central venous pressure, forearm blood flow, and forearm vascular conductance. About 73% of the decrease in conductance during venous pooling at LBNP - 40 mm Hg, which was sufficient to decrease arterial pressure and activate high pressure baroreceptor reflexes, occurred during low levels of venous pooling at LBNP - 10 mm Hg without changes in arterial pressure. This suggests that much of the forearm vasoconstriction with the high levels of venous pooling, which were sufficient to decrease arterial pressure, may be accounted for by reflexes originating in areas other than high pressure baroreceptors. The results of these studies suggest that low pressure baroreceptors exert an important influence on forearm vascular tone during decreases in venous return and central venous pressure in man.

Authors

Robert P. Zoller, Allyn L. Mark, Francois M. Abboud, Phillip G. Schmid, Donald D. Heistad

A collagenolytic system produced by primary cultures of rheumatoid nodule tissue

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A collagenase and a neutral protease have been insolated and characterized from primary cultures obtained from rheumatoid subcutaneous nodules. Release of both active enzymes was maximal between the 3rd and 7th days of culture and was stimulated by the presence of small amounts of colchicine (0.1 μg/ml) added to the culture medium.

Authors

Edward D. Harris Jr.

HL-A8: a genetic link between dermatitis herpetiformis and gluten-sensitive enteropathy

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Histocompatibility antigen HL-A8 was found in 58% of 26 patients with dermatitis herpetiformis (DH) compared to 24% of a normal group. This difference in antigen frequency is significant at the P < 0.003 level. In a previous study, the frequency of this same genetic marker was found to be significantly increased in patients with gluten-sensitive enteropathy (GSE) (88% in patients vs. 22% in controls). The finding of an increased incidence of the HL-A8 antigen in both DH and GSE supports the concept that these diseases are related and provides a genetic basis for the association between the two.

Authors

Stephen I. Katz, Z. Myron Falchuk, Mark V. Dahl, G. Nicholas Rogentine, Warren Strober

Identification of the colony-stimulating cell in human peripheral blood

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Bone marrow colony formation in soft gel culture may be stimulated by substances elaborated by human peripheral blood leukocytes. In order to determine the cell type responsible for colony stimulation, peripheral leukocytes were separated by Ficoll-Hypaque gradients and differential glass adhesion. Morphologic, histochemical, and functional criteria were applied to determine the purity of the monocyte, lymphocyte, and neutrophil fractions.

Authors

David W. Golde, Martin J. Cline

Oxygen equilibrium of hemoglobin E

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Oxygen equilibrium was determined on hemoglobin of individuals both heterozygous and homozygous for hemoglobin E. The whole blood oxyhemoglobin dissociation curve of AE blood was identical to that of normal AA blood. E hemoglobin, isolated by diethylaminoethyl Sephadex and carboxymethyl cellulose column chromatography, had oxygen affinity, heme-heme interaction, and Bohr effect identical to those of hemoglobin A prepared from the same column. Furthermore, the two hemoglobins had equal reactivity with 2,3-diphosphoglycerate. Phosphate-free hemolysates of blood from E and A homozygotes also had identical oxygen saturation curves. These results do not confirm earlier reports that hemoglobin E has an abnormally low oxygen affinity.

Authors

H. Franklin Bunn, W. Delano Meriwether, Stanley P. Balcerzak, Donald L. Rucknagel

The formation of abnormal bile and cholesterol gallstones from dietary cholesterol in the prairie dog

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Abstract

Authors