The Contribution of Local Factors to the Elevated Venous Tone of Congestive Heart Failure

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Abstract

Since the concept of an elevated venous tone in congestive heart failure (CHF) has been recently questioned, the venous volume of the elevated calf at a venous pressure of 30 mm Hg (VV[30]) was determined in 18 normal volunteers (N) and 10 CHF patients with a mercury-in-rubber strain gauge plethysmograph. CHF patients had a significantly lower VV[30] at rest and after intra-arterial phentolamine (2 mg) than normal subjects, suggesting that in these patients a state of peripheral venoconstriction existed (rest-N: 4.63±0.17, CHF: 1.7±0.23 ml/100 ml, P < 0.01; pre- and postphentolamine-N: 4.85±0.21 to 4.95±0.31, CHF: 2.26±0.29 to 2.68±0.38 ml/100 ml, P < 0.01). Of note is that alpha adrenergic blockade failed to increase VV[30] significantly in N, but did increase it in CHF (P < 0.05), suggesting that part of the decreased VV[30] in CHF in due to an augmented sympathoadrenal discharge. When sodium nitrite (30 mg) was given as a single intra-arterial injection before or after phentolamine or when given in four successive doses at 3-min intervals, the VV[30] of CHF patients was never increased to more than 3.62±0.42 ml/100 ml and was always less than N (P < 0.01). Importantly, VV[30] in CHF after these interventions was even significantly less than that of N before intervention (P < 0.05), suggesting that factors other than local active smooth muscle venoconstriction were operative in CHF to lower VV[30]. It is suggested that perhaps clinically undetectable edema and an elevated tissue pressure may account for these differences.

Authors

Robert Zelis

Effects of Hemorrhage on Regional Blood Flow Distribution in Dogs and Primates

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Abstract

The effects of hemorrhage on arterial pressure, blood flows, and resistances in the coronary, mesenteric, renal, and iliac beds of healthy, conscious dogs and intact, tranquilized baboons were studied. Mild nonhypotensive hemorrhage (14±2 ml/kg) increased heart rate and mesenteric and iliac resistances slightly but significantly, and decreased renal resistance (-13±2%). Moderate hypotensive hemorrhage, 26±2 ml/kg, reduced mean arterial pressure (-23±2 mm Hg) and blood flows to the mesenteric (-56±3%), iliac (-58±5%), and coronary (-39±4%) vascular beds, and increased heart rate (+89±9 beats/min) and resistances in the mesenteric (+73±15%), iliac (+102±19%), and coronary (+27±5%) beds. In contrast to the other beds, renal flow rose 11±6% above control and renal resistance fell 31±2% below control. Renal vasodilatation with hemorrhage was also observed in five baboons. The increases in mesenteric and iliac resistances were blocked almost completely by phentolamine, while the increase in coronary resistance was only partially blocked by phentolamine. The renal dilatation was not blocked by phentolamine, propranolol, atropine, or tripelennamine, but was prevented by indomethacin, suggesting that this dilatation was mediated by a prostaglandin-like compound.

Authors

Stephen F. Vatner

The Structure of Human High Density Lipoprotein and the Levels of Apolipoprotein A-I in Plasma as Determined by Radioimmunoassay

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The major apoprotein of high density lipoprotein is apolipoprotein A-I (ApoA-I). In addition to being a structural component of this class of lipoproteins, ApoA-I also has a physiologic role as an activator of lecithin-cholesterol acyl transferase, an enzyme important in the metabolism of all lipoproteins.

Authors

Gustav Schonfeld, Barbara Pfleger

Pinocytosis by Human Alveolar Macrophages COMPARISON OF SMOKERS AND NONSMOKERS

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Alveolar macrophages were obtained from human volunteers, smokers and nonsmokers, by bronchial lavage through a fiberoptic bronchoscope. Cells were incubated in a chemically defined medium containing [14C]sucrose (0.36 mM) and varying concentrations of rabbit serum. Pinocytosis was assessed by the cellular uptake of isotope over 30, 75, and 120-min periods. Pinocytic activity of smokers' cells was dependent on serum concentration but always less than the activity of nonsmokers' cells. The degree of pinocytosis by nonsmokers' cells was independent of serum concentration. It is concluded that the decreased level of pinocytic activity in smokers' alveolar macrophages as indicated by the uptake of sucrose in the presence of rabbit serum may represent a form of reticuloendothelial blockade.

Authors

Henry Yeager Jr., Steven M. Zimmet, Sorell L. Schwartz

Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES

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Abstract

To evaluate the possible role of microtubules in the cellular action of vasopressin on the mammalian kidney, the effects of microtubule-disrupting agents were studied in vivo and in vitro.

Authors

Thomas P. Dousa, Larry D. Barnes

Immunology of the Lower Respiratory Tract II. THE PLAQUE-FORMING RESPONSE OF CANINE LYPHOID TISSUES TO SHEEP ERYTHROCYTES AFTER INTRAPULMONARY OR INTRAVENOUS IMMUNIZATION

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Groups of dogs were immunized with sheep erythrocytes administered either directly into the lower respiratory tract (bronchoalveolar spaces) or intravenously. The hemolytic plaque-forming response (Jerne plaque assay) was studied in various canine lymphoid populations (bronchoalveolar cells, hilar lymph nodes, peripheral lymph nodes, and splenic and peripheral blood leukocytes) as a function of time after immunization and as a function of the dose of antigen administered. Serum hemagglutinating antibody titers against sheep erythrocytes were also measured.

Authors

H. B. Kaltreider, L. Kyselka, S. E. Salmon

Utilization of α-Keto and α-Hydroxy Analogues of Valine by the Growing Rat

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When 70-80-g male albino rats eat a diet furnishing daily requirement of valine for optimal growth (70 μmol/g) and all other nutrients (“complete diet”), they gain weight at an average rate of 3.0 g/100 g body wt/day. When valine is removed, they lose weight at an average 2.1 g/100 g body wt/day. The growth retardation is improved or corrected by adding valine to the diet, daily weight gain being proportional to dietary valine content over a range of 0-70 μmol/g.

Authors

Rajender K. Chawla, Daniel Rudman

Plasma Catecholamines and Carbohydrate Metabolism in Patients with Acute Myocardial Infarction

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Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness.

Authors

Niels Juel Christensen, Jørgen Videbaek

Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS

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Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants.

Authors

Louis David, Constantine S. Anast

Circulating Immune Complexes in the Serum in Systemic Lupus Erythematosus and in Carriers of Hepatitis B Antigen QUANTITATION BY BINDING TO RADIOLABELED Clq

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A sensitive and reproducible procedure for the detection of soluble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled C1q is reacted with sera containing immune complexes. Separation of free from complex bound [125I]C1q is achieved by selective precipitation with polyethylene glycol (PEG). The method is based on both the large molecular size and the C1q-binding property characterizing immune complexes. The minimal amount of aggregated immunoglobulins thus detected is about 10 μg and that of soluble human IgG-anti-IgG complexes is about 3 μg of complexed antibody. Some immune complexes formed in large antigen excess (Ag2Ab) can still be detected by this radiolabeled C1q binding assay. The specificity of the radiolabeled C1q binding test was documented by the inability of antigen-F(ab′)2 antibody complexes to lead to a precipitation of [125I]C1q in PEG.

Authors

Urs E. Nydegger, Paul H. Lambert, Heidi Gerber, Peter A. Miescher

Inhibition of In Vivo Insulin Secretion by Prostaglandin E₁

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To determine the effect of prostaglandin E1 (PGE1) infusion upon in vivo insulin secretion, serum insulin responses after an intravenous glucose pulse (2 g) were measured before and during an intravenous infusion of PGE1 (10 μg/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE1 infusion were significantly less than control responses. Three dogs received PGE1 infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE1 before its arrival at the pancreatic artery; inhibition of insulin secretion was again seen. Inhibition of insulin secretion could not be related to the degree of arterial hypotension induced by intravenous PGE1, and despite alpha adrenergic blockade with intravenous phentolamine, PGE1-induced inhibition of glucose-stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE1 infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE1 infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity.

Authors

R. Paul Robertson, David J. Gavareski, Daniel Porte Jr., Edwin L. Bierman

Inhibition of Penicillin Transport from the Cerebrospinal Fluid after Intracisternal Inoculation of Bacteria

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The effect of intracisternal inoculation of bacteria on the choroid plexus system, which transports penicillin from cerebrospinal fluid (CSF) to blood, was studied in vitro and in vivo. Meningeal and choroid plexus inflammations as well as CSF pleocytosis were induced in rabbits with intracisternal inoculations of Hemophilus influenzae or Staphylococcus aureus. At various times after bacterial inoculation, the choroid plexuses of the inoculated rabbits were removed and incubated in artificial CSF containing [14C]penicillin. The ability of the choroid plexuses to accumulate pencillin in vitro was measured and was found to be depressed as compared with controls. This depression of choroid plexus uptake reversed with resolution of the inflammatory process. In vivo on the day after intracisternal inoculation of Hemophilus influenzae, a decrease in the disappearance of penicillin relative to inulin in the inoculated rabbits (as compared to the controls) was observed when [14C]penicillin and [3H]inulin were injected intraventricularly and cisternal CSF was sampled 2 h later. This decrease could not be explained by penicillin binding to the CSF exudate. However, the choroid plexus transport system for penicillin was only partially depressed in those inoculated rabbits with bacterially induced inflammation, since in vitro the choroid plexuses could still accumulate penicillin and in vivo CSF penicillin levels could be further increased with probenecid pretreatment. These results suggest that CSF penicillin levels are increased in this model due to three factors: a depression of active efflux of penicillin from the CSF, an increase in permeability to penicillin of inflamed meninges, and, less significantly, by CSF binding of penicillin.

Authors

Reynold Spector, A. V. Lorenzo

Fatty Acid-Binding Protein in Small Intestine IDENTIFICATION, ISOLATION, AND EVIDENCE FOR ITS ROLE IN CELLULAR FATTY ACID TRANSPORT

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Abstract

A soluble fatty acid-binding protein (FABP), mol wt ∼ 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro.

Authors

Robert K. Ockner, Joan A. Manning

Studies on the In Vivo Effects of Antibody INTERACTION OF IgM ANTIBODY AND COMPLEMENT IN THE IMMUNE CLEARANCE AND DESTRUCTION OF ERYTHROCYTES IN MAN

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Purified human IgM isoagglutinins were utilized to sensitize 51Cr-labeled erythrocytes so as to produce a known number of complement-fixing sites. These cells were then reinfused into the erythrocyte donor. A minimum of 20 C1-fixing sites/erythrocyte were required for decreased survival. As the amount of antibody coating the erythrocytes was increased, a larger percentage was sequestered. With 80 C1-fixing sites, more than 75% of the injected erythrocytes were removed from the circulation within 10 min. In each case, the clearance pattern consisted of rapid hepatic sequestration followed by a gradual return of a portion of the erythrocytes into the circulation where they survived normally.

Authors

John P. Atkinson, Michael M. Frank

Acute Immunologic Pulmonary Alveolitis

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Acute immunologic injury of rat lung has been induced by the intrabronchial injection of heterologous antibody and the intravenous injection of radiolabeled antigen. Within 4 h an acute hemorrhagic neutrophil-rich exudate develops in alveolar and interstitial areas and then gradually fades. Lung injury in this model can be quantitated by measurements of increased vascular permeability and extractable hemoglobin. By the use of immunofluorescent techniques, alveolar and interstitial deposits of antigen and antibody have been demonstrated, but not the third component of complement (C3). Although not found in relation to immune complexes, C3 is nevertheless present in damaged lung as measured by accumulation of radiolabeled C3 from the circulation. Ablation experiments indicate the requirement for both circulating neutrophils and C3 for the development of lung injury. These studies provide definition for the development of lung damage induced by immune complexes.

Authors

Kent J. Johnson, Peter A. Ward

Jejunal Absorption and Secretion of Calcium in Patients with Chronic Renal Disease on Hemodialysis

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10 patients with chronic renal disease on hemodialysis and 8 normals were studied by constant jejunal perfusion of calcium gluconate solutions, using polyethylene glycol as a nonabsorbable marker. Results in normals indicated that calcium absorption from 1 and 5 mM calcium solutions is mainly active. Absorption from 5, 15, and 20 mM solutions was a linear function of luminal calcium concentration, suggesting that the active transport carrier is saturated when luminal calcium concentration is greater than 5 mM and indicating that the increment in absorption at higher luminal concentrations is mainly the result of passive absorption. With 1 mM calcium, normals absorbed calcium against a concentration gradient, whereas the patients secreted calcium. Absorption in the patients was much less than normal with 5, 15, and 20 mM luminal calcium concentrations; however, the slope of this linear (passive) portion of the curve was normal. Unidirectional calcium fluxes were measured with calcium-47. Flux out of the lumen was depressed 2.5-fold in the patients, but flux into the lumen was normal. Xylose, urea, and tritiated water were absorbed normally, indicating no generalized abnormality of jejunal transport in these patients. Endogenous calcium secretion, estimated by the amount of calcium added to a calcium-free solution, was normal in the dialysis patients. These results indicate that active calcium absorption is markedly depressed in patients with chronic renal disease who are receiving hemodialysis therapy. On the other hand, passive calcium movement and endogenous calcium secretions are normal.

Authors

Tom F. Parker, Pedro Vergne-Marini, Alan R. Hull, C. Y. C. Pak, John S. Fordtran

The Turnover of Cholesterol in Human Atherosclerotic Arteries

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The equilibration of cholesterol between plasma and atherosclerotic arteries was studied in 13 patients with obstructive atherosclerosis 2-96 days after the intravenous and/or oral administration of isotopic cholesterol. Arterial specimens were obtained in 12 patients during surgery for arterial reconstruction and in a 13th patient at autopsy. Equilibration was calculated as the specific radioactivity of cholesterol in the arterial tissue relative to that in the plasma (percent).

Authors

S. N. Jagannathan, W. E. Connor, W. H. Baker, A. K. Bhattacharyya

Release of Prostaglandin by Mitogen- and Antigen-Stimulated Leukocytes in Culture

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Abstract

The prostaglandin (PG) content of mitogen- and antigen-stimulated leukocyte cultures was examined by a radioimmunoassay procedure empolying an antiserum reactive with PGB1 and PGB2, the alkaline dehydration products of PGE and PGA. At 48 h, mitogen-activated mouse spleen cell cultures showed 2-10-fold increases in the PGE, but not in the PGA, component of immunoreactive PG (iPG) fractionated by silicic acid column chromatography. Increases in iPG were detectable by h 16 in spleen cell cultures incubated with staphylococcal enterotoxin B. Since iPG levels rose only in the culture supernates and not in cells exposed to mitogens for 48 h, increases reflected extracellular release of PG. The validity of the radioimmunoassay determinations of PGE in spleen cell cultures was supported by the results of concomitant assessment of the PGE2 content of basal and enterotoxin-stimulated cultures by gas chromatography/mass spectrometry. By the latter method, the PGE2 content was three-fold higher in enterotoxin-activated, compared to basal, cultures at 48 h. Aspirin effectively suppressed increases in both iPG and PGE2. In spleen cell cultures prepared from mice previously inoculated with an attenuated strain of yellow fever virus in vivo and then incubated with this virus in vitro, iPG levels increased twofold over basal at 48 h. By contrast, iPG content of spleen cell cultures prepared from saline-inoculated mice was not appreciably altered by exposure to the virus in vitro.

Authors

Victor A. Ferraris, Frederick R. DeRubertis, Thomas H. Hudson, Leon Wolfe

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

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Abstract

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58±3.63 SD μmol/g creatinine; normal, 4.02±0.70 μmol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 125I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453±154 SD mg/day was significantly higher than the control group's 211±42 mg/day. The urinary cAMP of 2.26±0.56 μmol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.

Authors

Charles Y. C. Pak, Masahiro Ohata, E. Clint Lawrence, W. Snyder

Serial Studies of Immunocompetence of Patients Undergoing Chemotherapy for Acute Leukemia

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Abstract

Immunocompetence was followed serially for 1 yr from the onset of treatment in 55 adult patients with acute leukemia. The tests used were delayed hypersensitivity responses to a battery of five recall antigens (dermatophytin, dermatophytin 0, candida, streptokinase-streptodornase, and mumps) and in vitro lymphocyte blastogenic responses to phytohemagglutinin and streptolysin 0. There was a strong correlation between immunocompetence at the start of treatment and a good prognosis; 32/39 patients who subsequently entered remission were initially immunocompetent compared to 4/15 who failed to enter remission. In the complete remission group there was a decline in competence starting from 2 to 5 mo after the onset of treatment. In those who remained in remission for 1 yr, competence recovered at 6 mo and remained vigorous thereafter. In those who relapsed before 1 yr, the decline in competence occurred 1 mo before relapse and competence continued to decline progressively during the 1 yr follow-up period. These studies suggest that therapeutic approaches which restore immunocompetence or prevent its decline will improve both the remission rate and the remission duration of patients with acute leukemia.

Authors

E. M. Hersh, J. U. Gutterman, G. M. Mavligit, K. B. McCredie, M. A. Burgess, A. Matthews, E. J. Freireich

Hemoglobin Affinity for Oxygen in the Anginal Syndrome with Normal Coronary Arteriograms

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Abstract

Oxyhemoglobin dissociation (OHD) curves were performed on whole blood (WB) from 20 patients with anginal pain, normal hemodynamics, and normal coronary arteries, as demonstrated by selective coronary cinearteriography. OHD curves in 19 of 20 patients, from zero to full saturation, were nearly identical to those in normal control subjects with values for P50 (Po2 at 50% saturation and pH 7.4) of 26.7±1.5 (mean±SD of the mean) torr (mm Hg) and red blood cell (RBC) levels of 2,3-diphosphoglyceric acid (2, 3-DPG) of 0.72±0.10 (mean±SD of the mean) M/M hemoglobin (Hb). Normal values for nonsmoking adults were: P50, 26.6±1.4 (mean±SD of the mean) torr: and RBC 2,3-DPG, 0.81±0.09 (mean±SD of the mean) M/M Hb. Mean levels of carbon monoxide were normal at 0.14±0.01 (mean±SEM) ml/100 ml WB in 10 patients who were nonsmokers and 0.45±0.15 (mean±SEM) ml/100 ml WB in 10 smokers. In one patient, a heavy smoker with markedly elevated blood carbon monoxide levels, an abnormal leftward shift of the OHD curve was observed. This was corrected after discontinuation of smoking. In utilizing these methods, we could not detect consistent abnormalities of Hb affinity for oxygen at rest in the patients studied, which suggests that a defect in oxygen transport at rest is an unlikely explanation for the symptoms of chest pain in patients with the anginal syndrome and normal coronary arteriograms.

Authors

Pantel S. Vokonas, Peter F. Cohn, Michael D. Klein, Myron B. Laver, Richard Gorlin

Secretion of Parathyroid Hormone in Patients with Medullary Thyroid Carcinoma

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Abstract

The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor.

Authors

Leonard J. Deftos, Jacqueline G. Parthemore

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

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Abstract

Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb [14C]5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [3H]5-HT to [3H]5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound [14C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease.

Authors

Harvey J. Weiss, Thomas B. Tschopp, John Rogers, Harvey Brand

Balanced Globin Chain Synthesis in Hereditary Persistence of Fetal Hemoglobin

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In two black families with the hereditary persistence of fetal hemoglobin (HPFH) gene there are eight A-F heterozygotes and two double heterozygotes for sickle cell trait and HPFH. These patients are clinically asymptomatic and have homogeneous acid elution smears. Measurement of globin chain synthesis in peripheral blood demonstrates balanced production of a α and non-α (β plus γ) chains. In these patients, the balance is achieved by increased γ globin production and increased activity of the remaining β globin allele. In two patients, one A-F and the other S-F there is also balanced globin synthesis in the bone marrow. In a double heterozygote for HPFH and β-thalassemia, anemia (Hb: 11.5 g/100 ml) is associated with a moderate degree of globin chain imbalance. There is a correlation between balanced globin chain synthesis and the absence of anemia in patients with HPFH.

Authors

C. L. Natta, G. A. Niazi, S. Ford, A. Bank

Cellular Reactivity Studies to Streptococcal Antigens MIGRATION INHIBITION STUDIES IN PATIENTS WITH STREPTOCOCCAL INFECTIONS AND REHEUMATIC FEVER

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The question of whether hypersensitivity to streptococcal antigens plays a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections remains at present unclear. As a first step in the approach to this question, the degree of cellular reactivity of peripheral blood leucocytes to streptococcal antigens was investigated in a number of rheumatic fever patients, patients with uncomplicated streptococcal infections, as well as normal healthy subjects.

Authors

Stanley E. Read, Vincent A. Fischetti, Virginia Utermohlen, Rudolf E. Falk, John B. Zabriskie

Relationship of Serum Complement Levels to Events of the Malarial Paroxysm

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Malarial paroxysms due to Plasmodium vivax were studied for alterations in whole serum complement (C′) and certain C′ components. The objective was to relate C′ values with events of the parasite cycle during schizogony and with the febrile pattern. Substantial decreases in C′ were found in 9 of 18 paroxysms studied during relapse. In contrast, only one of 22 paroxysms occuring during the primary attack was associated with a striking depression in C′, and this case exhibited certain characteristics of a relapse paroxysm. The mean change in C′ levels during paroxysms in relapse (-23%) was significantly different from paroxysms of the primary attack (-2%). Depletion of C′ was associated directly with degree of parasitemia and presence of complement-fixing (CF) antibody. Lowest levels of C′ were found within a few hours after completion of schizont repture and peak fever. C4 levels reflected changes in whole serum C′ and appeared to be a more sensitive indicator of C′ alterations during malaria. While the alterations in C4 as well as C1 and C2 indicated that the classical C′ pathway was involved, some preliminary results showed little or no depletion of late components, C3 and C6. Overall results are compatible with C′ activation and depletion during or soon after schizont repture if parasite density is sufficiently high and if CF antibody is present.

Authors

F. A. Neva, W. A. Howard, R. H. Glew, W. A. Krotoski, A. A. Gam, W. E. Collins, J. P. Atkinson, M. M. Frank

Interrelations in the Oxidative Metabolism of Free Fatty Acids, Glucose, and Glycerol in Normal and Hyperlipemic Patients A COMPARTMENTAL MODEL

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Abstract

Palmitate, glucose, and glycerol oxidation to CO2 have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-14C]palmitate, [1-14C]glucose, or [1-14C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO2 were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO2. A bicarbonate subsystem was also included in the model to account for its role in shaping the CO2 curves.

Authors

C. L. Malmendier, C. Delcroix, M. Berman

Pure Human Big Gastrin IMMUNOCHEMICAL PROPERTIES, DISAPPEARANCE HALF TIME, AND ACID-STIMULATING ACTION IN DOGS

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Abstract

Biological properties of pure natural human “big gastrin” (designated G-34 because it contains 34 amino acid residues) were compared with those of pure natural heptadecapeptide gastrins (G-17) from human and porcine sources. Radioimmunoassay inhibition curves indicated that G-17 was nearly 1.5 times more potent than G-34 with the antibody used in this study. This difference was confirmed by demonstration of increased immunoreactivity generated when G-34 was converted to G-17 by trypsinization.

Authors

John H. Walsh, Haile T. Debas, Morton I. Grossman

Abnormalities of Chemotactic Lymphokine Synthesis and Mononuclear Leukocyte Chemotaxis in Wiskott-Aldrich Syndrome

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Abstract

Wiskott-Aldrich syndrome is characterized by numerous humoral and cellular immune abnormalities including anergy, defective antibody production, and increased immunoglobulin synthesis. To define better the mechanisms of defective cellular immunity in this disorder, lymphoproliferative responses, lymphokine production, and the chemotactic responsiveness of mononuclear leukocytes (MNL) from patients with Wiskott-Aldrich syndrome were quantitated. Peripheral blood lymphocytes from these patients produced normal amounts of a lymphocyte-derived chemotactic factor (LDCF); however, their lymphoproliferative responses were frequently depressed, particularly to antigenic stimuli. In the absence of exogenous antigens or mitogens, lymphocytes from patients with Wiskott-Aldrich syndrome produced significantly more LDCF than unstimulated normal lymphocytes. In fact, this unstimulated LDCF production frequently approached the level produced by normal cells only after antigen or mitogen stimulation.

Authors

Leonard C. Altman, Ralph Snyderman, R. Michael Blaese

Thyroid-Stimulating Activity and Chorionic Gonadotropin

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Abstract

The nature of the substance with thyroid-stimulating activity (TSA) present in human chorionic gonadotropin (hCG) prepared from pregnancy urine was investigated. In the mouse thyrotropin bioassay, the characteristic maximum of blood radioactivity obtained with the TSA in hCG preparations occurred after that obtained with pituitary thyrotropin (hTSH) but before that obtained with long-acting thyroid stimulator. Antiserum to the α subunit of hCG produced significant neutralization of the TSA in hCG. Significant antagonism of hTSH biologic activity was achieved with certain doses of hCG, suggesting that the TSA in hCG was a partial agonist of hTSH. This antagonism was neutralized by antiserum to the β subunit of hCG. These immunologic results suggest that the substance with TSA in hCG preparations contains antigenic determinants similar to those of both the α and the β subunit of hCG. Amounts of highly purified hCG and crude commercial hCG of equal immunologic activity were biologically indistinguishable in the bioassay for TSA. Both hCG immunoreactivity and the TSA in hCG adsorbed to concanavalin A and eluted with 0.2 M methyl α-D-glucopyranoside. These results are consistent with the hypothesis that TSA is an intrinsic property of hCG or of a glycoprotein molecule physicochemically, biologically, and immunologically similar to hCG.

Authors

Bruce C. Nisula, Jean-Marie Ketelslegers