The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery.
James T. Willerson, Wm. John Powell Jr., Timothy E. Guiney, James J. Stark, Charles A. Sanders, Alexander Leaf
This study was designed to examine the pathogenesis of the excretory defect produced by bilateral ureteral obstruction in the rat. After release of obstruction of 24 hr duration glomerular filtration rate was reduced to 20% of normal. Free flow proximal tubular pressure was normal, excluding residual obstruction as a cause of depressed filtration, and indicating that an intrarenal hemodynamic abnormality was primarily responsible for the excretory defect. Total renal blood flow and cortical distribution of flow were normal. Clearance and micropuncture studies indicated the presence of marked heterogeneity of nephron function with residual excretory function residing primarily in vasodilated nephrons in which decreased postglomerular arteriolar resistance effected a reduction in glomerular filtration pressure. Heterogeneity of nephron function was evidenced by a wide scatter of values for single nephron filtration rate and from direct intratubular injection of dye which revealed that at least 28% of surface nephrons were either nonfiltering or had filtration rates too low to measure. The observed decrease in Hippuran extraction and increased ratio of Hippuran to inulin clearance ratio is characteristic of the vasodilated kidney. Further evidence of the vasodilated nature of residual functioning nephrons was demonstrated by the failure of intrarenal papaverine infusion to increase filtration rate in this lesion.
John R. Jaenike
The frequency and amount of IgM rheumatoid factor (RF) in the blood of patients with rheumatoid arthritis (RA) correlate with the severity of the disease and the number of complications. Though previous studies of RF in subacute bacterial endocarditis have shown that RF inhibits phagocytosis of microorganisms by granulocytes, the presence of low levels of complement (C) in blood and synovial fluid of patients with the highest titers of RF suggests that an interaction between RF and C may contribute to the inflammatory process in RA. We thus employed a quantitative methodology to examine the effect of RF on complement-dependent phagocytosis of sheep erythrocytes by rabbit granulocytes. Addition of 2500 molecules of IgM RF to sheep cells heavily coated with IgG antibody (195,000 molecules per cell) resulted in virtually complete inhibition of uptake of C3 (β1c) and prevention of phagocytosis, an effect resulting from inhibition of uptake of C1 by the cells. When erythrocytes coated with only 34,000 molecules of IgG antibody were employed, phagocytosis was similarly inhibited. However the effect of RF on such cells was shown to be primarily mediated through inhibition of C4 rather than C1 uptake. Although the results do not exclude the participation of an IgM RF of higher avidity, present only in the tissues in rheumatoid inflammation, circulating IgM RF probably does not play a potentiating role in rheumatoid inflammation.
F. C. McDuffie, H. W. Brumfield
We have examined the rate-limiting steps involved in bile acid absorption across the unstirred water layer and lipid cell membrane of the jejunal mucosa. Uptake of the polar bile acid taurocholate is limited solely by the cell membrane since this compound permeates the unstirred water layer more rapidly than the lipid cell membrane and stirring does not enhance uptake. With less polar bile acids which permeate the cell membrane relatively more rapidly, however, the unstirred water layer does exert resistance to mucosal uptake of these compounds. That the unstirred water layer is even more rate limiting to uptake from micellar solutions is indicated by the facts that the rate of bile acid absorption from such solutions is lower than from corresponding monomer solutions, stirring markedly enhances uptake from micellar solutions while increases in viscosity of the incubation media depress uptake and expansion of the micelle size further depresses absorption rates. We also have examined the important question of whether the micelle crosses the brush border intact once it reaches the aqueous-lipid interface. The observations that the calculated permeation rate of the micelle should be extremely low, the rate of mucosal cell uptake plateaus at a constant value when the critical micelle concentration is reached at the aqueous-lipid interface, and the different components of a mixed micelle are taken up at different rates indicate that uptake of the intact micelle does not occur; rather, bile acid absorption must be explained in terms of monomers in equilibrium with the micelle. Finally, after correction of the permeability coefficients of the various bile acids for the unstirred layer resistance the incremental partial molar free energy of solution of the hydroxyl group in the brush border membrane was calculated to equal −6126 cal·mole−1 indicating that passive diffusion of these compounds occurs through a very polar region of the cell membrane.
Frederick A. Wilson, John M. Dietschy
Hepatic secretions of biliary lipids were estimated in 43 patients with and without cholesterol gallstones. Studies were carried out by a marker dilution technique employing duodenal intubation with a three-lumen tube. Hourly secretion rates of cholesterol, bile acids, and phospholipids were determined during constant infusion with liquid formula.
Scott M. Grundy, Allan L. Metzger, Ronald D. Adler
Porphyria cutanea tarda (PCT) is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I. Clinical evidence has implicated iron in the pathogenesis of PCT. The synthesis of the normally occurring isomer of uroporphyrin, namely uroporphyrin III, from porphobilinogen (PBG) requires two enzymes; uroporphyrinogen I synthetase and uroporphyrinogen III cosynthetase (COSYN). In the absence of COSYN only uroporphyrinogen I is formed.
J. P. Kushner, G. R. Lee, S. Nacht
The left ventricular response to severe exercise was studied by telemetering direct measurements of left ventricular diameter (D) and pressure (P) and aortic blood flow from healthy dogs running at speeds up to 30 mph in the field. Severe exercise increased cardiac output from 101 to 478 ml/kg per min, heart rate from 95 to 297 beats/min, stroke volume from 31 to 44 ml, left ventricular isolength (iso) systolic pressure from 120 to 186 mm Hg, left ventricular end diastolic pressure from 6 to 18 mm Hg, and left ventricular end diastolic diameter from 58.9 to 60.1 mm, while end systolic diameter decreased from 53.0 to 52.2 mm. Two indices of myocardial contractility, (dP/dt)/P increased from 37 to 92 sec−1, while dD/dt, the velocity of myocardial fiber shortening at isolength, rose from 54 to 119 mm/sec. All of these changes were statistically significant. When, in resting dogs, heart rate was first raised to exercise levels by electrical stimulation, severe exercise subsequently increased left ventricular end diastolic diameter more profoundly, from 55.7 to 59.7 mm, while end systolic diameter remained constant and the increases in left ventricular pressure, (dP/dt)/P and velocityiso were roughly comparable to those occurring during exercise in spontaneous rhythm. After propranolol, 1.0 mg/kg, severe exercise resulted in significantly smaller increases in cardiac output (from 82 to 240 ml/kg), in heart rate (from 87 to 186 beats/min), in left ventricular pressureiso (from 122 to 150 mm Hg), in (dP/dt)/P (from 32 to 44 sec−1), in velocityiso (from 47 to 59 mm/sec), and in slightly greater increases in end diastolic diameter, from 59.8 to 62.0 mm and pressure from 8 to 22 mm Hg, while end systolic diameter did not change significantly.
Stephen F. Vatner, Dean Franklin, Charles B. Higgins, Thomas Patrick, Eugene Braunwald
The free fatty acid (FFA) uptake and oxidation and the carbohydrate substrate exchange of leg muscles were studied during exercise in 14 patients with occlusive disease of the iliac or femoral arteries before and 3-6 months after reconstructive vascular surgery and in 5 healthy subjects. 14C-labeled oleic acid was infused continuously at rest and during exercise at work loads of 150-400 kg-m/min. The arterial concentration of FFA was similar both at rest and during exercise in patients and controls. The patients showed a smaller increase in the fractional turnover of FFA during exercise. Leg uptake and release of FFA in terms of micromoles per liter plasma did not differ significantly either at rest or during exercise between patients and controls. FFA oxidation could not be measured at rest but exercise data showed a lower fractional oxidation of FFA (P < 0.001) in the patient group (53±6%) compared with the controls (84±2%). For the entire material, fractional oxidation of FFA showed a significant negative regression on the lactate/pyruvate ratio in femoral venous blood. The ventilatory respiratory quotient (RQ) and the leg muscle exchange of glucose and lactate in the patients exceeded that of the controls. When six patients were studied after reconstructive surgery, fractional oxidation of FFA had risen from a preoperative value of 47±8 to 90±10%, other data for leg muscle FFA metabolism being unchanged.
L. Hagenfeldt, J. Wahren, B. Pernow, R. Cronestrand, S. Ekeström
The effect of chronic renal disease on bone matrix and mineral maturation was evaluated in rats with experimental renal insufficiency of 2-11 wk duration utilizing bromoform-toluene gradient fractionation of bone powder, pulse labeling experiments with 45Ca and proline-3H differential extraction, and X-ray diffraction techniques.
J. E. Russell, L. V. Avioli
The content and concentration of immunoreactive growth hormone (GH) were measured in 117 human fetal pituitary glands from 68 days of gestation to term and in the pituitary glands of 20 children 1 month to 9 yr of age. Physicochemical and immunochemical properties of GH of fetal pituitary glands and GH from adult pituitary glands were indistinguishable by disc gel electrophoresis, immunoelectrophoresis, starch gel electrophoresis, and radioimmunoassay techniques. In the fetal pituitary gland, the GH content rose from mean levels of 0.44±0.2 μg at 10-14 wk of gestation, to 9.21±2.31 μg at 15-19 wk, to 59.38±11.08 μg at 20-24 wk, to 225.93±40.49 μg at 25-29 wk, to 577.67±90 μg at 30-34 wk, and to 675.17±112.33 μg at 35-40 wk. There was a significant positive correlation between growth hormone content of the pituitary and gestational age, crown-rump length, and the weight of the pituitary gland.
S. L. Kaplan, M. M. Grumbach, T. H. Shepard
The present data disagree with earlier suggestions that thrombin's effect on platelets is to cause a decrease in intracellular cyclic 3′,5′-adenosine monophosphate. Washed human platelets or platelet-rich plasma were incubated at 37°C with human thrombin. After centrifugation, the supernates were assayed for nucleotides and calcium released. The platelet pellets, and in some experiments the supernates as well, were assayed by radioimmunoassay for intracellular cyclic AMP. In the washed platelet system, increasing doses of thrombin to 0.5 U/cc induced increasing release of nucleotides and calcium. This was accompanied by an average twofold increase in intracellular cyclic AMP levels. Prostaglandin E1, which inhibited 30-50% of release, induced a four- to fivefold increase in cyclic AMP levels that was additive to the cyclic AMP-stimulatory effect of thrombin. Theophylline, which inhibited only 20-40% of nucleotide release, was synergistic with thrombin in the intracellular accumulation of cyclic AMP. The time-course of cyclic AMP accumulation in response to thrombin was slower than thrombin-induced nucleotide release. Similar findings were made in the platelet-rich plasma system where thrombin stimulation of nucleotide release also resulted in a marked accumulation of intracellular cyclic AMP. Thrombin did not appear to stimulate the release of intracellular cyclic AMP.
Michael J. Droller, Sidney M. Wolfe
A new procedure for the radioimmunoassay of l-triiodothyronine (T3) in human plasma is described in which the iodothyronines are separated from the plasma proteins before incubation with a specific antiserum to T3. The antibody bound and free T3 are separated with dextran-coated charcoal. In this system, the mean recovery of T3 added to plasma was 97.9% and both in vitro conversion of l-thyroxine (T4) to T3 and cross-reaction between T4 and the anti-T3 antibody were undetectable (less than 0.1%). The assay procedure allowed the measurement of T3 in up to 0.5 ml of plasma resulting in improved assay sensitivity (6 ng/100 ml). The mean plasma T3 in normal subjects was 146±24 ng/100 ml (sd). Mean T3 concentration was increased in hyperthyroidism (665±289 ng/100 ml) and decreased in hypothyroidism (44±26 ng/100 ml). In patients with severe hypothyroidism, plasma T3 was between 7 and 30 ng/100 ml. Plasma T3 concentration was relatively constant throughout the day in three euthyroid subjects. In contrast, in hypothyroid subjects on replacement therapy with T3, a T4: T3 combination or desiccated thyroid plasma T3 was markedly elevated for several hours after ingestion of the medication. Plasma T3 was unchanged throughout the day in patients treated with T4. Thus, insofar as plasma T3 levels are concerned, replacement therapy with T4 appears to mimic the euthyroid state more closely than other preparations.
Martin I. Surks, Alan R. Schadlow, Jack H. Oppenheimer
The effects of elevated glucose concentrations on the metabolism of the aortic wall were examined in a preparation of tubular segments of rabbit descending thoracic aorta comprised of intima and media only. Increased medium glucose concentrations (20-50 mm) resulted in increased aortic sorbitol and fructose concentrations and an increased rate of fructose release into the medium. This increased flux through the polyol pathway can be explained as a consequence both of an increased free intracellular glucose concentration and of the kinetic characteristics of the alditol: NADP oxidoreductase and the l-iditol: NAD oxidoreductase isolated and partially purified from rabbit thoracic aorta. Incubation with elevated glucose concentrations for 2 or more hr was also associated with a significant increase in the water content of the tissue without a significant increase in the inulin space. The oxygen uptake of the tissues incubated with elevated glucose concentrations was significantly reduced; this appears to result from a limitation imposed by oxygen diffusion at physiological oxygen tensions. A compensatory increase in glycolysis and an increase in the aortic lactate/pyruvate concentration ratio were also observed. The oxygen uptake and lactate production of tissue incubated with 50 mm glucose could be preserved at rates observed in tissue incubated with a physiological glucose concentration by the addition of 40 mm mannitol to the medium. Aortic intima and media from alloxan-diabetic rabbits also exhibit an increased water content and a decreased rate of oxygen uptake. These observations suggest that elevated ambient glucose concentrations result in significant alterations in the metabolism of aortic intima and media.
Anthony D. Morrison, Rex S. Clements Jr., Albert I. Winegrad
The ability of cultured lymphoblasts to stimulate autologous lymphocyte transformation in “one-way” mixed leukocyte culture has been studied. Intact, cultured lymphoblasts required physical contact with responding lymphocytes to induce transformation. In quantitative terms, lymphocytes incorporate as much thymidine when mixed with irradiated cultured lymphoblasts as they do in response to phytohemagglutinin. The stimulation of lymphocyte transformation by allogeneic cultured lymphoblasts did not parallel the stimulation of lymphocyte transformation by leukocytes from the donor of the lymphoblast culture. The stimulatory determinants on the cultured lymphoblast are unaffected by neuraminidase but destroyed by trypsin. The trypsin-treated cultured lymphoblasts regain their capacity to stimulate autologous lymphocyte transformation within 48 hr in culture. Cultured lymphoblasts possess concanavalin A binding sites. Concanavalin A inhibits the capacity of cultured lymphoblasts to stimulate autologous lymphocyte transformation. The relevance of these findings to EB virus infection of cultured lymphoblasts and to immune surveillance is discussed.
Marc E. Weksler, Gary Birnbaum
15 patients with Paget's bone disease were treated with varying schedules of porcine (3.8-157.5 MRCU/kg per wk) and/or salmon (1.5-210 MRCU/kg per wk) calcitonins over periods ranging from 4 to 24 months. All of the subjects experienced a striking decrease in serum alkaline phosphatase during the first 4 months of treatment. In six patients, however, resistance to these peptides was suggested by a subsequent elevation of alkaline phosphatase activity in spite of continued and augmented hormone administration. These rebounds in alkaline phosphatase levels correlated with the appearance of calcitonin-binding substances and neutralizing material in serum. Incubations of calcitonins-125I and sera from these six subjects resulted in the association of radioactivity with material whose behavior on chromatoelectrophoresis (6/6), sucrose density ultracentrifugation and immunoelectrophoresis (one subject) was identical with that of 7S immunoglobulin. Specific, reversible in vitro binding of salmon calcitonins-125I was observed in sera obtained from these patients 5 to 12 months after initiation of salmon calcitonin therapy. All six of these subjects' sera acquired the capacity to neutralize salmon calcitonin's hypocalcemic effect in rat bioassay. Neutralization titers correlated with maximal binding capacities, which ranged from 0.042 to 6.6 mg/liter of serum. Competitive displacement of calcitonins-125I from the sera of one patient treated with both porcine and salmon calcitonin indicated separate populations of antibodies to these hormones. In spite of return of disease activity comparable to baseline levels, 3/5 resistant subjects treated with salmon calcitonin failed to develop hypocalcemia after injection of 300-1000 MRCU of salmon calcitonin, but two of these patients developed hypocalcemia in response to the porcine hormone. The disappearance of total radioactivity from the circulation after intravenous administration of salmon calcitonin-125I was retarded and the amount of serum radioactivity precipitable in 50% (NH4)2SO4 greater in 3/3 resistant patients compared to control subjects. These observations on the incidence of significant titers of neutralizing antibodies to salmon (40%) and porcine (66%) calcitonins during their chronic (> 4 months) administration to man clearly indicate that an appraisal of this possibility be included in studies involving protracted use of these hormones.
John G. Haddad Jr., Joseph G. Caldwell
The technique of platelet aggregometry provides a simple, quantitative, and specific method for the detection of drug-dependent and isoimmune antiplatelet antibodies. In the presence of antiquinidine antibody, quinidine causes lysis of normal platelets in platelet-rich plasma. The resulting changes in optical density are readily detected in the aggregometer. The initial rate of lysis is a function of the antibody titer, but is relatively independent of the platelet count. In vitro, quinidine produces platelet swelling and inhibits aggregation of platelets by adenosine diphosphate, epinephrine, and collagen. Isoimmune antibodies cause aggregation of platelets in platelet-rich plasma. In studies of a single family the rate of aggregation is proportional to the number of HL-A antigens present on the normal platelets against which the antibody is directed. The simple technique of platelet aggregometry may be a useful adjunct in the selection of compatible donors for platelet transfusion. Serum derived from patients with idiopathic thromboytopenic purpura did not cause platelet aggregation.
Daniel Deykin, Lewis J. Hellerstein
This study investigated the role of the mast cell in the pulmonary arterial pressor response to hypoxia. We found that pulmonary arteries 50-500 μ in diameter have a predictable distribution of perivascular mast cells; that such pulmonary mast cells are degranulated in vivo during alveolar hypoxia; that hypoxia releases histamine from mast cells isolated from the peritoneal cavity without apparent injury to the cells; and that histamine is released from the lung of intact guinea pigs during alveolar hypoxia, with the rise in pulmonary vascular resistance during this period proportional to the amount of histamine released. These data point to the perivascular pulmonary mast cell in the rat and guinea pig as an important structure in the mediation of the pulmonary pressor response to hypoxia, even though the responsible humoral vasoconstrictor released from such a cell may not be histamine, or histamine alone.
Francois Haas, Edward H. Bergofsky
Antigenic recognition of four anti-bovine parathyroid hormone antisera was characterized by their reactivity with bovine hormonal fragments (1-34, 1-13, 14-34, 19-34, 53-84) and human hormone extracted from parathyroid adenomas. All antisera were found to have antibody populations which recognized more than one antigenic determinant and all antisera differed in their specificity and reactivity for the fragments of bovine hormone. By modification of two antisera, GP-1 and GP-133, by preincubation with excess concentrations of 1-34 or 53-84 fragments, antigenic recognition was restricted to defined regions of the hormonal sequence.
Gino V. Segre, Joel F. Habener, David Powell, Geoffrey W. Tregear, John T. Potts Jr.
A model system utilizing a highly purified partially desialylated thyroxine-(T4) binding protein (STBG) was studied. STBG was prepared by the same affinity chromatographic method we have reported for preparation of highly purified T4-binding globulin (TBG). The necessary prerequisite for preparation of STBG was the use of T4-substituted Sepharose which had been repeatedly exposed to large volumes of serum for purification of TBG. STBG moved more slowly on cellulose acetate electrophoresis than TBG but had the same molecular weight and antigenic determinants as TBG. It bound T4 with a 1: 1 molar ratio but its affinity for T4 was about 10 times less than that of TB. STBG had about onefourth the sialic acid content of TBG and the electrophoretic mobility of this protein was similar to that of a T4-binding protein with a mobility slower than that of TBG which has been seen in the electrophoretic patterns of some normal human serums and in serums of patients with hepatic cirrhosis and which does not appear to be an artifact caused by storage and freezing of serum. This fourth slowly migrating T4-binding region in electrophoretograms of cirrhotic serums is completely abolished by prior incubation with rabbit antiserum to TBG. The in vitro production of partially desialylated TBG from T4-Sepharose which had been previously exposed to large volumes of serum may be due to adsorption of neuraminidases to the Sepharose either directly from serum or as the result of bacterial contamination. Partial desialylation of TBG in vivo may be an early step in the catabolism of this protein.
James S. Marshall, Jack Pensky, Allan M. Green
Most patients with stable cirrhosis of the alcoholic have “target” red cells; however, a minority have “spur” cells and severe hemolytic anemia. These two syndromes were studied in 27 patients with target cells and 17 patients with spur cells, all of whom had advanced cirrhosis. The cholesterol and phospholipid content of red cell membranes effectively distinguished target cells from spur cells. Target cells alone were rich in lecithin, and both the cholesterol/phospholipid and cholesterol/lecithin mole ratios were greater in spur cells. The cholesterol/phospholipid mole ratio of both types of red cells correlated closely with the free cholesterol saturation of serum lipoproteins, as defined by the amount of free cholesterol relative to phospholipid and protein in these lipoproteins. Lecithin: cholesterol acyltransferase (LCAT) activity was decreased in most patients with target cells and spur cells; however, the relationship between this activity and the lipid abnormalities observed was weak. Serum bile acid levels also correlated poorly with serum and cell lipids. However, in patients with target cells the amount of cholic and deoxycholic acids in serum was approximately equal to the amount of chenodeoxycholic acid, whereas in patients with spur cells chenodeoxycholic acid (the precursor of lithocholic acid) predominated.
Richard A. Cooper, Milagros Diloy-Puray, Patricia Lando, Mortimer S. Greenberg
A constant withdrawal pump was used to determine the integrated concentration of growth hormone (ICGH) which was used in conjunction with the metabolic clearance rate (MCR) of growth hormone (GH) to calculate the GH production rates (GHPR) in normal adults, acromegalics, and normal controls receiving prednisone.
Robert G. Thompson, Ana Rodriguez, Avinoam Kowarski, Robert M. Blizzard
16 patients underwent renal transplantation from a sibling donor who was prospectively determined to be ABO compatible and HL-A identical with the recipient. Unidirectional mixed leukocyte reactions were performed; in each instance, lymphocyte stimulation in either direction was not observed.
H. F. Seigler, J. C. Gunnells Jr., R. R. Robinson, F. E. Ward, D. B. Amos, D. T. Rowlands, P. M. Burkholder, W. J. Klein, D. L. Stickel
12 patients with Wiskott-Aldrich syndrome were treated with therapeutic doses of transfer factor in an attempt to induce cellular immunity. Clinical improvement was noted after transfer factor therapy in 7 of the 12 patients treated. Because this disease has a variable course and temporary spontaneous improvement can occur, the observed improvement cannot necessarily be attributed to the transfer factor. However, in two patients repeated remissions consistently followed transfer factor administration on repeated occasions. This included freedom from infections, regression of splenomegaly, and clearing of eczema. An unexpected finding was a decrease in bleeding in 3 of the 10 patients who had bleeding. Conversion of skin reactivity was obtained in all seven patients who clinically seemed to respond to transfer factor. In vitro studies performed after the administration of transfer factor demonstrated that the lymphocytes of the patients now produced migration inhibitory factor in response to appropriate test antigens, but did not undergo increased radioactive thymidine incorporation in response to the same antigens. A defect in the monocyte IgG receptors has been found in certain patients with the disease, and the current study shows that all patients with defective monocyte IgG receptors responded to transfer factor, whereas only one patient with normal receptors showed any response. This test may thus prove to be useful in predicting the results of transfer factor therapy in patients with Wiskott-Aldrich syndrome, although evaluation of a larger series of patients will be necessary to confirm this point. We conclude that cellular immunity can be induced, that there appears to be clinical benefit in certain patients with Wiskott-Aldrich syndrome by the use of transfer factor, and that this mode of therapy warrents trial in these patients and others with defects of cellular immunity.
Lynn E. Spitler, Alan S. Levin, Daniel P. Stites, H. Hugh Fudenberg, Bernard Pirofsky, Charles S. August, E. Richard Stiehm, Walter H. Hitzig, Richard A. Gatti
We have identified two populations of human lymphocytes differing in responsiveness to the plant mitogen concanavalin A (Con-A). When peripheral blood lymphocytes are passed through a nylon column a population of lymphocytes highly responsive to Con-A adheres to the fibers while a second population of cells relatively unresponsive to Con-A emerges from the column. The untreated peripheral blood lymphocytes are termed “unfiltered” cells while the lymphocytes which pass through the column are termed “filtered” cells.
David Boldt, Sister Ann Marie Skinner, Stuart Kornfeld
Because maximum expiratory flow-volume rates in normal subjects are dependent on gas density, the resistance between alveoli and the point at which dynamic compression begins (Rus) is mostly due to convective acceleration and turbulence. We measured maximum expiratory flow-volume (MEFV) curves in asthmatics and chronic bronchitics breathing air and He-O2. In the latter and in some asthmatics, MEFV curves did not change, indicating that Rus is mostly due to laminar flow. Therefore, the point at which dynamic compression begins must be further upstream than in normal subjects and the site of obstruction must be in small airways. In other asthmatics, flow increased normally indicating obstruction in larger airways. The response to He-O2 did not correlate with initial values of pulmonary resistance, the initial MEFV curves or the response to bronchodilators. We conclude that the site of airway obstruction varies among asthmatics and that the site of obstruction is not detectable by measurement of the usual parameters of lung mechanics.
P. J. Despas, M. Leroux, P. T. Macklem
Human red blood cells display under appropriate circumstances a ouabain-sensitive K-K exchange when the flux measurements are made using radioisotopes. Such an exchange complicates measurements of the coupling of Na outflux to K influx in cells which are partially depleted of energy sources by deprivation of glucose since the K-K exchange has been found to be increased in depleted cells. When the measurements of flux are made by estimating net cation movements chemically, it is found that glucose deprivation results in a fall in both ouabain-sensitive Na outflux and ouabain-sensitive K influx. Since both fluxes fell in concert, there is no reason for believing that the fluxes are not coupled or that the source of ATP for the Na outflux is different from that for the K influx.
John R. Sachs