Albumin metabolism: effect of the nutritional state and the dietary protein intake

• Text
• PDF

Abstract

Authors

Studies on the prekallikrein (kallikreinagen)-kallikrein enzyme system of human plasma. I. Isolation and porification of plasma kallikreins

• Text
• PDF

Abstract

Authors

The resistance of collateral channels in excised human lungs

• Text
• PDF

Abstract

We measured the resistance of collateral channels, Rcol, in incomplete interlobar fissures in eight normal and eight emphysematous excised human lungs. Similar measurements were also made from the basal segments to the superior segment of the lower lobe in three normal and five emphysematous lungs. The lobe or segments were inflated through a bronchial cannula; air leaked through collateral channels and out of the other lobe or segment through a pneumotachograph which measured flow. Catheters inserted directly into the lung through the pleural surface on either side of the collateral channels measured the alveolar pressure difference producing collateral flow. Rcol is the ratio of this pressure difference to flow. By also measuring the inflating pressure and the airway pressure at the pneumotachograph, we calculated the lobar or segmental airway resistance, Raw. In the normal lungs Rcol varied inversely with lung volume and was higher on inflation than on deflation. Raw was very small compared to Rcol which ranged from 260 to 3300 cm H2O/liter per sec when the distending pressure was 20 cm H2O. In the emphysematous lungs on the other hand, Rcol was markedly decreased and ranged from 5 to 20 cm H2O/liters per sec at the same distending pressure and was less than Raw. We conclude that collateral channels are important ventilatory pathways in emphysema. When many units within a lung are ventilated by these pathways there may be disturbances of gas exchange and phase differences between normally and abnormally ventilated areas.

Authors

James C. Hogg, Peter T. Macklem, William M. Thurlbeck

Effects of potassium deficiency on renal function in the dog

• Text
• PDF

Abstract

Serial determinations of the renal clearance for inulin and para-aminohippuric acid (PAH), maximum renal tubular reabsorptive rate for glucose, maximum urinary concentrating ability, total exchangeable potassium, extracellular volume, and plasma sodium and potassium concentrations were done in seven dogs before and after dietary potassium depletion. The same measurements were also made in two of the dogs during potassium repletion.

Authors

Peter H. Abbrecht

Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia

• Text
• PDF

Abstract

Erythropoiesis in normal man was studied during periods of phlebotomy-induced anemia of varying severity. This study permitted a comparison of marrow production measurements over a wide range of marrow production levels. As long as the serum iron remained above 50 μg/100 ml, measurements of plasma iron turnover provided an excellent index of marrow production at all levels of red cell production. In contrast, the absolute reticulocyte count demonstrated a poor correlation with the other measurements. This was shown to be the result of a prolongation of the time required for circulating reticulocytes to lose their reticulum, which correlated with the severity of the anemia. For the clinical application of the reticulocyte count as a measurement of marrow production, an adjustment must be made for this alteration in the circulating reticulocyte maturation time.

Authors

Robert S. Hillman

Control of marrow production by the level of iron supply

• Text
• PDF

Abstract

The level of erythroid marrow production varies widely in different erythropoietic disorders. In part, this reflects the level of erythropoietin stimulation as determined by the severity of the anemia. However, iron supply plays an equally important role in the control of erythropoiesis. As demonstrated in normal individuals subjected to prolonged periods of phlebotomy-induced anemia, the erythroid marrow will increase production by as little as twice to as much as eight times normal, depending on the iron supply available from different iron pools. Whereas the iron delivered from normal reticuloendothelial stores or orally administered iron is sufficient for a marrow production response of only two to three times normal, the increased iron supply from nonviable red cells, hemolysis, or iron dextran infusions permits marrow production to rise acutely to levels of four to eight times normal.

Authors

Robert S. Hillman, Perry A. Henderson

Mannose metabolism in the human erythrocyte

• Text
• PDF

Abstract

The metabolism of mannose by human erythrocytes has been investigated. Phosphorylation of mannose is achieved by an enzyme with electrophoretic mobility on starch gel indistinguishable from the glucose-phosphorylating enzyme. Mannose phosphorylation is competitively inhibited by glucose; glucose phosphorylation is competitively inhibited by mannose. The Ki values of inhibition are similar to the Km values for uninhibited phosphorylation. The normal average mannose-phosphorylating activity was found to be 0.69 U/g of Hb; the normal average glucose-phosphorylating activity was found to be 0.64 U/g of Hb. The ratio of mannose-phosphorylating activity to glucose-phosphorylating activity of a hemolysate prepared from the red cells of a subject with hexokinase deficiency was found to be within the normal range.

Authors

Ernest Beutler, Leslie Teeple

Reflex Cardiovascular Depression Produced By Stimulation Of Pulmonary Stretch Receptors In The Dog

• Text
• PDF

Abstract

To study the possible reflex effects of stimulation of pulmonary stretch receptors on the cardiovascular system, experiments were designed that would allow separate assessment of the responses of the heart, the total peripheral vascular resistance, and the resistance of the innervated hindlimb that was perfused at a constant flow rate. In every experiment, inflation of the lungs to a positive pressure of 20 mm Hg produced significant negative inotropic and chronotropic effects. Heart rate fell an average of 22.3±3.8% (SEM) (P < 0.01), pressure recorded from within an isovolumic balloon in animals on total cardiopulmonary bypass fell an average of 14.3±4.6% (P < 0.05), dp/dt recorded from within the balloon declined an average of 31.4 ± 6.0% (P < 0.01), and contractile force measured with a Walton-Brodie strain gauge arch fell an average of 18.6 ±2.2% (P < 0.01). Similarly, a depressor response to inflation of the lungs was noted in the periphery as manifested by an average decrease in total peripheral vascular resistance of 21.9±2.5% in the animals on total cardiopulmonary bypass (P < 0.01), and by an average decrease in perfusion pressure in the isolated hindlimb of 26.0 ±3.8% (P < 0.01). After bilateral cervical vagotomy, the cardiovascular responses to inflation of the lungs were either abolished or markedly lessened. Thus, sudden expansion of the lungs activates the afferent arm of a depressor reflex, which produces negative inotropic and chronotropic responses, in addition to arterial vasodilation. The receptors are sensitive to stretch and the afferent pathway runs predominantly in the vagus nerves.

Authors

Gerald Glick, Andrew S. Wechsler, Stephen E. Epstein

Micropuncture study of water, electrolytes, and urea movements along the loops of henle in psammomys

• Text
• PDF

Abstract

The mechanism by which the osmotic pressure increases in tubular fluid along the descending limb of the loop of Henle was examined in Psammomys undergoing salt diuresis. In two series of experiments, micropuncture samples were collected either from proximal and distal convolutions at the surface of the cortex, or from loops of Henle and collecting ducts at the surface of the extrarenal part of the papilla. Inulin-3H, urea-14C, Na+, and K+ concentrations, as well as osmotic pressure, were determined in all micropuncture samples.

Authors

C. de Rouffignac, F. Morel

Indicator dilution measurements of extravascular water in the lungs

• Text
• PDF

Abstract

Multiple indicator dilution studies of the pulmonary circulation were carried out in conscious, resting and exercising, and anesthetized dogs under conditions where there was no pulmonary edema. Labeled red cells, water, and albumin were injected together into the pulmonary artery, and effluent dilution patterns were obtained from the descending thoracic aorta. The product of the mean transit time differences between labeled water and red cells, and the pulmonary water flow was used to estimate extravascular parenchymatous water; and this was expressed as a proportion of the water content of the blood-drained lung at postmortem examination. These estimates of the proportional water content were found to increase with flow, and to approach an asymptotic value. Reconsideration of the flow patterns in capillaries, however, led to the postulate that extravascular water should be calculated, utilizing as the appropriate vascular reference a substance that uniformly labels the water in red cells and plasma, and which is confined to the circulation, rather than a tracer that only labels red cells. The mean transit time of this substance is approximated by the sum of the mean transit times of labeled red cells and albumin, each weighted according to the proportion of the water content of blood present in that phase. The values for lung water content so computed also increased with flow, and appeared to approach an asymptote that corresponded to approximately two-thirds of the wet lung weight. The estimated values for the water space after pentobarbital anesthesia corresponded to the lower values obtained in the resting conscious animals. When the anesthetized animals were also bled, the estimated water space was disproportionately large, in relation to the previous values. These experimental results support the hypothesis that dilutional estimates of the lung water space reflect pulmonary capillary filling; that this filling increases with exercise; and that a relative increase in filling also occurs as part of the response to hemorrhage.

Authors

Carl A. Goresky, Robert F. P. Cronin, Brita E. Wangel

Hemodynamic effects of isoproterenol and norepinephrine in acute cardiac tamponade

• Text
• PDF

Abstract

The hemodynamic effects of isoproterenol infusion, 0.5 μg/kg per min were evaluated in eight intact anesthetized dogs during cardiac tamponade. During tamponade, the mean of pericardial pressures was increased from — 1.5 to 12.5 mm Hg, and the mean of right atrial pressures was increased from 1 to 12.4 mm Hg. Mean cardiac output fell from 144.8 to 44.8 ml/kg per min (P < 0.001), and rose to 105.6 ml/kg per min (P < 0.001) with isoproterenol. Mean cardiac stroke volume fell from 20.3 to 6.1 ml during tamponade (P < 0.001) and rose to 12.1 ml with isoproterenol (P < 0.001). The heart rate increased from 193.3 beats/min during tamponade to 217.5 beats/min with isoproterenol (P < 0.05). During isoproterenol infusion, the mean right atrial pressure and mean pericardial pressure decreased significantly. With cardiac tamponade, the mean blood pressure fell from 157.5 to 126.1 mm Hg (P < 0.01) and did not change significantly with isoproterenol, 11 additional animals were studied with norepinephrine infusion during tamponade. There were no consistent hemodynamic effects with infusions of 0.5 and 1 μg/kg per min. With norepinephrine 2, 5, and 10 μg/kg per min cardiac output rose in some experiments. Isoproterenol infusion increased the cardiac output during tamponade principally by increasing cardiac stroke volume and to a lesser degree by increasing the heart rate. It is postulated that the increased stroke volume resulted from an increased ejection fraction with greater decrease in end-systolic than end-diastolic ventricular volume. These effects are consistent with the known positive inotropic, peripheral vasodilator, and positive chronotropic effects of isoproterenol.

Authors

Noble O. Fowler, John C. Holmes

Studies on human thyroxine-binding globulin (TBG): I. Purification of TBG and immunologic studies on the relationship between TBG from normal persons and those with TBG “deficiency”

• Text
• PDF

Abstract

A method for obtaining highly purified thyroxine-binding globulin (TBG) from whole human serum is presented. The method employs relatively simple procedures of step-wise ammonium sulfate precipitation followed by column chromatography on DEAE cellulose and DEAE Sephadex. The final product produces a single protein band on disc electrophoresis. The sedimentation constant of the TBG thus purified is 3.91 and its calculated mol wt is 54,000. An antiserum to the highly purified TBG produced a single arc on immunoelectrophoresis. When the antiserum was reacted against normal human serum or against serum from subjects deficient in TBG, each produced two arcs—one identical with that produced by the antigen alone. The second arc is probably the result of a contaminating protein in the antigen, present in too low a concentration to be detectable by disc gel electrophoresis. It is concluded that some persons with TBG “deficiency” have a circulating protein, immunologically indistinguishable from TBG, which is defective in its ability to bind thyroxine.

Authors

James S. Marshall, Jack Pensky

Radioiodination of human intrinsic factor

• Text
• PDF

Abstract

Human intrinsic factor (IF) saturated with 60Co-labeled cyanocobalamin (60CoB12) was purified and then iodinated with 125I to yield 125I-labeled IF-60CoB12 preparations of high specific activity. Sephadex G200 and DEAE-cellulose chromatography of the iodinated IF-60CoB12 complex showed coincidence of the major 125I and the 60Co radioactivity peaks. During starch-gel electrophoresis 60Co radioactivity from noniodinated and iodinated complexes migrated to the same extent while 125I radioactivity from the iodinated complex migrated slightly further anodally than did the 60Co radioactivity. After the iodinated complex was mixed with antibody to the IF-B12 complex (antibody II) the 125I and 60Co radioactivity were: (a) precipitated in similar amounts by antiglobulin serum. (b) eluted coincidentally in the 19S region on Sephadex G200, and (c) excluded to the same extent from starch gel during electrophoresis. After equilibrium exchange of IF “blocking” antibody (antibody I) for 60Co-vitamin B12 on 125I-labeled IF. 125I radioactivity from the IF-antibody I complex: (a) was precipitated by antiglobulin serum, (b) was eluated in the 19S region on Sephadex G200 gel filtration, and (c) migrated slowly towards the anode on starch-gel electrophoresis. Urinary excretion of 60Co radioactivity in pernicious anemia patients after oral administration of 60Co-vitamin B12 bound to freshly prepared 125I-labeled IF was similar to that obtained with noniodinated intrinsic factor.

Authors

Iain L. Mackenzie, Robert M. Donaldson Jr., Robert F. Schilling

Hemoglobin Hiroshima (β¹⁴³ histidine → aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia

• Text
• PDF

Abstract

During a survey for hemoglobinopathies in over 9000 residents of Hiroshima Prefecture, Japan, a fast moving hemoglobin was identified in eight members of three generations in a Japanese family. The abnormal hemoglobin, named Hb Hiroshima, constitutes about 50% of the total hemoglobin in hemolysates from the carriers who have a mild erythremia but are otherwise apparently clinically unaffected. All preparations of Hb Hiroshima have increased affinity for oxygen, by either tonometric or oxygen electrode determinations. At pH 7.0, the oxygen pressure, P50 required to half saturate an unfractionated hemolysate from a carrier was one-half that of Hb A, and the P50 of a purified sample containing no Hb A was one-fourth that of Hb A. The pH dependence of the oxygen equilibrium (Bohr effect) is below normal, as shown by the absolute value of the Bohr effect factor which is about half that of Hb A, in the pH range between 7.0 and 7.4. The Hill constant, n, for Hb Hiroshima between pH 7.0 and 7.4 is 2-2.4, compared to 2.8-3 for Hb A under the same conditions, indicating reduction of, but not complete abolition of heme-heme interaction. Urea dissociation and canine hybridization tests located the biochemical lesion in the beta chain. Fingerprints (Ingram), carboxypeptidase digestion, and amino acid analysis demonstrated that the substitution was at residue 143 in the beta chain, where histidine was replaced by aspartic acid.

Authors

Howard B. Hamilton, Iwao Iuchi, Takaoki Miyaji, Susumu Shibata

Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid

• Text
• PDF

Abstract

Acetylsalicylic acid (aspirin) acetylates human serum albumin under physiologic conditions in vitro. These investigations were done to determine whether this phenomenon occurs in vivo and to delineate the site(s) of acetylation on the albumin molecule.

Authors

David Hawkins, R. Neal Pinckard, Irving P. Crawford, Richard S. Farr

The proteinpolysaccharides of human costal cartilage

• Text
• PDF

Abstract

Water-soluble proteinpolysaccharides, called PPL, can be extracted from bovine nucleus pulposus in yields of 45%, and from bovine nasal cartilage in yields of 37% of the dry tissue weight. From human costal cartilage only 7% can be extracted. The method used to separate PPL from each of the first two tissues into four distinct fractions separates the PPL of human costal cartilage into four fractions called PPL 3, PPL 4, PPL 5, and PPL 6, which show an increase in protein content, a decrease in chondroitin sulfate content, a nearly constant keratan sulfate content, and an increase in ease of sedimentability and molecular weight. From each of the three tissues mentioned. PPL 3 has a similar amino acid profile and so does PPL 5, but PPL 5 differs from PPL 3 in having a lower content of serine and higher contents of aspartic acid, tyrosine, and arginine. A more extensive effort to characterize these products has been made by analytical ultracentrifugation, and this has led to a further fractionation of PPL 5.

Authors

Lawrence Rosenberg, Blanche Johnson, Maxwell Schubert

Inherited deficiency of the third component of human complement (C′3)

• Text
• PDF

Abstract

A kindred has been investigated in which seven individuals were found to have half-normal serum concentrations of the third component of complement (C′3). This partial deficiency was transmitted as an autosomal dominant trait. Affected individuals were entirely healthy. Hemolytic complement titers were slightly reduced but immune adherence titers and reagent titrations of the classical complement components were normal.

Authors

Chester A. Alper, Richard P. Propp, Martin R. Klemperer, Fred S. Rosen, Lillian Watson

Recurrent fever of unknown etiology: failure to demonstrate association between fever and plasma unconjugated etiocholanolone

• Text
• PDF

Abstract

A sensitive method for determination of plasma unconjugated etiocholanolone by double-isotope-derivative dilution has been described. The mean values for normal subjects was 0.038±0.003 (SEM) μg/100 ml.

Authors

Jack M. George, Sheldon M. Wolff, Esther Diller, Frederic C. Bartter

Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects

• Text
• PDF

Abstract

We have examined the interrelationships among transpulmonary pressure, flow, and volume during exhausting exercise in 10 normal adult males. Expiratory transpulmonary pressures during exercise were compared with flow-limiting pressures measured at rest by two techniques. In no case did pressures developed during exercise exceed to an appreciable extent the flow-limiting pressures. This indicates that, during near-maximal exercise, ventilation remains efficient as judged in terms of the pressure-volume relationships of the lung. The mechanical properties of the lung do not appear to limit ventilation during exhausting exercise in normal subjects. We could find no relationship between the magnitude of transpulmonary pressure and exercise limitation. There was no evidence that lung mechanics changed during exhausting exercise in normal subjects. The two methods for estimating expiratory flow-limiting pressures, the orifice technique and the isovolume pressure-flow method, gave similar results.

Authors

Snorri Olafsson, Robert E. Hyatt

Liver and kidney metabolism during prolonged starvation

• Text
• PDF

Abstract

This study quantifies the concentrations of circulating insulin, growth hormone, glucose, free fatty acids, glycerol, β-hydroxybutyrate, acetoacetate, and alpha amino nitrogen in 11 obese subjects during prolonged starvation. The sites and estimated rates of gluconeogenesis and ketogenesis after 5-6 wk of fasting were investigated in five of the subjects.

Authors

Oliver E. Owen, Philip Felig, Alfred P. Morgan, John Wahren, George F. Cahill Jr.

Amino acid metabolism during prolonged starvation

• Text
• PDF

Abstract

Plasma concentration, splanchnic and renal exchange, and urinary excretion of 20 amino acids were studied in obese subjects during prolonged (5-6 wk) starvation. Splanchnic amino acid uptake was also investigated in postabsorptive and briefly (36-48 hr) fasted subjects.

Authors

Philip Felig, Oliver E. Owen, John Wahren, George F. Cahill Jr.