Characteristics of Hydrogen Ion Transport in Urinary Bladder of Water Turtle

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Abstract

The mechanism of acidification by the urinary bladder of the water turtle was studied in an in vitro system which permitted control and measurement of electrical and concentration driving forces. The rate of hydrogen ion secretion was measured by means of a pH stat technique in the absence of exogenous carbon dioxide and bicarbonate.

Authors

Philip R. Steinmetz

Independence of Hydrogen Ion Secretion and Transport of Other Electrolytes in Turtle Bladder

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Abstract

The relationship between hydrogen ion secretion and the transport of other electrloytes was examined in the isolated urinary bladder of the water turtle. Symmetrical solutions which were free from exogenous carbon dioxide and bicarbonate bathed the two surfaces of the preparation, and the spontaneous electrical potential of the bladder was nullified by a voltage clamp. Active transport of sodium from mucosal to serosal medium was confirmed by simultaneous bidirectional flux measurements and found to be slightly, but not significantly, greater than the short-circuit current. In the absence of sodium in the bathing solutions, the normal potential difference across the bladder reversed and the current required to nullify this reversed potential difference had the same magnitude as the simultaneously measured rate of hydrogen ion secretion. The results indicate that, under these experimental conditions, the bladder transports sodium and hydrogen ion actively, but that chloride movement does not contribute to the short-circuit current.

Authors

Philip R. Steinmetz, Rodney S. Omachi, Howard S. Frazier

The Significance of Basal Insulin Levels in the Evaluation of the Insulin Response to Glucose in Diabetic and Nondiabetic Subjects

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Abstract

The level of insulin after an overnight fast (basal) in 37 obese and nonobese male subjects with normal and abnormal carbohydrate tolerance was directly related to the increase in insulin concentration during a 3 hr 100 g oral glucose tolerance test. Obesity, but not diabetes, was associated with an elevation of this basal insulin level. Thus obesity predicted with the magnitude of the insulin response to glucose ingestion. When the individual insulin values were expressed as per cent change from the basal level, this effect of obesity was excluded. The insulin levels of all subjects with normal carbohydrate tolerance promptly rose 5-7-fold, and reached peak values 1 hr after oral glucose. In contrast, the diabetic response (as per cent increase) was markedly reduced during the 1st hr, and maximal (but still subnormal) insulin levels were not attained until 2 hr. In all subjects the insulin response (quantitated by calculation of the area circumscribed by a plot of the per cent change in insulin with time) showed a significant inverse correlation with the glucose response. Thus increasing degrees of carbohydrate intolerance were associated with decreasing insulin responses. Elevated levels of insulin, in both the basal state and in response to glucose, were related to obesity.

Authors

John D. Bagdade, Edwin L. Bierman, Daniel Porte Jr.

Aldosterone in Metabolic Alkalosis

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Abstract

Studies have been carried out in human volunteer subjects to evaluate the role of aldosterone in the development, maintenance, and correction of metabolic alkalosis induced by selective depletion of hydrochloric acid. During the first phase of our study the rate of aldosterone secretion was measured before the induction of alkalosis (while the subjects were on a low salt diet) and again after a steady state of metabolic alkalosis had been established. The data demonstrate a fall in aldosterone secretion from a value of approximately 500 μg/day to a value of approximately 200 μg/day. Thus, it appears that an increased rate of aldosterone secretion is not a prerequisite to the elevation of the renal bicarbonate threshold.

Authors

Jerome P. Kassirer, Frederick M. Appleton, Joseph A. Chazan, William B. Schwartz

Restoration of Parathyroid Responsiveness in Vitamin D—Deficient Rats by Parenteral Calcium or Dietary Lactose

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Abstract

The effects of treatment with vitamin D, calcium, or lactose on the responsiveness of vitamin D—deficient rats to parathyroid hormone were compared. In the absence of vitamin D, parenteral calcium or dietary lactose administration resulted in increases in serum calcium concentration although not to the normal values obtained in animals given vitamin D. Dietary lactose also partially restored the low bone calcium content of vitamin D—deficient rats. Untreated vitamin D—deficient rats showed no significant changes in serum calcium concentration after parathyroidectomy or parathyroid extract administration. Vitamin D, lactose, and calcium all restored responsiveness to parathyroid hormone; serum calcium concentration decreased after parathyroidectomy and showed a dose-related increase in response to parathyroid extract. Hence, the unresponsiveness to parathyroid hormone in vitamin D deficiency may be due to a lack of calcium at a local site of action, presumably bone, rather than to the absence of vitamin D as a specific cofactor.

Authors

William Y. W. Au, Lawrence G. Raisz

Electrolyte-Labile Increase of Oxygen Affinity during In Vivo Aging of Hemoglobin

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Abstract

Normal human erythrocytes were separated according to in vivo age by ultracentrifugation. The “young” and “old” erythrocytes had mean cell ages of approximately 40 and 79 days, respectively. “Young” erythrocytes had a lower oxygen affinity and a higher heme-heme interaction than did “old” erythrocytes. This indicates an impairment of the oxygen-carrying function of erythrocyte hemoglobin with age.

Authors

Miles J. Edwards, Demetrios A. Rigas

Brain Metabolism during Fasting

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Abstract

Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that β-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.

Authors

O. E. Owen, A. P. Morgan, H. G. Kemp, J. M. Sullivan, M. G. Herrera, G. F. Cahill Jr.

Fatty Acid Biosynthesis in Human Leukocytes

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Abstract

Extracts from human leukocytes have been examined for the enzymes of de novo fatty acid biosynthesis. These extracts do not catalyze the synthesis of long-chain fatty acids because they lack acetyl CoA carboxylase, the first enzyme unique to the fatty acid synthesis pathway.

Authors

Philip W. Majerus, Rene Lastra R.

Diffusion Equilibrium for Ammonia in the Kidney of the Acidotic Dog

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Abstract

Inflow of preformed ammonia in arterial blood, renal production of ammonia, outflow of ammonia in renal venous blood, and urinary excretion of ammonia were measured during the infusion of 15NH4Cl into one renal artery of dogs with chronic metabolic acidosis. Our results show that the specific activity of ammonia measured in the urine and that calculated in the renal pool agree within 95%. Pool specific activity is obtained by dividing the rate of infusion of isotope by the pool turnover rate, i.e., the sum of the rate of ammonia output in the urine and that in renal venous blood. An average of 35% of urinary ammonia is derived from arterial ammonia in these experiments.

Authors

William J. Stone, Sulamita Balagura, Robert F. Pitts

Radioimmunoassay of β-MSH in Human Plasma and Tissues

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Abstract

A radioimmunoassay method for β-melanocyte-stimulating hormone (β-MSH) has been developed and utilized in the identification and quantification of this hormone in human plasma and tissues. The concentration of β-MSH in two human pituitary glands was found to be approximately 350 μg/g. β-MSH was identified in the tumor tissue of all 11 patients with the ectopic ACTH syndrome who were studied; concentrations in individual cases ranged from 3 to 1600 ng/g. In plasma of chronically hyperpigmented patients with Addison's disease, Cushing's disease (after bilateral adrenalectomy), and the ectopic ACTH syndrome, β-MSH concentrations of 0.5-6 ng/ml were found. The degree of clinical hyperpigmentation was well correlated with the quantity of β-MSH in the plasma. β-MSH concentrations in the plasma of normal subjects were less than 0.09 ng/ml. In all of these circumstances, bioassays for MSH were also performed, and it was found that most of the biologic MSH activity of the plasma and tissues could be accounted for by β-MSH.

Authors

Kaoru Abe, Wendell E. Nicholson, Grant W. Liddle, Donald P. Island, David N. Orth

Physiologic Studies of the Pulmonary Capillary Bed after Barium Sulfate Embolization

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Abstract

22 anesthetized dogs were given a barium sulfate suspension intravenously in a dose sufficient to double mean pulmonary artery pressure. 10 sec breath-holding carbon monoxide diffusing capacity (DLCO10) was measured before and after this standard embolization in each dog. No post-embolic decrease in DLCO10 was observed. In the study of this apparent paradox, it was found that the potential for further increase in DLCO10 during exercise remained after embolization. During rest prolongation of breath holding to 60 sec decreased CO absorption significantly more in the embolized than in the nonembolized dogs. While DLCO10 was not affected by standard barium embolization, oxygen diffusing capacity was clearly decreased. The bronchial collateral circulation did not participate in preventing a DLCO10 decrease after embolization since surgical interruption of the bronchial circulation did not alter the response to barium. Microscopic examination of lung sections taken after standard embolization showed plugging of precapillary vessels in the 40-50 μ range. These studies suggest that acute precapillary embolic obstruction of vessels of this size interferes remarkably little with CO absorption over short periods of time, probably because of continued CO absorption in portions of the capillary net distal to the sites of impaction. The remarkable anastomotic nature of this capillary network with multiple sources of access possibly provides the anatomic basis for this observation. This study demonstrates a clear dissociation between acute changes in pulmonary vascular resistance and DLCO10—both during rest and exercise.

Authors

Walter J. Daly, John A. Waldhausen

Effect of Pulmonary Blood Flow upon Lung Mechanics

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Abstract

Airway pressure was continuously recorded in an isolated horizontally mounted canine heart-lung preparation during abrupt, stepwise 100-200 ml inflations to 20-25 cm water pressure, and subsequent deflations. With each change in volume there was a steep rise or fall in pressure, followed by stress relaxation to a static equilibrium airway pressure. Comparison was made between the nonperfused state and during perfusion with whole blood at 100 ml/kg dog wt per min, and left atrial pressure of 10 mm Hg. Pressure tracings were similar during deflation in the perfused and the nonperfused lung. During inflation, in the middle range of lung inflation volumes, the peak inflation and equilibrium airway pressures were greater in the nonperfused state; maximum difference of static pressures in nine preparations averaged 146% of perfused values and the average stress relaxation difference from eight of these was 276%. Lung distensibility was the same with packed red cells or plasma perfusates and was not changed by varying the perfusion rate up to 220 ml/kg per min. During cyclic ventilation, dynamic compliance was similarly greater in the perfused than in the nonperfused state in the middle range of inflation volumes. Static distention of the vascular bed produced similar results with progressive improvement in distensibility in mid-inflation range up to a hydrostatic pressure of 15 cm blood. These data suggest that the distended pulmonary vascular bed provides structural airway support which facilitates entry of gas into the terminal respiratory units at diminished pressure.

Authors

Stanley Giannelli Jr., Stephen M. Ayres, M. E. Buehler

Intestinal Lymphangiectasia: a Protein-Losing Enteropathy with Hypogammaglobulinemia, Lymphocytopenia and Impaired Homograft Rejection

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Abstract

Intestinal lymphangiectasia is a disease characterized by dilated intestinal lymphatics, protein-losing enteropathy, hypoalbuminemia, and edema. The immunologic status of 18 patients with intestinal lymphangiectasia was studied. Concentrations of IgG, IgA, and IgM were measured by immune precipitation and metabolism of these three immunoglobulins was studied using purified radioiodinated proteins. The serum concentration and total body pool of each immunoglobin were greatly reduced. The fraction of the intravascular protein pool catabolized per day was increased to 34% for IgG, 59% for IgA, and 66% for IgM; these are in contrast with control values of 7%, 28%, and 17%, respectively. Synthetic rates of the immunoglobulins were normal or slightly increased.

Authors

W. Strober, R. D. Wochner, P. P. Carbone, T. A. Waldmann

Ventricular Arrhythmias and K⁺ Transfer during Myocardial Ischemia and Intervention with Procaine Amide, Insulin, or Glucose Solution

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Abstract

To assess the relation of ventricular arrhythmias to myocardial K+ movement during ischemia, we placed an electrode catheter in the left anterior descending coronary artery for thrombus production in intact anesthetized dogs. 85Kr injections distal to the thrombus permitted serial coronary blood flow measurements. Animals of Group I with a moderate flow reduction exhibited no arrhythmia or myocardial egress of K+. In Group II, marked flow reduction was accompanied by an injury potential and loss of K+ from the ischemic site, before and during ventricular tachycardia.

Authors

Timothy J. Regan, Maureen A. Harman, Patrick H. Lehan, William M. Burke, Henry A. Oldewurtel

Influence of the Thyroid State on the Intrinsic Contractile Properties and Energy Stores of the Myocardium

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Abstract

The intrinsic contractile properties of isolated cat papillary muscles and myocardial high energy phosphate stores were examined at three levels of thyroid activity and correlated with hemodynamic measurements in the intact animal. In addition, the relationship of thyroid state to endogenous norepinephrine stores and myocardial responsiveness to certain inotropic interventions were studied. In muscles from hyperthyroid cats, the velocity of shortening and the rate of tension development were markedly augmented, while duration of active state was decreased, compared to euthyroid muscles. These findings occurred in the presence and absence of intact norepinephrine stores and over a wide range of temperature and contraction frequency. The opposite changes occurred in muscles from hypothyroid cats. Isometric tension was slightly higher in muscles from hyperthyroid and lower in muscles from hypothyroid cats. The inotropic response to both norepinephrine and strophanthidin varied inversely with the level of thyroid state and allowed all three groups of muscles to reach a common ceiling of isometric tension regardless of thyroid state. Creatine phosphate and adenosine triphosphate stores were intact at all three levels of thyroid state. Thus, the level of thyroid activity profoundly affects the intrinsic contractile state of cardiac muscle, independent of both norepinephrine stores and alterations in high energy phosphate stores, and, in addition, modifies the responsiveness of cardiac muscle to inotropic agents.

Authors

Robert A. Buccino, James F. Spann Jr., Peter E. Pool, Edmund H. Sonnenblick, Eugene Braunwald

The Effect of Pendelluft and Dead Space on Nitrogen Clearance: Mathematical and Experimental Models and their Application to the Study of the Distribution of Ventilation

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Abstract

Reinspired mixed dead space gas and Pendelluft may be considered to be part of a single process of interalveolar gas transfer. The effect of interalveolar gas transfer on nitrogen clearance from a two chamber lung model can be described by a single set of equations which hold for synchronous, and series ventilation.

Authors

Ivan Safonoff, George E. Emmanuel