Movement of the Feline Esophagus Associated with Respiration and Peristalsis. AN EVALUATION USING TANTALUM MARKERS

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Abstract

The outer, lateral esophageal walls in the distal half of the esophagus in each of five cats were labeled with small tantalum wires. About 8 wk later, esophageal motion associated with respiration and peristalsis, induced by injecting barium boli (5 ml each) into the proximal esophagus, was recorded on cine and serial biplane roentgenograms while recording intraluminal esophageal pressures simultaneously by manometry. Esophageal motion was also evaluated without a manometric tube in place. The coordinates for each marker were digitized and a computer was used to plot marker position against time. During respiration, the markers passively made a shallow, 2-10 mm excursion on the longitudinal esophageal axis. This movement was synchronous with thoracic and diaphragmatic movement and changes in intraluminal esophageal pressure. Immediately after the onset of peristalsis, the markers made a pronounced oral movement of 10 mm or more above their mean respiratory position, as if to engulf the bolus. Markers in opposing esophageal walls approximated one another and commenced an aboral movement as the bolus tail, which was essentially co-incident with onset of the manometric pressure complex, passed the marker sites. The markers returned to their respective rest positions essentially coincident with passage of the pressure complex peak and then moved below their respective rest positions. The aboral excursion occurred predominantly after the bolus had emptied into the stomach. The magnitude and duration of oral excursion was significantly greater for the distal than for the more proximal markers; conversely, the magnitude and duration of aboral excursion was greater for the proximal than for the more distal markers. During the peristaltic sequence, the labeled portion of the esophagus shortened from 26 to 46% of its resting length. No evidence of esophageal torque was shown. These findings suggest that both the longitudinal and circular esophageal musculature play an active and important role during peristaltic transport of a bolus through the esophagus.

Authors

Wylie J. Dodds, Edward T. Stewart, Donald Hodges, F. Frank Zboralske

Lower Esophageal Sphincter Relaxation: Studies on the Neurogenic Inhibitory Mechanism

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The purpose of this study was to determine the physiological mechanism of lower esophageal sphincter (LES) relaxation. Circular muscle of the esophagus, LES, and stomach were evaluated for their inhibitory response to electrical stimulation during a maintained tonic contraction produced by a superfusion of acetylcholine and physostigmine. Only the circular muscle of the distal esophagus showed an inhibitory response to electrical stimulation. The maximal inhibition of LES muscle was 63.9±5.9 (mean±SE)% of the acetylcholine produced tension and occurred at 80 V. Upper esophageal and gastric muscle were not inhibited. The inhibitory response of the LES muscle was antagonized by tetrodotoxin and hexamethonium but not by other specific antagonists. Adrenergic nerve destruction following 6-hydroxydopamine also did not abolish the LES inhibition. These data indicate that the distal esophagus, at the zone of the manometrically determined LES, is characterized by a nonadrenergic neural inhibitory system. We suggest that these nerves may mediate LES relaxation.

Authors

Arthur Tuch, Sidney Cohen

Renal Response to Chronic Intravenous Salt Loading in the Rat

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Abstract

The natriuresis of acute Ringer's loading is associated with a rise in the rate of delivery of fluid beyond the proximal tubule due both to a rise in glomerular filtration and a fall in absolute reabsorption, the latter being causally mediated, at least in part, by the accompanying fall in postglomerular vascular [protein]. To determine whether these factors also contribute to the renal response to chronic Ringer's loading, nine rats given continuous infusions, 30% body weight/day over 5-14 days, were studied using free-flow micro-puncture techniques. Results were compared with data from 10 chronic control rats given less than 1.5% body wt/day. Late proximal tubule fluid-to-plasma [inulin] ratios, (TF/P)IN, single nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption, and postglomerular vascular [protein] in chronic control rats and chronically loaded rats averaged 2.2±SE 0.1 (n = 35) and 1.5±0 (35), P<0.001; 37±2 (35) and 47±4 nl/min (35), P<0.05; 19±1 (35) and 16±2 nl/min (35), P>0.2; and 9.5±0.3 (8) and 8.6±0.3 g/100 ml (8), P>0.05, respectively. Thus the fall in (TF/P)IN and the rise in distal delivery during chronic Ringer's loading were due almost entirely to the rise in SNGFR, and not to any large fall in absolute reabsorption. Hence chronic and acute Ringer's loading increase delivery of proximal tubule fluid by different mechanisms, with chronic sodium homeostasis being governed overwhelmingly by adjustments in GFR. When, however, an acute Ringer's load was infused into chronically loaded rats, we observed significant and parallel reductions in absolute proximal reabsorption and postglomerular vascular [protein]. These findings suggest that the difference between the effects of chronic vs. acute Ringer's loading on absolute proximal reabsorption may have been due, at least in part, to the corresponding difference in the effects these two loading procedures have on postglomerular vascular [protein].

Authors

Terrance M. Daugharty, Iris F. Ueki, Delys P. Nicholas, Barry M. Brenner

Interchange of Apolipoproteins between Chylomicrons and High Density Lipoproteins during Alimentary Lipemia in Man

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Apolipoproteins of the “C” group in human blood plasma, which contain the activator of the lipoprotein lipase-substrate interaction, were found to be transferred specifically from serum to phospholipid-stabilized fat emulsion. Content and distribution of apoprotein activator were measured in healthy men in the postabsorptive state and 4 h after ingestion of meals containing 100 g fat. Content of activator protein in whole serum did not change after ingestion of the fat-rich meals but that contained in triglyceride-rich lipoproteins of density (d) <1.006 approximately doubled whereas that of high density lipoproteins fell by half. The increased activator content of triglyceride-rich lipoproteins was virtually confined to chylomicrons and its concentration in chylomicron apoprotein was substantially greater than that in very low density lipoproteins. This difference could be ascribed largely to a higher content of C apoproteins in chylomicron protein since both the concentration of C apoproteins and of apoprotein activator were directly proportional to particle diameter while the pattern of fast-migrating C apoproteins in polyacrylamide gels was similar among chylomicrons and subfractions of very low density lipoproteins. Apparent concentration of activator protein was much greater in the high density lipoprotein subfraction of d 1.063-1.125 than in the subfraction of d 1.125-1.21. In the subfraction of d 1.063-1.125, the concentration of activator protein and of fast-migrating C apoproteins in polyacrylamide gels decreased after the fat-rich meal. Concentration of phospholipids in this fraction increased gradually to a peak 43% above the basal value 6 h after the meal. The results obtained demonstrate that high density lipoproteins contribute certain functionally important polar constituents to chylomicrons during alimentary lipemia in man and suggest that they also receive surface constituents from chylomicrons during the course of their metabolism.

Authors

Richard J. Havel, John P. Kane, Moti L. Kashyap

Mechanism of the Redistribution of Renal Cortical Blood Flow during Hemorrhagic Hypotension in the Dog

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Studies were performed to define the mechanisms involved in the redistribution of renal cortical blood flow to inner cortical nephrons which occurs during hemorrhagic hypotension in the dog. The radioactive microsphere method was utilized to measure regional blood flow in the renal cortex. Renal nerve stimulation decreased renal blood flow 40% but had no effect on the fractional distribution of cortical blood flow. Pretreatment with phenoxybenzamine, phentolamine, propranolol, or atropine did not alter the redistribution of cortical flow during hemorrhage. A reduction in renal perfusion pressure by aortic constriction caused a qualitatively similar alteration in regional blood flow distribution as occurred during hemorrhage. When perfusion pressure was kept constant in one kidney by aortic constriction followed by hemorrhage, no redistribution occurred in the kidney with a constant perfusion pressure while the contralateral kidney with the normal perfusion pressure before hemorrhage had a marked increase in the fractional distribution of cortical flow to inner cortical nephrons. Additionally, retransfusion had no effect on the fractional distribution of flow in the kidney in which perfusion pressure was maintained at the same level as during hemorrhage while in the contralateral kidney in which pressure increased to normal there was a redistribution of flow to outer cortical nephrons. These studies indicate that the redistribution of renal cortical blood flow which occurs during hemorrhage is not related to changes in adrenergic activity but rather to the intrarenal alterations which attend a diminution in perfusion pressure.

Authors

Jay H. Stein, Sampanta Boonjarern, Richard C. Mauk, Thomas F. Ferris

Alterations in Cyclic Adenosine Monophosphate Metabolism in Human Bronchial Asthma. I. LEUKOCYTE RESPONSIVENESS TO β-ADRENERGIC AGENTS

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In an effort to better define the role of βadrenergic blockade in human bronchial asthma, peripheral blood leukocytes and lymphocytes from individuals with this condition were studied for possible alterations in cyclic AMP metabolism. Using a previously described radioimmunoassay to measure cyclic AMP, cells from asthmatic subjects were shown to have a highly significant decrease in their cyclic AMP response to β-adrenergic agents (isoproterenol, norepinephrine, and epinephrine) by comparison with normal control cells. The alteration in responsiveness was most marked at the time of severe active asthma and returned toward normal during periods of clinical remission. Evidence was presented to indicate that the reduced response in cells from asthmatic individuals was not due to marked alterations in the proportion of T and B lymphocytes. Five normal volunteers were treated with an oral bronchodilator preparation containing theophylline and ephedrine over a 2 wk period without a significant change in the lymphocyte cyclic AMP response.

Authors

Charles W. Parker, Jay W. Smith

Degradation of Thyroid Hormones by Phagocytosing Human Leukocytes

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Thyroxine (T4) and triiodothyronine (T9) are rapidly degraded by a purified preparation of myeloperoxidase (MPO) and H2O2 with the formation of iodide and material which remains at the origin on paper chromatography. Deiodination by MPO and H2O2 occurs more readily at pH 7.0 than at pH 5.0 in contrast to iodination by this system which is known to occur more readily at pH 5.0 than at pH 7.0. Degradation is inhibited by azide, cyanide, ascorbic acid, and propylthiouracil. Methimazole stimulates deiodination by MPO and H2O2 but inhibits this reaction when MPO is replaced by lactoperoxidase or horseradish peroxidase.

Authors

Seymour J. Klebanoff, William L. Green

Estrogen Receptors in Human Breast Cancer

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Specific quantitative techniques have been used to measure the cytoplasmic estradiol-binding protein (EBP) in human mammary carcinoma tissue specimens. Sucrose gradient centrifugation reveals EBP to sediment at 8S and 4S. Variable quantities of non-specific estradiol binding occurs in the 4S region of the sucrose gradient necessitating controls to insure specificity of the estradiol protein interaction.

Authors

William L. McGuire

Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis

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The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T4) distribution and metabolism and on serum total and free T4 concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T4 from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T4 disposal. In the infected monkeys, serum total T4 and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T4 were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T4 kinetics could neither be correlated with changes in the binding of T4 in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T4 disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T4 during bacterial sepsis, possibly related to phagocytic cell function in the host.

Authors

Frederick R. DeRubertis, Kenneth A. Woeber

Lingual Lipase and Its Role in the Digestion of Dietary Lipid

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The serous glands of rat tongue were found to contain a potent lipolytic enzyme which hydrolyzed triglyceride to mostly diglyceride and free fatty acids (FFA) at pH 4.5-5.4. Homogenates of lingual serous glands from adult rats hydrolyzed 40-70 mmol of triglyceride/g per h. The soft palate, anterior oral pharyngeal wall, and lateral oral pharyngeal glands also contained the activity, but at a much lower level. The lipolytic activity was also found in saliva collected through an esophageal cannula and in stomach contents of rats fed a fat-rich meal. The stomach contained very little activity, however, when saliva was excluded. Lipolytic activity was not found in the stomach wall or in the parotid, submandibular, and sublingual glands. The findings suggest that the lingual serous glands secrete a lipase which catalyzes in the stomach the conversion of triglyceride to partial glycerides and FFA. It is proposed that this reaction is the first step in the digestion of dietary lipid.

Authors

Margit Hamosh, Robert O. Scow

Erythropoietic Porphyria of the Fox Squirrel Sciurus niger

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Uroporphyrin I is found in high concentration in the bones, teeth, blood, soft tissues, and urine of the fox squirrel, Sciurus niger. The concentration of uroporphyrin in fox squirrel spleen is much higher than in liver, kidney or bone marrow, probably because of accumulation from phagocytosed red cells. Bleeding causes a marked increase in the uroporphyrin concentration of red cells and spleen, and a 3-8-fold increase in uroporphyrin excretion. Urinary excretion of δ-aminolevulinic acid and porphobilinogen is not greater in fox squirrels than in nonporphyric gray squirrels. Sciurus carolinensis, used as controls. In all these characteristics, as well as in the previously demonstrated deficiency of the enzyme uroporphyrinogen III cosynthetase in red cells, the physiological porphyria of fox squirrels resembles congenital erythropoietic porphyria, a hereditary disease of man and cattle. For squirrels differ in showing no evidence of cutaneous photosensitivity or hemolytic anemia.

Authors

Ephraim Yale Levin, Vagn Flyger

Studies on Mono- and Diiodohistidine. I. THE IDENTIFICATION OF IODOHISTIDINES FROM THYROIDAL IODOPROTEINS AND THEIR PERIPHERAL METABOLISM IN THE NORMAL MAN AND RAT

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The problem as to whether iodohistidines are normally biosynthetized in thyroglobulin and thyralbumin has been examined both in man and the rat. Evidence has been obtained for the first time that diiodohistidine (DIH) is present in both species in these two iodoproteins. The biosynthesis of monoiodohistidine (MIH) in the thyroglobulin of the normal rat has been confirmed and extended to rat thyralbumin and to human thyroid iodoproteins.

Authors

J. C. Savoie, P. Thomopoulos, F. Savoie

Studies on Mono- and Diiodohistidine. II. CONGENITAL GOITROUS HYPOTHYROIDISM WITH THYROGLOBULIN DEFECT AND IODOHISTIDINE-RICH IODOALBUMIN PRODUCTION

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Butanol-insoluble iodinated compounds in the urine of patients with congenital goiters have been generally regarded as iodopeptides. Monoiodohistidine (MIH) and diiodohistidine (DIH) were identified from the urine of four patients with congenital goitrous hypothyroidism. From radioiodine studies, 40-70% of the urinary radioactivity was in the iodide-free fraction from which about 40% was identified as MIH and DIH by crystallizations to a constant specific activity.

Authors

J. C. Savoie, J. P. Massin, F. Savoie

Mode of Action of Chemotherapy In Vivo on Human Acute Leukemia. I. DAUNOMYCIN

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The leukocytes of 16 adult patients with acute myeloblastic leukemia were studied by autoradiographic methods to elucidate the mode of action of daunomycin.

Authors

Pierre A. Stryckmans, Joseph Manaster, Françoise Lachapelle, Mireille Socqouet

Evidence for Secondary Hyperparathyroidism in Idiopathic Hypercalciuria

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Circulating levels of immunoreactive parathyroid hormone (PTH) were measured in 40 patients with idiopathic hypercalciuria (IH) before and during reversal of hypercalciuria with thiazide, and in four normal subjects before and during induction of hypercalciuria with furosemide. 26 patients with IH had elevated serum PTH levels. The remaining patients had normal levels. Although the correlation was not complete, high PTH levels were generally found in patients who had more severe average urinary calcium losses. When initially elevated. PTH levels fell to normal or nearly normal values during periods of thiazide administration lasting up to 22 months. When initially normal, PTH levels were not altered by thiazide. Reversal of hyperparathyroidism by thiazide could not be ascribed to the induction of hypercalcemia, since serum calcium concentration failed to rise in a majority of patients. Renal hypercalciuria produced by furosemide administration elevated serum PTH to levels equivalent to those observed in patients with IH.

Authors

Fredric L. Coe, Janet M. Canterbury, John J. Firpo, Eric Reiss

Some Characteristics of the Rabbit Vermiform Appendix as a Secreting Organ

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It has been confirmed that the rabbit vermiform appendix secretes spontaneously at a relatively rapid rate (1-12 ml·h-1; 1.4±0.24 μl·min-1·cm-2). The electrolyte composition is similar to that of ileal fluids and independent of the secretory rate. The transmural potential difference is about 12 mV, mucosa negative. Of the major electrolytes, only HCO3- is secreted grossly against its electrochemical potential difference. This finding plus the low hydraulic (or osmotic) permeability (Lp) and high secretory pressures of the organ strongly suggest that the secretion is an active one. The passive permeability to Na+ and Cl- appears to be, at most, somewhat less than for small bowel. Permeability to mannitol was estimated at 2.5 × 10-7 cm·s-1. On the basis of reasonable assumptions and results with luminal test solutions of differing osmolarities, it was concluded that (a) the Lp of the appendiceal epithelium is in the lower range of values reported for small bowel and colon; (b) the Lp is higher for osmotic absorption than for osmotic secretion; and (c) the rate of spontaneous secretion is insensitive to luminal anisotonicity over a wide range of values. But sufficiently hypotonic solutions can reverse net secretion to net absorption, more by inhibiting spontaneous secretion than increasing osmotic absorption. The rabbit vermiform appendix appears to be a useful model for the elucidation of intestinal secretory processes.

Authors

William D. Blackwood, Robin A. Bolinger, Nathan Lifson

Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function

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Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs.

Authors

Se Mo Suh, Armen H. Tashjian Jr., Nobutake Matsuo, David K. Parkinson, Donald Fraser

Primate Biliary Physiology VIII. THE EFFECT OF PHENOBARBITAL UPON BILE SALT SYNTHESIS AND POOL SIZE, BILIARY LIPID SECRETION, AND BILE COMPOSITION

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Phenobarbital, by inducing liver microsomal enzymes, may affect bile acid synthesis from cholesterol and thus alter the secretion of biliary lipids and the composition of bile. We, therefore, determined the effects of phenobarbital on bile flow, biliary lipid secretion, bile acid synthesis, and bile-acid pool size. Using an experimental preparation that allows controlled interruption of the enterohepatic circulation (1), we administered 5 mg/kg per day of phenobarbital to healthy Rhesus monkeys for 1-2 wk to achieve steady-state conditions. Three animals were studied with an intact enterohepatic circulation and three with a total bile fistula, each animal served as its own control. Total bile flow and secretion of bile salt, phospholipid, and cholesterol were measured every 24 h during steady-state conditions. Further, under conditions of an intact enterohepatic circulation bile-acid synthetic rate was measured in three animals and pool size estimated in two animals during both control and drug treatment periods.

Authors

Richard N. Redinger, Donald M. Small

Etiology of Hyperparathyroidism and Bone Disease during Chronic Hemodialysis. III. EVALUATION OF PARATHYROID SUPPRESSIBILITY

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Parathyroid function was assessed by calcium infusions (4-8 h) in 16 patients with chronic renal insufficiency being treated by long-term hemodialysis. The concentrations of two immunoreactive species of parathyroid hormone in plasma (iPTH-9, mol wt 9500; iPTH-7, mol wt 7000) were estimated by radioimmunoassays utilizing two relatively specific antisera. Control values of the smaller species, iPTH-7, were uniformly high, whereas values of iPTH-9 were normal in 12 of 19 studies. Response of iPTH-7 to calcium infusions was variable, with significant decreases occurring only five times in 27 infusions. Concentrations of iPTH-9, however, decreased during every calcium infusion. In contrast to these acute responses, five of six patients studied during periods of dialysis against both low (< 6 mg/100 ml) and high (7-8 mg/100 ml) calcium concentrations in the dialyzate showed a decrease in values of iPTH-7 during the period of dialysis against the higher calcium concentration. It is concluded that plasma concentrations of iPTH-9 reflect primarily the moment-to-moment secretory status of the parathyroid glands, while concentrations of iPTH-7 reflect more closely chronic parathyroid functional status. It is further concluded that the failure of iPTH-7 to decrease during induced hypercalcemia should not be equated with autonomy of parathyroid gland function.

Authors

Ralph S. Goldsmith, Jacob Furszyfer, William J. Johnson, Albert E. Fournier, Glen W. Sizemore, Claude D. Arnaud

Parathyroid Function in Primary Osteoporosis

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Two major species of serum immunoreactive parathyroid hormone (iPTH) were measured in 47 untreated patients with primary osteoporosis by using two highly specific radioimmunoassays. Mean iPTH was normal with one antiserum but was lower than normal (P < 0.001) with the other, iPTH values did not correlate with biochemical parameters or with the proportion of bone-resorbing surfaces in iliac crest bone biopsy specimens. These data suggest that the increased bone resorption is not due to increased parathyroid function in most osteoporotic patients. However, seven of our patients (15%) appear to represent a separate population because they had increased values with one or the other of the antisera.

Authors

B. Lawrence Riggs, Claude D. Arnaud, Jenifer Jowsey, Ralph S. Goldsmith, Patrick J. Kelly

Aldosterone Action and Sodium- and Potassium-Activated Adenosine Triphosphatase in Toad Bladder

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Urinary hemibladders obtained from toads soaked in water or saline were treated with aldosterone, 10-6 M, either 1½ or 16 h after mounting. After 2½ h exposure to the hormone, short-circuit current was increased by 110-192% and open-circuit potential by 20-44% as compared with untreated paired hemibladders. Mucosal cells were then assayed for sodium-potassium-stimulated adenosine triphosphatase (ATPase). No increase occurred in activity per milligram protein or in the portion of total activity dependent on sodium. Activity at low sodium concentrations was also measured and analyzed by means of the Hill equation in terms of K, the apparent dissociation constant of the enzyme-sodium complex, and n, a number that expresses the degree of interaction between binding sites. Neither K nor n was significantly altered by aldosterone. A few experiments were also carried out at low ATP concentrations (0.3 mM); again no change in sodium-dependent activity was noted. The results indicate that aldosterone does not stimulate sodium transport by increasing the quantity of sodium-potassium adenosine triphosphatase in mucosal cells or the dependence of this activity on sodium or ATP concentrations.

Authors

James H. Hill, Nadim Cortas, Mackenzie Walser

Quantitative Importance of Changes in Postglomerular Colloid Osmotic Pressure in Mediating Glomerulotubular Balance in the Rat

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In recent studies in this laboratory employing normal hydropenic rats we have demonstrated that the reduction in absolute proximal reabsorption that attends the experimental reduction of single nephron glomerular filtration rate (SNGFR) (glomerulotubular balance) is mediated, at least in part, by the accompanying decline in postglomerular vascular protein concentration, and therefore, postglomerular colloid osmotic pressure (πEA). The present study was undertaken to define the quantitative contribution of these changes in πEA to the changes in absolute proximal reabsorption measured under these conditions. A protocol was employed which enabled us to examine the effects on absolute proximal reabsorption of reductions in filtered load brought about under conditions in which πEA remained essentially unchanged. Thus, after partial aortic constriction in 16 plasma-loaded rats, near constancy of πEA was observed in 10 (a change in efferent arteriolar protein concentration of 0.4 g/100 ml or less) and in these, uniform reductions in SNGFR averaging 16.7 nl/min were attended by reductions in absolute proximal reabsorption averaging only 1.7 nl/min, or 7% of preconstriction values. These findings, taken together with previous observations from this laboratory, suggest that the proximal reabsorptive adjustment that characterizes glomerulotubular balance in the rat is markedly blunted when changes in πEA are prevented. In the remaining six rats, a mean reduction in filtered load comparable to that observed in the above group was attended by slightly to moderately greater reductions in efferent arteriolar protein concentration, thereby fulfilling less well the stated aim of this study. Nevertheless, in accord with the above conclusion, these relatively greater reductions in πEA were accompanied by correspondingly greater reductions in absolute proximal reabsorption.

Authors

Barry M. Brenner, Julia L. Troy, Terrance M. Daugharty, Robert M. MacInnes

The Occurrence of Single-Stranded DNA in the Serum of Patients with Systemic Lupus Erythematosus and Other Diseases

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Single-stranded DNA (SDNA) occurs in high incidence and in greatest concentration in the sera of patients with systemic lupus erythematosus (SLE), where levels as high as 250 μg/ml were observed. SDNA appears to be an imunogen for anti-SDNA antibodies and forms complexes in vivo of both anti-SDNA-SDNA and anti-NDNA-SDNA types, which apparently play a role in the pathogenesis of the glomerulonephritis found in patients with SLE, SDNA is also found in high incidence but at lower levels in the sera of patients with rheumatoid arthritis. Lesser amounts of SDNA are found in several other diseases in which a low incidence of anti-SDNA antibodies is observed.

Authors

David Koffler, Vincent Agnello, Robert Winchester, Henry G. Kunkel

Modulation of Pituitary Responsiveness to Throtropin-Releasing Hormone by Triiodothyronine

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The relative roles of triiodothyronine (T3) and thyroxine (T4) in modulating pituitary responsiveness to thyrotropin-releasing hormone (TRH) have been assessed. (a) 10 hyperthyroid patients with elevated serum T2 and T4 levels showed no pituitary response to TRH. After 2 wk of propylthiouracil therapy T4 levels had fallen to normal in only five patients while T2 levels were normal in all. Pituitary responsiveness to TRH returned in all patients with normal or high T4 concentrations. (b) Patients with isolated elevations of serum T3 (T3 toxicosis) failed to respond to TRH. TRH responsiveness was restored when T3 levels fell to normal after propylthiouracil therapy. (c) When pituitary responsiveness to TRH was tested 60 min after a single oral dose of 50 μg of T3, which increased serum T3 levels to slightly above the normal range, no rise in thyrotropin (TSH) was seen in six subjects. These findings indicate that T3 elevations alone can rapidly inhibit pituitary responsiveness to TRH.

Authors

Louis Shenkman, Terunori Mitsuma, Charles S. Hollander

Neural Regulation of Insulin Secretion in the Dog

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The effects of stimulation of the mixed autonomic nerve to the dog pancreas has been studied under conditions in which both pancreaticoduodenal vein blood flow and insulin concentration were determined. Stimulation resulted in increased insulin output, which was blocked by prior administration of atropine. Blood flow was reduced by stimulation in proportion to the rate of stimulation. At 40 stimuli/s a maximum effect was found at 1 min with a gradual return toward base line despite continued application of the stimulus. Atropinization had no effect on blood flow changes. Insulin responses to 0.1 g/kg glucose were reduced on the average 40% by simultaneous stimulation of the pancreatic nerve at 40 cycles/s in atropinized animals. These studies establish this preparation as a reproducible model for the direct examination of autonomic influences on endocrine pancreatic function. From them it is concluded that the nerve supply to the endocrine pancreas of the dog is sufficient to inhibit insulin secretion by activation of the sympathetic nerves and to stimulate insulin secretion by activation of the parasympathetic nerves.

Authors

Daniel Porte Jr., Lucien Girardier, Josianne Seydoux, Yasunori Kanazawa, Jean Posternak

Effects of sugars and amino acids on sodium and potassium influx in rabbit ileum.

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Abstract

Authors

R A Frizzell, H N Nellans, S G Schultz

Homocystinuria: Heterozygote Detection using Phytohemagglutinin-Stimulated Lymphocytes

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Deficiency of cystathionine synthase activity results in the clinical syndrome of homocystinuria. Using phytohemagglutinin (PHA)-stimulated lymphocytes as a readily available source of this enzyme, its activity has been compared in 48 control subjects, seven homozygotes affected with homocystinuria, and 17 obligate heterozygotes. PHA-induced enzyme levels were highest in controls (mean ±SEM, 666.9±70.2 pmol cystathionine formed/mg protein per 4 h), intermediate in heterozygotes (114.4±27.3), and absent to severely deficient in homozygotes (2.0±1.6). Since only three of the 17 values from the obligate heterozygotes overlapped into the control range, this simple method may become clinically useful for heterozygote detection of carriers of the gene for abnormal cystathionine synthase. In addition, this system for induction of cystathionine synthase in lymphocytes has a more general relevance to human biochemical genetics in that it demonstrates that the absence of an enzyme in a normal cell does not preclude using that source for diagnosis of genetic disease if the enzyme can be induced.

Authors

Joseph L. Goldstein, Barbara K. Campbell, Stanley M. Gartler