bluuebunny/crossref_metadata_2025 huggingface dataset:
Covalent Structure and Bioactivity of the Type AII Lantibiotic Salivaricin A2
Authors: Geng Mengxin , Austin Frank , Shin Ronald , Smith Leif
Published: December 2017

Lantibiotics are a class of lanthionine-containing, ribosomally synthesized, and posttranslationally modified peptides (RiPPs) produced by Gram-positive bacteria. Salivaricin A2 belongs to the type AII lantibiotics, which are generally considered to kill Gram-positive bacteria by binding to the cell wall precursor lipid II via a conserved ring A structure. Salivaricin A2 was first reported to be isolated from a probiotic strain,
Streptococcus salivarius
K12, but the structural and bioactivity characterizations of the antibiotic have remained limited. In this study, salivaricin A2 was purified and its covalent structure was characterized. N-terminal analogues of salivaricin A2 were generated to study the importance for bioactivity of the length and charge of the N-terminal amino acids. Analogue salivaricin A2(3-22) has no antibacterial activity and does not have an antagonistic effect on the native compound. The truncated analogue also lost its ability to bind to lipid II in a thin-layer chromatography (TLC) assay, suggesting that the N-terminal amino acids are important for binding to lipid II. The creation of N-terminal analogues of salivaricin A2 promoted a better understanding of the bioactivity of this antibiotic and further elucidated the structural importance of the N-terminal leader peptide. The antibacterial activity of salivaricin A2 is due not only to the presence of the positively charged N-terminal amino acid residues, but to the length of the N-terminal linear peptide.

IMPORTANCE
The amino acid composition of the N-terminal linear peptide of salivaricin A2 is crucial for function. Our study shows that the length of the amino acid residues in the linear peptide is crucial for salivaricin A2 antimicrobial activity. Very few type AII lantibiotic covalent structures have been confirmed. The characterization of the covalent structure of salivaricin A2 provides additional support for the predicted lanthionine and methyl-lanthionine ring formations present in this structural class of lantibiotics. Removal of the N-terminal Lys1 and Arg2 residues from the peptide causes a dramatic shift in the chemical shift values of amino acid residues 7 through 9, suggesting that the N-terminal amino acids contribute to a distinct structural conformer for the linear peptide region. The demonstration that the bioactivity could be partially restored with the substitution of N-terminal alanine residues supports further studies aimed at determining whether new analogues of salivaricin A2 for novel applications can be synthesized.
Evaluation of Protective Efficacy of Selected Immunodominant B-Cell Epitopes within Virulent Surface Proteins of Streptococcus pneumoniae
Authors: Papastamatiou Theodora , Routsias John G. , Koutsoni Olga , Dotsika Eleni , Tsakris Athanassios , Spoulou Vana
Published: December 2017

Four previously identified immunodominant B-cell epitopes, located within known virulent pneumococcal proteins CbpD, PhtD, PhtE, and ZmpB, had shown promising
in vivo
immunological characteristics, indicating their potential to be used as vaccine antigens. In this study, we further evaluated the opsonophagocytic activity of antibodies against these epitopes and their capacity to protect mice from pneumococcal sepsis. An opsonophagocytic killing assay (OPKA) revealed that OPKA titers of human anti-peptide antibodies against pneumococcal serotypes 1, 3, and 19A were significantly higher (
P
< 0.001) than those of the control sera, suggesting their functional potential against virulent clinical isolates. Data obtained from mice actively immunized with any of the selected epitope analogues or with a mixture of these (G_Mix group) showed, compared to controls, enhanced survival against the highly virulent pneumococcal serotype 3 (
P
< 0.001). Moreover, passive transfer of hyperimmune serum from G_Mix to naive mice also conferred protection to a lethal challenge with serotype 3, which demonstrates that the observed protection was antibody mediated. All immunized murine groups elicited gradually higher antibody titers and avidity, suggesting a maturation of immune response over time. Among the tested peptides, PhD_pep19 and PhtE_pep40 peptides, which reside within the zinc-binding domains of PhtD and PhtE proteins, exhibited superior immunological characteristics. Recently it has been shown that zinc uptake is of high importance for the virulence of
Streptococcus pneumoniae
; thus, our findings suggest that these epitopes deserve further evaluation as novel immunoreactive components for the development of a polysaccharide-independent pneumococcal vaccine.
Modeling and simulation of group formation and crowd dynamics with smoke effect
Authors: Wei Juan , Wu Zhenya , You Lei , He Junlin , Zhang Hong , Wang Xiaofei
Published: December 2017

In order to depict crowd dynamics in the case of smoke effect, a novel evacuation model is presented based on the extended cellular automaton. In the model, the moving probability of the target position in the next time step is given by combining distance gain and smoke gain at first. Through considering individual kinship and group effect, group disbanding and regrouping rules are defined, and the optimal evacuation route planning is determined. At last, the simulation was conducted to study the key factors influencing evacuation efficiency. The results showed that when the group size was small and the smoke spreading velocity was slow, priority selection of the shortest route strategy was good for reducing evacuation time, and large-scale group should be avoided as much as possible in evacuation process.
Are Short Proofs Narrow? QBF Resolution Is
Not
So Simple
Authors: Beyersdorff Olaf , Chew Leroy , Mahajan Meena , Shukla Anil
Published: December 2017

The ground-breaking paper “Short Proofs Are Narrow -- Resolution Made Simple” by Ben-Sasson and Wigderson (J. ACM 2001) introduces what is today arguably
the
main technique to obtain resolution lower bounds: to show a lower bound for the width of proofs. Another important measure for resolution is space, and in their fundamental work, Atserias and Dalmau (J. Comput. Syst. Sci. 2008) show that lower bounds for space again can be obtained via lower bounds for width.

In this article, we assess whether similar techniques are effective for resolution calculi for quantified Boolean formulas (QBFs). There are a number of different QBF resolution calculi like Q-resolution (the classical extension of propositional resolution to QBF) and the more recent calculi ∀Exp+Res and IR-calc. For these systems, a mixed picture emerges. Our main results show that the relations both between size and width and between space and width drastically
fail
in Q-resolution, even in its weaker tree-like version. On the other hand, we obtain positive results for the expansion-based resolution systems ∀Exp+Res and IR-calc, however, only in the weak tree-like models.

Technically, our negative results rely on showing width lower bounds together with simultaneous upper bounds for size and space. For our positive results, we exhibit space and width-preserving simulations between QBF resolution calculi.
Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport.
Authors: Hollander D , Rim E , Muralidhara K S
Published: December 2017

Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.
Effect of serotonin treatment on intestinal transport in the rabbit.
Authors: Donowitz M , Charney A N , Heffernan J M
Published: December 2017

The hormone serotonin (5-hydroxytryptamine) has been implicated as the cause of the diarrhea seen in many patients with the carcinoid syndrome. To determine whether serotonin is an intestinal secretagogue, the effect of serotonin on intestinal water and electrolyte transport was evaluated in the rabbit. Two weeks of daily subcutaneous injection of serotonin suspended in oil resulted in a blood serotonin level elevated to twice that of controls. Intestinal transport was studied in vivo by a perfusion technique. Serotonin treatment resulted in ileal secretion and decreased mid-jejunal absorption of water and electrolytes but did not effect water absorption in the proximal jejunum or colon. Intestinal absorption of D-glucose and the amino acid L-tryptophan and glucose-dependent water and electrolyte absorption were normal in serotonin-treated animals. Serotonin-induced ileal secretion was reversed by methysergide, a peripheral antagonist of serotonin action. No alterations in intestinal histology or permeability occurred in serotonin-treated animals. Serotonin-induced intestinal secretion was not associated with alterations in the activities of intestinal mucosal adenylate cyclase, cyclic nucleotide phosphodiesterase, or Na-K-ATPase.
Copper metabolism in pregnant and pospartum rat and pups.
Authors: Terao T , Owen C A
Published: December 2017

A detailed study was made of copper metabolism in rats during and after pregnancy and in the fetuses and pups up to the age of 6 wk. Maternal ceruloplasmin levels increase only briefly at the beginning of the third (and last) week of pregnancy. They then decrease to normal levels at term and decrease markedly in the early postpartum period. Bilary excretion of copper and 67Cu almost stops at term and remains decreased for 2 wk. In spite of this, there is no increase in hepatic copper levels. Except for a 1- to 2-day period shortly after delivery, maternal rats have a positive copper balance if lacteal elimination of copper is ignored. Levels of copper in milk drop at about the fourth day postpartum. Fetal hepatic copper levels are already above adult levels, but the concentration almost doubles during the first week after birth; it decreases to adult levels by 6 wk of age. Ceruloplasmin levels, which are found to be very low in the pups at birth, increase sharply in the first 24 h and quickly achieve adult levels. Large quantitative differences also occur between the pups and adults in concentrations of copper in the brain and kidney. Qualitative differences, measured with 67Cu, are most notable when the neonatal liver is compared with the adult liver.
Effects of prostaglandin E2 and prostaglandin inhibitors on adrenal regeneration hypertension.
Authors: Paulson D J , Eversole W J
Published: December 2017

The effects of prostaglandin E2 (PGE2) and a prostaglandin inhibitor, indomethacin, on the development of adrenal regeneration hypertension (ARH) were investigated. Weanling female rats underwent right adrenonephrectomy and left adrenal enucleation. PGE2 was injected subcutaneously daily in dosages of 0, 20, 40 and 80 mug/day. Indomethacin, 1 mg/kg, was administered twice daily by gavage. Blood pressures were determined by a tail and cuff plethysmographic method at 3, 5, and 7 wk after surgery. Increases in dosage of PGE2 produced a progressive reduction in mean blood pressures, heart, and kidney weights. Indomethacin produced significant increases in mean blood pressure, heart, kidney, and adrenal weights. The effects of aspirin and indomethacin on the blood pressures of rats with right adrenalectomy, left adrenal enucleation, and intact kidneys were studied. Administration of asprin twice daily (25 or 50 mg/kg) produced a fall in blood pressure, body and heart weight. Administration of 1 mg/kg twice daily of indomethacin resulted in a significant increase in blood pressure at 3 wk, and 0.1 or 1 mg/kg caused significant increases at 5 wk. The heart, kidney, and adrenal weights also showed increases with indomethacin administration. This study suggests that a deficiency of renal PGE2 may be involved in the etiology of ARH.
Vitamin A and retinol-binding protein metabolism during fetal development in the rat.
Authors: Takahashi Y I , Smith J E , Goodman D S
Published: December 2017

Studies were conducted on the metabolism and placental transport of vitamin A and plasma retinol-binding protein (RBP) during fetal development in the rat. Vitamin A accumulated in the conceptus in three phases: an early phase (days 7-9 of gestation) characterized by a high vitamin A concentration; a second phase (days 11-14) where vitamin A and RBP accumulated in parallel; and a third phase of continued vitamin A and RBP accumulation (days 16-20) in which vitamin A was stored in the fetal liver. The early phase of vitamin A accumulation may reflect a mechanism that exists to prepare the conceptus to meet the presumably higher vitamin A requirements of the critical period (days 10-14) of organ differentiation. Fetuses and placentas from retinol-deficient dams showed low levels of RBP through days 16-18 of gestation. A retinol-repletion study suggested, moreover, that the maternal retinol-RBP complex crossed the placenta. The various studies all suggest that vitamin A is transported from dam to fetus, from and after day 11, mainly by transplacental transport of maternal retinol-RBP. Finally, evidence was obtained indicating that the fetal liver begins to synthesize RBP around the 16th day of gestation and that by the 20th day, the fetal liver has a considerable capacity for RBP synthesis.
Canine gastric emptying of solids and liquids.
Authors: Hinder R A , Kelly K A
Published: December 2017

In four dogs, gastric emptying of a digestible solid (50 g of liver tagged with [57Co]-cyanocobalamine and diced into 1-cm cubes), an indigestible solid (40 radiopaque plastic spheres, diameter 7mm), and a liquid (400 ml of either 1 or 10% dextrose tagged with polyethylene[1,2-3H]glycol were simultaneously assessed by quantitating the rate of appearance of the gastric markers in the duodenum. The rate of gastric emptying of cubed liver was similar whether the liver was given alone or with solutions of the rapidly emptying 1% dextrose, but its rate of emptying was slowed by the slower emptying 10% dextrose. Homogenization of the liver speeded its emptying. Moreover, the homogenized liver emptied even faster when dispersed in 1% dextrose and emptied more slowly when dispersed in 10% dextrose, but in both instances the liver emptied at the same rate as the solution in which it was mixed. Indigestible spheres were nearly all retained, whereas the liver and the dextrose were emptied. Our conclusion is that the stomach empties liquids and retains solids for reduction to a smaller size, after which they are discharged at the same rates as the liquid then present in the stomach.
Oxygen consumption during cimetidine and prostaglandin E2 inhibition of acid secretion.
Authors: Cheung L Y , Moody F G , Larson K , Lowry S F
Published: December 2017

Oxygen consumption was determined during cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion in exteriorized segments of the greater curvature of dog stomach. Steady-state acid secretion during histamine infusion correlated well with O2 consumption (r = 0.85, P less than 0.01). Cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion produced a reduction of oxygen consumption to resting levels. In contrast, oxygen consumption did not decrease appreciably during thiocyanate inhibition of acid secretion. These observations suggest that the inhibitory action of cimetidine and 16,16-dimethyl prostaglandin E2 precedes, whereas that of thiocyanate is at a point beyond the transfer of energy to the process of acid production.
Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells.
Authors: Bitar K N , Zfass A M , Makhlouf G M
Published: December 2017

Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.
Interaction of somatostatin with PTH and AVP: renal effects.
Authors: Brautbar N , Levine B S , Coburn J W , Kleeman C R
Published: December 2017

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.
Required neural involvement in control of canine migrating motor complex.
Authors: Ormsbee H S , Telford G L , Mason G R
Published: December 2017

This study evaluated the effects of muscarinic, nicotinic, and adrenergic neuronal blockade on the migrating motor complex (MMC) in four unanesthetized dogs. Circular muscle contractile activity was recorded from eight strain gauge force transducers implanted on the stomach and small intestine of each dog. Both atropine sulfate and hexamethonium bromide significantly increased the period of the MMC. When the complex returned after hexamethonium administration, the period of the succeeding complexes was significantly decreased when compared to control. Guanethidine sulfate significantly increased contractile activity on the pylorus, duodenum, and jejunum with a corresponding disruption of the MMC pattern. The migrating motor complex requires the preganglionic release of acteylcholine and possibly an inhibitory input from the sympathetic nervous system for its normal appearance.
Pancreatic and gastric release of somatostatinlike immunoreactivity during intestinal phase of a meal.
Authors: Schusdziarra V , Rouiller D , Pietri A , Harris V , Zyznar E , Conlon J M , Unger R H
Published: December 2017

The present study was designed to examine pancreatic and gastric D-cell function during the intestinal phase of a liver meal. The intraduodenal instillation of a 20% liver meal (5 ml/min) elicited a significant rise in the plasma levels of somatostatinlike immunoreactivity (SLI) in the pancreatic vein and inferior vena cava, together with the rise in glucagon and insulin levels. The rise in pancreatic vein SLI was not reduced after truncal vagotomy or during atropine infusion. In the stomach, the intestinal liver meal elicited a significant rise in antral but not fundic vein SLI levels. The rise in antral vein SLI was augmented after truncal vagotomy and abolished during atropine infusion, as was the rise in inferior vena caval SLI. In contrast to the protein meal, intravenous infusion of an amino acid mixture elicited a rise in pancreatic vein SLI but not antral or fundic vein SLI. It is concluded that during the intestinal phase of a protein meal, pancreatic and antral but not fundic SLI release is stimulated. The effects of truncal vagotomy and atropine infusion on these responses suggest a close interaction between the vagus and muscarinic cholinergic mechanisms and the D cells of the stomach and pancreas.
Prolactin in human milk: correlation with lactose, total protein, and alpha-lactalbumin levels
Authors: Healy D. L. , Rattigan S. , Hartmann P. E. , Herington A. C. , Burger H. G.
Published: December 2017

To determine whether prolactin (PRL) could be conclusively demonstrated in human milk, samples from nine puerperal women were examined by radioimmunoassay techniques. Recovery of 78 +/- 5% (mean +/- SE) PRL added to eight milk samples and mean recoveries of 83, 92, and 92% of PRL after 1, 2, and 3 h incubation at 21 degrees C indicated that quantitative recovery was possible. PRL immunoreactivity was not lost by dialysis for 96 h. Serial dilution of milk samples before and after dialysis gave inhibition curves parallel to PRL standards. Milk PRL concentrations were high for the first 3 days after birth, with a peak mean value of 157 +/- 18 ng/ml (SE) on the third day. Milk PRL levels then fell sharply to a mean of 24 ng/ml 13 days after delivery. Milk PRL concentrations showed a significant negative correlation (P less than 0.001) with milk lactose (r = -0.59) and positive correlations (P less than 0.01) with total milk protein (r = 0.49) and alpha lactalbumin (r = 0.33) estimations. We conclude that i) PRL is a normal constituent of human milk, ii) high concentrations of PRL are present in human milk for the first 3 days postpartum but subsequently fall rapidly, and iii) milk PRL levels correlate significantly with milk lactose, total protein, and alpha-lactalbumin values.
Regulation of calcium fluxes in pancreatic islets: two calcium movements' dissociated response to glucose
Authors: Herchuelz A. , Malaisse W. J.
Published: December 2017

At normal extracellular 40Ca concentration (1.0--1.5 mM), D-glucose initially reduces and subsequently increases 45Ca efflux from prelabeled rat pancreatic islets, whether in the absence or presence of 20 mM Ca-EGTA. Thus, the initial fall cannot be attributed to a reuptake of effluent 45Ca. Both the fall and rise in effluent 45Ca represent sustained and rapidly reversible phenomena partially masked by one another. The dose-action relationship for the initial fall in 45Ca efflux (Km = 4.2 mM) differs vastly from that characterizing the secondary rise in 45Ca efflux (Km = 9.1 mM). Mannoheptulose, iodoacetate, and low temperature inhibit both the early fall and secondary rise in effluent radioactivity normally evoked by glucose. D-Glucose (8.3 mM) and D-glyceraldehyde (10 mM) exert comparable effects on 45Ca efflux. The initial fall and later increase in 45Ca efflux evoked by glucose, although dependent on the integrity of glucose metabolism, correspond to two distinct processes in the rapid regulation of Ca handling by the islet cells.
Arginine vasopressin and prolactin after hemorrhage in the fetal lamb
Authors: Drummond W. H. , Rudolph A. M. , Keil L. C. , Gluckman P. D. , MacDonald A. A. , Heymann M. A.
Published: December 2017

Chronically prepared fetal lambs had basal plasma arginine vasopressin (AVP) levels of 1.6 +/- 0.23 pg/ml throughout the final third of gestation. Fetal AVP levels measured by radioimmunoassay were increased significantly to 5.8 +/- 0.92, 9.95 +/- 0.95, and 10.0 +/- 5 pg/ml in association with surgical stress, acute exteriorization, and acidosis or hypoxia, respectively. At 59-65 days gestation three lamb fetuses had a 50-fold increase in plasma AVP levels after acute exteriorization and hemorrhage indicating that the 0.4 gestation lamb fetus is capable of secreting pituitary AVP stores after intravascular volume change, temperature stress, and tactile stimulation. In six chronically catheterized third trimester fetuses, a 10-min, 20% hemorrhage caused a significant fall in fetal blood pressure, heart rate, and hematocrit. Plasma AVP increased significantly to 24.3 +/- 5.8 ng/ml without change in arterial blood gases or pH. Basal plasma prolactin concentration of 9.0 +/- 2.0 ng/ml was unchanged after hemorrhage in five fetuses.
Effect of adrenergic agonists on big and small renin
Authors: Iwao H. , Lin C. S. , Michelakis A. M.
Published: December 2017

The effect of alpha- and beta-adrenergic agonists on renal and submaxillary renin of different molecular weights was studied using male albino mice as experimental animals. Phenylephrine or isoproterenol was administered intravenously after removal of the submaxillary glands and/or kidneys. Renin was isolated from plasma by column chromatography and then measured by a direct radioimmunoassay. Phenylephrine increased both 68,500-dalton renin (big renin) and 38,000-dalton renin (small renin) in the plasma of nephrectomized mice. Isoproterenol increased big and small renin in the plasma of mice whose submaxillary glands were removed. In both cases, the increase of small renin was significantly greater than that of big renin. The results suggest that the alpha-adrenergic agonist phenylephrine affects the submaxillary gland, leading to the increase of both big and small plasma renin. In contrast, the beta-adrenergic agonist isoproterenol affects the kidney, leading to the increase of both big and small plasma renin.
Effect of calcitonin on calcium and magnesium transport in rat nephron
Authors: Quamme G. A.
Published: December 2017

Renal calcium and magnesium reabsorption was investigated in young, thyroparathyroidectomized rats receiving synthetic salmon calcitonin. Kidney and tubular function was assessed by clearance and in vivo microperfusion techniques, respectively. Calcitonin reduced urinary calcium and magnesium excretion that was attributed to increased reabsorption within the loop of Henle. This enchanced reabsorption was independent of parathyroid hormone; however, it is contingent on a decline in plasma calcium concentration. Prevention of hypocalcemia by CaCl2 infusion in rats acutely administered calcitonin resulted in loop function comparable to animals not receiving the hormone. Calcitonin had little effect on proximal tubule or distal tubule electrolyte reabsorption. These results are consistent with a transport model for calcium and magnesium in the loop of Henle involving a contraluminal transfer step modulated by absolute extracellular calcium or magnesium. Furthermore, these studies suggest that the discrepancies present in the literature concerning renal effects of calcitonin on electrolyte reabsorption are due to variations in observed hormone action, namely, the effect on plasma calcium concentration.
Effects of diabetes on protein synthesis in fast- and slow-twitch rat skeletal muscle
Authors: Flaim K. E. , Copenhaver M. E. , Jefferson L. S.
Published: December 2017

The effects of acute (2-day) and long-term (7-day) diabetes on rates of protein synthesis, peptide-chain initiation, and levels of RNA were examined in rat skeletal muscles that are known to have differing proportions of the three fiber types: fast-twitch white, fast-twitch red, and slow-twitch red. Short-term diabetes resulted in a 15% reduction in the level of RNA in all the muscles studied and an impairment in peptide-chain initiation in muscles with mixed fast-twitch fibers. In contrast, the soleus, a skeletal muscle with high proportions of slow-twitch red fibers, showed little impairment in initiation. When the muscles were perfused as a part of the hemicorpus preparation, addition of insulin to the medium caused a rapid reversal of the block in initiation in mixed fast-twitch muscles but had no effect in the soleus. The possible role of fatty acids in accounting for these differences is discussed. Long-term diabetes caused no further reduction in RNA, but resulted in the development of an additional impairment to protein synthesis that also affected the soleus and that was not corrected by perfusion with insulin. The defect resulting from long-term diabetes may involve elongation or termination reactions.
Adaptation to dietary calcium and phosphorus restriction changes with age in the rat
Authors: Armbrecht H. J. , Zenser T. V. , Gross C. J. , Davis B. B.
Published: December 2017

The purpose of this study was to characterize the changes that take place in adaptation to chronic calcium (Ca) or phosphorus (P) restriction with age. Adaptation in male F344 rats aged 1.5, 3, 12, and 18 mo was studied by feeding rats either a low-Ca diet, a low-P diet, or a high-Ca-P diet for 14 days. Plasma Ca remained relatively constant with age, but plasma P markedly decreased between 3 and 12 mo regardless of diet. Intestinal adaptation was determined by measuring the active transport of Ca by the intestine and by measuring the production of vitamin D-dependent calcium-binder protein. There was significant intestinal adaptation to Ca or P restriction at 1.5 mo, but there was none thereafter because Ca transport declined rapidly with age regardless of diet. The kidney adapted to the low-P diet by significantly reducing P excretion at all ages. In rats on a low-P diet, there was an increase in urinary P, which was due to a decrease in the tubular reabsorption of P and a decrease in urinary Ca with age. These changes in adaptation may reflect a decrease in serum 1,25-dihydroxyvitamin D levels and an increase in parathyroid hormone levels with age.
Hyperglucagonemia after removal of lower bowel in rats
Authors: Smith S. S. , Penhos J. C. , Recant L.
Published: December 2017

Surgical removal of the jejunum, ileum, and colon from rats (LBX) results in greatly elevated levels of plasma immunoreactive glucagon (pIRG) 24 h after surgery (0.98 +/- 0.07 ng/ml, n = 51 vs. 0.20 +/- 0.02 ng/ml, n = 34 in sham-operated controls). Such elevations in pIRG were not noted after gut transection or the removal of ileum, jejunum, or colon alone, ileum plus jejunum, or stomach plus duodenum. Coupled with the failure of adrenal demedullation, adrenalectomy or ganglionic blockade to lower pIRG in LBX animals, these findings suggest that surgical stress alone is an unlikely cause for LBX-induced hyperglucagonemia. It was also shown that alpha-cells in LBX animals retained their responsiveness to both the inhibitory effects of somatostatin and glucose infusion as well as the stimulatory effects of arginine infusion. Chromatography revealed a normal pattern of IRG in the plasma of LBX animals. It is postulated that LBX-induced hyperglucagonemia may result from the removal of an inhibitory factor present in the lower bowel.
Feeding responses of Zucker fatty rat to 2-deoxy-D-glucose, norepinephrine, and insulin
Authors: Ikeda H. , Nishikawa K. , Matsuo T.
Published: December 2017

From the pathophysiological viewpoint, feeding responses to various stimuli were examined in Zucker fatty rats and their lean littermates. Intraventricular administration of norepinephrine (NE, 10 micrograms/rat) stimulated food intake in both rats. Intraventricular administration of 2-deoxy-D-glucose (2DG, 3.8 mg/rat) induced hyperphagia and concomitant hyperglycemia in lean rats. However, in fatty rats, the blood glucose was elevated but food intake was unaltered after 2DG administration. Subcutaneous administration of insulin (2 or 8 U/kg) stimulated food intake of both rats. Streptozotocin (STZ)-induced hypoinsulinemia produced transient reduction of food intake followed by sustained diabetic hyperphagia in lean rats. In fatty rats, the experimental hypoinsulinemia caused transient aphagia but not sustained diabetic hyperphagia. Daily injection of insulin (5 U/rat) restored energy assimilation in both diabetic rats. An increase in food intake due to insulin injection was remarkable only in diabetic fatty rats. From these findings, the regulatory system of food intake in fatty rats appears to be sensitive to changes in the circulating insulin level but insensitive to either glucoprivation or changes in body storage of energy.
In vivo incorporation of tritium from 3H2O into pulmonary lipids of meal-fed and starved rats
Authors: Todhunter D. A. , Scholz R. W.
Published: December 2017

In vivo fatty acid synthesis, as measured by tritium incorporation from 3H2O into fatty acids, was examined in the lungs of meal-fed and starved rats. In meal-fed animals, 74% of the radioactivity isolated from pulmonary lipids was found in the phospholipid fraction, with phospholipid fatty acids accounting for approximately 89% of total radioactivity in this fraction. Starving rats for 72 h markedly reduced in vivo 3H2O incorporation into pulmonary lipids. Intraperitoneal injection of (-)-hydroxycitrate prior to 3H2O administration also markedly reduced isotope incorporation into pulmonary lipid fractions of fed rats. These studies demonstrated net in vivo synthesis of fatty acids in pulmonary tissue of rats using a method that is not complicated by potential differences in metabolic pool sizes or peculiarities of specific carbon substrate sources. Synthesis of fatty acids in vivo was affected by the nutritional state of the animal and citrate appears to be a significant source of cytoplasmic acetyl-CoA for de novo pulmonary lipogenesis in the fed rat.
Mechanism of enhanced lipolysis in adipose tissue of exercise-trained rats
Authors: Bukowiecki L. , Lupien J. , Follea N. , Paradis A. , Richard D. , LeBlanc J.
Published: December 2017

The effects of exercise training and food restriction on the regulation of lipolysis were studied comparatively in adipocytes isolated from male and female rats. Exercise training inhibited cell proliferation in parametrial, but not in epididymal adipose tissue, whereas it significantly reduced adipocyte size in both fat depots. Adipocyte capacity for responding lipolytically to epinephrine (10 microns) or to ACTH (1 micron) was markedly increased by exercise training. Enhanced lipolysis was also observed when cells isolated from exercise-trained animals were stimulated by bypassing with dibutyryl cyclic AMP (5 mM) or theophylline (5 mM) the early metabolic steps associated with hormonal activation of the adenylate cyclase complex. Significantly, binding of (-)-[3H]dihydroalprenolol to cellular receptor sites was not affected by exercise training. It is therefore concluded that exercise training increases adipocyte responsiveness to lipolytic hormones at a metabolic step distal to stimulus recognition by adrenoreceptors, possibly at the level of protein kinases or lipases. Food restriction markedly reduced adipocyte size and partially mimicked the effects of exercise training on adipocyte proliferation and lipolysis.
A role for leucine in regulation of protein turnover in working rat hearts
Authors: Chua B. H. , Siehl D. L. , Morgan H. E.
Published: December 2017

Effect of leucine on protein turnover was examined in perfused hearts provided with 1 (0.2 mM) or 5 times (1 mM) plasma levels of leucine and normal plasma levels of other amino acids. When hearts were perfused as Langendorff or working preparations with buffer that contained 15 mM glucose, protein degradation was 2–3 times faster than protein synthesis. As a result, the heart was in marked negative nitrogen balance. Addition of 1 mM leucine significantly improved the nitrogen balance (24–33%) by stimulating protein synthesis in Langendorff preparations (25%) and inhibiting protein degradation in both preparations (14–29%). The stimulatory effect of leucine on protein synthesis was associated with a reduction in levels of ribosomal subunits. In hearts supplied physiological levels of glucose, lactate, beta-hydroxybutyrate, insulin, and glucagon, protein synthesis was more nearly equal to protein degradation. Provision of 1 mM leucine stimulated protein synthesis only in Langendorff preparations (32%) but did not have a significant effect on protein degradation in either preparation. Although leucine did not have a significant effect on either protein synthesis or degradation in working hearts, nitrogen balance became positive with addition of 1 mM leucine. These results suggest that leucine may exert an effect on myocardial nitrogen balance in vivo under conditions that elevate plasma leucine concentrations.
In vivo cell nuclear binding of 17 beta-[3H]estradiol in rat adipose tissues
Authors: Gray J. M. , Dudley S. D. , Wade G. N.
Published: December 2017

Rat adipose tissues contain high-affinity, hormone-specific cytoplasmic estrogen receptors. If adipose tissues are actually estrogen target tissues, then it should be possible to demonstrate in vivo binding and retention of 17 beta-[2H]estradiol in adipose tissue cell nuclei, the putative subcellular site of steroid action. Gonadectomized rats were given an intravenous injection of 40 microCi (0.11 microgram) 17 beta-[2,4,6,7-3H]estradiol. Animals were then killed, and cell nuclei were isolated from hypothalamus and various fat pads. Cell nuclear levels of radioactivity peaked at 1 h in both hypothalamus and parametrial adipose tissue, but the peak cell nuclear concentration in the fat pad was more than twice that in hypothalamus. At 1 h, 89% of the adipose tissue nuclear radioactivity migrated with 17 beta-estradiol on thin-layer plates. Radioactivity was retained in cell nuclei for more than 6 h in both tissues. This cell nuclear binding was estrogen specific. Pretreatment with radioinert estrogens (17 beta-estradiol or R 2858) abolished cell nuclear 17 beta-[3H]estradiol uptake, but other steroids (progesterone, corticosterone, and 5 alpha-dihydrotestosterone) were without effect. Cell nuclear binding was found in all fat pads studied in both males and females. Levels were highest in parametrial (females) and epididymal (males) fat pads, the depots with the highest concentration of cytoplasmic estrogen receptor. There were no sex differences in cell nuclear binding. Taken together these findings provide strong support for the contention that 17 beta-estradiol could affect lipid metabolism and body fat content in part by direct action on adipose tissues.
Osmotic regulation of vasopressin in the cat
Authors: Reaves T. A. , Liu H. M. , Qasim M. M. , Hayward J. N.
Published: December 2017

This study examines the effects of blood osmolality on the release of arginine vasopressin (AVP) in the cat. Prior to the beginning of the experiments, the chamber-isolated, unanesthetized cat, allowed water ad libitum had a constant plasma osmolality averaging 320 +/- 2 (SE) mosmol/kg and a constant plasma AVP averaging 3.4 +/- 0.7 microU/ml. Water loading decreased plasma osmolality to 312 +/- 2 mosmol/kg and lowered plasma AVP to 1.3 +/- 0.2 microU/ml. As dehydration occurred during fluid restriction, the plasma osmolality increased and plasma AVP rose to 8 times the base line after 2 days. The rise in plasma AVP correlated linearly with the rise in plasma osmolality (r = 0.81; P less than 0.01). The cat's osmotic-vasopressin relationships are unique among mammals, revealing an elevated osmotic "set point" (threshold) and with regression analysis an increased "gain" or "'sensitivity" (increased slope of the regression line). We speculate that these unusual osmotic-AVP relationships may be related to some specialized features of the cat, such as hypothalamic anatomy or cerebral arterial blood supply.
Nonsteroidal adrenal feedback demarcates two types of pathways to CRF-ACTH release
Authors: Wilkinson C. W. , Engeland W. C. , Shinsako J. , Dallman M. F.
Published: December 2017

We have tested the relationship between corticosterone (B) and the number of adrenal glands on stimulated corticotropin (ACTH) levels in rats. Rats were supplied throughout the experiment with various doses of B in the drinking fluid beginning 15-20 h before adrenal surgery. Bilateral, unilateral, or sham adrenalectomy was followed on the 3rd day by the stimulus of ether vapor or ether and laparotomy with intestinal traction. Plasma ACTH levels 3 min after the stimuli were decreased by both the dose of B and adrenal number; the adrenal number of adrenals, although prestimulus ACTh and B levels were similar across groups. The decrease in ACTH after ether resulted from an interaction between the dose of B and the however there was no interaction between the inhibitors after laparotomy with intestinal traction. These results show that 1) in addition to B, some aspect of adrenal gland number or mass inhibits the ACTH response to stimuli; and 2) the adrenal number input serves as a marker to distinguish between stimuli to ACTH secretion that are inhibited by B at sites proximal and those that are inhibited by B at sites distal to this input.
Effects of dietary composition on glucose metabolism in rat adipose cells
Authors: Salans L. B. , Foley J. E. , Wardzala L. J. , Cushman S. W.
Published: December 2017

The effect of altered dietary carbohydrate and fat content on equilibrium insulin binding to, and glucose transport activity and metabolism in, isolated rat epididymal adipose cells has been studied. Alterations in basal and insulin-stimulated total glucose utilization induced by changes in the ratio of dietary carbohydrate to fat are accounted for by specific effects of dietary composition at two levels of cellular function: 1) glucose transport across the cell's plasma membrane, specifically, the number of functional glucose transport systems, and 2) the cell's maximal capacity for glucose metabolism. These effects occur without alterations in insulin binding or the cell's sensitivity to insulin. Furthermore, diet-induced changes in the pattern of 14CO2, and 14C-triglyceride glycerol and fatty acid production appear to be accounted for primarily by the influence of dietary composition on the total amount of glucose entering the cell. Thus, under the conditions of this study, changes in dietary composition alter the adipose cell's capacities for glucose transport and metabolism without altering the mechanisms of insulin action or regulating the metabolic flow of glucose carbons.
Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach
Authors: Goto Y. , Berelowitz M. , Frohman L. A.
Published: December 2017

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.
Effect of concomitant fasting and cold exposure on sympathoadrenal activity in rats
Authors: Young J. B. , Landsberg L.
Published: December 2017

Fasting decreases and cold exposure increases sympathetic nervous system activity. The present studies examine the effect of fasting and cold together on sympathoadrenal function. At 4 degrees C animals fasted for 2 days excreted 29% less norepinephrine (NE) than fed animals, averaging 458 +/- 32ng NE/mg creatinine and 646 +/- 68, respectively (P less than 0.005), but 122% more epinephrine (E) 77.9 +/- 11.7 ng E/mg creatinine and 35.1 +/- 6.7, respectively (P less than .01). Fasting for 2 days reduced cardiac NE turnover, a direct measure of sympathetic neuronal activity, 33% in animals at 22 degrees C from 28.2 +/- 3.6 ng NE . heart-1 . h-1 to 18.9 +/- 4.8 (95% confidence intervals) and 25% in animals acutely exposed to 4 degrees C from 60.7 +/- 8.0 to 45.6 +/- 9.5. Similar reductions in urinary NE excretion and cardiac NE turnover were observed in adrenal-demedullated rats. Thus fasting at 4 degrees C lowers sympathetic activity and enhances adrenal medullary secretion. This pattern of decreased sympathetic and increased adrenal medullary activity, previously seen with fasting hypoglycemia, suggests an important role for the adrenal medulla in internal homeostasis at times when the sympathetic nervous system is suppressed.
Evidence for modulation of insulin action and degradation independently of insulin binding
Authors: Caro J. F. , Amatruda J. M.
Published: December 2017

The interrelationships between insulin binding, action, and degradation were investigated in isolated hepatocytes with the aid of an insulin-receptor antibody (IRA) preparation that does not affect insulin binding. These IRA have insulin-like effects as determined by their ability to stimulate [14C]acetate incorporation into lipids. However, this effect is less than that of insulin; and in the presence of insulin and IRA, the effects of insulin are partially inhibited. The IRA have no effect on lipogenesis stimulated by postreceptor insulin "mimickers." The IRA also significantly inhibit insulin degradation. However, they do not affect insulin degradation in the presence of a large excess of unlabeled hormone. Taken together these data demonstrate that insulin action and degradation can be modulated independently of binding and suggest that the IRA partially inhibit insulin action and degradation through a portion of the insulin receptor that is not a determinant of insulin binding. It is possible, however, that there exist in the antiserum heterogeneous antibodies that bind to nonreceptor sites on the plasma membrane and mediate some of the phenomena observed.
Hormonal control of postnatal development of corticosteroid-binding globulin
Authors: D'Agostino J. , Henning S. J.
Published: December 2017

The hormonal regulation of the ontogenic rise in serum corticosteroid-binding globulin (CBG) has been studied in the rat. Pups received daily injections of estrogens (either estradiol, estrone, or diethylstilbesterol, each at 0.05 microgram/g body wt) or thyroxine (0.1 microgram/g body wt) on postnatal days 2-7. When CBG binding capacity was determined on day 8, only the thyroxine-injected pups were found to have elevated CBG. This effect of thyroxine on CBG binding capacity was further studied by daily administration of the hormone (0.1 microgram.g body wt-1.day-1) between postnatal days 5-12. This caused a precocious rise in serum CBG, with CBG values 6- to 38-fold higher than euthyroid controls on days 8, 10, and 12. Conversely, in pups made hypothyroid by administration of propylthiouracil, the normal ontogenic increase in CBG was suppressed. Thyroxine replacement resulted in the reappearance of the CBG rise. These results suggest that the developmental rise in the binding capacity of CBG is independent of estradiol and estrone and instead is elicited by the rising concentrations of circulating thyroxine that normally occur in the early postnatal period.