bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiated and functional human airway epithelium regeneration in tracheal xenografts
Authors: Dupuit F. , Gaillard D. , Hinnrasky J. , Mongodin E. , de Bentzmann S. , Copreni E. , Puchelle E.
Published: December 2017

To investigate the regeneration process of a well-differentiated and functional human airway epithelium, we adapted an in vivo xenograft model in which adult human nasal epithelial cells adhere and progressively repopulate denuded rat tracheae grafted in nude mice. The proliferating activity, the degree of differentiation, and the barrier integrity of the repopulated epithelium were studied during the regeneration process at optical and ultrastructural levels with immunocytochemistry and a permeability tracer. Three days after implantation in nude mice, tracheal xenografts were partially repopulated with a flattened nonciliated and poorly differentiated leaky epithelium. By the end of the first week after the graft, cell proliferation produced on the entire surface of the rat trachea an epithelium that was stratified into multiple layers and tightly sealed. During successive weeks, cell proliferation dramatically decreased. Moreover, the epithelium became progressively columnar, secretory, ciliated, and transiently leaky. At 4–5 wk, a fully differentiated pseudostratified functional epithelial barrier impermeable to a low-molecular-weight tracer was reconstituted. The regeneration of a well-differentiated and functional human airway epithelium in rat tracheae grafted in nude mice includes several steps that mimic the regeneration dynamics of airway epithelium after injury.
Hyperoxia synergistically increases TNF-α-induced interleukin-8 gene expression in A549 cells
Authors: Allen Geoffrey L. , Menendez Ingrid Y. , Ryan Marnie A. , Mazor Robert L. , Wispé Jonathan R. , Fiedler Michael A. , Wong Hector R.
Published: December 2017

Interleukin (IL)-8 is an important mediator of acute lung injury. Hyperoxia induces IL-8 production in some cell types, but its effect on IL-8 gene expression in respiratory epithelium is not well described. In addition, IL-8 gene expression resulting from the combined effects of hyperoxia and proinflammatory cytokines has not been well characterized. We treated cultured respiratory epithelial-like cells (A549 cells) with hyperoxia alone, tumor necrosis factor (TNF)-α alone, or the combination of TNF-α and hyperoxia and evaluated IL-8 gene expression. Hyperoxia alone had a minimal effect on IL-8 gene expression, and TNF-α alone increased IL-8 gene expression in a time-dependent manner. In contrast, the combination of TNF-α and hyperoxia synergistically increased IL-8 gene expression as measured by ELISA (TNF-α alone for 24 h = 769 ± 89 pg/ml vs. hyperoxia + TNF-α for 24 h = 1,189 ± 89 pg/ml) and Northern blot analyses. Experiments involving IL-8 promoter-reporter assays, electromobility shift assays, and Western blot analyses demonstrated that hyperoxia augmented TNF-α-mediated activation of the IL-8 promoter by a nuclear factor (NF)-κB-dependent mechanism and increased the duration of NF-κB nuclear translocation after concomitant treatment with TNF-α. Additional reporter gene assays demonstrated, however, that increased activation of NF-κB does not fully account for the synergistic effect of hyperoxia and that the NF-IL-6 site in the IL-8 promoter is also required for the synergistic effect of hyperoxia. We conclude that hyperoxia alone has a minimal effect on IL-8 gene expression but synergistically increases IL-8 gene expression in the presence of TNF-α by a mechanism involving cooperative interaction between the transcription factors NF-κB and NF-IL-6.
Maturational differences in hyperoxic AP-1 activation in rat lung
Authors: Yang G. , Madan A. , Dennery P. A.
Published: December 2017

Immature organisms (neonates; <12 h old) have vastly differing responses to hyperoxic injury than adults. A common feature of hyperoxic gene regulation is involvement of activator protein (AP)-1. We evaluated lung AP-1 binding as well as that of the AP-1 subunit proteins c-Fos, c-Jun, phosphorylated c-Jun, Jun B, and Jun D after exposure to >95% O2for 3 days. Unlike adults, neonates showed no increased AP-1 binding in hyperoxia despite a high affinity of the AP-1 binding complexes for phosphorylated c-Jun and Jun D as demonstrated by supershift of these antibodies with the AP-1 complexes. Moreover, neonatal lungs exhibited two distinguishable AP-1 binding complexes, whereas adult lungs had one. In neonates, sequential immunoprecipitation revealed that the lower AP-1 complex was composed of proteins from both the Fos and Jun families, whereas the upper complex consisted of Jun family proteins, with predominance of Jun D. In adults, the single AP-1 complex appeared to involve other Fos or non-Fos or non-Jun family proteins as well. Neonatal lungs showed a higher level of Jun B and Jun D immunoreactive proteins in both air and hyperoxia compared with those in adult lungs. These results suggest that significant maturational differences in lung AP-1 complexes exist and that these may explain transcriptional differences in hyperoxic gene regulation.
Mesothelial cell apoptosis is confirmed in vivo by morphological change in cytokeratin distribution
Authors: Marchi E. , Liu W. , Broaddus V. C.
Published: December 2017

Apoptosis of mesothelial cells has been demonstrated in vitro but not in vivo. To identify apoptotic pleural cells as mesothelial, we used cytokeratin as a marker and found a striking spheroid, aggregated appearance of cytokeratin in apparently apoptotic mesothelial cells. In in vitro studies, we found that the aggregated cytokeratin pattern correlated with apoptosis in primary mesothelial cells from mice, rabbits, and humans and was not seen with necrosis. In in vivo studies in mice, we then used this cytokeratin pattern to identify and quantitate apoptotic mesothelial cells. Apoptotic mesothelial cells were best harvested by pleural lavage, indicating that they were loosely adherent or nonadherent. Instillation of RPMI 1640 medium or wollastonite for 24 h induced apoptosis in 0.1 ± 0.1 (SE) and 1.0 ± 0.7%, respectively, of all mesothelial cells recovered, whereas instillation of known apoptotic stimuli, crocidolite asbestos (25 μg) for 24 h or actinomycin D plus murine tumor necrosis factor-α for 12 h, induced apoptosis in 5.1 ± 0.5 and 22.4 ± 4.5%, respectively (significantly greater than in control experiments, P < 0.05). By analysis of cytokeratin staining, mesothelial cell apoptosis has been confirmed in vivo.
Cellular disposition of transported polyamines in hypoxic rat lung and pulmonary arteries
Authors: Babal Pavel , Manuel S. Machelle , Olson Jack W. , Gillespie Mark N.
Published: December 2017

The polyamines putrescine, spermidine (SPD), and spermine are a family of low-molecular-weight organic cations essential for cell growth and differentiation and other aspects of signal transduction. Hypoxic pulmonary vascular remodeling is accompanied by depressed lung polyamine synthesis and markedly augmented polyamine uptake. Cell types in which hypoxia induces polyamine transport in intact lung have not been delineated. Accordingly, rat lung and rat main pulmonary arterial explants were incubated with [14C]SPD in either normoxic (21% O2) or hypoxic (2% O2) environments for 24 h. Autoradiographic evaluation confirmed previous studies showing that, in normoxia, alveolar epithelial cells are dominant sites of polyamine uptake. In contrast, hypoxia was accompanied by prominent localization of [14C]SPD in conduit, muscularized, and partially muscularized pulmonary arteries, which was not evident in normoxic lung tissue. Hypoxic main pulmonary arterial explants also exhibited substantial increases in [14C]SPD uptake relative to control explants, and autoradiography revealed that enhanced uptake was most evident in the medial layer. Main pulmonary arterial explants denuded of endothelium failed to increase polyamine transport in hypoxia. Conversely, medium conditioned by endothelial cells cultured in hypoxic, but not in normoxic, environments enabled hypoxic transport induction in denuded arterial explants. These findings in arterial explants were recapitulated in rat cultured main pulmonary artery cells, including the enhancing effect of a soluble endothelium-derived factor(s) on hypoxic induction of [14C]SPD uptake in smooth muscle cells. Viewed collectively, these results show in intact lung tissue that hypoxia enhances polyamine transport in pulmonary artery smooth muscle by a mechanism requiring elaboration of an unknown factor(s) from endothelial cells.
Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro
Authors: Woods Catherine M. , Neslund Gerald , Kornbrust Elisabeth , Flaim Stephen F.
Published: December 2017

Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed >40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation ( P < 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung.
Total body water and the exchangeable hydrogen. I. Theoretical calculation of nonaqueous exchangeable hydrogen in man
Authors: Culebras J. M. , Moore F. D.
Published: December 2017

A theoretical calculation of the total nonaqueous exchangeable hydrogen in protein, carbohydrates, and fat in man has been made. It shows that of the total exchangeable hydrogen in the body 5.22% is located in biochemical components, soluble in body water, containing hydrogen that is exchangeable with the isotope. This value represents a maximum upward distortion of total body water measurements by isotope dilution, due to the maximum possible exchangeability in these molecular conformations. From comparative measurements reported in the literature it is clear that this maximum is not achieved during the short period of time during which tritium-dilution studies are performed. It is the authors' belief that the hard-to-exchange amide hydrogens described by Blout in the protein conformations account for this failure of the isotope to achieve complete exchange in the short time allowed.
Drinking following intracarotid infusions of hypertonic solutions in dogs
Authors: Wood R. J. , Rolls B. J. , Ramsay D. J.
Published: December 2017

Eight dogs were prepared with bilateral carotid loops and trained to stand quietly in a modified Pavlov stand. In each of the dogs, 0.3, 0.45, and 0.6 M NaCl were infused, split between the two carotids at a rate of 0.6 ml-kg-1-min-1 for 10 min and the effect on drinking assessed. A graded increase in drinking was obtained with increased osmolality of the saline (R = 0.59, N = 32, P less than 0.001). Infusion of 0.3 M NaCl was associated with an increase in jugular venous osmolality, but no significant increase in systemic osmolality. Intravenous infusion of 0.3 M NaCl at 0.6 ml-kg-1-min-1 had no effect on drinking. Intracarotid infusion of 0.3 M sucrose in 0.15 M NaCl stimulated drinking to a similar extent as 0.3 M NaCl, whereas intracarotid 0.3 M urea in 0.15 M NaCl had no effect. Increasing the systemic plasma osmolality by infusing 1.04 M NaCl intravenously stimulated drinking, an effect which was abolished by removing the central osmotic stimulus with intracarotid infusions of water. These results are compatible with a central osmoreceptor theory of thirst.
Computer simulation of energy metabolism in anoxic perfused rat heart
Authors: Achs M. J. , Garfinkel D.
Published: December 2017

We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed.
Effect of volume expansion and veratrine on salt gland secretion in the goose
Authors: Zucker I. H. , Gilmore C. , Dietz J. , Gilmore J. P.
Published: December 2017

The influence of acute intravascular volume expansion on salt gland secretion of conscious, adult geese was investigated. The intravenous administration of 5% dextran in Krebs-bicarbonate-Ringer solution in an amount equivalent to 30% of the estimated blood volume caused a transient but highly significant increase in salt gland secretion independent of changes in plasma osmolality or sodium concentration. Intravenous veratrine (60 microng) caused a similar increase in salt gland secretion only when administered after the volume load. Intravenous 5% NaCl always caused a prolonged and significant increase in salt gland secretion which was not potentiated by veratrine. Volume expansion and hypertonic saline caused a significant tachycardia while veratrine caused a significant bradycardia. It is concluded that a volume component may contribute to the initiation of salt gland secretion in the goose and that the peripheral receptor involved is most likely vascular in origin.
Brainstem control of shivering in the cat. I. Inhibition
Authors: Amini-Sereshki L.
Published: December 2017

Regions containing heat gain tonic inhibitory areas in mesencephalon and upper pons were studied using topical microinjection of a local anesthetic. This inhibition was compared in the mesencephalic decerebrated and intact animals. In mesencephalic animals that failed to shiver, bilateral injections of procaine into the ventromedial pontine tegmental areas released some heat gain responses and in intact anesthetized cats injections in the same regions increased intensity of shivering. These effects on inhibitory areas are reversible and can be repeated in the same preparation several times. Permanent effects were obtained by electrolytic lesions or by the local microinjections of 1% osmic acid. In summary, it is shown, by means of microinjection of local anesthetic, that a tonic inhibitory area located in the ventromedial pontine reticular formation completely inhibits shivering in the mesencephalic decerebrate preparation and partially inhibits shivering in the intact anesthetized preparation.
Hormonal control of neutrophil chemotactic activity in the rat vagina
Authors: Jungi T. W. , Besedovsky H. O. , Sorkin E. , Schardt M.
Published: December 2017

A sexual-hormone-dependent neutrophil chemotactic factor(s), operative under physiological conditions, is described. Rat vaginal washouts were shown to be both chemotactic and chemokinetic for rat neutrophils in vitro, whereas macrophages were not attracted. Peak activity was observed at the end of estrus and preceded maximal neutrophil infiltration in the vagina. In order to mimic these events, gonadectomized animals were treated with estradiol for a week. They showed a similar peak of chemotactic activity 30-36 h after estradiol withdrawal, accompanied by a massive neutrophil accumulation. These data suggest that a decrease in estradiol level permits the expression of the chemotactic signal. There was no evidence for chemotaxis and/or migration inhibitors before and during estrus or during long-term estradiol treatment of gonadectomized rats. Induced neutrophil accumulation in the peritoneal cavity and chemotactic responsiveness of these cells in vitro were similar in all stages during the estrus cycle. Estradiol, progesterone, testosterone, and hydrocortisone neither promoted nor significantly inhibited the neutrophil migratory behavior over a wide range of concentrations. Our experiments suggest that the periodic neutrophil accumulation in the rat vagina after estrus is triggered by locally expressed chemotactic mechanisms that are controlled by sexual hormones. The data provide the first evidence that hormonal changes can control chemotactic factors and thus indirectly control cell migration.
Neurons in medullary areas controlling ACTH: atrial input and rostral projections
Authors: Ward D. G. , Baertschi A. J. , Gann D. S.
Published: December 2017

To examine hindbrain pathways mediating release of adrenocorticotropin (ACTH) in response to hemodynamic changes we tested, in 19 cats (chloralose/urethan), 70 neurons in ACTH-active areas of the medulla for their response to volume pulsation (+/- 1 ml, 1 Hz, 60 s) of the right atrium (RA) or to hemorrhage (3 ml/kg per 30 s), and to electrical stimulation in ACTH-active areas of the dorsal rostral pons (DRP). The activity of 16 neurons was increased (P less than 0.05) by RA. Of these, 6 were driven antidromically from the locus subcoeruleus (LSC), and were located in the lateral solitary nucleus and in posteromedial nucleus intercalatus (NI). The activity of 11 neurons was decreased by RA. Of these, 5 were driven antidromically from LSC and lateral ventral tegmental nucleus and were located in anterolateral NI. No rostral projections were found to more medial sites in DRP. Responses to the first trial of RA were rapid, but slowed and attenuated with repeated trials. Responses to hemorrhage were rapid and in the opposite direction, but did not attenuate. The results suggest that pathways displaying rate sensitivity project from the right atrium via B-receptors to the DRP.
Analysis of lung ventilation in the aestivating lungfish Protopterus aethiopicus
Authors: DeLaney R. G. , Fishman A. P.
Published: December 2017

During aestivation, the breathing pattern of the lungfish changed from the usual aquatic pattern of a single breath followed by prolonged apnea to the pattern of alternating tachypnea and apnea that characterizes Cheyne-Stokes breathing. As aestivation continued, the number of breaths per tachypneic period increased gradually to reach a steady level at about the 3rd mo. During the bouts of tachypnea, minute ventilation increased because of the increase in respiratory frequency even though tidal volumes decreased. Ventilation of the lungs during aestivation appeared to involve the same mechanism as during life in water, i.e., a buccal force pump. The breathing cycle began with the aspiration of air into the mouth as the buccal cavity enlarged. Lung deflation then occurred abetted by contraction of the abdominal muscles. Lung inflation followed and involved the “swallowing” of air form the posterior buccal region into the lungs. Cycles of deflation and partial inflation of the lungs were repeated 8–40 times (tachypneic period). At the end of the tachypneic cycle, after the last deflation, a series of larger buccal force-pump maneuvers reinflated the lungs before the start of the apneic period.
Myocardial inotrophy of CO2 in water- and air-breathing vertebrates
Authors: Poupa O. , Gesser H. , Johansen K.
Published: December 2017

A negative-inotropic effect of CO2 on myocardial contractility presumably occurs because increasing H+ concentration competes with Ca2+ at cellular membranes and proteins. Since air-breathing vertebrates have higher blood and tissue CO2 concentration than water breathers the question was raised whether the cardiac cell has a modified sensitivity to CO2 correlated with the evolutionary transition of vertebrates from water breathers to air breathers. The water-breathing fish, Salmo gairdneri, and the air-breathing turtle, Pseudemys scripta, were selected as experimental animals, since their total CO2 concentration differs markedly (3.0 and 16.0 mmol.kg-1). Electrically paced isometric ventricular strips from both species were subjected to a stepwise increase in PCO2 from 25 to 114 Torr (pH0 7.80 to 7.0; HCO3- 30 mM). Trout were additionally exposed to the same pH0 changes at 5 mM HCO3- by a stepwise increase in PCO2 (4.5-12 Torr). At each increase in PCO2 the turtle heart showed a lesser negative inotropic effect than trout. The present findings offer direct evidence that the negative inotropic effect of CO2 on heart muscle is inversely proportional to the in vivo levels of tissue CO2 concentration. The results obtained are discussed in relation to phylogenetical and ecological aspects of acid-base balance.
Circulatory effects on osmotic water exchange in Rana pipiens
Authors: Mahany T. M. , Parsons R. H.
Published: December 2017

Tritiated water (3H2O) exchange was shown to be more sensitive to circulatory changes than to arginine vasopressin (ADH)-induced permeability changes. Reducing the circulation (sciatic artery ligation) and increasing the circulation (severing the sciatic nerve) caused the 3H2O exchange in frog legs to decrease from 6.0 +/- 1.3 (5) to 3.5 +/- 0.5 and increase from 6.0 +/- 0.7 (10) to 8.6 +/- 0.6 ml.h-1, respectively. In contrast injection of ADH caused a negligible increase in 3H2O exchange from whole frogs, while at the same time causing a significant increase in osmotic water exchange from 0.22 +/- 0.08 (6) to 0.63 +/- 0.13 (6) g.100 cm-2.h-1.200 mosM-1. Circulatory changes in whole frogs were produced by inducing a diving bradycardia that was less pronounced in a bath aerated with oxygen than with air. The bradycardia caused a reduction in skin circulation, as measured by 3H2O exchange, from 0.210 +/- 0.007 (16) to 0.17 +/- 0.006 (16) ml.h-1.cm-2 in air mixed media and from 0.149 +/- 0.009 (16) to 0.135 +/- 0.011 (16) in oxygen mixed media. Diving bradycardia was also found to affect osmotic water uptake which decreased from 0.61 +/- 0.05 (16) to 0.39 +/- 0.03 (16) g.100 cm-2.h-1.200 mosM-1 in air mixed media and from 0.61 +/- 0.05 (16) to 0.51 +/- 0.04 (16) in oxygen mixed media. The results indicate that circulation affects osmotic water exchange.
Effect of transferrin saturation on iron delivery in rats
Authors: Christensen A. C. , Huebers H. , Finch C. A.
Published: December 2017

Studies were carried out in rats to evaluate the release of iron from monoferric and diferric transferrin. Isoelectric focusing was carried out on plasma tagged at low and high saturations, and it was shown that these represented primarily monoferric and diferric transferrin, respectively. In vivo studies with these tagged plasmas were carried out on normal, iron-deficient, and hypertransfused rats. In all three groups there was a greater in vivo uptake of iron from diferric transferrin by all tissues monitored. Though the amount varied in different animals, the ratio of uptake between diferric and monoferric transferrin iron varied between 1.56 and 2.10 in the erythron and between 2.38 and 2.65 in the liver. These studies indicate that changes in transferrin saturation, by changing the proportion of monoferric to diferric transferrin iron, changed the amount of iron released to tissues.
Satiety effects of cholecystokinin and caerulein in rabbits
Authors: Houpt T. R. , Anika S. M. , Wolff N. C.
Published: December 2017

Six adult rabbits were maintained on an 18 h fast, 6 h feeding schedule. At the end of the fast either 0.5-40 Ivy dog units (IDU)/kg cholecystokinin (CCK) or 0.9% NaCl were injected intravenously. Feed intake was then measured for 15 min. Significant depression of intake was found at 1 IDU/kg, a 50% depression of intake after 5.5 IDU/kg, and no intake after 40 IDU/kg. Caerulein in similar experiments gave significant depression of intake at 0.125 microgram/kg, a 50% depression after 0.28 microgram/kg, and no intake after 5.0 microgram/kg. In three of these rabbits subdiaphragmatic vagotomy did not abolish the satiety effects of CCK and caerulein. The synthetic octapeptide of CCK was less potent in causing satiety. After CCK or caerulein the rabbits showed typical postprandial behavior. Taste aversion tests failed to demonstrate a strong aversion to flavors associated with the compounds used. These results indicate that exogenous CCK can act as a satiety agent at levels of the same order as the physiological range.
Some control conditions for self-organization--what the control theorist can learn from biology
Authors: Tomovic R.
Published: December 2017

The general control task, as expressed formally in engineering science or mathematical systems theory, is presented briefly. Characteristics of technological control systems are then contrasted with the control processes revealed by molecular biology. It is emphasized that the control processes of living systems have certain features not represented in formal control theory. One of these features is the use of positive feedback in a novel way to achieve a “positive control potential.” The environmental conditions necessary for positive control potential to arise are considered. It is concluded that achievements in life sciences offer a challenge to extend formal control theory into new domains, but at the same time, existing control theory helps to highlight what it is that living systems uniquely do, even though it cannot explain how they do it.
Internal synchronization among several circadian rhythms in rats under constant light
Authors: Honma K. I. , Hiroshige T.
Published: December 2017

Three biological rhythms (locomotor activity, body temperature, and plasma corticosterone) were measured simultaneously in individual rats under light-dark cycles and continuous light. Spontaneous locomotor activity was recorded on an Animex and body temperature was telemetrically monitored throughout the experiments. Blood samples were obtained serially at 2-h intervals on the experimental days. Phase angles of these rhythms were calculated by a least-squares spectrum analysis. Under light-dark cycles, the acrophases of locomotor activity, body temperature, and plasma corticosterone were found at 0029, 0106, and 1940 h, respectively. When rats were exposed to 200 lx continuous light, locomotor activity and body temperature showed free-running rhythms with a period of 25.2 h on the average. Plasma corticosterone levels determined at 12 days after exposure to continuous light exhibited a circadian rhythm with the acrophase shifted to 0720. The acrophases of locomotor activity and body temperature, determined simultaneously on the same day, were found to be located at 1303 and 1358 h, respectively. Phase-angle differences among the three rhythms on the 12th day of continuous light were essentially the same with those under the light-dark cycle. These results suggest that circadian rhythms of locomotor activity, body temperature, and plasma corticosterone are most probably coupled to a common internal oscillator in the rat.
Intrathoracic electrical impedance measurements from an esophageal probe
Authors: Mitchell M. M. , Newbower R. S.
Published: December 2017

The sensing of intrathoracic electrical impedance from an esophageal probe may allow relatively noninvasive monitoring of cardiac and respiratory functions of particular interest in anesthesia and intensive care. We have obtained a partial solution of the intrathoracic current-field problem for impedance measurements made from a four-terminal linear array of electrodes located in the esophagus. It allows prediction that aortic root motion will exceed aortic distension as a major determinant of the cardiac intrathoracic esophageal impedance signal. This prediction was confirmed for a specific carefully selected and placed electrode array in anesthetized dogs. In general, motions of organs will be more important than volume changes in affecting the esophageal impedance signal. Thus, timing information (preejection period and left ventricular ejection time) is available from electrodes on an esophageal probe, but cardiac output information appears to be inaccessible for fundamental reasons.
Development of fever in the newborn lamb
Authors: Kasting N. W. , Veale W. L. , Cooper K. E.
Published: December 2017

Newborn lambs do not become febrile in response to intravenous (iv) bacterial endotoxin in moderate doses. Newborn lambs were tested to see if they could become febrile to large doses of endotoxin or to endogenous pyrogen. At 5 h of age lambs do not become febrile to relatively large doses of endotoxin or to endogenous pyrogen, but rather become hypothermic. At 32 h and all subsequent times, fevers could be elicited. Onset time of fevers in lambs was short initially and gradually lengthened over 9 days, at which time it was similar to the onset time of the adult fever. With respect to the febrile response, newborn lambs showed varying degrees of tolerance after 10 days of daily injections of endotoxin, as compared to the ewe which becomes tolerant in 2 or 3 days.
Bradycardia during stimulation of the septum and somatic afferents in the rabbit
Authors: Brickman A. L. , Calaresu F. R. , Mogenson G. J.
Published: December 2017

Experiments were done in paralyzed rabbits anesthetized with either pentobarbital sodium or alpha-chloralose to test the possibility that the septum may alter the cardiovascular responses elicited by stimulation of somatic afferent fibers. Electrical stimulation of the lesser saphenous nerve (LSN), a branch of the sciatic nerve, at certain parameters elicited bradycardia, which could be abolished by bilateral vagotomy or intravenous injection of atropine methylbromide. Distinct and characteristic changes in mean arterial pressure and heart rate were elicited by electrical stimulation of histologically localized sites in five septal areas. Septal sites from which stimulation elicited bradycardia were chosen for the study of interaction between the septum and LSN. The cardiac slowing elicited by combined stimulation of the lateral septum and LSN was significantly greater than the sum of the responses elicited by separate stimulation of the two different structures. In contrast, the bradycardia elicited by combined stimulation of medial septal structures and LSN was significantly smaller than the sum of the individual responses. These experiments demonstrate that the magnitude of heart rate responses elicited by stimulation of somatic afferent fibers may be modified by the septum.
Laryngeal reflex apnea in the chemodenervated newborn piglet
Authors: Fagenholz S. A. , Lee J. C. , Downing S. E.
Published: December 2017

Effects of peripheral arterial chemodernervation on laryngeal reflex-induced apnea were studied in 18 piglets of either sex varying in age from 4 to 63 days. The distal trachea was cannulated with a cuffed endotracheal tube to secure a free airway and permit ventilatory measurements with a pneumotachograph. The proximal trachea was used to introduce fluids into the larynx. Water elicited apnea, bradycardia, and arterial hypertension, whereas saline caused only transient disturbances. Electrical stimulation of the superior laryngeal nerves reproduced, and conduction anesthesia ablated, the effects of water in the larynx. Carotid body contribution to respiratory drive was assessed by the ventilatory responses to increased (100%) and decreased (10%) anbient oxygen concentration. These indicated significant peripheral chemoreceptor ventilatory activity from birth with little further change in the neonatal period. Ventilatory responses to oxygen were ablated by carotid chemodenervation, but there was no change in the duration of laryngeal reflex apnea. We conclude that attenuation of laryngeal-induced apnea during postnatal development is independent of peripheral chemoreceptor activity. Our findings may have relevance to the clinical problem of sudden infant death syndrome, in which carotid body abnormalities have recently been described.
Oral motor deficits following lesions of the central nervous system in the rat
Authors: Brimley C. C. , Mogenson G. J.
Published: December 2017

The effects of lesions of the zona incerta (ZI), globus pallidus (GP), midlateral and far lateral hypothalamus (MLH and FLH), and the central amygdaloid complex (CAC) on oral motor deficits were investigated. Lesions of the ZI, GP, and CAC resulted in a significant reduction in tongue extension and lap volume. MLH lesions significantly reduced tongue extension whereas FLH lesions significantly reduced both tongue extension and lap volume. Injections of 6-hydroxydopamine into the GP, MLH, and CAC also significantly reduced tongue extension and lap volume. Water and/or food intakes were reduced in some of the lesioned groups but the oral motor deficits were observed both in the presence and in the absence of reduced water and food intakes. The possibility that oral motor deficits are associated with damage to striatal and non-striatal dopamine neurons needs further investigation.
Computer simulation of metabolism in pyruvate-perfused rat heart. I. Model construction
Authors: Kohn M. C. , Achs M. J. , Garfinkel D.
Published: December 2017

A computer model of energy metabolism was constructed for the pyruvate-perfused rat heart subjected to a sudden increase in work load. The model construction techniques are explained and justified. Hypotheses defining a plausible sequence of physiological events resulting in the observed behavior of the organ were arrived at from the measured metabolite time profiles. There is a lag in increasing pyruvate utilization following the work-jump. A transient increase in fatty acid oxidation is required to account for the observed respiration rate. The observed increase in lactate production of this preparation is due to a transient “burst” of glycogenolysis after which the remaining lactate is imported from the interstitium and oxidized, reversing lactate dehydrogenase and hence the alpha-ketoglutarate-malate portion of the malate-aspartate shuttle.
Facilitation of female reproductive behavior from mesensephalic central gray in the rat
Authors: Sakuma Y. , Pfaff D. W.
Published: December 2017

Electrical stimulation in the mesencephalic central gray (CG) and adjacent subtectum through chronically implanted electrodes in free-moving estrogen-primed ovariectomized female rats elicited a rapid and large facilitation of the lordosis reflex in response to either male mounts or manula cutaneous stimuli. Unilateral stimulation was sufficient for this effect. The facilitation increased in a graded manner to increased stimulus intensity, and was optimally evoked by stimuli delivered at 50--150 Hz. Facilitation disappeared rapidly following the end ot electrical stimulation, and within 15 min, reflex performance returned to the prestimulation level. Lordosis facilitation appeared when no aversive responses occurred; stimulation with comparable parameters at the lateral edge of CG or in the mesencephalic reticular formation often resulted in postural changes or aversive responses but was not able to facilitate lordosis. Lordosis refelx facilitation was probably mediated by projections descending from neurons in and around the CG, and represents stimulation of a functional link between ascending somatosensory and descending motor systems for the control of lordosis behavior.
Dehydration elevates osmotic threshold for salt gland secretion in the duck
Authors: Kaul R. , Hammel H. T.
Published: December 2017

Acute salt and water balance measurements were made in two conscious salt water-acclimated Pekin ducks at and above their osmotic threshold for salt gland secretion. Intravneous infusion of 1,000 mosmol/kg H2O NaCl at 0.350 ml/min increased plasma tonicity less than 0.5% and increased secretion from nearly zero to a rate matching the infusion. Continuous secretion at a similar submaximal rate was driven by 5,600 mosmol/kg H2O NaCl infused at 0.070 ml/min. Osmolality of secreted fluid was constant for any secretion rate, so that net water loss occurred when the concentration of infusate exceeded that of secreted fluid. Threshold plasma osmolality increased by 9 mosmol/kg H2O after the loss of 77 g water (3% body wt). Solutes were always secreted at the infusion rate, even when body fluid osmolality increased while body water decreased. We conclude that the salt gland controller is sensitive to more than just extracellular fluid (ECF) tonicity, and we suggest that elevation of the osmotic threshold may occur in response to decreased ECF volume.
Regulation of body volume by salivation in a tick challenged with fluid loads
Authors: Kaufman W. R. , Aeschlimann A. A. , Diehl P. A.
Published: December 2017

Injection into the hemolymph of 1.2% NaCl, 11.2% sucrose, 2.3% urea (all approximately isosmotic to hemolymph), or distilled water induced salivary fluid secretion in the ixodid tick Amblyomma hebraeum Koch. Saline gave the largest response at high doses. Injection of hyperosmotic NaCL into the hemolymph did not induce salivation but led to the drinking of distilled water in amounts sufficient to dilute the salt load to isosmolarity. Atropine only partially inhibited salivation induced by NaCl, sucrose, and distilled water. Reserpine markedly inhibited salivation induced by NaCl. We propose that at least two sensory pathways (one cholinergic, one not) converge on the secretory nerve. The physiological significance of the cholinergic pathway is not known. The other pathway probably mediates the regulation of hemolymph volume, possibly via stretch receptors, but its transmitter is not known.
Water balance in embryos of Fundulus heteroclitus and F. bermudae in seawater
Authors: Guggino W. B.
Published: December 2017

The purpose of this study is to examine the mechanisms of osmoregulation in embryos of Fundulus heteroclitus and F. bermudae. The turnover rate of tritiated water in intact embryos of F. heteroclitus increases from 0.05 to 0.013 h-1 at 4 days to 0.12 +/- 0.030 h-1 at 7 days and to 0.18 +/- 0.060 h-1 at 10 days, corresponding to estimated diffusional water permeabilities of 0.4, 1.0, and 1.6 x 10(-6) cm . s-1, respectively. These values are low when compared to other organisms but not sufficiently low to maintain embryos in water balance. The osmolality of the embryonic extracellular fluids decreases during development from 362 +/- 9.2 mosmol . kg-1 at 4 days to 344 +/- 6.9 mosmol . kg-1 at 10 days. Water loss is balanced by drinking seawater at a rate of 600 pl . mg-1 . h-1 for 7- to 8-day embryos. The embryo possesses a pair of branchial chambers that communicate anteriorly with the pharynx through embryonic gill slits and posteriorly with the perivitelline space by means of pores. In the absence of a mouth it is probably through these pores that seawater is injested.
Nucleus accumbens to globus pallidus GABA projection subserving ambulatory activity
Authors: Jones D. L. , Mogenson G. J.
Published: December 2017

The present experiments investigated the hypothesis of a projection relating to the release of gamma-aminobutyric acid (GABA) from the nucleus accumbens to the globus pallidus subserving ambulatory activity in the rat. The GABA antagonist picrotoxin, microinjected into the globus pallidus, elicited dose-dependent increases in ambulatory activity. The administration of dopamine into the nucleus accumbens had a synergistic effect and further stimulated ambulatory activity. GABA injected into the ventral posterior globus pallidus significantly attenuated the ambulatory activity stimulated by injecting dopamine into the nucleus accumbens. These observations provide evidence of a GABAergic projection from the nucleus accumbens to the globus pallidus and implicate it in the initiation of ambulatory activity.
Role of C-4 pathway in crustacean chloride cell function
Authors: Conte F. P.
Published: December 2017

A hypothetical model for the bioenergetic regulation of ion transport in the chloride cell of the larval crustacean salt gland is presented. Current data dealing with the ultrastructural, electrochemical, and biochemical events associated with cytodifferentiation of the crustacean (Artemia salina) salt-excreting epithelia is compiled and tabulated. A C-4 dicarboxylic aicd pathway is postulated to serve as a facultative anaerobic shunt to meet the demands of the high rate of glycolysis required by salt-secreting epithelium. This mechanism involves the fixation of CO2 from exogenous bicarbonate while forming net amounts of metabolic water and high energy nucleotide equivalents from stored diGDP.
Physical causality and brain theories
Authors: Yates F. E.
Published: December 2017

The history of deterministic theories in physics is reviewed, and four levels of determinism are found: 1) absolute, 2) asymptotic, 3) probabilistic, and 4) absolute indeterminism. Nagel's view that all causal laws are deterministic in the frame of the state descriptions to which they refer is acknowledged, but the inevitability of macroscopic measurement noise may hint that dynamical laws are innately noisy. Quantum mechanical effects are not the noise source. Symmetry and broken symmetry are introduced as physical concepts that can account both for lawfulness, and for the hierarchical nature of the universe. Physical ideas are chosen over those of formal systems with indirect self-reference as the basis of a global theory of brains. By exclusion it is concluded that only a statistical thermodynamics, combined with nonlinear mechanics, has the features needed for theorizing about brains in a physical sense. Quantum mechanics is judged not to be relevant. New statistical thermodynamic theories are briefly described, and their strengths and weaknesses noted. The question, “Why should neuroscience look to physics for its theories?” is raised and answered. Some concrete objectives for a program of theoretical research are stated.
Role of the renin-angiotensin system in potassium control
Authors: Young D. B. , McCaa R. E.
Published: December 2017

To determine the importance of the renin-angiotensin system in control of plasma potassium concentration and excretion, potassium control was studied in two groups of dogs in response to a 20-fold increase in sodium intake (from 10 to 200 meq/day). Group I was intact whereas group II lacked feedback control of the renin-angiotensin system, which was eliminated by continuous infusion of 10 ng . kg-1 . min-1 angiotensin II. This rate of infusion reduced endogenous plasma renin activity (PRA) to undetectable levels throughout the study. The sodium forcing did not result in measurable changes in plasma potassium concentration or excretion in group I, in which PRA fell to 40% and plasma aldosterone concentration (PAC) to 60% of the low sodium levels. In group II the same sodium forcing produced a 12% decrease in plasma potassium concentration and a 79% increase in urinary potassium excretion. PAC also fell to 60% of the low sodium level in group II. The results demonstrate the importance of the renin-angiotensin system as a link between the nephron and the zona glomerulosa that is essential in controlling plasma potassium concentration and excretion during changes in sodium balance.
Water flux in animals: analysis of potential errors in the tritiated water method
Authors: Nagy K. A. , Costa D. P.
Published: December 2017

Laboratory studies indicate that tritiated water measurements of water flux are accurate to within -7 to +4% in mammals, but errors are larger in some reptiles. However, under conditions that can occur in field studies, errors may be much greater. Influx of environmental water vapor via lungs and skin can cause errors exceeding +/- 50% in some circumstances. If water flux rates in an animal vary through time, errors approach +/- 15% in extreme situations, but are near +/- 3% in more typical circumstances. Errors due to fractional evaporation of tritiated water may approach -9%. This error probably varies between species. Use of an inappropriate equation for calculating water flux from isotope data can cause errors exceeding +/- 100%. The following sources of error are either negligible or avoidable: use of isotope dilution space as a measure of body water volume, loss of nonaqueous tritium bound to excreta, binding of tritium with nonaqueous substances in the body, radiation toxicity effects, and small analytical errors in isotope measurements. Water flux rates measured with tritiated water may be expected to be within +/- 10% of actual flux rates in most situations.
Chronic, nonocclusive, and maintenance-free central venous cannula in the rat
Authors: Kaufman S.
Published: December 2017

To provide a means of taking repeated blood samples from conscious, stress-free rats, we devised a method to chronically cannulate the inferior vena cava. The rat was anesthetized with pentobarbital sodium plus methoxyflurane. The inferior vena cava was exposed through a midline abdominal incision. Silastic tubing (0.020 in. ID, 0.037 in. OD) was pushed through a tiny hole punctured in the wall of the vein; it remained in place without leaking due to the elasticity of the vessel wall. The cannula was advanced towards the heart until its tip lay at the level of the xiphisternum at which point blood could be aspirated. A series of silk (4-0) sutures to the psoas muscle and body wall held the cannula secure without compromising blood flow. The cannula ran subcutaneously to the back of the neck where it was ligated to the underside of the skin (prolene 4-0 suture), plugged with a short metal obturator, and exteriorized through a small stab wound. The cannula was filled with heparinized saline, but it was not necessary to regularly flush it through to maintain patency. Sepsis did not occur and animals autopsied several months after cannulation showed no tissue reaction around the cannula.
Extracellular hyperosmolality and body temperature during physical exercise in dogs
Authors: Kozlowski S. , Greenleaf J. E. , Turlejska E. , Nazar K.
Published: December 2017

The purpose of this study was to test the hypothesis that thermoregulation during exercise can be affected by extracellular fluid hyperosmolality [Osm] without changing the plasma Na+ concentration. The effects of preexercise venous infusions of hypertonic mannitol and NaCl solutions on rectal temperature (Tre) responses were compared in dogs running at moderate intensity for 60 min on a treadmill. Plasma E1Na+] was increased by 12 meq/l (P less than 0.05) after NaCl infusion, and decreased by 9 meq/l (P less than 0.05) after mannitol infusion. Both infusions increased plasma [Osm] by 15 mosmol/kg (P less than 0.05). After both infusions, Tre was essentially constant during 60 min rest. However, compared with the noninfusion exercise increase in Tre of 1.3 degrees C, Tre increased by 1.9 degrees C (delta delta Tre = 0.5 degrees C, P less than 0.05) after both postinfusion exercise experiments. It was concluded that inducing extracellular hyperosmolality, without elevating plasma [Na+], can induce excessive increases in Tre during exercise but not at rest.