bluuebunny/crossref_metadata_2025 huggingface dataset:
Histamine alters endothelial barrier function at cell-cell and cell-matrix sites
Authors: Moy Alan B. , Winter Michael , Kamath Anant , Blackwell Ken , Reyes Gina , Giaever Ivar , Keese Charles , Shasby D. M.
Published: December 2017

To determine how histamine regulates endothelial barrier function through an integrative cytoskeletal network, we mathematically modeled the resistance across an endothelial cell-covered electrode as a function of cell-cell, cell-matrix, and transcellular resistances. Based on this approach, histamine initiated a rapid decrease in transendothelial resistance predominantly through decreases in cell-cell resistance in confluent cultured human umbilical vein endothelial cells (HUVECs). Restoration of resistance was characterized by initially increasing cell-matrix resistance, with later increases in cell-cell resistance. Thus histamine disrupts barrier function by specifically disrupting cell-cell adhesion and restores barrier function in part through direct effects on cell-matrix adhesion. To validate the precision of our technique, histamine increased the resistance in subconfluent HUVECs in which there was no cell-cell contact. Exposure of confluent monolayers to an antibody against cadherin-5 caused a predominant decrease in cell-cell resistance, whereas the resistance was unaffected by the antibody to cadherin-5 in subconfluent cells. Furthermore, we observed an increase predominantly in cell-cell resistance in ECV304 cells that were transfected with a plasmid containing a glucocorticoid-inducible promoter controlling expression of E-cadherin. Transmission electron microscopy confirmed tens of nanometer displacements between adjacent cells at a time point in which histamine maximally decreased cell-cell resistance.
HumanSP-Cgene sequences that confer lung epithelium-specific expression in transgenic mice
Authors: Glasser Stephan W. , Burhans Michael S. , Eszterhas Susan K. , Bruno Michael D. , Korfhagen Thomas R.
Published: December 2017

We used transgenic mice to identify cis-active regions of the human pulmonary surfactant protein C ( SP-C) gene that impart tissue- and cell-specific expression in vivo in the lung. Approximately 3.7 kb of genomic SP-C DNA upstream of the transcription start site was sufficient to direct chloramphenicol acetyltransferase ( CAT) reporter gene expression specifically in bronchiolar and alveolar epithelial cells of the lung. To further define cis-active regulatory elements that mediate cell-specific expression, we tested deletions of the parental 3.7-kb human SP-C sequence in transgenic mice. Tissue CAT assays of mice generated with truncations or overlapping internal deletions of the 3.7-kb construct functionally map alveolar cell-specific regulatory elements to within −215 bp of the SP-C promoter. Analysis of SP-C promoter deletions demonstrate that sequences between −3.7 kb and −1.9 kb contain enhancer sequences that stimulate SP-C transgene expression. In situ hybridization studies demonstrate that deletion of the −1,910- to −215-bp region abolishes the ectopic bronchiolar expression seen with the original 3.7-kb SP-C promoter construct. Comparison of sequences from −215 to +1 bp identified consensus binding sites for the homeodomain transcription factor thyroid transcription factor-1 (TTF-1). Cotransfection assays of the human 3.7-kb SP-C or −1,910- to −215-bp SP-C deletion construct with a TTF-1 expression plasmid demonstrates that TTF-1 transactivates the human SP-C gene. These results suggest that the TTF-1 cis-active sites are important in directing cell-specific expression of the SP-C gene in vivo.
Human SP-A protein variants derived from one or both genes stimulate TNF-α production in the THP-1 cell line
Authors: Wang Guirong , Phelps David S. , Umstead Todd M. , Floros Joanna
Published: December 2017

In humans, two functional genes of surfactant protein (SP) A, SP-A1 and SP-A2, and several alleles of each functional gene have been characterized. SP-A is a multimeric molecule consisting of six trimers. Each trimer contains two SP-A1 molecules and one SP-A2 molecule. Until now, it has been unclear whether a single SP-Agene product is functional or whether there are functional differences either among alleles or between single-gene SP-A products and SP-A products derived from both genes. We tested the ability of in vitro expressed SP-A variants to stimulate tumor necrosis factor (TNF)-α production by THP-1 cells. We observed that 1) single-gene products and products derived from both genes stimulate TNF-α production, 2) there are differences among SP-A1 and SP-A2 alleles in their ability to stimulate TNF-α production, and 3) the increases in TNF-α production are lower after treatment with the SP-A1 alleles than after treatment with the SP-A2 alleles. Furthermore, coexpressed SP-As from SP-A1 and SP-A2 genes have a higher activity compared with SP-As from individual alleles or mixed SP-As from SP-A1and SP-A2 genes. These data suggest that the SP-A-induced increases in TNF-α levels differ among SP-A variants and appear to be affected by SP-A genotype and whether SP-A is derived from one or both genes.
Evaluation of the Grodins respiratory model via dynamic end-tidal forcing
Authors: Swanson G. D.
Published: December 2017

The Grodins model for respiratory physiology is very descriptive in simulating the lung-blood-tissue gas transport and exchange system, including detail not found in previous or more recent models. Three alternative controllers have been proposed for control of this gas exchange system. This paper indicates how dynamic endtidal forcing enhances behavioral differences among these three controllers and therefore enhances discrimination when the behavior is compared with subject data. Previously published end-tidal forcing data are used in the comparison. Several deficiencies in the controllers for the Grodins model are indicated.
Sleep and hibernation in ground squirrels (Citellus spp): electrophysiological observations
Authors: Walker J. M. , Glotzbach S. F. , Berger R. J. , Heller H. C.
Published: December 2017

Electroencephalogram (EEG), electrooculogram, electromyogram, and electrocardiogram were recorded from ground squirrels (Citellus beldingi and C. lateralis) during the summer and also during the hibernation season. Summer recordings revealed that the animals spent an average of 66% of the 24-h period asleep (49% of the 12-h light period and 84% of the 12-h dark period); 19% of the total sleep time (TST) consisted of rapid-eye-movement (REM) sleep, and 81% of TST consisted of slow-wave sleep (SWS). Recordings obtained during the hibernation season showed that hibernation was entered through sleep, but the distribution of sleep states was different than in euthermic sleep. During the early entrance when brain temperature (Tbr) was between 35 and 25 degrees C, the animals were asleep 88% of the time, but only 10% of the TST was spent in REM sleep. The EEG amplitude declined with decreased Tbr so that classical sleep stages could not be identified below a Tbr of 25 degrees C. The frequency of the EEG increased as Tbr decreased; but activity in the 0–4 cycles/s band occupied the majority of the record even at a Tbr of 10 degrees C. Below a Tbr of 10 degrees C the EEG was isoelectric except for intermittent bursts of spindles. It was concluded from these and other results that the entrance into hibernation represents an extension of the thermoregulatory adjustments that occur during SWS.
Fast, rate-sensitive corticosteroid negative feedback during stress
Authors: Kaneko M. , Hiroshige T.
Published: December 2017

Characteristics of the fast, rate-sensitive, negative-feedback regulation of adrenocorticotropin secretion during stress was quantitatively analyzed using rats anesthetized with pentobarbital sodium. Various levels of plasma corticosterone were achieved during morning hours by infusing corticosterone solutions of different concentrations. Blood was sampled serially from the carotid artery. An increase in plasma corticosterone concentration 15 min after intravenous, pulsed injection of histamine (230 microgram) during saline intravenous infusion was defined as the “control response”. When plasma corticosterone was rising during corticosterone infusion, the response to histamine stimulus was distinctly inhibited (fast, rate-sensitive feedback inhibition), whereas such an inhibition was not observed when plasma corticosterone levels were not rising, regardless of the absolute level. The critical rate of rise of plasma corticosterone, at or above which the fast rate-sensitive feedback was manifested, was 4-6 microgram/100 ml per min. When three graded doses of histamine were injected while plasma corticosterone levels were increasing at a rate of 6 microgram/100 ml per min, the absolute value of the inhibition observed was indepxendent of the administered dose of the stressor. A hypothetical model for the mechanism of this feedback inhibition, based on the assumption that the hormone effect was proportional to the rate of formation of hormone-receptor complex, satisfied the quantitative characteristics of the inhibition experimentally observed in this study.
Overall characteristics of arterial pressure control system studied by mild hemorrhage
Authors: Hosomi H.
Published: December 2017

The overall, static, open-loop gain of the negative-feedback arterial pressure control system was determined repeatedly in anesthetized cats under normal and hypovolumic states. The gain, H, was assessed as (deltaAPI/deltaAPS)-1, where deltaAPI is the immediate fall and deltaAPS the steady-state fall in arterial pressure following a stepwise reduction in blood volume. When the step size was increased from 1.25 to 25% of the total blood volume, H decreased from 30 to less than unity. Considering this amplitude dependence of H, a small amount (1.25%) of quick (in less than 0.3 s) hemorrhage was used to determine H throughout the rest of the experiments. Time-dependent variation of H was evident after a large amount (6.25%) of blood loss. During the initial 10 min, H increased to 126% of the control value, decreased to 43% over the subsequent 20--70 min, and showed a trend toward recovery. The small signal analysis permits a quantitative characterization of the time and input size dependent nature of the arterial pressure control system after various degrees of hemorrhage.
A field and circuit thermodynamics for integrative physiology. I. Introduction to the general notions
Authors: Iberall A. S.
Published: December 2017

Page R171: A. S. Iberall. “A field and circuit thermodynamics for integrative physiology. I. Introduction to the general notions.” Page R176: delete Vs,s from Eqs. 8 and 9, which should now read

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Circadian rhythm dissociation in an environment with conflicting temporal information
Authors: Sulzman F. M. , Fuller C. A. , Hiles L. G. , Moore-Ede M. C.
Published: December 2017

The relative contributions of light-dark (LD) cycles and feeding (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-h LD cycles consisting of 12 h of 600 lx followed by 12 h of less than 1 ls and concurrent 24-h EF cycles in which the animals ate for 3 h and then fasted for 21 h. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-h LD cycles (LD 11.5:11.5) and 24-h EF cycles (EF 3:21). Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.
Unstable state of the arterial pressure control system after a mild hemorrhage
Authors: Hosomi H.
Published: December 2017

The stability of the arterial pressure control system after a mild hemorrhage (5 ml/kg body wt) was studied in 10 anesthetized cats by analyzing the responses of arterial pressure and of heart rate and the dead time (L) of heart rate response to a minute, rapid test hemorrhage (1 ml/kg body wt). The overall open-loop gain (H) of the arterial pressure control system was estimated from the ratio of arterial pressure fall immediately after the quick hemorrhage over the steady-state fall. Increases in H and L were correlated with the tendency of the arterial pressure control system to be unstable and oscillate. Oscillation in arterial pressure was always accompanied by a marked increase in heart rate (deltaHR), which represents an enhanced activity of the sympathetic nervous system and serves to restore arterial pressure toward the prehemorrhage level. The present study indicates that the magnitude of deltaHR also serves as a good predictor of arterial pressure oscillation.
Metabolism of the acutely ischemic dog heart. II. Interpretation of a model
Authors: Garfinkel D. , Achs M. J.
Published: December 2017

The glycolytic oscillations occurring in an acutely ischemic dog heart are analyzed with a computer model. The major regulations of the glycolytic pathway flux occur at phosphohexose isomerase, which is inhibited by accumulated pentose shunt intermediates; at phosphorylase, which shapes the first cycle of the oscillation; and at aldolase, which shapes the last two cycles. Aldolase is not under normal substrate control. Its activity, and that of some subsequent glycolytic enzymes, appears to be regulated by known interactions with the muscle proteins. The mitochondria become reduced as a result of anoxia, and their metabolism reorganizes to export rather than import reducing equivalents. It is in general feasible to account for the behavior of this preparation in terms of the known metabolism of less severely perturbed hearts, especially (but not completely) in terms of effects of anoxia. The reasons for the inapplicability of the crossover theorem previously used to analyze this preparation are described.
Development of angiotensin-converting enzyme in fetal rat lungs
Authors: Wallace K. B. , Bailie M. D. , Hook J. B.
Published: December 2017

Angiotensin-converting enzyme (ACE) catalyzes rapid hydrolytic cleavage of angiotensin I to form angiotensin II (AII). Inasmuch as converting enzyme activity is present at birth and increases postnatally to adult values it was of interest to determine the prenatal development of ACE. Converting enzyme activity was determined in the 20,000 x g supernatant fraction of lung homogenates using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Hippuric acid liberated by the hydrolysis of HHL was quantified spectrophotometrically. ACE activity was first detectable at 18 days of gestation and increased fourfold prior to birth (21 days gestation). Pulmonary ACE activity of 1-day-old animals was twice that of fetuses at day 20 of gestation; however, this increase did not appear to result from ventilation alone. The Michaelis-Menten constant for fetal ACE (2.0 mM HHL) was not different from that calculated for ACE of adult rat lungs (2.6 mM). These data were interpreted to indicate that the age-related increase in ACE activity was due to greater ACE content as opposed to further activation of preexisting enzyme. This increase in fetal ACE activity may play an important role in preparing the renin-angiotensin system for postnatal function.
Influence of thermal acclimation on membrane lipid composition of rainbow trout liver
Authors: Hazel J. R.
Published: December 2017

Rainbow trout (Salmo gairdneri) acclimated to 5 degrees C possessed larger livers and less neutral lipid per gram of liver than 20 degrees C-acclimated animals; quantities of liver glycolipid, phospholipid, and cholesterol did not vary significantly with acclimation temperature. The relative proportions of phosphatidylethanolamine increased significantly following cold exposure, whereas the quantities of sphingomyelin and cardiolipin declined. For all phosphatides examined (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, lysolecithin, cardiolipin, sphingomyelin) cold acclimation resulted in 1) an increase in the quantity of polyunsaturated fatty acids, 2) a reduction in the level of saturated fatty acids, and 3) little change in the total content of monoenes and dienes. The increased content of polyunsaturated fatty acids in choline and ethanolamine phosphatides following cold acclimation was confined to the 2-position and occurred at the expense of monoenes and dienes. The relative proportions of n - 3 fatty acids, and less frequently n - 6 fatty acids, increased in phosphatides of cold-acclimated trout, whereas the relative proportions of n - 9 fatty acids declined. These data suggest a preferential incorporation of fatty acids belonging to the linolenic acid family at reduced temperatures. Temperature-induced changes in the chemical composition of trout liver phospholipids counteracted the effects of acute temperature change on nonelectrolyte permeability of isolated liposomes.
Effect of brain 5-hydroxytryptamine alterations on reflex bradycardia in rats
Authors: Lin M. T. , Chern S. I.
Published: December 2017

The vasopressor and bradycardia responses to an intravenous dose of epinephrine were assessed in saline-controlled, 5-hydroxytryptamine-(5-HT) depleted, and 5-HT-potentiated rats. Regardless of the previous treatment epinephrine produced an insignificant change in the basal levels of mean arterial pressure and heart rate. However, brain serotonin alteration did produce some influences on the reflex bradycardia in response to an elevation in arterial pressure. Elevating 5-HT contents in brain with 5-hydroxytryptophan (5-HTP) after peripheral decarboxylase inhibition with Ro 4-4602 produced a significant reduction in reflex bradycardia compared to the controls. In contrast, depleting 5-HT contents in brain with either p-chlorophenylalanine (PCPA) or 5,7-dihydroxytryptamine (5,7-DHT) led to an enhancement of epinephrine-induced bradycardia. Moreover, the enhanced reflex bradycardia induced by PCPA treatment was readily blocked by the replacement of the depleted brain 5-HT with 5-HTP and Ro 4-4602. The results suggest that serotoninergic systems play a role in the elaboration or modulation of reflex bradycardia. Specifically, 5-HT appears to inhibit reflex bradycardia since its depletion facilitated and its elevation inhibited reflex bradycardia.
Diabetes, dietary tryptophan, and protein intake regulation in weanling rats
Authors: Woodger T. L. , Sirek A. , Anderson G. H.
Published: December 2017

The effects of streptozotocin-induced diabetes and tryptophan content of the protein fed on protein intake regulation by weanling rats selecting from 10 and 60% casein diets were evaluated. In uncompensated diabetes the ratio of tryptophan to other selected neutral amino acids in plasma and brain tryptophan were reduced, protein intake per unit of body weight was increased, and serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were unaffected. Enrichment of the tryptophan content of the ingested protein caused a decrease in protein, but not energy consumption of both diabetic and nondiabetic rats. The reduction in protein intake correlated inversely with increases in the tryptophan content relative to the neutral amino acids in plasma and with increases in brain tryptophan and serotonin levels in both diabetic and nondiabetic rats. The data suggest that protein-feeding behavior is regulated by a mechanism that includes brain serotonergic activity with insulin, through its influence on circulating amino acids, determining the quantity of protein consumed in relation to body weight.
Mesencephalic mechanisms for integration of female reproductive behavior in the rat
Authors: Sakuma Y. , Pfaff D. W.
Published: December 2017

Placement of bilateral electrolytic lesions in the mesencephalic central gray (CG) of estrogen-primed ovariectomized female rats produced an immediate decline in performance of the lordosis reflex. Lesions that destroyed the dorsal half of the CG and the adjacent subtectal region were effective. The decrease in individual animals in terms of the lordosis reflex score ranged from 20 to 100% of the prelesion performance. Such lesions abolished the facilitation of lordosis by electrical stimulation of the ventromedial nucleus of the hypothalamus. Similar abrupt losses of lordosis followed bilateral lesions of either a) the area between CG and the cuneiform nucleus of the mesencephalic reticular formation (NCf); or b) the ventrolateral quadrant of the NCf. The difference between these two lesions was that the effect of the latter could be overridden by electrical stimulation of the CG, whereas that of the former could not. We conclude that the CG is an important supraspinal component of the circuit for lordosis behavior, constituting a link between ascending somatosensory and descending motor systems for lordosis. It probably facilitates lordosis when activated by behaviorally relevant peripheral somatosensory and/or ventromedial hypothalamic inputs.
Computer simulation of ventilatory control by both neural and humoral CO2 signals
Authors: Yamamoto W. S.
Published: December 2017

A mathematical model portraying a humoral signal derived from time-dependent variations in arterial carbon dioxide tension (PaCO2) and a neural signal proportional to the metabolic CO2 production was tested by computer simulation. The signals were assumed to enter the central mechanism through afferent pathways connected in reciprocal inhibition. The central mechanism, previously described, contained proportional, gradient, and positive feedback components. The model simulates steady-state isocapnic hyperpnea under endogenous CO2 load and hyperpnea proportional to PaCO2 under exogenous CO2 load. This behavior is consistent whether the neural signal is present alone, the humoral signal is present alone, or both are present and synergistic. When the neural and humoral signals are opposed hypocapnia and hyperventilation ensue; the values being consistent with the isometabolic hyperbola. The model also portrays steady-state behavior when CO2 is inhaled during exercise. During hypometabolic states of rest the mechanism appears to become insensitive to PaCO2 levels.
Regulation of nucleic acid synthesis in Artemia salina nauplii by environmental salinity
Authors: Ewing R. D. , Conte F. P. , Peterson G. L.
Published: December 2017

Ribonucleic acid synthesis in Artemia salina nauplii was strongly inhibited by increasing salinity in the surrounding media, as measured by incorporation of tritiated uridine. Although precursor pools varied in both concentration and specific activity with increasing salinity, these changes did not account for the reduction in ribonucleic acid synthesis. Low levels of oxygen at high salt concentrations did not account for this effect. Intracellular ATP concentrations decreased as the salinity of the environment was increased. Levels of ATP were not affected either by increased oxygen or by the presence of ouabain in the medium.
Tubular system membranes of teleost chloride cells: osmotic response and transport sites
Authors: Philpott C. W.
Published: December 2017

Chloride cells represent the sites of branchial osmoregulatory activity of teleosts. The cells undergo characteristic changes with osmotic challenge and the response is mediated by hormones. Either increased salinity or cortisol treatment will elicit well-known changes in chloride cells; these changes are clearly interrelated and may be collectively referred to as the “hyperosmotic response” of chloride cells. Fundamental features of the “hyperosmotic response” include proliferation and hypertrophy of chloride cells, an amplification of the cell's extensive tubular network or tubular system (TS), an increase in the specific activity of the transport-associated enzyme, Na-K-ATPase, and a concomitant increase in electrolyte transport. The TS displays frequent examples of continuity with the basolateral plasmalemma and the Na-K-ATPase enzyme complex resides in the membranes of the TS. The enzyme complex maintains its conventional polarity with regard to internal substrate and sodium binding sites and external or TS luminal surface, potassium, and ouabain binding sites. The luminal surface of the TS is anionic at pH 1.8 and above. The TS membranes display in situ, in isolation, and by freeze fracture, a characteristic asymmetric structure consisting of repeating particles; larger particles are associated with the cytoplasmic surface of the membrane and smaller particles with the external or luminal surface of tubules. The dimensions of the particles, and their disposition with respect to the cytoplasmic and external surfaces of the TS membrane, support the hypothesis that they are the visual manifestation of the transport-associated Na-K-ATPase complex. The TS and its associated transport activity represent essential components of a recently proposed paracellular transport model for chloride cells. The TS of the pseudobranch cell is also discussed in this review.
Preferential resynthesis of muscle glycogen in fasting rats after exhausting exercise
Authors: Fell R. D. , McLane J. A. , Winder W. W. , Holloszy J. O.
Published: December 2017

Despite carbohydrate starvation (fasting or fat feeding) considerable glycogen accumulation, ranging from 20 to 30 mumol glucose/g, occurred in hindlimb muscles of rats following exhausting exercise that caused severe muscle and liver glycogen depletion and hypoglycemia. The largest increase in muscle glycogen occurred during the first 3 h after exercise when plasma levels of glucagon and epinephrine were very high and insulin concentration was low. The concentrations of glycogen attained in different hindlimb muscles in the fasting and fat-fed animals were between 50 and 100% of the values found in rats fed carbohydrate after the exhausting exercise. In rats fed carbohydrate following exercise, liver glycogen accumulation greatly exceeds muscle glycogen accumulation. A remarkable difference in the response of liver glycogen was seen in the carbohydrate starved rats. In contrast to the rapid increase in muscle glycogen, liver glycogen was still essentially completely depleted in the fasting and fat-fed rats 24 h after exercise. This indicates that the glucose made available via gluconeogenesis was preferentialy channeled away from liver glycogen synthesis into muscle glycogen.
Effects of brain monoamine depletions on thermoregulation in rabbits
Authors: Lin M. T.
Published: December 2017

Biochemical analyses revealed that 5,7-dihydroxytryptamine- (5,7-DHT) treated and 6-hydroxydopamine- (6-OHDA) treated rabbits, respectively, had a significant reduction in diencephalic 5-hydroxytryptamine (5-HT) and norepinephrine (NE) with minimal alterations in the other monoamines. Both 5,7-DHT-treated and 6-OHDA-treated animals, although showing the maintenance of normal body temperatures, did exhibit specific alterations in the thermoeffector outputs. The 5-HT-depleted animals displayed an increase in ear skin blood flow, respiratory heat loss, and metabolism at both ambient temperatures (Ta) of 22 and 2 degrees C. The NE-depleted animals displayed a decrease in metabolism at all levels of Ta tested. Also, the peripheral temperature threshold for the onset of heat loss responses were displaced to higher values than in control animals. In addition, the prostaglandin E1-induced fever was attenuated after the pretreatment of rabbits with either 5,7-DHT or 6-OHDA. The data indicate that brain levels of 5-HT and NE alter, in an apparently reciprocal fashion, the thermoregulatory responses of rabbits. Also, the integrity of 5-HT and NE pathways in brain is vital for the full functioning of a prostaglandin in producing a fever.
Reflex effects of hepatic baroreceptors on renal and cardiac sympathetic nerve activity
Authors: Kostreva D. R. , Castaner A. , Kampine J. P.
Published: December 2017

The reflex effects of hepatic low-pressure baroreceptors on renal and cardiopulmonary sympathetic efferent nerve activity were studied in mongrel dogs anesthetized with pentobarbital sodium. Systemic blood pressure, central venous pressure, hepatic, renal, and portal venous pressures were all measured during occlusion of the thoracic vena cava above the diaphragm, below the liver, and during occlusion of the portal vein. Renal and cardiopulmonary sympathetic efferent nerve activity was continuously recorded along with the hepatic efferent nerve activity during the caval occlusions. Hepatic baroreceptor excitation resulted in marked increases in hepatic afferent nerve activity and reflex increases in renal and cardiopulmonary sympathetic efferent nerve activity without a change in heart rate. Section of the anterior hepatic nerves eliminated the reflex increase in renal efferent nerve activity, but did not eliminate the increase in cardiopulmonary sympathetic efferent nerve activity. Carotid sinus denervation, bilateral cervical vagotomy, and phrenectomy did not alter the reflex responses to hepatic baroreceptor excitation. These hepatorenal and hepatocardiopulmonary reflexes may be important reflex mechanisms that are activated during congestive heart failure and cirrhosis of the liver.
Acclimation, temperature selection, and heat exchange in the turtle, Chrysemys scripta
Authors: Crawshaw L. I. , Johnston M. H. , Lemons D. E.
Published: December 2017

Turtles acclimated to temperatures between 3 and 19 degrees C were placed in a thermal gradient. The animals usually selected temperatures above 28 degrees C within 1 h after placement in the gradient, attaining a final thermal preferendum between 31 and 33 degrees C. Turtles placed in the gradient for extended periods of time were more active during the day; the temperature selected was not related to activity or time of day. Turtles were transferred from a constant temperature bath at 10 or 30 degrees C to a calorimeter at 30 or 10 degrees C. Mean body temperature (Tb) and temperatures of the heart (The), brain (Tbr), and cloaca (Tcl) as well as heart rate were continuously monitored. In a 0.76-kg turtle, temperatures increased to two-thirds of the final difference between the initial temperature and the final temperature in the following times (min): Tb, 5.5; The, 6.0; Tcl, 9.0. The increase in Tbr varied depending on whether the head was extended or retracted. Rapid changes in ambient water temperature had relatively little effect on the heart rate of a submerged turtle. Heart rates were closely related to The and were practically independent of brain temperature.
Parameter and structural identifiability concepts and ambiguities: a critical review and analysis
Authors: Cobelli C. , DiStefano J. J.
Published: December 2017

The notion of identifiability addresses the question of whether it is at all possible to obtain unique solutions for unknown parameters of interest in a mathematical model, from data collected in well-defined stimulus-response experiments performed on a dynamic system represented by the model. This critical aspect of the modeling and data reduction problem is reviewed, analyzed, and unified, with emphasis on applications in biology. Several physiological system models are examined in detail. They illustrate the importance of identifiability analysis prior to performing a parameter estimation experiment, the algebraic difficulties, possible pitfalls, and not-so-apparent ambiguities that may be encountered--even for simple models--and the utility of the concept in experiment design. Methods for testing for identifiability also are reviewed and compared, with emphasis on applicability and limitations. The usefulness of a given model for predicting the time course of system variables (not parameters) of interest normally inaccessible to direct measurement (e.g., tissue concentrations), a common use for quantitative models, is shown to depend intimately on the identifiability properties of the model, in a manner not easy but essential to assess: state variable predictions made in this manner can be inherently ambiguous.
Postural reactions of dogs to sinusoidal motion in the peripheral visual field
Authors: Talbott R. E.
Published: December 2017

Dogs were trained to stand quietly on a movable table that was surrounded by a movable roof. The position of the dogs was monitored while the table was stationary and the roof was moved to provide an optokinetic stimulus restricted to the lateral visual fields. Sinusoidal oscillation of the visual surround caused these quietly standing dogs to generate consistent changes in body position. At low frequencies (around 0.1 Hz) the body position changes tended to lead the position of the optokinetic stimulus. At higher frequencies of visual surround oscillation, the dogs' position changes lagged the optokinetic stimulus position by larger amounts as the frequency of motion got higher. These data showing a postural reaction due to motion of the optokinetic stimulus demonstrate a strong visual component of the postural control system.
Thermoregulatory and related responses to 2-deoxy-D-glucose administration in humans
Authors: Thompson D. A. , Lilavivathana U. , Campbell R. G. , Welle S. L. , Craig A. B.
Published: December 2017

Hypothermia in humans during insulin-induced glucopenia has been largely attributed to impaired heat production. To further study the mechanism for hypothermia during glucoprivation six normal males were given 20-min intravenous infusions of 2-deoxy-D-glucose (2-DG), 50 mg/kg, a competitive inhibitor of glucose utilization. Oxygen and carbon dioxide exchange was measured to determine heat production by indirect calorimetry. Decreases in core temperature were initially associated with activation of mechanisms for heat loss such as sweating and hyperpnea 30-120 min after 2-DG infusion. Hypothermia persisted in spite of markedly increased plasma catecholamine, glucose, and free fatty acid levels from 60 to 180 min and increased heat production from 120 to 180 min after 2-DG infusion. Thus in contrast to the proposed mechanism for insulin-induced hypothermia, the hypothermia of 2-DG-induced glucoprivation is a consequence of increased heat loss and not of decreased heat production.
Effects of 6-hydroxydopamine and pimozide on temperature maintenance by the chicken
Authors: Rowe-Murphy D. L. , van Tienhoven A. , Scott N. R. , Hillman P. E. , Wood C. L. , Johnson A. L. , Schwark W. S.
Published: December 2017

Intraventricular implants of pimozide in adult white leghorn hens were used to block dopamine (DA) receptors, and 6-hydroxydopamine (6-OHDA) was injected intraventricularly to destroy the noradrenergic system locally. The hens were exposed to ambient temperatures of 5 and 35 degrees C, and their core temperature was measured. One hundred micrograms of 6-OHDA significantly reduced the norepinephrine (NE) but not the DA content of the hypothalamus and reduced the uptake of [3H]NE but not of [3H]DA by synaptosomes in vitro. Neither of the drug treatments nor their combination affected average core body temperature (Tb) at either 5 or 35 degrees C. Pimozide treatment caused a lower maximum Tb at 35 degrees C and a higher maximum Tb at 5 degrees C than the control treatment. No evidence was obtained that 6-OHDA treatment affected body temperature regulation. It is concluded that neither the DA nor the NE system is essential for normal temperature maintenance in the hen exposed to either 5 or 35 degrees C.
Interaction between primary afferent nerves in the elicitation of reflex swallowing
Authors: Weerasuriya A. , Bieger D. , Hockman C. H.
Published: December 2017

In adult cats anesthetized with urethan, a number of observations were made that support the concept that some control over the rate of reflexly induced swallowing occurs in the intermediate network at the level of the nucleus of the solitary tract. It was shown that different nerves, e.g., the two superior laryngeal and glossopharyngeal nerves, when activated in sequence interact in such a manner as to facilitate reflex swallowing. It was also shown that the decrement in the reflex response observed to continuous stimulation of a primary afferent nerve, e.g., one superior laryngeal, can be reversed by switching the stimulation to another nerve either on the same or contralateral side. And finally, following discrete medullary lesions, it was observed that that portion of the nucleus of the solitary tract located 2 mm or more rostral to the rostralmost point of the dorsal medial sulcus appears to contain an integral component of the intermediate network that governs reflexly induced swallowing, whereas lesions restricted to the ventrolateral portion of the nucleus of the solitary tract have no effect on the reflex response.
Entrainment by red light of running activity and ovulation rhythms of rats
Authors: McCormack C. E. , Sontag C. R.
Published: December 2017

Controversy exists regarding whether or not the circadian rhythms of nocturnal rodents can be entrained by red light. Female albino rats that were free-running in continuous darkness (DD) were exposed to 2 h of red light (> 650 nm) near the beginning (dusk signals) or the end (dawn signals) of their active 12-h period of running. Red dawn signals advanced and red dusk signals delayed the onset of running on subsequent days. Because the altered onsets of running persisted in DD, the red light had produced a true entrainment of the circadian rhythm of running activity. The fact that the time of ovulation was similarly shifted by red light suggests that the circadian rhythm of luteinizing hormone secretion was also entrained by red light.
Effect of anodal blockade of myelinated fibers on vagal C-fiber afferents
Authors: Hopp F. A. , Zuperku E. J. , Coon R. L. , Kampine J. P.
Published: December 2017

The effects of monopolar cathodal, monopolar anodal, and bipolar anodal polarizing currents on vagal A- and C-fiber activity were studied in anesthetized dogs. Monopolar cathodal polarization consistently produced excitation of spontaneous and evoked A- and C-fibers. Monopolar anodal and bipolar anodal polarizations differentially blocked A-fibers as a function of fiber diameter. The specific purpose of this study was to compare the effects of monopolar anodal and bipolar anodal currents on C-fiber excitability. Small fiber preparations were dissected from the vagal trunk, cut centrally, and placed on recording electrodes. A constant-current stimulus pulse was applied to the nerve at various distances from the blocking electrodes. The stimulus current strength was increased until an isolated C-fiber spike was observed. This value was defined as 100% of threshold. The stimulus current was then reduced to zero, the blocking current was increased slowly to 100 microA, and the procedure repeated. Threshold data obtained in this manner for each set of stimulation electrodes was plotted as a function of distance from the blocking electrode(s) for both modes of anodal blockade. No significant change in C-fiber excitability was observed with bipolar anodal blockade, whereas excitability was significantly (P less than or equal to 0.05) decreased using the monopolar technique. Thus, monopolar anodal block may reduce the possibility of asynchronous C-fiber discharge, which has been associated with a bipolar block of A-fibers.
Interaction of estradiol and progesterone: effects on circadian locomotor rhythm of female golden hamsters
Authors: Takahashi J. S. , Menaker M.
Published: December 2017

The phase and activity level of the locomotor rhythms of female golden hamsters (Mesocricetus auratus) vary in synchrony with the 4-day estrous cycle. We investigated the effects of estradiol and progesterone administration in ovariectomized hamsters to explore the interaction of these two ovarian hormones in modulating circadian locomotor rhythms. Silastic implants of estradiol shorten the period length of the rhythm, change the pattern and level of activity, and decrease the observed variance of the activity onset. Progesterone implants have no effects on the rhythm when given alone; however, when progesterone is given in combination with estradiol, all three estradiol-induced changes are blocked. These results correlate well with the observed locomotor behavior of normal female hamsters. If the levels of both estradiol and progesterone in the serum are taken into account, this correlation holds for a number of hormonal conditions including those found during the 4-day estrous cycle as well as during pregnancy and lactation. These data suggest that progesterone antagonizes the effects of estradiol in the normal animal and that the interaction of estradiol and progesterone modulates the circadian activity of female hamsters on a day-to-day basis.
Functional consequences of expanded aortic bulb: a model study
Authors: Campbell K. B. , Rhode E. A. , Cox R. H. , Hunter W. C. , Noordergraaf A.
Published: December 2017

An investigation of the mechanical effects and physiological functions of the dilated ascending aorta of diving mammals was undertaken with mathematic modeling methods. A mathematical model of a prototype (canine) arterial system was constructed and was evaluated by comparing model-predicted pressure and flow wave forms at four vascular locations with published accounts of experimental measurements. The prototype model was modified to serve as a model of the diving mammal arterial system by changing peripheral vascular parameters and by changing the dimensions of the ascending aorta section of the model. This modified model gave a very good simulation of pressure and flow behavior in diving mammal arteries during a dive. Various distribution patterns of compliance addition to the prototype aortic pattern were evaluated as to the effect of these patterns on aortic input properties. It was concluded that the geometric distribution pattern found in diving mammal arteries was optimal with respect to reducing aortic impedance and peak systolic pressure development and thus favored the function of the left ventricle. This mechanical function could represent an important part of the total picture of adaptation to prolonged ischemia.
Characterization of angiotensin pressor responses in the turtle Pseudemys scripta
Authors: Zehr J. E. , Standen D. J. , Cipolle M. D.
Published: December 2017

Studies were conducted in turtles (Pseudemys scripta) to characterize vascular responses to administration of exogenous angiotensin [Asp1-Ile5]angiotensin II (AII). Marked pressor responses were present following AII administration (2 microgram/kg iv). The pressor response was completely blocked by concomitant administration of an analogue of AII, [Sar1-Ile8]AII. Both alpha-receptor blockade with phenoxybenzamine or catecholamine depletion by reserpine administration reduced the pressor response approximately 50%. Further treatment with [Sar1-Ile8]AII completely blocked the AII pressor response. We conclude that the pressor response to AII in this species that represents an ancient group of reptiles includes a catecholamine-dependent component and direct vascular receptors, both of which are sensitive to AII.
Subcutaneous interstitial fluid pressure during external loading
Authors: Reddy N. P. , Palmieri V. , Cochran G. V.
Published: December 2017

Interstitial fluid pressure (IFP) distribution generated as a result of externally applied pressure (EAP) may play an important role in the etiology of decubitus ulcers. In the forelimbs of 10 thiopental sodium-anesthetized Yorkshire pigs, weighing 16-20 kg, we placed wick catheters 2-5 mm below the skin. After equilibration, we applied a pediatric cuff and added EAP. With zero EAP, the IFP was -3.9 +/- 1.4 (SD) mmHg. In each case of EAP, IFP as measured with the wick catheter increased and reached a plateau within 10-15 min. In normal tissues, IFP reached approximately 65-75% of EAP. When we created an edematous condition by preinfusing with excess saline, IFP was found to reach 100% of EAP. The total normal stress in the tissue, generated as a result of external cuff pressure, can be considered as a sum of interstitial fluid pressure and extranormal stress. Integrity of the fibrous network and pore fraction may be important in transmitting pressure to the fluid.
Structural organization of the renal medulla: comparative and functional aspects
Authors: Kriz W.
Published: December 2017

The renal medulla develops very differently among species, being more prominent in those with a high urinary concentrating capacity. Attempts to correlate structure and function must consider loops of Henle, collecting ducts, vessels, interstitium, and pelvis. Two types of loops of Henle, long and short, are distinguished. Numerical relationships between both differ among species. Based on the epithelial lining a short loop consists of a thick descending limb (pars recta of proximal tubule), a thin descending limb, and a thick ascending limb. Long loops, in addition, have a thin ascending limb; their descending thin limbs are different from those of short loops and are site of considerable interspecies differences. Collecting ducts form in the cortex by joining several nephrons. Patterns with and without arcade formation are distinguished. On entering inner medulla, collecting ducts fuse successively. Collecting duct epithelium consists of principal and intercalated cells whose individual functions are subject to debate. Blood vessels are arranged in a very strict pattern reflecting that, in addition to nourishment, unique requirements in maintaining the corticomedullary osmotic gradient are to be met. Ultrastructural organization of medullary vessels is less specific compared to cortical vessels. Two types of renal medulla are distinguished. The simple type has vascular bundles consisting only of de- and ascending vasa recta; in the complex type, descending thin limbs of short loops are also integrated into vascular bundles. Functional implications of this difference are considerable. Striking interspecies differences also occur in the renal pelvis.
Gonadal hormones organize and modulate the circadian system of the rat
Authors: Albers H. E.
Published: December 2017

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.
Ratio of central nervous system to body metabolism in vertebrates: its constancy and functional basis
Authors: Mink J. W. , Blumenschine R. J. , Adams D. B.
Published: December 2017

We present and document an hypothesis that healthy adults of most vertebrate species use 2-8% of their basal metabolism for the central nervous system (CNS). This relationship is constant across all classes of vertebrates, as we found by examining data from 42 species, including 3 fish, 3 amphibia, 2 reptiles, 6 birds, and 28 mammals. To explain its constancy, we hypothesize that an optimal functional relationship between the energy requirements of an animal's executor system (muscle metabolism) and its control system (CNS metabolism) was established early in vertebrate evolution. Three types of exceptional cases are discussed in terms of the hypothesis: very large animals, domesticated animals, and primates.