bluuebunny/crossref_metadata_2025 huggingface dataset:
Washout kinetics of red cells and plasma from the spleen
Authors: Levesque MJ , Groom AC
Published: December 2017

Radioiodinated (125I) serum albumin was injected inttravenously in cats and allowed to equilibrate in the circulation. Red cell and plasma washout from the isolated spleens were enrom the isolated spleens were then compared during perfusion with oxygenated Ringer solution, the respective concentrations in the outflow being measured by celloscope and scintillation counters. Washout kinetics yielded three exponential components for cells (perfusate volumes for 50% washout (V1/2) being 0.067, 4.70, and 97 ml/g spleen) but only two for plasm (V1/2, 0.14 and 2.40 ml/g). There is no plasma counterpart to the slowly released cells, i.e., they do not represent a separate vascular space. This is an accord with a previous view that these are immature cells, delayed through adherence to fine structures of the red pulp. Compartment analysis indicates that the plasma and two remaining cell components represent washout from two separate vascular spaces, containing 0.09 ml/g blood at arterial hematocrit 37% and 0.42 ml/g blood at hematocrit 75%, perfused by 0.9 and 0.1 of the arterial inflow respectively. Evidence suggests these spaces are i) blood vessels, and ii) red pulp.
Effect of glycodihydrofuisidate on sulfobromophthalein transport maximum in the hamster
Authors: Delage Y , Dumont M , Erlinger S
Published: December 2017

The effect on sulfobromophathalein transport maximum (Tm) and biliary lipid secretion of sodium glyco-24,25-dihydrofusicate, a micelle-forming compound secreted into bile, has been studied in the hamster and compared to that of a physiological bile salt, sodium taurocholate. Biliary phospholipid and cholesterol secretion increased both during glycodihydrofusidate and taurocholate administration, an observation which suggest that both compounds increased th biliary secretion of micelle-forming compounds. In contrast, only taurocholate increased sulfobromophthalein Tm into bile, while glycodihydrofusidate administration decreased it. This observation suggests that the increase in sulfobromophthalein Tm observed during taurocholate administration is not the result of micellar sequestration. It could rather be the consequence of a specific effect of bile salts on the dye transport system.
Mechanism of ATP-induced leukocyte adherence to cultured pulmonary artery endothelial cells
Authors: Parker A. L. , Likar L. L. , Dawicki D. D. , Rounds S.
Published: December 2017

Previously we have shown that ATP enhances the adherence of HL-60 cells and human neutrophils to bovine pulmonary artery endothelial cells. The current investigations extend earlier findings by showing that ATP and UTP dose-dependently stimulate human neutrophil adherence to human pulmonary artery endothelial cells. We have also explore the mechanisms of ATP- and UTP-stimulated adherence. We have found that fucose, a component of selectin receptors, inhibits ATP-stimulated HL-60 cell-bovine pulmonary artery endothelial cell adhesion. Additionally, pretreatment of HL-60 cells with neuraminidase abolishes ATP enhancement. However, fucose does not affect ATP- or thrombin-induced adhesion of freshly isolated human neutrophils to human endothelial cells. Antibodies to human P-selection intercellular adhesion molecule (ICAM)-1, and the beta-subunit of CD11/CD18 do not alter ATP-induced adherence of HL-60 cells to bovine endothelial cells. Similarly, antibodies to human P-selectin and ICAM-1 do not inhibit human neutrophil-human pulmonary artery endothelial cell adhesion. The platelet-activating factor receptor antagonists, WEB-2086 and L-659,989, are effective in attenuating ATP- and UTP-stimulated adherence. Preincubation of neutrophils or human pulmonary artery endothelial cells with ATP or UTP also enhances adherence, an effect that is blocked by L-659,989. Thus platelet activating factor, associated with both neutrophils and endothelial cells, mediates ATP- and UTP-induced neutrophil adherence. ATP, released during vascular injury, may exacerbate neutrophil-endothelial cell interaction and thereby contribute to neutrophil-induced injury.
Cell cycle arrest in G0/G1 phase by contact inhibition and TGF-beta 1 in mink Mv1Lu lung epithelial cells
Authors: Wu F. , Buckley S. , Bui K. C. , Yee A. , Wu H. Y. , Liu J. , Warburton D.
Published: December 2017

We postulated that contact inhibition and transforming growth factor (TGF)-beta 1 may target the same molecules to negatively regulate the Mv1Lu cell cycle in G0/G1. Both contact inhibition and TGF-beta 1 suppressed the expression of a 45-kDa protein (p45); cyclins D2 and B1; cyclin-dependent protein kinase (Cdk)-4, Cdc-2, and Cdc-2-associated activity; and the phosphorylation of retinoblastoma tumor-suppressor protein (pRb) but did not affect the expression of cyclins D1, E, and A or the expression of Cdk-2 and Cdk-5. Expression of p45 reappeared 12 h after release from contact inhibition and 6-8 h after release from TGF-beta 1, while TGF-beta 1 prevented release from contact inhibition and maintained suppression of both p45 and cyclin D2. Additionally, cyclin D2 phosphorylation and its associated kinase activity were strongly inhibited by contact inhibition and TGF-beta 1. Thus suppression of p45, cyclin D2/Cdk-4, and cyclin B1/Cdc-2 expression and/or activities is targeted both by contact inhibition and by TGF-beta 1 and may define common mechanisms through which these negative growth signals are integrated.
Increased elastase release by CF neutrophils is mediated by tumor necrosis factor-α and interleukin-8
Authors: Taggart Clifford , Coakley Raymond J. , Greally Peter , Canny Gerry , O'Neill Shane J. , McElvaney Noel G.
Published: December 2017

Cystic fibrosis (CF) is a lethal, hereditary disorder characterized by a neutrophil-dominated inflammation of the lung. We sought to determine whether neutrophils from individuals with CF release more neutrophil elastase (NE) than neutrophils from normal subjects. Our results showed that peripheral blood neutrophils (PBNs) from normal subjects and individuals with CF contained similar amounts of NE, but after preincubation with CF bronchoalveolar lavage (BAL) fluid, significantly more NE was released by CF PBNs, a release that was amplified further by incubation with opsonized Escherichia coli. To determine which components of CF BAL fluid stimulated this excessive NE release from CF PBNs, we repeated the experiments after neutralization or immunoprecipitation of tumor necrosis factor (TNF)-α and interleukin (IL)-8 in CF BAL fluid. We found that subsequent NE release from CF PBNs was reduced significantly when TNF-α and IL-8 were removed from CF BAL fluid. When TNF-α and IL-8 were used as activating stimuli, CF PBNs released significantly greater amounts of NE compared with PBNs from control subjects and individuals with bronchiectasis. These results indicate that CF PBNs respond abnormally to TNF-α and IL-8 in CF BAL fluid and react to opsonized bacteria by releasing more NE. This may help explain the increased NE burden seen in this condition.
Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats
Authors: Tang Jen-Ruey , le Cras Timothy D. , Morris Kenneth G. , Abman Steven H.
Published: December 2017

We hypothesized that disrupted alveolarization and lung vascular growth caused by brief perinatal hypoxia would predispose infant rats to higher risk for developing pulmonary hypertension when reexposed to hypoxia. Pregnant rats were exposed to 11% inspired oxygen fraction (barometric pressure, 410 mmHg; inspired oxygen pressure, 76 mmHg) for 3 days before birth and were maintained in hypoxia for 3 days after birth. Control rats were born and raised in room air. At 2 wk of age, rats from both groups were exposed to hypoxia for 1 wk or kept in room air. We found that brief perinatal hypoxia resulted in a greater increase in right ventricular systolic pressure and higher ratio of right ventricle to left ventricle plus septum weights after reexposure to hypoxia after 2 wk of age. Moreover, perinatal hypoxic rats had decreased radial alveolar counts and reduced pulmonary artery density. We conclude that brief perinatal hypoxia increases the severity of pulmonary hypertension when rats are reexposed to hypoxia. We speculate that disrupted alveolarization and lung vascular growth following brief perinatal hypoxia may increase the risk for severe pulmonary hypertension with exposure to adverse stimuli later in life.
Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbitSP-Bgene
Authors: Margana Ramgopal , Berhane Kiflu , Alam M. Nurul , Boggaram Vijayakumar
Published: December 2017

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B mRNA is expressed in a cell type-restricted manner in alveolar type II and bronchiolar (Clara) epithelial cells of the lung and is developmentally induced. In NCI-H441 cells, a lung cell line with characteristics of Clara cells, a minimal promoter region comprising −236 to +39 nucleotides supports high-level expression of chloramphenicol acetyltransferase reporter activity. In the present investigation, we characterized the upstream promoter region, −236 to −140 nucleotides, that is essential for promoter activity. Deletion mapping identified two segments, −236 to −170 and −170 to −140 nucleotides, that are important for promoter activity. Mutational analysis and gel mobility shift experiments identified thyroid transcription factor-1, Sp1, and Sp3 as important trans-acting factors that bind to sequences in the upstream promoter region. Our data suggest that SP-B promoter activity is dependent on interactions between factors bound to upstream and downstream regions of the promoter.
Effect of bradykinin on membrane properties of guinea pig bronchial parasympathetic ganglion neurons
Authors: Kajekar Radhika , Myers Allen C.
Published: December 2017

The effect of bradykinin on membrane properties of parasympathetic ganglion neurons in isolated guinea pig bronchial tissue was studied using intracellular recording techniques. Bradykinin (1–100 nM) caused a reversible membrane potential depolarization of ganglion neurons that was not associated with a change in input resistance. The selective bradykinin B2 receptor antagonist HOE-140 inhibited bradykinin-induced membrane depolarizations. Furthermore, the cyclooxygenase inhibitor indomethacin attenuated bradykinin-induced membrane depolarizations to a similar magnitude (∼70%) as HOE-140. However, neurokinin-1 and -3 receptor antagonists did not have similar inhibitory effects. The ability of bradykinin to directly alter active properties of parasympathetic ganglion neurons was also examined. Bradykinin (100 nM) significantly reduced the duration of the afterhyperpolarization (AHP) that followed four consecutive action potentials. The inhibitory effect of bradykinin on the AHP response was reversed by HOE-140 but not by indomethacin. These results indicate that bradykinin can stimulate airway parasympathetic ganglion neurons independent of sensory nerve activation and provide an alternative mechanism for regulating airway parasympathetic tone.
P. cariniiinduces selective alterations in component expression and biophysical activity of lung surfactant
Authors: Atochina Elena N. , Beers Michael F. , Scanlon Seth T. , Preston Angela M. , Beck James M.
Published: December 2017

Studies of Pneumocystis carinii pneumonia (PCP) suggest an important role for the surfactant system in the pathogenesis of the hypoxemic respiratory insufficiency associated with this infection. We hypothesized that PCP induces selective alterations in alveolar surfactant component expression and resultant biophysical properties. PCP was induced by intratracheal inoculation of 2 × 105P. carinii organisms into C.B-17 scid/ scid mice. Six weeks after inoculation, large (LA)- and small (SA)-aggregate surfactant fractions were prepared from bronchoalveolar lavage fluids and analyzed for expression of surfactant components and for biophysical activity. Total phospholipid content was significantly reduced in LA surfactant fractions from mice infected with PCP (53 ± 15% of uninfected mice; P < 0.05). Quantitation of hydrophobic surfactant protein (SP) content demonstrated significant reductions of alveolar SP-B and SP-C protein levels in mice with PCP compared with those in uninfected mice (46 ± 7 and 19 ± 6%, respectively; P < 0.05 for both). The reductions in phospholipid, SP-B, and SP-C in LA fractions measured during PCP were associated with an increase in the minimum surface tension of LAs as measured by pulsating bubble surfactometer (13.1 ± 1.1 vs. 5.4 ± 1.8 mN/m; P < 0.05). In contrast to decreases in the hydrophobic SPs, SP-D content in the SA fraction was markedly increased (343 ± 30% of control value; P < 0.05) and SP-A levels in LA surfactant were maintained (93 ± 26% of control value) during P. carinii infection. In all cases, the changes in SP content were reflected by commensurate changes in the levels of mRNA. We conclude that PCP induces selective alterations in surfactant component expression, including profound decreases in hydrophobic protein contents and resultant increases in surface tension. These changes, demonstrated in an immunologically relevant animal model, suggest that alterations in surfactant could contribute to the hypoxemic respiratory insufficiency observed in PCP.
Selective restoration of calcium coupling to muscarinic M3 receptors in contractile cultured airway myocytes
Authors: Mitchell Richard W. , Halayko Andrew J. , Kahraman Sibel , Solway Julian , Wylam Mark E.
Published: December 2017

We previously demonstrated that after several days of serum deprivation about one-sixth of confluent cultured canine tracheal myocytes acquire an elongated, structurally and functionally contractile phenotype. These myocytes demonstrated significant shortening on ACh exposure. To evaluate the mechanism by which these myocytes acquire responsiveness to ACh, we assessed receptor-Ca2+ coupling using fura 2-AM fluorescence imaging and muscarinic receptor expression using Western analysis. Cells were grown to confluence in 10% fetal bovine serum and then maintained for 7–13 days in serum-free medium. A fraction of serum-deprived cells exhibited reproducible intracellular Ca2+ mobilization in response to ACh that was uniformly absent from airway myocytes before serum deprivation. The Ca2+ response to 10− 4 M ACh was ablated by inositol 1,4,5-trisphosphate (IP3) receptor blockade using 10− 6 M xestospongin C but not by removal of extracellular Ca2+. Also, 10− 7 M atropine or 10− 7 M 4-diphenylacetoxy- N-methylpiperidine completely blocked the response to ACh, but intracellular Ca2+ mobilization was not ablated by 10− 6 M pirenzepine or 10− 6 M methoctramine. In contrast, 10− 5 M bradykinin (BK) was without effect in these ACh-responsive myocytes. Interestingly, myocytes that did not respond to ACh demonstrated robust increases in intracellular Ca2+ on exposure to 10− 5 M BK that were blocked by removal of extracellular Ca2+ and were only modestly affected by IP3 receptor blockade. Serum deprivation increased the abundance of M3 receptor protein and of BK2 receptor protein by two- to threefold in whole cell lysates within 2 days of serum deprivation, whereas M2receptor protein fell by >75%. An increase in M3receptor abundance and restoration of M3 receptor-mediated Ca2+ mobilization occur concomitant with reacquisition of a contractile phenotype during prolonged serum deprivation. These data demonstrate plasticity in muscarinic surface receptor expression and function in a subpopulation of airway myocytes that show mutually exclusive physiological and pharmacological diversity with other cells in the same culture.
Pharmacological analysis of sympathetic function in the embryonic chick heart
Authors: Culver N. G. , Fischman D. A.
Published: December 2017

Sympathetic nerve cells enter the embryonic chick heart on the fifth day in ovo, but it is uncertain when these nerves become functional. Using pharmacological probes known to affect the embryonic circulation, sympathetic nerve function was examined at various stages of development. Exogenous norepinephrine elicited cardioacceleration in the hearts of embryos with intact extraembryonic circulation both before (stage 20-24) and after (stage 28-32) sympathetic innervation of the heart, and this acceleration could be inhibited by propranolol and practolol. In contrast, ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicited cardioacceleration only after stages 27-28 (i.e., after sympathetic innervation), producing a 25-30% increase in heart rate over the predrug levels of 148.7 +/- 1.8 beats/min. DMPP-elicited positive chronotropy was reduced by beta-receptor antagonists, hexamethonium, guanethidine (GuE), and tetrodotoxin. In preparations of the embryonic thorax in which the innervated heart was separated from brain and adrenal influences, DMPP elicited a GuE-sensitive cardioacceleration. It is concluded that during chick embryonic development, no more than a 1-day interval exists between the appearance of sympathetic nerves in the heart and the onset of neuronal function in that organ.
Control of extracellular sodium concentration by antidiuretic hormone-thirst feedback mechanism
Authors: Young D. B. , Pan Y. J. , Guyton A. C.
Published: December 2017

The effectiveness of the antidiuretic hormone (ADH)-thirst feedback mechanism to control extracellular sodium concentration was studied in dogs. The design consisted of increasing daily sodium intake from 10 to 200 meq in a group of dogs, first in the normal condition and second with a continuous 24 h/day infusion of an amount of ADH sufficient to maintain urine osmolarity at a maximal level and with fixed water intake. We were therefore able to compare the effectiveness of sodium concentration control in the same dogs with and without feedback control of the ADH-thirst mechanism, the difference in effectiveness being a quantitative measure of the control capability of the system. In the normal condition the increase in sodium intake resulted in a steady-state 2.3% elevation in sodium concentration. With the feedback control of ADH secretion and water intake blocked, the same sodium forcing produced an 11.9% increase in extracellular sodium concentration. The minimum feedback gain for the system calculated from the data is -4.2. We conclude that control of sodium concentration in the intact state is accomplished mainly by the ADH-thirst feedback mechanism.
CNS regulation of body temperature in euthermic and hibernating marmots (Marmota flaviventris)
Authors: Florant G. L. , Heller H. C.
Published: December 2017

Hypothalamic thermosensitivity of marmots was characterized during euthermia and hibernation. Hypothalamic temperature (Thy) was manipulated with chronically implanted, water-perfused thermodes while the animal's rate of oxygen consumption was continuously measured. The threshold Thy for eliciting an increase in metabolic heat production (MHP) and the proportionality constant (alphaMHP) relating rate of MHP to Thy were determined. In four euthermic marmots alphaMHP averaged -1.1 W-kg-1-degrees C-1. During the entrance into hibernation, as body temperature (Tb) declined from 36 to 8 degrees C, the threshold Thy for the MHP response progressively declined and was demonstrable at all times. The Thy of marmots in deep hibernation at an ambient temperature (Ta) of 5 degrees C plateaued near 7.5 degrees C, but threshold Thy for MHP showed a continuous slow decline of 0.2-0.4 degrees C a day, until one day prior to arousal. Proportional regulation of Tb was demonstrable at all times during deep hibernation. The average proportionality constant for the MHP response to hypothalamic cooling during deep hibernation in three marmots was -0.08 W-kg-1-degrees C-1. These results demonstrate that the hypothalamic regulator of Tb is active throughout hibernation and that there are progressive changes in its thermosensitivity.
Sites of cholinergic vasoconstriction in trout gills
Authors: Smith D. G.
Published: December 2017

Sites of cholinergic vasoconstriction were investigated in isolated saline-perfused holobranchs of trout (Salmo gairdneri and S. trutta). Acetylcholine (ACh) always increased overall branchial vascular resistance (BVR) and, in addition, decreased the proportion of the total inflow appearing at the outflow cannula from the efferent arch artery. Since this was observed in both constant pressure and constant flow situations, it was concluded that ACh exerted most of its effect at a site downstream from the secondary lamellae, probably at the bases of the efferent filament arteries. Prussian blue dye injections indicated that, in addition, ACh caused a marked reduction in flow to the distal halves of the filaments and that flow within the proximal secondary lamellae was restricted during ACh administration to the inner and outer marginal channels of the lamellae. The results are discussed in terms of recent findings concerning the vascular anatomy of teleost gills.
Cortisol-mediated synchrinization of circadian rhythm in urinary potassium excretion
Authors: Moore-ede M. C. , Schmelzer W. S. , Kass D. A. , Herd J. A.
Published: December 2017

Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 h daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 h daily. When the timing of cortisol adminisration (with or without aldosterone) was phase-delayed by 8 h, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3–4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 h, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the cirdacian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.
Computer simulation of rat heart metabolism after adding glucose to the perfusate
Authors: Achs M. J. , Garfinkel D.
Published: December 2017

Page R175: M. J. Achs and D. Garfinkel.“Computer simulation of rat heart metabolism after adding glucose to the perfusate.” Page R184: add the following acknowledgment: This study was supported by National Institutes of Health Grants HL-15622 and GM-16501.
Angiotensin-converting enzyme in developing lung and kidney
Authors: Wallace K. B. , Bailie M. D. , Hook J. B.
Published: December 2017

Angiontensin-converting enzyme (ACE) catalyzes rapid conversion of angiotensin II (AII). This enzyme has been identified in the vascular endothelium of nearly every tissue. Inasmuch as AII is the biologically active component of the renin-angiotensin system, and since age-related differences exist in the renin-angiotensin system, it was of interest to determine converting enzyme activity during development. ACE activity was quantified by measuring the optical density of hippuric acid liberated from hippuryl-L-histidyl-L-leucine (HHL) following incubation with the 20,000 X g supernatant of tissue homogenates. Pulmonary ACE activity of near-term fetal rats was not different than 1-day-old animals. Therafter, ACE activity increased during the first 6 wk postpartum in a biphasic manner. A similar age-dependent increase in converting enzyme activity was observed in rat kidney, mouse kidney, and mouse lung. Substrate affinity of all enzymes measured was similar, suggesting that the age-related increase in activity was due to increased enzyme content. The low activity of ACE in the newborn might function to limit AII production.
Contributions of the communication sciences to physiology
Authors: Siebert W. M.
Published: December 2017

This paper reviews the impact on physiology of the revolutions in the communication sciences and technology that have occurred in the last 35 years. Particular attention is given to the significance of the cybernetic suggestions of Norbert Wiener--specifically, the ideas of negative feedback, of the computer as a brain metaphor, and of signal-and-noise considerations in information processing. It is argued that the first two of these have not in fact made much lasting contribution to physiology beyond providing loose analogies. On the other hand, the ready availability of a wide variety of electronic measuring and signal-processing devices from communication technology has clearly had a substantial impact. And it is proposed that the kind of models and concepts that are necessary for the characterization of the nervous system as an information-processing device play now, and will continue to play in the future, a major role in physiology.
Oxygen exchange and vascular resistance in the totally perfused rainbow trout
Authors: Wood C. M. , McMahon B. R. , McDonald D. G.
Published: December 2017

A whole trout preparation (Salmo gairdneri) externally ventilated with water and internally perfused with artificial medium via a cardiac pump is discribed for the study of O2 exchange and vascular resistance. As cardiac output (Q) was raised, ventral and dorsal aortic pressures increased while branchial (Rg) and systemic (Rs) vascular resistances fell, reflecting considerable passive distensibility. Arterial oxygenation was negative at low Qs due to significant internal O2 demand by the gill tissue, but increased to zero or positive values at intermediate Qs, and eventually declined at high Qs because of transit time limitation. O2 uptake from the ventilatory flow rose with increasing Q. Epinephrine (10(-5) M) decreased Rg, increased Rs, and enhanced arterial oxygenation. Artificial elevation of dorsal aortic pressure decreased Rg but did not affect arterial oxygenation. A 10-fold elevation of ventilatory flow increased arterial oxygenation but did not alter Rg or Rs. Endogenous metabolism of branchial tissue accounted for 11.7% of resting O2 uptake in vivo, and comprised an internal component taking O2 from perfusion flow and an external component drawing O2 from ventilatory flow.
Cerebral blood flow and oxygen consumption in the newborn dog
Authors: Hernandez M. J. , Brennan R. W. , Vannucci R. C. , Bowman G. S.
Published: December 2017

Cerebral blood flow (CBF), CBF responses to changes in arterial CO2 tension, and cerebral metabolic rate for oxygen (CMRO2) were measured in newborn dogs, by means of a modification of the Kety and Schmidt technique employing 133Xe. Mongrel dogs of 1-7 days of age were paralyzed and passively ventilated with 70% N2O and 30% O2. CBF was derived by analysis of paired serial 20-microliter samples of arterial and of cerebral venous blood from the superior sagittal sinus. At an arterial PCO2 of 36.9 +/- 3.7 Torr and a mean arterial blood pressure of 62 +/- 10 Torr, CBF was 23 +/- 8 ml/min per 100 g. The arteriovenous oxygen content difference averaged 5.6 vol%, and CMRO2 was 1.13 +/- 0.30 ml O2/min per 100 g. CBF increased or decreased by 0.58 ml/min/100 g per Torr change in PCO2. Our results suggest that in the newborn, basal CBF and CBF responses to CO2 are considerably lower than in the adult and parallel the lower metabolic needs of the newborn brain.
Cholesterol oxidation in primates by simultaneous sterol balance and breath analysis
Authors: Redinger R. N. , Chow L. , Grace D. M.
Published: December 2017

Six female adult rhesus monkeys and baboons with exteriorized enterohepatic circulations were simultaneously assessed following [26-14C]cholesterol pulse labeling by 14CO2 breath analysis and combined isotopic and chromatographic sterol balance during metabolic steady state. Bile acid synthesis and/or secretion were compared with 14CO2 breath analysis of cholesterol oxidation during short term physiological changes, and with total bile acid diversion and feedback inhibition, and biliary tract obstruction. Cholesterol oxidation by breath analysis compared closely with acidic sterol losses during steady-state conditions (145.6 +/- 23.9 vs 144.6 +/- 24.4 mg/24 h) and was sensitive enough to detect changes resulting from diurnal variation and fasting. The 14CO2 test detected inhibition of bile acid synthesis consequent to bile acid feedback (355 +/- 32 to 88 +/- 31 mg/24 h, P less than 0.001) or biliary tract obstruction (158 +/- 27 to 60 +/- 28 mg/24 h, P less than 0.05) but underestimated increased synthesis induced by acute bile diversion (245 +/- 24 vs. 868 +/- 104 mg/24 h, P less than 0.01 at 24 h). Insignificant 14C was detected by carcass analysis following cessation of exhaled 14CO2.
Calibrating compartmental models of neurons
Authors: Perkel D. H. , Mulloney B.
Published: December 2017

Numerical parameters for a compartmental model of a neuron can be chosen to conform both to the neuron's structure and to its measured steady-state electrical properties. A systematic procedure for assigning parameters is described that makes use of the matrix of coefficients of the set of differential equations that embodies the compartmental model. The inverse of this matrix furnishes input resistances and voltage attenuation factors for the model, and an interactive modification of the original matrix and its inverse may be used to fit the model to anatomic and electrical measurements.
Controlled cellular energy conversion in brown adipose tissue thermogenesis
Authors: Horowitz J. M. , Plant R. E.
Published: December 2017

Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.
Spinal cord, hypothalamic, and air temperature: interaction with arousal states in the marmot
Authors: Miller V. M. , South F. E.
Published: December 2017

Yellow-bellied marmots, Marmota flaviventris, prepared with U-shaped thermodes in the epidural space of the thoracic vertebral canal, a thermode in the preoptic hypothalamus, and cortical surface and hippocampal electrodes, were used to investigate the interaction of arousal states with temperature regulation. It was found that arousal state of the animal influences the thermoregulatory responses initiated in either the spinal cord or hypothalamus. Further, changes in ambient temperature affected both the gain and the threshold of these responses. The interaction of the hypothalamus and spinal cord was not an additive function, however the threshold for shivering of each could be altered by temperature manipulation of the other. Future studies in modeling of temperature regulation should consider the contributions of temperature receptors of the spinal cord and the arousal state of the animal during the stimulation period.
Metabolism of the acutely ischemic dog heart. I. Construction of a computer model
Authors: Achs M. J. , Garfinkel D.
Published: December 2017

Construction of a computer model of glycolysis, the Krebs cycle, and related metabolism in acutely ischemic dog heart, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. A previous model of the same metabolism in normal-flow rat heart was modified to fit ischemic dog heart experimental data to within experimental error. The result resembles other models of ischemic heart preparations, implying common underlying mechanisms. The principal change made was reduction of enzyme amounts, consistent with the generally slower metabolism of large animals, suggesting that differing enzyme amounts are a major component of interspecies metabolic difference. Glycolytic intermediates oscillate, asynchronously and with large changes in level; pyridine nucleotides become highly reduced; pH falls, but mitochondria stay alkaline relative to cytoplasm even after oxidative phosphorylation stops.
Sensory functions of the liver--a review
Authors: Sawchenko P. E. , Friedman M. I.
Published: December 2017

In this paper we critically review anatomic, electrophysiological, physiological, and behavioral evidence for neural receptors in the liver. Several lines of evidence suggest that the afferent innervation of the liver may be substantial, although few anatomic studies have directly addressed the question of an hepatic sensory supply. On the other hand, there is convincing functional evidence for a variety of hepatic sensory receptors. Hepatic osmo-, ion, and baroreceptors, sensitive to changes in the osmolarity and electrolyte concentrations in blood and to variations in portal venous pressure, modulate diuresis and natriuresis. Metabolic receptors, for which the adequate stimuli have not yet been specified, influence feeding behavior and gastric acid secretion in response to alterations in hepatic metabolism associated with changes in the supply of metabolic fuels. Directions for future research are suggested and general conclusions about the role of hepatic receptors in homeostasis are discussed.
Osmosensitivity of rat third ventricle and interactions with angiotensin
Authors: Buggy J. , Hoffman W. E. , Phillips M. I. , Fisher A. E. , Johnson A. K.
Published: December 2017

Injections of hyperosmotic solutions (1- to 5-microliter injections of NaCl or sucrose solutions ranging in osmolarity from 0.34 to 0.90 osmol/l) into the anteroventral third ventricle (AV3V) of rats resulted in short latency drinking antidiuretic, and pressor responses. AV3V injections or infusions of combined angiotensin-hyperosmotic NaCl solution did not result in drinking greater than the sum of drinking to angiotensin and hyperosmotic NaCl separately administered. Differences in water versus saline drinking fluid preferences provided a behavioral dissociation of angiotensin and hyperosmotic sensitive neural mechanisms. Comparison of AV3V and lateral preoptic injection sites provided an additional separation since angiotensin was equally effective at both sites whereas osmotic stimulation was more effective at the AV3V site. AV3V lesions have previously been reported to abolish drinking, antidiuretic, and pressor responses to angiotensin and hyperosmotic stimulation. The data reported here provide additional evidence that angiotensin and hyperosmotic stimuli may both act on tissue surrounding AV3V but suggest that the neural substrates for these stimuli are not identical.
Diminished sympathetic silent period in spontaneously hypertensive rats
Authors: Schramm L. P. , Barton G. N.
Published: December 2017

To determine if elevated sympathetic activity occurs in spontaneously hypertension, the silent period induced in splanchnic nerves following electrical stimulation of dorsal medullary sympathoexcitatory sites was compared in anesthetized normotensive Wistar Kyoto rats (WKYs) and Okamoto spontaneously hypertensive rats (SHRs). The strength of silent periods was defined as the degree of inhibition of responses to testing stimuli delivered at various latencies following conditioning trains, and it was assumed to be inversely related to the level of sympathetic activity. Weanling SHRs exhibited weaker silent periods than weanling WKYs although, at that age, the arterial pressures of the strains were not significantly different. Silent periods were also weaker in adult SHRs than in adult WKYs. This difference persisted after arterial pressures, which fell under anesthesia, were raised by phenylephrine infusions to the respective "normal" levels in each strain. These results support the hypothesis that elevated sympathetic activity exists during both the development and maintenance of spontaneous hypertension in rats.
Complementarity vs. reduction as explanation of biological complexity
Authors: Pattee H. H.
Published: December 2017

The classical structure-function relation is presented as an example of an epistemological complementarity. Complementarity implies that a satisfactory explanation requires two modes of description, neither derivable from nor reducible to the other, as well as mutual incompatibility in a formal logical sense. Complementarity arose from the difficulty in describing conditional measurement processes in the language of causal microscopic laws of physics. Biological structure is associated with description in the language of physical laws, whereas biological function is associated with description of informational processes, i.e., measurement and control, that are complementary in the above sense. An explicit incompatibility between these two modes of description is that laws are expressed as rate-dependent equations, whereas informational processes are expressed as rate-independent nonintegrable constraints. The functional mode allows a simplification of structurally complex organization that is essential, not only for explanation, but for self-description at all levels of biological organization.
Analysis of circadian periodicity of plasma cortisol in normal man and in Cushing's syndrome
Authors: Vagnucci A. H.
Published: December 2017

In normal subjects, adjusted to a circadian environment, half-hourly plasma cortisol levels over a 24-h span (time series, TS) outline a circadian sinusoidal pattern that may be masked by superimposed short-lived oscillations. The periodogram objectively defines the features (amplitude, phase) of this pattern in individual TS and, more efficiently, in the average and concatenation of homogeneous TS. Concatenation is a procedure by which homogeneous short TS are attached one after the other. Homogeneity is inferred by variance analysis and by a new measure, h, with statistical significance, derived from the spectrum of the concatenated TS. Through concatenation, autocovariance for periodicity identification becomes possible. The TS from three groups of volunteers are highly homogeneous and have a predominant, statistically significant amplitude with peak time near 1100 h. The patterns from patients with Cushing's disease differ markedly in their means and periodic features; by the above criteria, we identify a subgroup with significant h measure and 24-h amplitude. This analysis provides a tool for investigation of the circadian clock in man.
Preabsorptive intestinal satiety controls of food intake in pigs
Authors: Houpt T. R. , Anika S. M. , Houpt K. A.
Published: December 2017

Pigs, 1--3 mo of age, weighing 5--80 kg, were fitted with duodenal, intraportal, or intrajugular catheters. After a 4-h fast, preloads were delivered to the duodenum, and food intake then measured for 10 min (no drinking water). Glucose (5--40%) and NaCl (0.9--6.5%) solutions were used as preloads (5 ml/kg body wt). Food intake expressed as percent control intake (Y) was depressed in proportion to preload concentration (X): for glucose, Y = 109 - 2X; for NaCl, Y = 107 - 13X. When expressed in osmoconcentration, glucose and NaCl preloads had nearly identical satiety effects. Preloads of 40% sorbitol depressed intake to 74% control. Intrathoracic vagotomy reduced the satiety effects of glucose and NaCl solutions by 50%. Tetracaine (0.5%) in the hypertonic preloads blocked 80% of the satiety effects of the glucose and NaCl preloads, but had no effect on sorbitol satiety effect. Injection of glucose or NaCl solutions into the portal or jugular veins had no significant effect. It was concluded that duodenal osmoconcentration to the degree that it exceeds body fluid tonicity contributes to the immediate satiety seen during a meal.
Effects of central injection of biogenic amines during arousal from hibernation
Authors: Glass J. D. , Wang L. C. H.
Published: December 2017

Page R162: J. D. Glass and L. C. H. Wang. “Effects of central injection of biogenic amines during arousal from hibernation.” Pages R164 and R165: in results and Fig. 1 the unit for measurements of HP and HL should read cal/wt0.75 per 5 min.
Liver glycogenolysis during exercise without a significant increase in cAMP
Authors: Winder W. W. , Boullier J. , Fell R. D.
Published: December 2017

Liver glycogenolysis may be controlled by glucagon or catecholamine-induced changes in cAMP or by cAMP-independent mechanisms. The purpose of these experiments was to determine whether an increase in liver cAMP occurs during exercise at a time when the rate of liver glycogenolysis is greatly accelerated. Rats were taught to run on a treadmill 10 min/day for 6 wk. They were then run continuously for periods of time ranging from 0 to 120 min at 0.8 mph up a 15% grade. Liver glycogen was depleted by the end of 90 min in fed animals and by 20 min in overnight-fasted animals. Liver cAMP was not significantly increased in fed animals during the first 60 min of exercise. The major increase in liver cAMP occurred after liver glycogen was depleted, at which time the rat must rely entirely on gluconeogenesis for maintenance of blood glucose. This increase in cAMP corresponded to large increases in plasma glucagon and catecholamines. We conclude that liver glycogenolysis in the rat can occur during exercise independently from significant detectable increases in cAMP concentrations.
Ontogeny of feeding controls in suckling and weanling rats
Authors: Henning S. J. , Chang S. S. , Gisel E. G.
Published: December 2017

To rationalize conflicting data in the literature, the latency of attachment of fed and fasted rat pups to the nipples of their anesthetized mother has been studied at various postnatal ages. At 10 and 14 days of age, the mode of fasting had a critical effect on the results: pups fasted in a 30 degrees C incubator had shorter attachment latencies than fed pups, whereas when pups were fasted in a 34 degrees C incubator or with a nonlactating foster mother at room temperature, their latencies were no different from those of fed pups. Thus maternal deprivation has an important influence on attachment latencies, unless other steps are taken to maintain the body temperature of fasted pups. When this variable is controlled, it is apparent that at 10 and 14 days of age, the feeding behavior of rat pups is not related to nutritional status. In contrast, from 17 days onward, latencies of fed pups were significantly longer than those of faster pups, regardless of the mode of fasting. This appearance of appetitive behavior during the 3rd postnatal wk was shown to have a temporal correlation with the beginning of weaning, as measured by the appearance of chow in the stomachs.
Influence of enteric parasitism on hormone-regulated pancreatic secretion in dogs
Authors: Dembinski A. B. , Johnson L. R. , Castro G. A.
Published: December 2017

The objective of this study was to test the hypothesis that enteric parasites affect pancreatic secretion in their host. Pancreatic bicarbonate and protein outputs were studied in dogs with gastric and pancreatic fistulas to determine the secretory response to exogenously administered secretin and cholecystokinin and to intraduodenal stimulation with hydrochloric acid and sodium oleate to release endogenous hormones. Bicarbonate and protein concentrations in pancreatic juice were measured prior to infection with Trichinella spiralis and at various periods during primary and secondary infections. Dose-related increases in secretory activity were observed in uninfected hosts in response to all stimuli. Infected dogs responded like controls to exogenous hormones, but showed reduced secretion under duodenal stimulation during the 1st wk of primary infection. This altered response returned to normal 3 wk after primary infection and did not occur following secondary infection. Results support the conclusion that reduced pancreatic secretion is associated with enteric parasitism and is due to a defect in hormone release or in the supply of hormone available for release.
Reversal of phosphorylase activation in muscle despite continued contractile activity
Authors: Conlee R. K. , McLane J. A. , Rennie M. J. , Winder W. W. , Holloszy J. O.
Published: December 2017

During studies of the regulation of phosphorylase activity and glycogenolysis in contracting muscle, it was found that conversion of phosphorlyase beta to alpha is transient. Reversal of phosphorylase activation during both continuous and intermittent stimulation in the plantaris might, in part, have been due to development of fatigue. However, a complete reversal of phosphorylase activation was also evident within 5 min in the absence of fatigue in soleus muscles stimulated tetanically with 100-ms-long trains at a rate of 60/min. These muscles showed no significant decline in contractile force. Glycogen breakdown stopped in the soleus when phosphorylase reverted to the beta form, providing evidence that phosphorylase beta was not active. This lack of activity is probably explained by the finding that ATP and AMP concentrations changed little, while glucose 6-phosphate increased. Reversal of phosphorlyase activation soon after the onset of steady-state work may be a mechanism for conserving glycogen when the supply of other substrates is adequate to meet the muscles' energy needs.
Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model
Authors: Garfinkel D. , Achs M. J.
Published: December 2017

Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed
Comparison of effects of standard diuretics and indanone in isolated toad cornea and bladder
Authors: Schnieders J. R. , Ludens J. H.
Published: December 2017

Short-circuit current (SCC) techniques were used to monitor effects of various diuretic agents on Na+ transport in toad bladder and Cl- transport in toad cornea. In bladder, various agents from different "classes" of diuretics inhibited SCC whereas in cornea only "loop diuretics," i.e., those with a primary site of action in the ascending limb of the loop of Henle, inhibited SCC. Classification of the diuretics based on sensitivity in cornea and bladder revealed that diuretics with a common renal site of action gravitated into common classification groups. Thus, our studies suggested that cornea may be a suitable model of the thick ascending limb of the loop of Henle and that cornea and bladder, studied jointly, may serve as an in vitro system for predicting potential renal sites of action of new diuretics. This system, when used to characterize the new diuretic indanone, revealed that this agent, in all respects, displayed the characteristics of a loop diuretic.