bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of graded doses of cortisol on total body calcium in rats
Authors: Yasumura S , Ellis KJ , Fairchild E , Brook D , Cohn SH
Published: December 2017

Male rats with an average body weight of 250 g were injected (sc) daily for 4 wk with 0.05, 0.20, 0.75, or 3.00 mg of cortisol acetate. Intact and adrenalectomized control animals were injected daily with 0.1 ml of vehicle (corn oil). Total body calcium (TBCa) was measured weekly in each rat by in vivo neutron activation analysis. The gain is body weight of rats treated with 0.75 mg cortisol was significantly less than controls, and the animals treated with 3.00 mg cortisol lost weight. In spite of these differences in body weight, the TBCa of all rats increased to an equal degree from an average of 1.93 g to 2.81 g in 4 wk. In addition, there were no significant differences in tibial ash calcium. However, calcium (mg) per unit length (mm) of tibia was increased in rats treated with the higher doses of cortisol; thus bone density was increased. These results demonstrate that the TBCa increases even when rats are subjected to cortisol. This is explained in part by the normal rate of intestinal calcium absorption in cortisol-treated rats.
Transepithelial transport kinetics and Na entry in frog skin: effects of novobiocin
Authors: Cruz LJ , Biber TU
Published: December 2017

Na+ entry across the outer surface of frog skin and transepithelial Na transport were studied simultaneously at different [Na] in either the presence or absence of novobiocin by direct measurements of J12 (unidirectional uptake) and Io (short-circuit current). J12 consisted of two components: one linear, the other saturable. The kinetic parameters of the saturating components in controls were close to the kinetic parameters of overall transepithelial transport (Jm12 = 1.68+/-0.13 mleq cm-2h-1; Io =1.80+/-0.14 mueq cm-2h-1. K12 = 6.02+/-1.27 mM;Kio=6.12+/-1.33 mM). Novobiocin significantly augmented net transepithelial Na transport by increasing J13. J31 remained unaffected. A 1:1 relationship between the saturating component of J12 and Io was observed in both treated and untreated skins at all [Na] tested. (Jm12Iom, k12, and Kio were significantly larger in treated skins, but despite very drastic changes in transport rates, a close correlation between kinetic parameters of entry step and transepithelial transport was maintained. This suggests that the kinetics of transepithelial transport may simply reflect those of the rate-limiting step: the Na entry across the outer barrier of the skin. The results indicate that the linear component of J12 is not involved in transepithelial transport kinetics.
Inhibition of human leukocyte elastase by mineral dust particles
Authors: Oberson D. , Desfontaines L. , Pezerat H. , Hornebeck W. , Sebastien P. , Lafuma C.
Published: December 2017

After isolation, purification, and radiolabeling of elastin from baboon aorta and lung, the rates of hydrolysis of both 3H-labeled elastins by porcine pancreatic elastase (PPE or by human leukocyte elastase (HLE) were compared. PPE (30 nM) degraded aorta and lung elastins at rates of 40 and 75 micrograms/h, respectively, leading to their complete solubilization. In contrast, the low rate of hydrolysis of lung elastin (10 micrograms/h) by HLE was paradoxically accompanied with a fivefold decrease in the Michaelis constant value and became negligible after 1 h of incubation. Moreover, HLE adsorption isotherms showed that 0.87 nmol HLE was adsorbed on 1 mg of aorta elastin vs. 1.30 nmol/mg lung elastin. Also, increasing ionic strength was found to enhance the elastolytic potential of HLE toward lung elastin. Investigations were carried out to explain why baboon lung elastin exhibited low susceptibility to hydrolysis by HLE. Solubilization of lung elastin with PPE produced a residue that exhibited inhibitory capacity toward HLE when either 3H-labeled aorta elastin or succinyl trialanine nitroanilide was used as a substrate. When analyzed by transmission electron microscopy, this residue was found to consist of several mineral dust particles, mainly kaolinite (53%) of environmental origin. The HLE-inhibitory capacities of various mineral or coal mine dust particles were then analyzed. Mineral aluminium-silicate dusts were found to be potent HLE inhibitors: 5 micrograms of either kaolinite or montmorillonite totally abolished the activity of 0.45 micrograms of HLE. All these results allowed us to propose that HLE inhibition by aluminium-silicate dusts may be of importance in the pathogenesis of industrial pneumoconiosis and in opportunistic lung infections.
Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats
Authors: Mathew Rajamma , Fan Newton Y.-T. , Yuan Ning , Chander Praveen N. , Gewitz Michael H. , Stier Charles T.
Published: December 2017

To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N ω-nitro-l-arginine (l-NNA; 15 mg ⋅ kg−1 ⋅ day−1orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. l-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 ± 2 vs. 19 ± 1%).l-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 ± 7 vs. 88 ± 4% for WKY) was associated with an increase in WT (37 ± 1%) and RV/BW (0.76 ± 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.
cDNA-RDA of genes expressed in fetal and adult lungs identifies factors important in development and function
Authors: Cooper Paul , Mueck Beatrice , Yousefi Shida , Potter Suzanne , Jarai Gabor
Published: December 2017

The identification of genetic factors important in lung development and function will help in understanding the underlying molecular mechanisms of respiratory disease. Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based subtractive enrichment procedure for the isolation of differentially expressed genes. We performed cDNA-RDA and isolated genes expressed more abundantly in fetal and adult lungs. Fifty-four clones potentially representing genes with higher transcript levels in the fetal lung were sequenced. Sequence similarity searches indicated that these clones included 12 known genes, a discoidin-like domain-containing gene, six expressed sequence tags (ESTs), and one novel sequence. Fifty-six clones potentially representing genes expressed more abundantly in the adult lung were also cloned and sequenced. Of these, 16 known human genes were represented along with two sequences significantly similar to known mouse genes and two novel sequences. Several of these known genes are implicated in stress response and lung protection. Thus cDNA-RDA was successfully used to isolate known and novel differentially expressed genes, which putatively play an important role in human lung development.
Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries
Authors: Zhu Daling , Bousamra Michael , Zeldin Darryl C. , Falck John R. , Townsley Mary , Harder David R. , Roman Richard J. , Jacobs Elizabeth R.
Published: December 2017

Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5,6-, 8,9-, 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10−5M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse-phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.
Substance P and neurokinin-1 receptor expression by intrinsic airway neurons in the rat
Authors: Fontán J. Julio Pérez , Cortright Daniel N. , Krause James E. , Velloff Christine R. , Karpitskyi Vladimir V. , Carver Terry W. , Shapiro Steven D. , Mora Bassem N.
Published: December 2017

Tachykinins and their receptors are involved in the amplification of inflammation in the airways. We analyzed the expression of preprotachykinin-A (PPT-A) and neurokinin-1 (NK-1) receptor genes by intrinsic airway neurons in the rat. We also tested the hypothesis that PPT-A-encoded peptides released by these neurons fulfill the requisite role of substance P in immune complex injury of the lungs. We found that ganglion neurons in intact and denervated airways or in primary culture coexpress PPT-A and NK-1 receptor mRNAs and their protein products. Denervated ganglia from tracheal xenografts ( nu/nu mice) or syngeneic lung grafts had increased PPT-A mRNA contents, suggesting preganglionic regulation. Formation of immune complexes in the airways induced comparable inflammatory injuries in syngeneic lung grafts, which lack peptidergic sensory fibers, and control lungs. The injury was attenuated in both cases by pretreatment with the NK-1 receptor antagonist LY-306740. We conclude that tachykinins released by ganglia act as a paracrine or autocrine signal in the airways and may contribute to NK-1 receptor-mediated amplification of immune injury in the lungs.
Pulmonary-specific expression of SP-D corrects pulmonary lipid accumulation inSP-Dgene-targeted mice
Authors: Fisher James H. , Sheftelyevich Vladimir , Ho Ye-Shih , Fligiel Suzanne , McCormack Francis X. , Korfhagen Thomas R. , Whitsett Jeffrey A. , Ikegami Machiko
Published: December 2017

Targeted disruption of the surfactant protein (SP) D ( SP-D) gene caused a marked pulmonary lipoidosis characterized by increased alveolar lung phospholipids, demonstrating a previously unexpected role for SP-D in surfactant homeostasis. In the present study, we tested whether the local production of SP-D in the lung influenced surfactant content in SP-D-deficient [SP-D(−/−)] and SP-D wild-type [SP-D(+/+)] mice. Rat SP-D (rSP-D) was expressed under control of the human SP-C promoter, producing rSP-D, SP-D(+/+) transgenic mice. SP-D content in bronchoalveolar lavage fluid was increased 30- to 50-fold in the rSP-D, SP-D(+/+) mice compared with the SP-D(+/+) parental strain. Lung morphology, phospholipid content, and surfactant protein mRNAs were unaltered by the increased concentration of SP-D. Likewise, the production of endogenous mouse SP-D mRNA was not perturbed by the SP-D transgene. rSP-D, SP-D(+/+) mice were bred to SP-D(−/−) mice to assess whether lung-selective expression of SP-D might correct lipid homeostasis abnormalities in the SP-D(−/−) mice. Selective expression of SP-D in the respiratory epithelium had no adverse effects on lung function, correcting surfactant phospholipid content and decreasing phosphatidylcholine incorporation significantly. SP-D regulates surfactant lipid homeostasis, functioning locally to inhibit surfactant phospholipid incorporation in the lung parenchyma and maintaining alveolar phospholipid content in the alveolus. Marked increases in biologically active tissue and alveolar SP-D do not alter lung morphology, macrophage abundance or structure, or surfactant accumulation.
IGFBP-3 mediates TGF-β1-induced cell growth in human airway smooth muscle cells
Authors: Cohen Pinchas , Rajah Roopmathy , Rosenbloom Joel , Herrick David J.
Published: December 2017

Both insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor-β (TGF-β) have been separately shown to have cell-specific growth-inhibiting or growth-potentiating effects. TGF-β stimulates IGFBP-3 mRNA and peptide expression in several cell types, and TGF-β-induced growth inhibition and apoptosis have been shown to be mediated through the induction of IGFBP-3. However, a link between the growth stimulatory effects of TGF-β and IGFBP-3-induction has not been shown. In this study, we investigated the role of IGFBP-3 in mediating TGF-β1-induced cell growth using human airway smooth muscle (ASM) cells as our model. TGF-β1 (1 ng/ml) treatment induced a 10- to 20-fold increase in the levels of expression of IGFBP-3 mRNA and protein. Addition of either IGFBP-3 or TGF-β1 to the growth medium resulted in an approximately twofold increase in cell proliferation. Coincubation of ASM cells with IGFBP-3 antisense (but not sense) oligomers as well as with an IGFBP-3 neutralizing antibody (but not with control IgG) blocked the growth induced by TGF-β1 ( P < 0.001). Several IGFBP-3-associated proteins were observed in ASM cell lysates, which may have a role in the cellular responses to IGFBP-3. These findings demonstrate that IGFBP-3 is capable of mediating the growth stimulatory effect of TGF-β in ASM cells.
Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells
Authors: Suzuki Tomoko , Yamaya Mutsuo , Sekizawa Kiyohisa , Yamada Norihiro , Nakayama Katsutoshi , Ishizuka Satoshi , Kamanaka Masahito , Morimoto Tetsushi , Numazaki Yoshio , Sasaki Hidetada
Published: December 2017

To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the expression of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, on epithelial cells, and it increased the production of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in supernatants. Dexamethasone reduced the viral titers of supernatants and cell lysates, viral RNA of infected cells, and susceptibility of RV14 infection in association with inhibition of cytokine production and ICAM-1 induction. In contrast to RV14 infection, dexamethasone did not alter RV2 infection, a minor group of RVs. These results suggest that dexamethasone may inhibit RV14 infection by reducing the surface expression of ICAM-1 in cultured human tracheal epithelial cells. Glucocorticoid may modulate airway inflammation via reducing the production of proinflammatory cytokines and ICAM-1 induced by rhinovirus infection.
TRAIL expression in vascular smooth muscle
Authors: Gochuico Bernadette R. , Zhang Jie , Ma Bei Yang , Marshak-Rothstein Ann , Fine Alan
Published: December 2017

TRAIL is a cell-associated tumor necrosis factor-related apoptosis-inducing ligand originally identified in immune cells. The ligand has the capacity to induce apoptosis after binding to cell surface receptors. To examine TRAIL expression in murine vascular tissue, we employed in situ hybridization and immunohistochemistry. In these studies, we found that TRAIL mRNA and protein were specifically localized throughout the medial smooth muscle cell layer of the pulmonary artery. Notably, a similar pattern of expression was observed in the mouse aorta. Consistent with these findings, we found that cultures of primary human aorta and pulmonary artery smooth muscle cells express abundant TRAIL mRNA and protein. We also found that these cells and endothelial cells undergo cell lysis in response to exogenous addition of TRAIL. Last, we confirmed that TRAIL specifically activated a death program by confirming poly(ADP ribose) polymerase cleavage. Overall, we believe that these findings are relevant to understanding the factors that regulate cell turnover in the vessel wall.
Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury
Authors: Pryhuber Gloria S. , O'Brien David P. , Baggs Raymond , Phipps Richard , Huyck Heidie , Sanz Inaki , Nahm Moon H.
Published: December 2017

Hyperoxic lung injury, believed to be mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines, complicates the care of many critically ill patients. The cytokine tumor necrosis factor (TNF)-α is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-α treatment and blockade with anti-TNF antibodies increased survival in mice exposed to hyperoxia. In the current study, to determine if pulmonary oxygen toxicity is dependent on either of the TNF receptors, type I (TNFR-I) or type II (TNFR-II), TNFR-I or TNFR-II gene-ablated [(−/−)] mice and wild-type control mice (WT; C57BL/6) were studied in >95% oxygen. There was no difference in average length of survival, although early survival was better for TNFR-I(−/−) mice than for either TNFR-II(−/−) or WT mice. At 48 h of hyperoxia, slightly more alveolar septal thickening and peribronchiolar and periarteriolar edema were detected in WT than in TNFR-I(−/−) lungs. By 84 h of oxygen exposure, TNFR-I(−/−) mice demonstrated greater alveolar debris, inflammation, and edema than WT mice. TNFR-I was necessary for induction of cytokine interleukin (IL)-1β, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1β, MIP-2, interferon-γ-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-α. However, IL-1β, IL-6, macrophage migration inhibitory factor, MIP-1α, MIP-2, and MCP-1 mRNAs were comparably induced by hyperoxia in TNFR-I(−/−) and WT lungs. In contrast, mRNA for manganese superoxide dismutase and intercellular adhesion molecule-1 were induced by hyperoxia only in WT mice. Differences in early survival and toxicity suggest that pulmonary oxygen toxicity is in part mediated by TNFR-I. However, induction of specific cytokine and chemokine mRNA and lethality in response to severe hyperoxia was independent of TNFR-I expression. The current study supports the prediction that therapeutic efforts to block TNF-α receptor function will not protect against pulmonary oxygen toxicity.
Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo
Authors: Arai Toru , Abe Kin'Ya , Matsuoka Hiroto , Yoshida Mitsuhiro , Mori Masahide , Goya Sho , Kida Hiroshi , Nishino Kazumi , Osaki Tadashi , Tachibana Isao , Kaneda Yasufumi , Hayashi Seiji
Published: December 2017

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day −3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-α mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-β-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.
Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia
Authors: Aguirre J. I. , Morrell N. W. , Long L. , Clift P. , Upton P. D. , Polak J. M. , Wilkins M. R.
Published: December 2017

Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries during hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.
KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT
Authors: Panoskaltsis-Mortari Angela , Ingbar David H. , Jung Patricia , Haddad Imad Y. , Bitterman Peter B. , Wangensteen O. Douglas , Farrell Catherine L. , Lacey David L. , Blazar Bruce R.
Published: December 2017

We investigated keratinocyte growth factor (KGF) as a pretreatment therapy for idiopathic pneumonia syndrome (IPS) generated as a result of lung damage and allogeneic T cell-dependent inflammatory events occurring in the early peri-bone marrow (BM) transplant (BMT) period. B10.BR (H2k) recipient mice were transplanted with C57BL/6 (H2b) BM with spleen cells after lethal irradiation with and without cyclophosphamide conditioning with and without subcutaneous KGF pretreatment. KGF-pretreated mice had fewer injured alveolar type II (ATII) cells at the time of BMT and exhibited ATII cell hyperplasia at day 3 post-BMT. The composition of infiltrating cells on day 7 post-BMT was not altered by KGF pretreatment, but the frequencies of cells expressing the T-cell costimulatory molecules B7.1 and B7.2 and mRNA for the cytolysin granzyme B (usually increased in IPS) were decreased by KGF. Sera from KGF-treated mice had increases in the Th2 cytokines interleukin (IL)-4, IL-6, and IL-13 4 days after cessation of KGF administration (i.e., at the time of BMT). These data suggest that KGF hinders IPS by two modes: 1) stimulation of alveolar epithelialization and 2) attenuation of immune-mediated injury as a consequence of failure to upregulate cytolytic molecules and B7 ligand expression and the induction of anti-inflammatory Th2 cytokines in situ.
CNS, CSF, and extradural fluid uptake of various hydrophilic materials in the dogfish
Authors: Fenstermacher J. D. , Patlak C. S.
Published: December 2017

The distribution of 10 radioactively labeled materials from blood to CSF, extradural fluid (EDF), telencephalon (cerebrum), medulla, and spinal cord was studied in the dogfish shark. Plasma volumes, blood flows, and blood-to-tissue or fluid-transfer half-times (t1/2) were calculated from these distribution data. Blood-EDF exchange occurred at slow but similar rates for all tracers. Urea uptake by the CSF was very rapid compared to that of the other compounds and may be facilitated by a special mechanism. The tissue plasma spaces of all three CNS regions were small (1.1-1.5%). The calculated rates of tissue blood flow (in ml/g-min) were 0.11 for telencephalon and medulla and 0.055 for spinal cord. Choroid plexus blood flow was estimated to be 2.3 ml/g-min, a surprisingly high rate. Transport between blood and tissue was most rapid for water ethylene glycol and slowest for inulin. The tissue t1/2's of urea indicated that a significant portion of this compound's net uptake by periventricaul brain tissue occurred via the CSF.
Prolactin and fetal osmoregulation: water transport across isolated human amnion
Authors: Leontic E. A. , Tyson J. E.
Published: December 2017

The addition of human or ovine prolactin to the fetal side of the human amnion is associated with a latent decrease in membrane permeability. The specificity of this effect of prolactin is observed when equimolar concentrations of human placental lactogen and human growth hormone were used in place of ovine prolactin and failed to influence water transport. Likewise, the extracellular transport of p-aminohippurate across human amnion was unaffected by the addition of ovine prolactin. Tritiated water transport under these circumstances, however, remained impaired. The addition of antibody to ovine prolactin completely blocked the effect of this polypeptide on membrane permeability. Permeability to tritiated water remained unchanged when synthetic arginine vasopressin was added to the fetal side of the amnion. The results imply an active role for prolactin on water transport across human amnion. Moreover, the latent period between the addition of the polypeptide and its subsequent influence on permeability suggests a biologic effect of this hormone. That this effect is related to ion transfer remains to be shown.
Brainstem control of shivering in the cat. II. Facilitation
Authors: Amini-Sereshki L.
Published: December 2017

Regions containing areas and pathways mediating heat gain responses in the mesencephalon and upper pons and in the medulla were studied using topical microinjection of a local anesthetic. These facilitatory areas and pathways were compared in the decerebrated and intact cats. In lower pontine preparations shivering was abolished by bilateral injections of procaine into the lateral medullary reticular formation. Injections into the same areas in the intact anesthetized cat resulted in the cessation of shivering. These effects on facilitatory areas are reversible and can be repeated in the same preparation several times. Permanent effects were obtained by electrolytic lesions or by the local microinjections of 1% osmic acid. In summary it shown, by means of microinjection of local anesthetic, that the pathways mediating shivering in the intact and lower pontine cats are located in the same area in lateral reticular formation of pons and medulla.
Dynamic responses of CO2-sensitive avian intrapulmonary chemoreceptors
Authors: Osborne J. L. , Burger R. E. , Stoll P. J.
Published: December 2017

Single-unit extracellular potentials from CO2-sensitive intrapulmonary chemoreceptors (IPC) were recorded with tungsten microelectrodes from the nodose ganglia of unidirectionally, artificially ventilated White Leghorn cockerels. The responses of IPC to step and sinusoidal forcing functions of fractional concentration of carbon dioxide (FCo2) indicate that 1) about two-thirds of IPC are bidirectionally rate sensitive, 2) delay to forcing varies from essentially zero to several times larger than the time of nitrogen gas passage through the lung and, on the average, is significantly shorter to step decrease than step increase in fco2, and 3) IPC with irregular discharge intervals are more rate sensitive and respond to higher frequencies than IPC with regular interspike intervals. The physical and chemical properties of the "receptor-lung" complex are probably important in determining the dynamic responses of IPC by partitioning of CO2 from other gases within the lumen of the parabronchus. IPC are located along the length of the bronchial gas exchange areas of the avian lung and transmit information to the CNS concerning the mean level, rate, and direction of change in the partial pressure of carbon dioxide (PCo2).
Preoptic-hypothalamic periventricular lesions: thirst deficits and hypernatremia
Authors: Buggy J. , Jonhson A. K.
Published: December 2017

To assess the significance of stimulation studies suggesting an anteroventral third ventricle (AV3V) dipsogenic site of action for hyperosmotic and angiotensin thirst stimuli, electrolytic lesions of periventricular tissue surrounding AV3V were produced under ether anesthesia in rats preselected for responsiveness to subcutaneous angiotensin and hypertonic NaCl thirst challenges. Lesions limited to preoptic-anterior hypothalamic periventricular substrates resulted in adipsia; those rats resuming ad lib. drinking after a period of adipsia exhibited persistent drinking deficits to angiotensin and hypertonic NaCl thirst challenges, reduced drinking after water deprivation, and increased plasma osmolality and sodium. Drinking to polyethylene glycol-induced hypovolemia and feeding after food deprivation did not differ between lesioned and sham-lesioned animals. The disturbances in behavioral control of fluid balance imply that AV3V periventricular tissue normally plays a key role in mediating regulatory drinking. It is proposed that these AV3V periventricular lesion-induced effects on drinking behavior are due to destruction of receptors and/or integrative systems monitoring fluid-borne angiotensin and hyperosmotic stimuli.
Involuntary ankle oscillations from normal subjects
Authors: Stiles R. N. , Rietz R. R.
Published: December 2017

Spectral analysis of ankle tremor records obtained from normal seated subjects during continuous elevation of the heel for 10-45 min revealed that the root-mean-square (rms) displacement amplitude of the tremor increased from minimum values of about 4 micronm to values as large as 4,000 micronm. Associated with this increase in the displacement amplitude was a systematic decrease in the tremor frequency from values of 7-8 Hz to values of 5-6 Hz. Spectral analysis of demodulated soleus EMG records indicated that the rms value of this EMG (calculated at the tremor frequency) and the rms displacement of the tremor are related by a power function, with the rms value of the EMG increasing over a range of about 4-40 micronV as the tremor displacement increased from about 4 to 4,000 micronm. The negative relation between frequency and rms displacement amplitude values for postural ankle tremor was similar to that found previously for postural hand tremor.
Mechanical work in terrestrial locomotion: two basic mechanisms for minimizing energy expenditure
Authors: Cavagna G. A. , Heglund N. C. , Taylor C. R.
Published: December 2017

The work done during each step to lift and to reaccelerate (in the forward direction) and center of mass has been measured during locomotion in bipeds (rhea and turkey), quadrupeds (dogs, stump-tailed macaques, and ram), and hoppers (kangaroo and springhare). Walking, in all animals (as in man), involves an alternate transfer between gravitational-potential energy and kinetic energy within each stride (as takes place in a pendulum). This transfer is greatest at intermediate walking speeds and can account for up to 70% of the total energy changes taking place within a stride, leaving only 30% to be supplied by muscles. No kinetic-gravitational energy transfer takes place during running, hopping, and trotting, but energy is conserved by another mechanism: an elastic “bounce” of the body. Galloping animals utilize a combination of these two energy-conserving mechanisms. During running, trotting, hopping, and galloping, 1) the power per unit weight required to maintain the forward speed of the center of mass is almost the same in all the species studied; 2) the power per unit weight required to lift the center of mass is almost independent of speed; and 3) the sum of these two powers is almost a linear function of speed.
Water exchange in the placenta: a mathematical model
Authors: Wilbur W. J. , Power G. G. , Longo L. D.
Published: December 2017

To better understand the complicated interplay of forces affecting human placental water exchange, we developed a system of differential equations describing the flows of water, glucose, bicarbonate ion, amino acids, CO2, O2, passive cations (such as Na+ and K+), and chloride ion transplacentally and across the erythrocytes. The equations are based largely on the flux equations of irreversible thermodynamics, although Goldman's hypothesis and equation are employed to treat the ionic currents across the erythrocyte membrane. Bicarbonate ion and dissolved carbon dioxide were found to be major forces acting early in capillary transit to produce a large flow of water toward the fetus. Near the end of the capillary an almost equal amount of water returns to the mother, an effect due predominantly to the effect of glucose. For small deviations from accepted normal values, water transfer is most sensitive to changes in passive cations and chloride, followed by bicarbonate and CO2, plasma solutes (including lactate and glucose), hydrostatic pressure, and amino acids. A simple equation is given to summarize the model's results for water transfer when many factors change simultaneously. Uneven distribution of maternal-to-fetal blood flows tends to favor fetal water acquisition.
Vagal bradycardia elicited by stimulation of the external cuneate nucleus in the cat
Authors: Ciriello J. , Calaresu F. R.
Published: December 2017

The role of the external cuneate nucleus (ECN) in the control of heart rate was systematically investigated in 26 chloralosed and 2 decerebrated, paralyzed, and artifically ventilated cats. Electrical stimulation of histologically verified sites in the ventral ECN and dorsal spinal trigeminal tract elicited a marked decrease in heart rate, with threshold currents of 5-25 muA and an optimal frequency of 20 Hz when using a 0.2 ms pulse; this response was shown to be due to vagal excitation. In seven experiments intravenous pentobarbital sodium decreased the magnitude of the bradycardia elicited by stimulation of the ECN, of the nucleus ambiguus (AMB), and of the cervical vagus significantly less than the response from the nucleus of the tractus solitarius. In eight additional experiments in cats with lesions of the AMB made 11-27 days earlier stimulation of the ECN elicited a bradycardia of the same magnitude as that observed in intact animals, although the bradycardia elicited by stimulation of the ipsilateral cervical vagus was significantly reduced by the lesion. Similarly, lesions of the ECN in four cats significantly attenuated the bradycardia elicited by stimulation of the ipsilateral cervical vagus. These results suggest that the ECN is a site of origin of cardioinhibitory axons in the cat.
Induction of delta-aminolevulinic acid synthetase in muscle by exercise or thyroxine
Authors: Holloszy J. O. , Winder W. W.
Published: December 2017

There is evidence that delta-aminolevulinic acid (ALA) synthetase is the rate-limiting enzyme in heme biosynthesis. Accumulation of the apoproteins of the mitochondrial cytochromes appears to be regulated by availability of heme. Exercise and thyrotoxicosis bring about increases in the cytochromes, and in other mitochondrial enzymes, in muscle. In this context, we have examined the effects of exercise and of thyroid hormones on ALA synthetase activity in skeletal muscle. Treadmill running and injection of thyroid hormones both resulted in significant increases in muscle ALA synthetase activity. A rise in ALA synthetase activity was evident within 17 h after a bout of vigorous exercise and 14 h after a single injection of thyroid hormones. The increase in ALA synthetase preceded the increase in cytochrome c, which was used as a mitochondrial marker. These results are compatible with the hypothesis that a relationship exists between heme synthesis and mitochondrial growth in which the rate-controlling step is ALA synthetase activity.
Some aspects of temperature regulation in newborn harp seal pups
Authors: Blix A. S. , Grav H. J. , Ronald K.
Published: December 2017

Harp seals are born on the drifting ice of the North Atlantic Ocean during arctic winter when temperatures of -20 degrees C, occasionally in combination with wind of 10 m/s, might prevail for days. At birth the pups lack subcutaneous blubber and the wet infantile fur has a conductance value of 30.0 W . m-2 . degrees C-1, as compared with only 2.0 W . m-2 . degrees C-1 when dry. While still wet immediately after birth the pups are nevertheless able to retain body core temperature by shivering. This activity leads to reduction of muscle fat and glycogen stores. Nonshivering thermogenesis commences in thermogenic adipose tissue by virtue of loosely coupled mitochondria. Thermogenic adipose tissue is found at birth both as a subcutaneous layer along the back and as internal deposits around venous plexuses in the neck, on the pericardium, on the kidneys, and the abdominal walls. After about 3 days of suckling the subcutaneous adipose tissue loses its thermogenic function being gradually transformed into blubber, whereas the internal deposits persist at least until the pups venture into water at the age of 3-4 wk.
Investigation of hot flashes by ambulatory monitoring
Authors: Molnar G. W.
Published: December 2017

The unpredictability of hot flashes makes their investigation difficult. A method for continuous monitoring of subjective arousals and their objective correlates is here described and illustrated with results from one subject. Temperatures of special interest with respect to hot flashes--toe, cheek, vagina, and air--were recorded on a protable magnetic tape during routine living at home. The subject signaled the “on” and “off” of each perceived flash with a hand switch and also entered information in a notebook. She signaled 63 flashes on 5 days, during which the cheek and toe temperatures showed transient increments. Some of the flashes were labeled uncertain in the notebook. The subject also had 23 episodes of these temperature increments that she did not identify by signals as flashes. In these episodes, therefore, the mechanism of consciousness was not activated. Perceptions that coincided with transient temperature increments thus ranged as follows: subconscious, uncertain, definite but bearable, mildly distressful, and strongly distressful. Hence ambulatory monitoring can provide objective evidence of transient activation of the hypothalamic heat loss mechanism, whether perceived or not.
Endogenous nature of circadian rhythms in calcium metabolism
Authors: Staub J. F. , Perault-Staub A. M. , Milhaud G.
Published: December 2017

Rats studied when the lights are on from 0600 to 1800 daily and fed only in the dark period displayed circadian rhythms in plasma calcium (ionized and total) and 45Ca concentrations, 6 and 8 days after 45Ca administration. In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. In the calcium-deficient rats, significant correlations between plasma calcium and 45Ca and between plasma calcium and magnesium were observed throughout the 24 h; circadian periodicity of calcium metabolism persisted in rats fasted overnight, regardless of the illumination schedule. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy (TPTX), were restored by feeding the TPTX rats a high-calcium diet. These results demonstrate clearly that circadian rhythms of calcium metabolism occurred irrespective of the light-dark schedule, the calcium supply through intestines and the thyroparathyroid system. An attractive suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism.
Distribution of vagal cardioinhibitory neurons in the medulla of the cat
Authors: Ciriello J. , Calaresu F. R.
Published: December 2017

Experiments were done in cats anesthetized with chloralose, paralyzed and artificially ventilated cats to obtain electrophysiological evidence on the medullary site of origin of vagal cardioinhibitory fibers. The regions of the nucleus ambiguus (AMB), dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarius (NTS), and external cuneate nucleus (ECN) were systematically explored for units responding both to antidromic stimulation of the cardiac branches of the vagus (CBV) and to orthodromic stimulation of the carotid sinus and aortic depressor nerves. Eighty-six single units conforming to these criteria were found in the medulla: 30 in the AMB, 26 in the DMV, 12 in the NTS, 8 in the NTS-DMV border region, and 10 in the ECN. Antidromically evoked spikes had durations of 0.5--2.5 ms and followed stimulation frequencies of 20--500 Hz. The axons of these units conducted at velocities of 3.3--20.8 m/s. The specificity of activation of medullary units by cardioinhibitory fibers was tested in 11 units, which were found to respond consistently with an antidromic spike to stimulation of CBV but not to stimulation of the thoracic vagus. In eight spinal animals low threshold (less than 15 microA) sites eliciting vagal bradycardia were found in the same medullary nuclei where cardioinhibitory units had been located. These results indicate that vagal cardioinhibitory axons, originate in at least three medullary nuclei, the AMB, DMV, and NTS. Unit activity from the ECN may have been recorded from carioinhibitory fibers because of the short duration of the spike potentials.
Morphology of gill epithelia in fish
Authors: Laurent P. , Dunel S.
Published: December 2017

In fish of all groups examined including Teleostei, Chondrostei, Holostei, Chondrichytes, and Dipnoi, the primary epithelium that surrounds the primary lamellae has a close relationship with the venous compartment. Except in Dipnoi that displays a specialized epithelial drainage, the venous compartment consists of a central venous sinus that is connected with the systemic vasculature by noninnervated muscular arteriovenous anastomoses and drains into the branchial veins. Primary epithelium contains the chloride cells, which vary in morphology and number according to the milieu where the fish lives. The presence of an accessory cell beside the chloride cell is characteristic of seawater or seawater-adapted fish. The secondary epithelium that covers the free part of the secondary lamellae has an exclusive relationship with the arterioarterial vasculature, i.e., the pillar capillary compartment. This compartment is actively controlled by innervated sphincters located in the primary lamellae and in lower species by pre- and postlamellar noninnervated sphincters. Contraction of pillar cells may also contribute to this control. The secondary epithelium consists of an outermost layer of pavement cells that exhibited structural characteristics suggestive of cell coat secretion and an innermost layer of less differentiated cells. In contrast to the primary epithelium, the secondary epithelium does not exhibit any obvious differences between freshwater and seawater fish or undergo any obvious change during transfer of fish from fresh- to seawater. However, in conditions which exaggerate the absorptive functions of freshwater chloride cells, the secondary epithelium become modified by an intensive differentiation of freshwater chloride cells from its innermost layer of cells. These observations suggest possible specialized functional relationships between seawater chloride cells and the central venous sinus, and freshwater chloride cells and the arterioarterial compartment.
Ion-secreting epithelia: chloride cells in the head region of Fundulus heteroclitus
Authors: Karnaky K. J.
Published: December 2017

Transporting cells of ion-secreting epithelia are characterized by similar morphological patterns that include rich supplies of mitochondria, exotic patterns of surface amplification, and basolateral, plasma-membrane location of Na-K-ATPase, even though the direction of sodium transport across these epithelia is toward the apical side. Several new models for NaCl secretion propose that sodium, extruded into the intercellular space by Na-K-ATPase, reaches the apical side via the zonulae occludentes. Very recent freeze-fracture electron microscopy of avian salt gland and teleost chloride cells reveals that transporting cells are joined by simple, shallow zonulae occludentes. These observations lend morphological support to the concept that paracellular sodium ion permeation plays a central role in secretion. The chloride ion may traverse the epithelium via a transcellular route, entering the cell at the basolateral membrane by a chloride carrier linked to the cotransport of sodium down its electrochemical gradient into the cell. Finally, the chloride ion may exit the cell across the apical membrane by electrical forces. This review summarizes biochemical, morphological, and electrophysiological aspects of these new secretory models and the important contribution of a half century of research on teleost osmoregulatory mechanisms, including the chloride cell, to our understanding of sodium and chloride transport across secretory epithelia.
Freeze fracture of the gill epithelium of euryhaline teleost fish
Authors: Sardet C.
Published: December 2017

We briefly discuss the information one can obtain using freeze fracture. We used this technique to precisely identify the types of junctions that link the cells of the gill epithelium of euryhaline teleosts. In particular we demonstrate that seawater adaptation is characterized by the appearance of new apical tight junctions between chloride cells. Another particularity of these cells, the extensive network of tubules, extension of the basolateral plasma membrane, is shown to be made of repetitive units. We discuss the functional importance of the observations with respect to the adaptation of fish to different salinities.
Cl--HCO3--ATPase in gills of the rainbow trout: evidence for its microsomal localization
Authors: Bornancin M. , de Renzis G. , Naon R.
Published: December 2017

The intracellular localization of a Cl--HCO3--ATPase, which is inhibited by SCN-, was studied in the gills of the rainbow trout, Salmo gairdneri. This activity can be measured in the absence of contamination by mitochondria (i.e., in the absence of succinate dehydrogenase or cytochrome c oxidase activities). The distribution of the 5'-nucleotidase and of the ATPase stimulated by Cl- and HCO3- after sucrose density gradient centrifugation of the microsomal fraction was compared. Because those activities cannot be separated, it is postulated that the anion-stimulated ATPase is located in the plasma membrane. The activation of this microsomal anion ATPase by chloride has been studied extensively. The possible role of the Cl--HCO3--ATPase of trout gills in the Cl-/HCO3- exchange and in the regulation of the internal acid-base balance is discussed.