bluuebunny/crossref_metadata_2025 huggingface dataset:
Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans
Authors: Mack Gary W. , Cordero Doug , Peters Jochen
Published: December 2017

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without α-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 ± 8 W) protocols with and without baroreceptor unloading induced by application of −40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 ± 0.08 and 0.31 ± 0.10°C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 ± 0.10 and 0.50 ± 0.10°C ( P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.
Chronic hypoxia attenuates resting and exercise-induced VEGF, flt-1, and flk-1 mRNA levels in skeletal muscle
Authors: Olfert I. Mark , Breen Ellen C. , Mathieu-Costello Odile , Wagner Peter D.
Published: December 2017

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF, its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming growth factor-β1. Wistar rats were exposed to chronic hypoxia ( n = 12) or room air ( n = 12). After the exposure period, six animals from each group were subjected to a single 1-h treadmill exercise bout (18 m/min on a 10° incline) in room air while the remaining six animals served as rest controls. Morphological analysis revealed that chronic hypoxia did not increase skeletal muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively ( P < 0.05). The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither transforming growth factor-β1 nor basic fibroblast growth factor mRNA was significantly altered by chronic hypoxia. In conclusion, prolonged exposure to hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in rat gastrocnemius muscle. These findings may provide an explanation for the lack of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.
Invited Review: Physiological and pathophysiological responses to intermittent hypoxia
Authors: Neubauer Judith A.
Published: December 2017

This mini-review summarizes the physiological adaptations to and pathophysiological consequences of intermittent hypoxia with special emphasis given to the pathophysiology associated with obstructive sleep apnea. Intermittent hypoxia is an effective stimulus for evoking the respiratory, cardiovascular, and metabolic adaptations normally associated with continuous chronic hypoxia. These adaptations are thought by some to be beneficial in that they may provide protection against disease as well as improve exercise performance in athletes. The long-term consequences of chronic intermittent hypoxia may have detrimental effects, including hypertension, cerebral and coronary vascular problems, developmental and neurocognitive deficits, and neurodegeneration due to the cumulative effects of persistent bouts of hypoxia. Emphasis is placed on reviewing the available data on intermittent hypoxia, making extensions from applicable information from acute and chronic hypoxia studies, and pointing out major gaps in information linking the genomic and cellular responses to intermittent hypoxia with physiological or pathophysiological responses.
Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in vivo
Authors: Muramatsu Tadashi , Muraoka Tetsuro , Takeshita Daisuke , Kawakami Yasuo , Hirano Yuichi , Fukunaga Tetsuo
Published: December 2017

Load-strain characteristics of tendinous tissues (Achilles tendon and aponeurosis) were determined in vivo for human medial gastrocnemius (MG) muscle. Seven male subjects exerted isometric plantar flexion torque while the elongation of tendinous tissues of MG was determined from the tendinous movements by using ultrasonography. The maximal strain of the Achilles tendon and aponeurosis, estimated separately from the elongation data, was 5.1 ± 1.1 and 5.9 ± 1.6%, respectively. There was no significant difference in strain between the Achilles tendon and aponeurosis. In addition, no significant difference in strain was observed between the proximal and distal regions of the aponeurosis. The results indicate that tendinous tissues of the MG are homogenously stretched along their lengths by muscle contraction, which has functional implications for the operation of the human MG muscle-tendon unit in vivo.
Inspiratory lung impedance in COPD: effects of PEEP and immediate impact of lung volume reduction surgery
Authors: Kaczka David W. , Ingenito Edward P. , Body Simon C. , Duffy Sabine E. , Mentzer Steven J. , DeCamp Malcolm M. , Lutchen Kenneth R.
Published: December 2017

Frequency-dependent characteristics of lung resistance (Rl) and elastance (El) are sensitive to different patterns of airway obstruction. We used an enhanced ventilator waveform (EVW) to measure inspiratory Rl and El spectra in ventilated patients during thoracic surgery. The EVW delivers an inspiratory flow waveform with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the coefficients in a trigonometric approximation of the EVW flow and transpulmonary pressure inspirations yielded inspiratory Rl and Elspectra. We applied the EVW in a group with mild obstruction undergoing various thoracoscopic procedures ( n = 6), and another group with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery ( n = 8). Measurements were made at positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH2O. Inspiratory Rl was similar in both groups despite marked differences in spirometry. The chronic obstructive pulmonary disease patients demonstrated a pronounced frequency-dependent increase in inspiratory El consistent with severe heterogeneous peripheral airway obstruction. PEEP appears to have beneficial effects by reducing peripheral airway resistance. Lung volume reduction surgery resulted in increased inspiratory Rl and El at all frequencies and PEEPs, possibly due to loss of diseased lung tissue, pulmonary edema, increased mechanical heterogeneity, and/or an improvement in airway tethering.
Fall in intracellular Po2at the onset of contractions inXenopussingle skeletal muscle fibers
Authors: Hogan Michael C.
Published: December 2017

It remains uncertain whether the delayed onset of mitochondrial respiration on initiation of muscle contractions is related to O2availability. The purpose of this research was to measure the kinetics of the fall in intracellular Po2at the onset of a contractile work period in rested and previously worked single skeletal muscle fibers. Intact single skeletal muscle fibers ( n = 11) from Xenopus laevis were dissected from the lumbrical muscle, injected with an O2-sensitive probe, mounted in a glass chamber, and perfused with Ringer solution (Po2= 32 ± 4 Torr and pH = 7.0) at 20°C. Intracellular Po2was measured in each fiber during a protocol consisting sequentially of 1-min rest; 3 min of tetanic contractions (1 contraction/2 s); 5-min rest; and, finally, a second 3-min contractile period identical to the first. Maximal force development and the fall in force (to 83 ± 2 vs. 86 ± 3% of maximal force development) in contractile periods 1 and 2, respectively, were not significantly different. The time delay (time before intracellular Po2began to decrease after the onset of contractions) was significantly greater ( P < 0.01) in the first contractile period (13 ± 3 s) compared with the second (5 ± 2 s), as was the time to reach 50% of the contractile steady-state intracellular Po2(28 ± 5 vs. 18 ± 4 s, respectively). In Xenopus single skeletal muscle fibers, 1) the lengthy response time for the fall in intracellular Po2at the onset of contractions suggests that intracellular factors other than O2availability determine the on-kinetics of oxidative phosphorylation and 2) a prior contractile period results in more rapid on-kinetics.
Quantitative electrophoretic analysis of myosin heavy chains in single muscle fibers
Authors: Tikunov Boris A. , Sweeney H. Lee , Rome Lawrence C.
Published: December 2017

To better understand the molecular basis of the large variation in mechanical properties of different fiber types, there has been an intense effort to relate the mechanical and energetic properties measured in skinned single fibers to those of their constituent cross bridges. There is a significant technical obstacle, however, in estimating the number of cross bridges in a single fiber. In this study, we have developed a procedure for extraction and quantification of myosin heavy chains (MHCs) that permits the routine and direct measurement of the myosin content in single muscle fibers. To validate this method, we also compared MHC concentration measured in single fibers with the MHC concentration in whole fast-twitch (psoas and gracilis) and slow-twitch (soleus) muscles of rabbit. We found that the MHC concentration in intact psoas (184 μM) was larger than that in soleus (144 μM), as would be expected from their differing mitochondrial content and volume of myofibrils. We obtained excellent agreement between MHC concentration measured at the single fiber level with that measured at the whole muscle level. This not only verifies the efficacy of our procedure but also shows that the difference in concentration at the whole muscle level simply reflects the concentration differences in the constituent fiber types. This new procedure should be of considerable help in future attempts to determine kinetic differences in cross bridges from different fiber types.
Method for measuring long-term function of muscle-powered implants via radiotelemetry
Authors: Trumble Dennis R. , Magovern James A.
Published: December 2017

Long-term remote monitoring of muscle-powered implants has been made possible with development of an adjustable workload that can be remotely monitored to assess device function. This technique obviates the need for percutaneous access lines and allows test animals to remain untethered, eliminating deleterious effects caused by infection, sedation, or animal stress. Hardware components include a latex bladder fixed within a hermetically sealed canister, multichannel implantable telemetry unit, and subcutaneous access port (for pressure charge adjustment). To validate this method, in vitro tests were performed by using a third-generation muscle energy converter designed to function as an implantable hydraulic pump. Two channels of telemetered pressure data were collected and used to calculate six indexes of device function. Calculated parameters were then compared with measured values to determine accuracy. Correlation between measured and calculated parameters was high in all instances, with most estimates yielding errors of <3%. These results demonstrate the utility of this approach and support its use as a means to monitor muscle-powered devices during long-term animal trials.
Invited Review: Respiratory plasticity following intermittent hypoxia: developmental interactions
Authors: Gozal Evelyne , Gozal David
Published: December 2017

Intermittent hypoxia (IH) is the most frequent form of hypoxia occurring in the developing mammal. On one hand, the maturational process of neural, mechanical, pulmonary, and sleep state-dependent factors will favor the occurrence of IH during early postnatal life. On the other hand, it has also become clear that hypoxia, even when short lasting, can modify subsequent respiratory responses to hypoxia and induce a variety of genes whose consequences will persist for much longer periods than the duration of the hypoxic stimulus itself, i.e., functional and adaptive plasticities. The dynamic interactions between the overall duration and recurring frequency of IH, the severity of IH, and the level of neural maturity at the time of IH will modify the ventilatory, metabolic, and cardiovascular responses to hypoxia. We propose that the earlier IH will occur in the developmental course the more likely that the physiological responses to an ulterior hypoxic challenge will be altered even into adulthood. At this point in time, a critical examination of the field would suggest that the short-term alterations of the hypoxic ventilatory response (HVR) of the developing mammal to IH are qualitatively similar to those of the adult and display a biphasic pattern, namely, initial enhancement of the HVR followed by a reduction in HVR. However, the short- and long-term effects of IH on the modulation of neurotransmitter release, receptor binding and expression, intracellular signaling cascades, transcriptional regulation, and gene expression as a function of animal maturity are almost completely unknown. Further delineation of such complex responses to IH may permit the formulation of interventional strategies aiming at reducing the overall vulnerability of the young infant and child to apnea and sudden death.
Theagoutigene product stimulates pancreatic β-cell Ca2+signaling and insulin release
Authors: XUE B. Z. , WILKISON W. O. , MYNATT R. L. , MOUSTAID N. , GOLDMAN M. , ZEMEL M. B.
Published: December 2017

Xue, B. Z., W. O. Wilkison, R. L. Mynatt, N. Moustaid, M. Goldman, and M. B. Zemel. The agouti gene product stimulates pancreatic β-cell Ca2+signaling and insulin release. Physiol. Genomics 1: 11-19, 1999.—Ubiquitous expression of the mouse agouti gene results in obesity and hyperinsulinemia. Human agouti is expressed in adipose tissue, and we found recombinant agouti protein to stimulate lipogenesis in adipocytes in a Ca2+-dependent fashion. However, adipocyte-specific agouti transgenic mice only became obese in the presence of hyperinsulinemia. Because intracellular Ca2+concentration ([Ca2+]i) is a primary signal for insulin release, and we have shown agouti protein to increase [Ca2+]iin several cell types, we examined the effects of agouti on [Ca2+]iand insulin release. We demonstrated the expression of agouti in human pancreas and generated recombinant agouti to study its effects on Ca2+signaling and insulin release. Agouti (100 nM) stimulated Ca2+influx, [Ca2+]iincrease, and a marked stimulation of insulin release in two β-cell lines (RIN-5F and HIT-T15; P < 0.05). Agouti exerted comparable effects in isolated human pancreatic islets and β-cells, with a 5-fold increase in Ca2+influx ( P < 0.001) and a 2.2-fold increase in insulin release ( P < 0.01). These data suggest a potential role for agouti in the development of hyperinsulinemia in humans.
Phenotypic differences in cardiovascular regulation in inbred rat models of aerobic capacity
Authors: KOCH LAUREN GERARD , BRITTON STEVEN L. , BARBATO JOHN C. , RODENBAUGH DAVID W. , DiCARLO STEPHEN E.
Published: December 2017

Koch, Lauren Gerard, Steven L. Britton, John C. Barbato, David W. Rodenbaugh, and Stephen E. DiCarlo. Phenotypic differences in cardiovascular regulation in inbred rat models of aerobic capacity. Physiol. Genomics 63–69, 1999.—The Dark Aouti (DA) inbred strain of rats has superior aerobic treadmill running capacity compared with the Copenhagen (COP) strain of inbred rats. This difference in aerobic capacity provides a model to explore the genetic basis of variation in this trait. The present study evaluated intermediate phenotypic differences between 10 male COP inbred rats and 10 male DA inbred rats that might contribute to the difference in aerobic capacity between the strains. Five autonomically regulated cardiovascular variables were evaluated during rest or exercise by measuring the response to autonomic antagonists. The DA rat had enhanced autonomic function for the regulation of peripheral blood flow and cardiac output. Specifically, at rest the DA rats had significantly more sympathetic (123 ± 8 vs. 99 ± 7 beats/min) and parasympathetic (35 ± 5 vs. 12 ± 3 beats/min) tonus for heart rate control and more sympathetic support of blood pressure (70 ± 7 vs. 38 ± 6 mmHg) compared with the COP rats. During three graded levels of treadmill exercise the DA rats had higher blood pressures (16% on average) and higher heart rates (4% on average) relative to the COP rats. In addition, the DA rats had a 27% greater heart weight-to-body weight ratio compared with the COP strain of rats (3.63 ± 0.08 vs. 2.85 ± 0.07 g/kg). All five of these intermediate phenotypes could participate as variables causative of the difference in treadmill running capacity between the DA and COP strains of rats.
A high-throughput MS-PCR method on MADGE gels for ANG II type-1 receptor A1166C polymorphism
Authors: HUNT CLIVE C. J. , BURLEY JODI E. , CHAPMAN CAROLINE M. L. , BEILBY JOHN P.
Published: December 2017

Hunt, Clive C. J., Jodi E. Burley, Caroline M. L. Chapman, and John P. Beilby. A high-throughput MS-PCR method on MADGE gels for ANG II type-1 receptor A1166C polymorphism. Physiol. Genomics 1: 71–73, 1999.—We have developed a highly accurate, low-cost, single-step, mutagenically separated polymerase chain reaction (MS-PCR) method for the determination of angiotensin II type-1 receptor (AT1) A1166C gene polymorphism. The genotypes are determined using the microtiter array diagonal gel electrophoresis (MADGE) system. We have compared the MS-PCR method with allele-specific oligonucleotide hybridization and Dde I digestion techniques for determining the AT1 A1166C genotype. The combination of MS-PCR and MADGE serves as a model for high-throughput single-nucleotide polymorphism genotyping in large population studies.
Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats
Authors: COWLEY A. W. , STOLL MONIKA , GREENE ANDREW S. , KALDUNSKI MARY L. , ROMAN RICHARD J. , TONELLATO PETER J. , SCHORK NICHOLAS J. , DUMAS PIERRE , JACOB HOWARD J.
Published: December 2017

Cowley, A. W., Jr., Monika Stoll, Andrew S. Greene, Mary L. Kaldunski, Richard J. Roman, Peter J. Tonellato, Nicholas J. Schork, Pierre Dumas, and Howard J. Jacob. Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats. Physiol Genomics 2: 107–115, 2000.—A genetic segregation analysis was performed to identify genes that cosegregate with arterial blood pressure traits reflective of salt sensitivity. A population of 113 F2 male rats was derived from an intercross of inbred SS/JrHsd/Mcw (Dahl salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats were maintained on an 8% salt diet from the age of 9 to 13 wk, and arterial pressure was measured for 3 h daily during the 4th wk of high salt intake in unanesthetized rats using implanted arterial catheters. At the end of the 3rd day of high-salt pressure recordings, the arterial pressure response to salt depletion was determined 1.5 days following treatment with Lasix and a low-sodium (0.4%) diet. A genome-wide scan using 265 polymorphic simple sequence length polymorphism (SSLP) markers found that seven arterial pressure phenotypes determined at different times and circumstances, and representing two distinct indexes of salt sensitivity, mapped to the same region of rat chromosome 18. The trait of salt sensitivity was strongly influenced by the presence of SS alleles in this region of chromosome 18, and those rats which were homozygote SS/SS exhibited a significantly greater reduction of mean arterial pressure following sodium depletion (29 ± 2 mmHg) than homozygote BN/BN (17 ± 3 mmHg) or heterozygotic (22 ± 2 mmHg) rats. This region of rat chromosome 18 corresponds to the long arm of human chromosome 5 and a region of human chromosome 18 that has been linked to hypertension in humans. Given the unlikely chance of these different blood pressure traits mapping to the same region, we believe these data provide evidence that this region of rat chromosome 18 plays an important role in salt-induced hypertension.
Encroaching genomics: adapting large-scale science to small academic laboratories
Authors: EINARSON MARGRET B. , GOLEMIS ERICA A.
Published: December 2017

Einarson, Margret B., and Erica A. Golemis. Encroaching genomics: adapting large-scale science to small academic laboratories. Physiol Genomics 2: 85–92, 2000.—The process of conducting biological research is undergoing a profound metamorphosis due to the technological innovations and torrent of information resulting from the execution of multiple species genome projects. The further tasks of mapping polymorphisms and characterizing genome-wide protein-protein interaction (the characterization of the proteome) will continue to garner resources, talent, and public attention. Although some elements of these whole genome size projects can only be addressed by large research groups, consortia, or industry, the impact of these projects has already begun to transform the process of research in many small laboratories. Although the impact of this transformation is generally positive, laboratories engaged in types of research destined to be dominated by the efforts of a genomic consortium may be negatively impacted if they cannot rapidly adjust strategies in the face of new large-scale competition. The focus of this report is to outline a series of strategies that have been productively utilized by a number of small academic laboratories that have attempted to integrate such genomic resources into research plans with the goal of developing novel physiological insights.
The two isozymes of rat intestinal alkaline phosphatase are products of two distinct genes
Authors: XIE Q. , ALPERS D. H.
Published: December 2017

Xie, Q., and D. H. Alpers. The two isozymes of rat intestinal alkaline phosphatase are products of two distinct genes. Physiol Genomics 3: 1–8, 2000.—Rat intestinal alkaline phosphatases (IAP-I and -II) differ in primary structure, substrate specificity, tissue localization, and response to fat feeding. This study identifies two distinct genes (∼5–6 kb) corresponding to each isozyme and containing 11 exons of nearly identical size. The exon-intron junctions are identical with those found in IAP genes from other species. The 1.7 and 1.2 bp of 5′ flanking regions isolated from each gene, respectively, contain Sp1 and gut-enriched Kruppel-like factor (GKLF) binding sites, but otherwise show little identity. There is a potential CAAT-box 14 bp 5′ to the transcriptional start site, 36 bp upstream from IAP-I, and a TATA-box 31 bp 5′ to the transcriptional start site, 55 bp upstream from IAP-II. Transfection of these promoter regions (linked to luciferase as a reporter gene) into a kidney cell line, COS-7, produced the differential response to oleic acid expected from in vivo studies, i.e., threefold increase using the 5′ flanking region of IAP-II, but not IAP-I. This response was not reproduced by 5,8,11,14-eicosatetraynoic acid (ETYA) or clofibrate, suggesting that peroxisome proliferator response elements are not involved. Isolation of the IAP-II gene will allow determination of the sequences responsible for dietary fat response in the enterocyte.
A fuzzy logic approach to analyzing gene expression data
Authors: WOOLF PETER J. , WANG YIXIN
Published: December 2017

Woolf, Peter J., and Yixin Wang. A fuzzy logic approach to analyzing gene expression data. Physiol Genomics 3: 9–15, 2000.—We have developed a novel algorithm for analyzing gene expression data. This algorithm uses fuzzy logic to transform expression values into qualitative descriptors that can be evaluated by using a set of heuristic rules. In our tests we designed a model to find triplets of activators, repressors, and targets in a yeast gene expression data set. For the conditions tested, the predictions made by the algorithm agree well with experimental data in the literature. The algorithm can also assist in determining the function of uncharacterized proteins and is able to detect a substantially larger number of transcription factors than could be found at random. This technology extends current techniques such as clustering in that it allows the user to generate a connected network of genes using only expression data.
Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle
Authors: HAMMOND T. G. , BENES E. , O’REILLY K. C. , WOLF D. A. , LINNEHAN R. M. , TAHER A. , KAYSEN J. H. , ALLEN P. L. , GOODWIN T. J.
Published: December 2017

Hammond, T. G., E. Benes, K. C. O’Reilly, D. A. Wolf, R. M. Linnehan, J. H. Kaysen, P. L. Allen, and T. J. Goodwin. Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle. Physiol Genomics 3: 163–173, 2000.—Three-dimensional suspension culture is a gravity-limited phenomenon. The balancing forces necessary to keep the aggregates in suspension increase directly with aggregate size. This leads to a self-propagating cycle of cell damage by balancing forces. Cell culture in microgravity avoids this trade-off. We determined which genes mediate three-dimensional culture of cell and tissue aggregates in the low-shear stress, low-turbulent environment of actual microgravity. Primary cultures of human renal cortical cells were flown on the space shuttle. Cells grown in microgravity and ground-based controls were grown for 6 days and fixed. RNA was extracted, and automated gene array analysis of the expression of 10,000 genes was performed. A select group of genes were regulated in microgravity. These 1,632 genes were independent of known shear stress response element-dependent genes and heat shock proteins. Specific transcription factors underwent large changes in microgravity including the Wilms’ tumor zinc finger protein, and the vitamin D receptor. A specific group of genes, under the control of defined transcription factors, mediate three-dimensional suspension culture under microgravity conditions.
Increased susceptibility to fatigue of slow- and fast-twitch muscles from mice lacking the MG29 gene
Authors: NAGARAJ RAMAKRISHNAN Y. , NOSEK CHRISTOPHER M. , BROTTO MARCO A. P. , NISHI MIYUKI , TAKESHIMA HIROSHI , NOSEK THOMAS M. , MA JIANJIE
Published: December 2017

Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.
Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2
Authors: DELANY NATALIE S. , HURLE MICHAEL , FACER PAUL , ALNADAF TANJA , PLUMPTON CHRISTOPHER , KINGHORN IAN , SEE CHEE GEE , COSTIGAN MICHAEL , ANAND PRAVEEN , WOOLF CLIFFORD J. , CROWTHER DANIEL , SANSEAU PHILIPPE , TATE SIMON N.
Published: December 2017

Remarkable progress has been made recently in identifying a new gene family related to the capsaicin (vanilloid) receptor, VR1. Using a combination of in silico analysis of expressed sequence tag (EST) databases and conventional molecular cloning, we have isolated a novel vanilloid-like receptor, which we call VRL-2, from human kidney. The translated gene shares 46% and 43% identity with VR1 and VRL-1, respectively, and maps to chromosome 12q23–24.1, a locus associated with bipolar affective disorder. VRL-2 mRNA was most strongly expressed in the trachea, kidney, and salivary gland. An affinity-purified antibody against a peptide incorporating the COOH terminal of the receptor localized VRL-2 immunolabel in the distal tubules of the kidney, the epithelial linings of both trachea and lung airways, serous cells of submucosal glands, and mononuclear cells. Unlike VR1 and VRL-1, VRL-2 was not detected in cell bodies of dorsal root ganglia (DRG) or sensory nerve fibers. However, VRL-2 was found on sympathetic and parasympathetic nerve fibers, such as those innervating the arrector pili smooth muscle in skin, sweat glands, intestine, and blood vessels. At least four vanilloid receptor-like genes exist, the newest member, VRL-2 is found in airway and kidney epithelia and in the autonomic nervous system.
Expression of hypoglossal long-term facilitation differs between substrains of Sprague-Dawley rat
Authors: FULLER D. D. , BAKER T. L. , BEHAN M. , MITCHELL G. S.
Published: December 2017

Long-term facilitation (LTF) is a prolonged, serotonin-dependent augmentation of respiratory motor output following episodic hypoxia. Previous observations lead us to hypothesize that LTF is subject to genetic influences and, as a result, differs between Sprague-Dawley (SD) rats from two vendors, Harlan (H) and Charles River Laboratories/Sasco (CRL/S). Using a blinded experimental design, we recorded integrated phrenic (∫Phr) and hypoglossal neurograms in anesthetized, vagotomized, paralyzed, and ventilated rats. At 60 min following three 5-min hypoxic episodes (PaO2 = 40 ± 1 Torr; 5-min hyperoxic intervals), ∫Phr was elevated from baseline in both SD substrains (i.e., LTF; P < 0.05). Conversely, hypoglossal LTF was present in CRL/S but not H rats ( P < 0.05 between substrains). Serotonin immunoreactivity within the hypoglossal nucleus was not different between H and CRL/S rats. We conclude that the expression of hypoglossal LTF differs between SD rat substrains, indicating a difference in their genetic predisposition to neural plasticity.
Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles
Authors: GRANGE ROBERT W. , ISOTANI EIJI , LAU KIM S. , KAMM KRISTINE E. , HUANG PAUL L. , STULL JAMES T.
Published: December 2017

During skeletal muscle contraction, NO derived from neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers or from endothelial cells (eNOS) may relax vascular smooth muscle contributing to functional hyperemia. To examine the relative importance of these pathways, smooth muscle myosin regulatory light chain (smRLC) phosphorylation was assessed as an index of vascular tone in isolated extensor digitorum longus (EDL) muscles from C57, nNOS−/−, and eNOS−/−mice. The smRLC phosphorylation (in mol phosphate per mol smRLC) in C57 resting muscles (0.12 ± 0.04) was increased 3.7-fold (0.44 ± 0.03) by phenylephrine (PE). Reversal of this increase with electrical stimulation (to 0.19 ± 0.03; P < 0.05) was partially blocked by Nω-nitro-l-arginine (NLA). In nNOS−/−EDL, the PE-induced increase in smRLC phosphorylation (0.10 ± 0.02 to 0.49 ± 0.04) was partially decreased by stimulation (0.25 ± 0.04). In eNOS−/−EDL, the control value for smRLC was increased (0.24 ± 0.04), and PE-induced smRLC phosphorylation (0.36 ± 0.06) was decreased by stimulation even in the presence of NLA (to 0.20 ± 0.02; P < 0.05). These results suggest that in addition to NO-independent mechanisms, NO derived from both nNOS and eNOS plays a role in the integrative vascular response of contracting skeletal muscle.
Long-term telemetric measurement of cardiovascular parameters in awake mice: a physiological genomics tool
Authors: BUTZ GENELLE M. , DAVISSON ROBIN L.
Published: December 2017

The recent miniaturization of implantable radiotelemetric devices offers the possibility of an accurate, reliable, and simple phenotyping tool for long-term, hands-off measurement of blood pressure in unrestrained, untethered mice; however, use has been limited because of high morbidity and mortality in all but larger-than-average mice. Also, because the device was developed for abdominal aorta implantation at the renal artery level, its use has not been feasible in studies where infrarenal blood flow is critical, i.e., in pregnant mice. We provide details of a very successful alternative approach for implanting radiotelemeters in mice, whereby thoracic aortic implantation of the pressure-sensing catheter is combined with subcutaneous placement of the transmitter body along the right flank. We used female C57/BL6 (C57) or BPH/5 mice, a strain derived from the cross of inbred hypertensive and hypotensive mouse strains. We show that this is a reliable procedure for providing high-fidelity mean arterial pressure (MAP) and heart rate (HR) recordings for 50–60 days in mice weighing 22 g on average but as small as 17 g. No morbidity or mortality was observed in either strain using this procedure. Importantly, neither strain fully recovered from anesthesia and surgery, as indicated by a return of normal circadian rhythms, until 5–7 days postsurgery. This was also reflected in significantly elevated baseline MAP and HR levels in both strains during this recovery period. Moreover, strain-related differences in relative increases in MAP during the first 5 days of recovery masked the significant elevation in BPH/5 baseline MAP (vs. C57) observed in fully recovered mice. This suggests that methods must allow at least 5–7 days recovery from surgery to provide accurate cardiovascular (CV) phenotyping in mice. Finally, we show that CV parameters can be monitored continuously before, during, and after pregnancy in mice using this alternative implantation approach. The device did not interfere with conception, gestation, delivery, or postnatal care of pups. These results demonstrate the feasibility of stress-free, long-term monitoring of CV parameters in pregnant or nonpregnant mice of typical size and offer exciting possibilities for application in CV functional genomic research.
Genetic variation in mRNA coding sequences of highly conserved genes
Authors: TEN ASBROEK ANNELOOR L. M. A. , OLSEN JEFFREY , HOUSMAN DAVID , BAAS FRANK , STANTON VINCE
Published: December 2017

The frequency and distribution of genetic polymorphism in the human genome is a question of major importance. We have studied this in highly conserved genes, which encode crucial functions such as DNA replication, mRNA transcription, and translation. Evolutionary comparisons suggest that these genes are under particularly strong selective pressure, and their frequency of nucleotide sequence polymorphism would be expected to represent a minimum estimate for sequence variation throughout the genome. We have analyzed the complete coding sequence and the 3′-untranslated region (3′-UTR) of 22 human genes, most of which have homologs in all cellular organisms and all of which are at least 25% amino acid identical to homologs in yeast. Comparisons with similar studies of less conserved human disease genes indicate that 1) evolutionarily conserved genes are, on average, less polymorphic than disease related genes; 2) the difference in polymorphism levels is attributable almost entirely to reduced levels of variation in protein coding sequences, whereas noncoding sequences have similar levels of polymorphism; and 3) the character of polymorphism, in terms of the spectrum and frequency of mutational changes, is similar.
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate
Authors: INOUE MASASHI , LI XIA , McCAUGHEY STUART A. , BEAUCHAMP GARY K. , BACHMANOV ALEXANDER A.
Published: December 2017

In mice, behavioral acceptance of the bitter compound sucrose octaacetate (SOA) depends on allelic variation of a single gene, Soa. The SW.B6- Soabcongenic mouse strain has the genetic background of an “SOA taster” SWR/J strain and an Soa-containing donor chromosome fragment from an “SOA nontaster” C57BL/6J strain. Using microsatellite markers polymorphic between the two parental strains, we determined that the donor fragment spans 5–10 cM of distal chromosome 6. The SWR/J mice avoided SOA in two-bottle tests with water and had strong responses to SOA in two gustatory nerves, the chorda tympani (CT) and glossopharyngeal (GL). In contrast, the SW.B6- Soab mice were indifferent to SOA in two-bottle tests and had very weak responses to SOA in both of these nerves. The SWR/J and SW.B6- Soab mice did not differ in responses of either nerve to sucrose, NaCl, HCl, or the bitter-tasting stimuli quinine, denatonium, strychnine, 6- n-propylthiouracil, phenylthiocarbamide, and MgSO4. Thus the effect of the Soa genotype on SOA avoidance is mediated by peripheral taste responsiveness to SOA, involving taste receptor cells innervated by both the CT and GL nerves.
Microarray analysis of nicotine-induced changes in gene expression in endothelial cells
Authors: ZHANG SHAOLI , DAY IAN N. M. , YE SHU
Published: December 2017

Cigarette smoking causes vascular endothelial dysfunction and is a major risk factor for cardiovascular diseases. Nicotine, a major constituent of cigarette smoke, has been shown to alter gene expression in endothelial cells; however, the regulatory pathways involved remain to be defined. We hypothesized that there might be distinct pathways that could be identified by systematic transcriptome analysis. Using the cDNA microarray approach, we ascertained the expression of over 4,000 genes in human coronary artery endothelial cells and identified a number of nicotine-modulated genes encoding a protein involving in signal transduction or transcriptional regulation. Among these were phosphatidylinositol phosphate kinase and diacylglycerol kinase, which are regulators of the inositol phospholipid pathway. Changes were also detected for transcription factors cAMP response element binding protein and nuclear factor-κB, of which the activities of both have been previously shown to be altered in nicotine-stimulated cells. The data from this study are relevant to understanding the mechanisms underlying the pathophysiological effect of nicotine and smoking, particularly on endothelial function and pathogenesis of atherosclerosis.
Mapping of microsatellite loci and association of aorta atherosclerosis with LG VI markers in the rabbit
Authors: KORSTANJE R. , GILLISSEN G. F. , KODDE L. P. , DEN BIEMAN M. , LANKHORST A. , VAN ZUTPHEN L. F. M. , VAN LITH H. A.
Published: December 2017

Twenty-three rabbit microsatellites were extracted from the EMBL nucleotide database. Nine of these markers, together with nine earlier published microsatellite markers, were found to be polymorphic between the AX/JU and IIIVO/JU inbred strains. By using an F2intercross we could integrate five markers into the rabbit linkage map. One anonymous microsatellite marker could be assigned to chromosome 1, and one microsatellite marker, located within the metallothionein-1 gene, could be added to linkage group VI (LG VI). Three microsatellite markers (one anonymous, one located within the PMP2 gene, and one located within the FABP6 gene) constitute a new linkage group (LG XI). We also measured the degree of dietary cholesterol-induced aorta atherosclerosis in the F2animals. A significant cosegregation was found between the degree of aorta atherosclerosis and the allelic variation of the biochemical marker Est-2 on LG VI in male rabbits. This association was not found in female rabbits.
Further chromosomal mapping of a blood pressure QTL in Dahl rats on chromosome 2 using congenic strains
Authors: DUTIL JULIE , DENG ALAN Y.
Published: December 2017

Both linkage and use of congenic strains have shown that a region on rat chromosome 2 (Chr 2) of Dahl salt-sensitive rats (S) contained a quantitative trait locus (QTL) for blood pressure (BP). A congenic strain was made by replacing a segment of the S rat by the homologous region of the Milan normotensive (MNS) rat. Since the region was roughly 80 cM in size, a further reduction is required toward the final identification of the QTL. Currently, three congenic substrains were made by replacing smaller sections within the 80 cM. Each strain contains a specific region of MNS in the S genetic background. Two of the three congenic strains shared a segment in common, and both showed a BP-lowering effect. One of the three congenic strains carried a unique segment and had the same BP as S. Deducing the fragment shared in the two substrains having an effect, the BP QTL has to be present in a region of roughly 15 cM. In contrast to BP, heart rates of all the congenic rats were the same as that of the S rat. Thus BP and the heart rate are under the control of independent genetic determinants.
Latrodectismo. Caso clínico y revisión de la literatura
Authors: Corsi Sotelo Oscar Felipe , Del Río Otto Esteban , Peña Riveros Arturo , Acuña Ramírez David
Published: December 2017

El latrodectismo es un cuadro clínico causado por la mordedura de una araña del género Latrodectus spp., ampliamente distribuido en todo Chile continental. Generalmente las mordeduras se asocian a faenas agrícolas. El veneno del género Latrodectus contiene α-latrotoxina, una neurotoxina que actúa a nivel presináptico del sistema nervioso autónomo aumentando la liberación de acetilcolina.El cuadro clínico es inespecífico y hasta en un tercio de los casos ocurren síntomas sistémicos. El diagnóstico es clínico y depende del antecedente de la mordedura por una araña con un cuadro clínico compatible. El pronóstico es favorable: se reporta una letalidad entre 0 y 6%. El manejo es esencialmente sintomático, principalmente analgésico.Presentamos el caso de un hombre de 62 años, proveniente de Santa Cruz, VI región, trabajador en una plantación de trigo. Consulta por dolor torácico asociado a mialgias generalizadas y diaforesis. Por sospecha de latrodectismo, se administra neostigmina con buena respuesta clínica.
Prevalence, Characteristics, and Outcomes of Valvular Heart Disease in Patients With Atrial Fibrillation: Insights From the ORBIT‐AF (Outcomes Registry for Better Informed Treatment for Atrial Fibrillation)
Authors: Thomas Kevin L. , Jackson Larry R. , Shrader Peter , Ansell Jack , Fonarow Gregg C. , Gersh Bernard , Kowey Peter R. , Mahaffey Kenneth W. , Singer Daniel E. , Thomas Laine , Piccini Jonathan P. , Peterson Eric D.
Published: December 2017

Background

The presence of valvular heart disease (
VHD
) may affect the risk of stroke and mortality in patients with atrial fibrillation (
AF
). Community‐based estimates of prevalence and outcomes of specific forms of
VHD
in patients with
AF
are lacking.

Methods and Results

We examined the prevalence of
VHD
, anticoagulation use, mortality, stroke/transient ischemic attack, and bleeding among a community cohort of patients with
AF
. Significant
VHD
was defined as follows: (1) moderate/severe mitral stenosis or mechanical valve; (2) bioprosthetic valve, surgical repair, or balloon valvuloplasty; and (3) moderate/severe aortic regurgitation or stenosis, mitral regurgitation, or tricuspid regurgitation. Proportional hazards models were performed to test the association between
VHD
groups and outcomes. Among 9748 patients with
AF
, 2705 (27.7%) had significant
VHD
. Anticoagulation use was highest among patients with mitral stenosis/mechanical valve (91.8%). Compared with individuals with no significant
VHD
, individuals with aortic regurgitation/aortic stenosis, mitral regurgitation, or tricuspid regurgitation (hazard ratio, 1.23; 95% confidence interval, 1.07–1.42) had the highest risk of death. There were no differences in stroke or transient ischemic attack and major bleeding among individuals with and without significant
VHD
. Patients with
AF
and aortic stenosis had the highest risk of death (hazard ratio, 1.32; 95% confidence interval, 1.08–1.62).

Conclusions

Significant
VHD
is common among patients with
AF
in community practice. In a community cohort of patients with
AF
and
CHA
2
DS
2
‐
VAS
c score ≥2, most were anticoagulated. Individuals with
AF
and moderate‐to‐severe biological
VHD
have more comorbidities and a higher mortality risk; however, stroke and major bleeding are similar among those with and without significant
VHD
.
Contemporary Trends in the Use and Outcomes of Surgical Treatment of Tricuspid Regurgitation
Authors: Alqahtani Fahad , Berzingi Chalak O. , Aljohani Sami , Hijazi Mohamad , Al‐Hallak Ahmad , Alkhouli Mohamad
Published: December 2017

Background

Tricuspid regurgitation (
TR
), if untreated, is associated with an adverse impact on long‐term outcomes. In recent years, there has been an increasing enthusiasm about surgical and transcatheter treatment of patients with severe
TR
. We aim to evaluate the contemporary trends in the use and outcomes of tricuspid valve (TV) surgery for
TR
using the National Inpatient Sample.

Methods and Results

Between January 1, 2003 and December 31, 2014, an estimated 45 477 patients underwent
TV
surgery for
TR
in the United States, of whom 15% had isolated
TV
surgery and 85% had
TV
surgery concomitant with other cardiac surgery. There was a temporal upward trend to treat sicker patients during the study period. Patients who underwent isolated
TV
repair or replacement had a distinctly different clinical risk profile than those patients who underwent
TV
surgery simultaneous with other surgery. Isolated
TV
replacement was associated with high in‐hospital mortality (10.9%) and high rates of permanent pacemaker implantation (34.1%) and acute kidney injury requiring dialysis (5.5%). Similarly, isolated
TV
repair was also associated with high in‐hospital mortality (8.1%) and significant rates of permanent pacemaker implantation (10.9%) and new dialysis (4.4%). Isolated
TV
repair and
TV
replacement were both associated with protracted hospitalizations and substantial cost.

Conclusions

In contemporary practice, surgical treatment of
TR
remains underused and is associated with high operative morbidity and mortality, prolonged hospitalizations, and considerable cost.
Building the Data City of the Future
Authors: Blauer Beth
Published: December 2017

This article examines government’s opportunities and challenges as it relates to the use of data as the key strategy to prepare cities for the future. It examines what is possible when twenty-first-century data management practices are effectively implemented in city government. The article offers examples from real-world implementation and service delivery and provides tactics and strategies that will prime cities for the next transformative era in technology.
STF Project 90
Authors: Kirschner Joseph , Gilbert Beth , Barstow Barbara
Published: December 2017

To keep the ASTA membership apprised of the activities of the School Task Force, the next issues of the journal will present current activities, current concerns, past achievements, and future plans. We hope the ASTA membership will communicate with us—questions, suggestions, and particularly, responses to help achieve the goals of the task force. The Hotline is always open.
1992 National Convention
Authors: Gazda Doris
Published: December 2017

Photos, unless noted, were taken by Richard Millbourn, S.J., honored as the Outstanding Photo journlism Student of 1991 by the Loyola Communications Department. He is currently managing editor of the Loyola Maroon.