bluuebunny/crossref_metadata_2025 huggingface dataset:
Case of femoral pseudarthrosis due to Scedosporium apiospermum in an immunocompetent patient with successful conservative treatment and review of literature
Authors: Dinh Aurélien , Demay Olivier , Rottman Martin , Gaudot Fabrice , Bougnoux Marie‐Elisabeth , Bouchand Frédérique , Coignard Hélène , Rouzaud Claire , Davido Benjamin , Duran Clara , Nich Christophe
Published: December 2017

Scedosporium apiospermum is a ubiquitous filamentous fungus, commonly found in soil, sewage and polluted waters. It is rarely pathogenic but can cause a broad spectrum of clinical diseases, which can be localised or disseminate to distant organs. The disseminated form of the disease is mostly seen among immunocompromised patients. However, some rare cases of disseminated disease have been reported in immunocompetent individuals. Treatment of these infections is challenging because of their natural resistance to many antifungal agents. Here, we report the case of a 57‐year‐old immunocompetent patient diagnosed with femoral pseudarthrosis due to S. apiospermum, despite having no obvious clinical sign of infection. Previously, the patient had undergone four iterative femoral surgeries following a road traffic accident which occurred 20 years before. During its last surgery for pseudarthrosis, no clinical or biological signs of infection were present. Per operative samples tested positive for S. apiospermum. The patient was successfully treated with oral voriconazole during 6 months with an excellent tolerance. We also provide a review of literature on bone and joint infections due to Scedosporium spp. (S. apiospermum, Scedosporium boydii and Scedosporium aurantiacum), discussing the evolution of their management and outcome which seems to improve since the use of voriconazole.
Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes
Authors: Knöpfel Nicole , Noguera‐Morel Lucero , Hernández‐Martin Angela , García‐Martin Adela , García Marta , Mencía Ángeles , Pedrero Rocío Maseda , de Lucas Raúl , Escámez Maria José , Torrelo Antonio
Published: December 2017

Dystrophic epidermolysis bullosa is a rare blistering condition caused by mutations in the COL7A1 gene. Different clinical variants have been described, with dominant and recessive inheritance, but no consistent findings have been elucidated to establish a genotype–phenotype correlation. We present three unrelated patients with two identical pathogenic compound heterozygous mutations in the COL7A1 gene that developed different clinical forms of dystrophic epidermolysis bullosa—epidermolysis bullosa pruriginosa and mild recessive non‐Hallopeau–Siemens—raising the possibility of other genetic or environmental modifying factors responsible for the phenotype of the disease.
Structural and functional integrity of Sulla carnosa photosynthetic apparatus under iron deficiency conditions
Authors: Elkhouni A. , Rabhi M. , Ivanov A. G. , Krol M. , Zorrig W. , Smaoui A. , Abdelly C. , Huner N. P. A.
Published: December 2017

The abundance of calcareous soils makes bicarbonate‐induced iron (Fe) deficiency a major problem for plant growth and crop yield. Therefore, Fe‐efficient plants may constitute a solution for use on calcareous soils.

We investigated the ability of the forage legume Sulla carnosa (Desf.) to maintain integrity of its photosynthetic apparatus under Fe deficiency conditions. Three treatments were applied: control, direct Fe deficiency and bicarbonate‐induced Fe deficiency.

At harvest, all organs of deficient plants showed severe growth inhibition, the effect being less pronounced under indirect Fe deficiency. Pigment analysis of fully expanded leaves revealed a reduction in concentrations of chlorophyll a, chlorophyll b and carotenoids under Fe deficiency. Electron transport rate, maximum and effective quantum yield of photosystem II (PSII), photochemical quenching (qP), non‐photochemical quenching (qN) as well as P700 activity also decreased significantly in plants exposed to direct Fe deficiency, while qN was not affected. The effects of indirect Fe deficiency on the same parameters were less pronounced in bicarbonate‐treated plants. The relative abundances of thylakoid proteins related to PSI (PsaA, Lhca1, Lhca2) and PSII (PsbA, Lhcb1) were also more affected under direct than indirect Fe deficiency.

We conclude that S. carnosa can maintain the integrity of its photosynthetic apparatus under bicarbonate‐induced Fe deficiency, preventing harmful effects to both photosystems under direct Fe deficiency. This suggests a high capacity of this species not only to take up Fe in the presence of bicarbonate (HCO3−) but also to preferentially translocate absorbed Fe towards leaves and prevent its inactivation.
Semi-Supervised Approaches to Efficient Evaluation of Model Prediction Performance
Authors: Gronsbell Jessica L. , Cai Tianxi
Published: December 2017

In many modern machine learning applications, the outcome is expensive or time consuming to collect whereas the predictor information is easy to obtain. Semi-supervised (SS) learning aims at utilizing large amounts of ‘unlabelled’ data along with small amounts of ‘labelled’ data to improve the efficiency of a classical supervised approach. Though numerous SS learning classification and prediction procedures have been proposed in recent years, no methods currently exist to evaluate the prediction performance of a working regression model. In the context of developing phenotyping algorithms derived from electronic medical records, we present an efficient two-step estimation procedure for evaluating a binary classifier based on various prediction performance measures in the SS setting. In step I, the labelled data are used to obtain a non-parametrically calibrated estimate of the conditional risk function. In step II, SS estimates of the prediction accuracy parameters are constructed based on the estimated conditional risk function and the unlabelled data. We demonstrate that, under mild regularity conditions, the estimators proposed are consistent and asymptotically normal. Importantly, the asymptotic variance of the SS estimators is always smaller than that of the supervised counterparts under correct model specification. We also correct for potential overfitting bias in the SS estimators in finite samples with cross-validation and we develop a perturbation resampling procedure to approximate their distributions. Our proposals are evaluated through extensive simulation studies and illustrated with two real electronic medical record studies aiming to develop phenotyping algorithms for rheumatoid arthritis and multiple sclerosis.
Electoral Institutions, Social Diversity and Fragmentation of Party Systems: A Reassessment
Authors: Flick Witzig Martina , Vatter Adrian
Published: December 2017

The article examines the determinants of party fragmentation based on electoral district data from the Swiss cantons (2010‐2015). In contrast to previous studies, three different dependent variables are taken into account: firstly, the raw number of parties, secondly, the effective number of parties based on vote shares and, thirdly, the effective number of legislative parties. On all three levels, the exclusion magnitude proves to be the most important factor. Compared to this, other institutional variables contribute little explanatory power. However, apparentments are relevant in the first stage of our analysis as they increase the raw number of parties standing for election. In terms of sociological factors, we only find limited relevance. Denominational and linguistic heterogeneity do not have any impact. This can be explained by the fact that linguistic heterogeneity is only weakly pronounced at district level. The finding emphasises the importance of district‐based data for the analysis of party system fragmentation in general.
Action cameras and the Roter interaction analysis system to assess veterinarian‐producer interactions in a dairy setting
Authors: Ritter Caroline , Barkema Herman W , Adams Cindy L
Published: December 2017

Herd health and production management (HH&PM) are critical aspects of production animal veterinary practice; therefore, dairy veterinarians need to effectively deliver these services. However, limited research that can inform veterinary education has been conducted to characterise these farm visits. The aim of the present study was to assess the applicability of action cameras (eg, GoPro cameras) worn by veterinarians to provide on‐farm recordings, and the suitability of these recordings for comprehensive communication analyses. Seven veterinarians each recorded three dairy HH&PM visits. Recordings were analysed using the Roter interaction analysis system (RIAS), which has been used to evaluate medical conversations in human and companion animal contexts, and provided insights regarding the importance of effective clinical communication. However, the RIAS has never been used in a production animal environment. Results of this pilot study indicate that on‐farm recordings were suitable for RIAS coding. Dairy practitioners use a substantial amount of talk allocated to relationship‐building and farmer education but that communication patterns of the same veterinarian vary considerably between farm visits. Consecutive studies using this method will provide observational data for research purposes and promise to aid in the improvement of veterinary education through identification of communication priorities and gaps in dairy advisory discussions.
SHARING SCIENCE: CHARACTERISTICS OF EFFECTIVE SCIENTIST-TEACHER INTERACTIONS
Authors: Pelaez Nancy J. , Gonzalez Barbara L.
Published: December 2017

Despite national guidelines to reform K-12 science education, our students are not learning science any better. Conducted under the auspices of the American Association for the Advancement of Science, a symposium examined several programs where professional scientists interact with classroom teachers to improve science education. Symposium participants described their projects and discussed the factors that contribute or detract from each project’s success. The events of this symposium are critically analyzed. Four themes emerged as issues that affect the successful implementation and continuation of science education reform projects: scientific literacy as a primary goal, personal characteristics and commitment of project partners, curricular change built on social and developmental goals, and the incentive/reward structures in universities and school systems. This review of the emergent themes places the opinions of the symposium participants into the larger context of a growing science education research literature to inform others about synergy between professional scientists and classroom teachers. Our aim is to help others learn about the characteristics of effective partnerships to improve science education.
Use of frog ventricle to examine mechanical and electrical activity of heart.
Authors: Knight V A , Richardson D R , Makoba B
Published: December 2017

This report describes a Langendorff heart preparation, which utilizes frog rather than mammalian hearts to demonstrate both mechanical and electrical events of the cardiac cycle. The preparation is durable in that it can be maintained for several hours while being perfused with room-temperature solutions that are not supplemented with oxygen. Ventricular perfusion is achieved via a fluid-filled reservoir coupled to a truncus arteriosus catheter advanced into the ventricle. By varying the height of the reservoir relative to the heart, changes in ventricular pressure and the rate of ventricular pressure change during systole can be recorded by way of a side port on the catheter tubing. The former is indicative of Starling's law of the heart, whereas the latter is reflective of the contractility. Electrical activity of the heart can be observed by measuring injury potentials via a needle electrode inserted into the ventricle. These are extracellular potentials that reflect ventricular action potentials. In addition, surface electrodes placed on the ventricle can be used to detect an integrated ventricular electrocardiogram. Recording of ventricular pressure simultaneously with at least one of these two electrical recordings allows a direct comparison of electrical and mechanical events of the heart. In summary, the Langendorff frog heart preparation is economical in terms of both financial cost and simplicity; yet it enables a thorough examination of both electrical and mechanical properties of the heart either as a student lab exercise or as a classroom demonstration.
A comparison, for teaching purposes, of three data-acquisition systems for the Macintosh.
Authors: Swanson H D
Published: December 2017

Three commercial products for data acquisition with the Macintosh computer, known by the trade names of LabVIEW, Analog Connection WorkBench, and MacLab were reviewed and compared, on the basis of actual trials, for their suitability in physiological and biological teaching laboratories. MacLab scored highest for ease of use but low for power and versatility. LabVIEW is the most powerful but requires extensive training. Analog Connection WorkBench offers a combination of versatility and ease of use.
Breath hydrogen testing as a physiology laboratory exercise for medical students.
Authors: Montes R G , Gottal R F , Bayless T M , Hendrix T R , Perman J A
Published: December 2017

Breath hydrogen testing (BHT) is a simple and reliable method for identifying impaired carbohydrate absorption. We describe a laboratory exercise in physiology for medical students using BHT as the teaching tool. The students collect fasting samples of expired air from each other using a simple nasal prong technique. They then drink one of several different aqueous carbohydrate solutions. Additional samples of expired air are collected by the students at 90 and 120 min after substrate ingestion and are analyzed by gas chromatography. Between sampling periods, discussions of digestive physiology are provided by the faculty. Students tabulate their BHT results as well as recording any symptoms using a standard scoring system. A total of 460 students have participated. We found that the percentage of students who malabsorbed a given substrate was similar each year. The results obtained in these student exercises closely parallel those reported in the literature. We conclude that BHT is an excellent teaching tool for illustrating carbohydrate digestion and absorption, even when performed by minimally trained subjects.
A simple analogue of lung mechanics.
Authors: Sherman T F
Published: December 2017

A model of the chest and lungs can be easily constructed from a bottle of water, a balloon, a syringe, a rubber stopper, glass and rubber tubing, and clamps. The model is a more exact analogue of the body than the classic apparatus of Hering in two respects: 1) the pleurae and intrapleural fluid are represented by water rather than air, and 2) the subatmospheric "intrapleural" pressure is created by the elasticity of the "lung" (balloon) rather than by a vacuum pump. With this model, students can readily see how the lung is inflated and deflated by movements of the "diaphragm and chest" (syringe plunger) and how intrapleural pressures change as this is accomplished.
The oxygen-carrying flask: a representational transform of the oxygen dissociation curve of hemoglobin.
Authors: Sircar S S
Published: December 2017

The teaching of oxygen transport by hemoglobin is supported by a graphic depiction of the sigmoid O2 dissociation curve of hemoglobin. However, a reconstruction of the same curve into an alternate paradigm, the "O2-carrying flask," affords a visual demonstration of the significance of its sigmoid shape and the implications of its shifts, which should be useful in elucidating certain aspects of O2 transport to undergraduate students of physiology. This article provides a mathematical justification for the flask design.
A hydrostatic model of membrane potential.
Authors: Sircar S S
Published: December 2017

A model based on the elementary principles of hydrostatic and air pressures is proposed for classroom demonstration of some concepts related to membrane potential. The instrument comprises a system of U tubes, pressure gauges, stopcocks, and syringes. Intracellular and extracellular ionic concentrations are represented in the model by the pressure heads of fluid columns in the twin limbs of the U tubes. Membrane channels are simulated by stopcocks interposed at the bends of the U tubes. The Na(+)-K+ pump is represented by the syringes that shunt fluid from one limb of the U tube to the other. The pressure of air trapped above the fluid columns is equivalent to electrical potential.
Effectiveness of an active method in teaching physiology.
Authors: Cağlayan S
Published: December 2017

A three-year study was conducted in search of a better method of teaching physiology that would enhance the critical thinking skills of first-year nursing students in Istanbul University, Florence Nightingale College of Nursing. Three different methods of teaching were used: 1) a straight lecture method, 2) an active method with no previous preparation of students, 3) an active method with previous preparation. Each method was evaluated by end-of-term marks, student feedback in that year, and a follow-up the next year by questionnaires distributed to both students and nursing teachers. The results of end-of-term examinations and Student Acceptance Indexes, as well as comments of nursing teachers, show that the active method of teaching is better than straight lecture and that the active method is most effective when students are familiarized with it beforehand.
Mathematical model of oxygen transport: a teaching aid for normal physiology adaptable to extracorporeal oxygenation circuits.
Authors: Seear M , Anderson B , Hall R , Hui H
Published: December 2017

The ultimate aim of most intensive care therapies is to improve tissue oxygen delivery; consequently, a detailed knowledge of this area of physiology is important to a wide range of Critical Care Staff. We describe a simple mathematical model of oxygen transport that was initially written as a training aid for extracorporeal oxygenation training. The model has subsequently proved useful for explaining the determinants of oxygen transport to a broader audience. It is based on simple linear equations and is easily displayed with a standard computer spreadsheet. Apart from its teaching value, the model can also generate a graph of oxygen saturation vs. inspired oxygen fraction for different degrees of pulmonary shunt. This provides a noninvasive method for determining the magnitude of pulmonary venous admixture and may also prove to have some clinical value.
Myers-Briggs psychological type and achievement in anatomy and physiology.
Authors: Harasym P H , Leong E J , Juschka B B , Lucier G E , Lorscheider F L
Published: December 2017

Results from the Myers-Briggs Type Indicator (MBTI) for 259 nursing students were compared with their achievement on examinations in an undergraduate course in anatomy and physiology. Factor analysis demonstrated that no relationship existed between any of the eight individual personality traits purported to be measured by MBTI (i.e., E, Extrovert; I, Introvert; S, Sensing; N, Intuition; T, Thinking; F, Feeling; J, Judging; P, Perceiving) and examination scores in this course. The analysis also showed that the bipolar scales S vs. N and J vs. P collapsed into a single bipolar scale (S/J vs. N/P). This means that the MBTI is only capable of measuring three bipolar scales of personality traits instead of four scales as currently claimed. Contrary to other findings, results from an analysis of variance revealed no meaningful relationship between course achievement and psychological types.
Modeling blood flow in vessels with changeable caliber for physiology and biophysics courses.
Authors: Kozlova E K , Badicov V I , Chemysh A M , Bogushevich M S
Published: December 2017

A model based on elementary principles of hydrodynamics and mathematics is proposed for classroom research on concepts related to blood flow physiology. This is an analog model of the vascular system in which blood flow is represented by electrical current flowing in a resistance circuit. The model permits analysis of the change in hemodynamics with local stenosis of both large and peripheral vessels.
"The Queen has been dreadfully shocked": aspects of teaching experimental physiology using animals in Britain, 1876-1986.
Authors: Tansey E M
Published: December 2017

Animal experimentation has been subject to legislative control in the United Kingdom since 1876. This paper reviews the impact of that legislation, which was replaced in 1986, on the teaching of practical physiology to undergraduate students. Highlights and case studies are also presented, drawing on Government reports and statistics, published books and papers, and unpublished archival data.
Learning physiology from cardiac surgery patients.
Authors: Nicol S , Narkowicz C
Published: December 2017

A number of pressures have led to a very great reduction or complete abandonment of the use of animals in the teaching of physiology in most medical schools. Often animal experiments have been replaced by computer simulations, but a simulation is only as good as the model or algorithm on which it is based and can never contain the depth of information or unpredictability displayed by real animals or patients. We used a computer-based system to collect cardiovascular data from patients instrumented for cardiac surgery, allowing students to "replay" an operation. These recordings were annotated with notes, diagrams and video clips, and a student workbook was written. The resulting package contained a wealth of physiological data and was perceived by students to be very clinically relevant. The very wealth of information, however, tended to overwhelm students, and so a series of introductory Computer tutorials were written to provide students with the background necessary to cope with the clinical data.
What is the future of problem-based learning in medical education?
Authors: Galey W R
Published: December 2017

Student-centered problem-based learning (PBL) has been implemented as an alternative curriculum by several medical schools in the United States and elsewhere. Recently, attempts to integrate PBL with lecture-based curricula have created "hybrid" curricula with varying amounts of the philosophical underpinnings of student-centered PBL. Greater clinical and research demands on faculty time threaten to diminish the use of PBL in existing curricula, whereas opportunities for expansion of PBL in medical education are being created by community-based and interdisciplinary education programs.
Defining the boundaries of physiological understanding: the benchmarks curriculum model.
Authors: Lemons D E , Griswold J G
Published: December 2017

We set out to develop an anatomy and physiology (A&P) curriculum with a content that was relevant and well rationalized. To do this, we developed a benchmarks curriculum process that helps us to determine what our students need to learn in A&P and then to make sure there is alignment between those learning objectives and what we teach and how we assess our students. Using the benchmarks process, we first set the broad skill and content goals of the course. We then prioritize the topic areas to be covered, allocating the course time accordingly, and declare the learning objectives for each topic. To clarify each learning objective, a set of benchmark statements are written that specify in operational terms what is required to demonstrate mastery. After the benchmarks are written, we assemble the learning activities that help students achieve them and write assessment items to evaluate achievement. We have implemented the curriculum in a relational database that allows us to specify the numerous links that exist between its different elements. In the future, the benchmarks model will be used for ongoing A&P curriculum development with geographically distributed contributors accessing it via the World Wide Web. This mechanism will allow for the continuing evolution of the A&P curriculum.
Experiment demonstrating skeletal muscle biomechanics.
Authors: DiCarlo S E , Sipe E , Layshock J P , Varyani S
Published: December 2017

Many students have limited opportunities to develop scientific expertise. This is caused, in part, by the scarcity of scientific educational materials and the expense of supplies and equipment. To address these concerns, we developed an inexpensive laboratory experience that introduces students to the scientific process. Our objective was to create an interactive experiment that requires minimal equipment. To this end, we created an exercise that examines muscle biomechanics. The students conduct a hands-on experiment as researchers and as subjects by investigating the physiological concepts of muscle biomechanics using only supplies that can be found at any school. Questions are interspersed throughout the text to highlight key principles and challenge student thinking on the important concepts. This exercise not only provides an opportunity for students to interact and discuss the important physiological principles but also provides a window through which students may see a future in science.
Laboratory demonstration of vascular smooth muscle function using rat aortic ring segments.
Authors: Gonzales R J , Carter R W , Kanagy N L
Published: December 2017

This laboratory exercise uses a simple preparation and a straightforward protocol to illustrate many of the basic principles of vascular biology covered in an introductory physiology course. The design of this laboratory allows students to actively participate in an exercise demonstrating the regulation of arterial tone by endothelial and extrinsic factors. In addition, this hands-on laboratory allows students to gather data using well-known basic biomedical research techniques. Specifically, students are introduced to an isolated organ-chamber technique that is widely used to study cellular mechanisms of many tissues including vascular smooth muscle contraction and dilation. On the basis of student evaluations, participation in the experiments and interpreting data reinforce lecture materials on smooth muscle and endothelial cell function and illustrate mechanisms regulating vascular tone. Students come away with a greater understanding of vascular biology, a deeper appreciation of integrative physiology, and an understanding of the process of conducting tissue-chamber experiments.
Who wants to be a physician? An educational tool for reviewing pulmonary physiology.
Authors: Moy J R , Rodenbaugh D W , Collins H L , DiCarlo S E
Published: December 2017

Traditional review sessions are typically focused on instructor-based learning. However, experts in the field of higher education have long recommended teaching modalities that incorporate student-based active-learning strategies. Given this, we developed an educational game in pulmonary physiology for first-year medical students based loosely on the popular television game show Who Wants To Be A Millionaire. The purpose of our game, Who Wants To Be A Physician, was to provide students with an educational tool by which to review material previously presented in class. Our goal in designing this game was to encourage students to be active participants in their own learning process. The Who Wants To Be A Physician game was constructed in the form of a manual consisting of a bank of questions in various areas of pulmonary physiology: basic concepts, pulmonary mechanics, ventilation, pulmonary blood flow, pulmonary gas exchange, gas transport, and control of ventilation. Detailed answers are included in the manual to assist the instructor or player in comprehension of the material. In addition, an evaluation instrument was used to assess the effectiveness of this instructional tool in an academic setting. Specifically, the evaluation instrument addressed five major components, including goals and objectives, participation, content, components and organization, and summary and recommendations. Students responded positively to our game and the concept of active learning. Moreover, we are confident that this educational tool has enhanced the students' learning process and their ability to understand and retain information.
WORKSHOP ON TEACHING PHYSIOLOGY
Authors: Hansen Penelope
Published: December 2017

This is a report of a workshop presented at the Third Congress of the African Association of Physiological Sciences, Pretoria, South Africa, September 7–8, 2000.
INTERNATIONAL WORKSHOP: MODERN APPROACHES TO TEACHING AND LEARNING PHYSIOLOGY
Authors: Sefton Ann
Published: December 2017

The very successful workshop (San Jose, Costa Rica, November 16–18th, 2000) was attended by 70 participants from 19 countries, Central and South America, with some additional expertise from Australia, Canada, Costa Rica, New Zealand, and the USA. The organization was very capably undertaken by staff of la Universidad de Iberoamerica (UNIBE). The local arrangements for the workshop were excellent, and all the participants would wish to record their appreciation to UNIBE for its foresight and for the substantial support that it provided. Discussion was very lively both in the plenary sessions and in the interactive workshops. It was particularly pleasing to see that local students contributed actively. Simultaneous translation (Spanish/English) of the formal presentations and some of the discussion sessions greatly assisted communication and ensured the free exchange of ideas.
AN INQUIRY-BASED LEARNING MODEL FOR AN EXERCISE PHYSIOLOGY LABORATORY COURSE
Authors: Kolkhorst Fred W. , Mason Cheryl L. , DiPasquale Dana M. , Patterson Patricia , Buono Michael J.
Published: December 2017

We developed an inquiry-based learning model to better stimulate undergraduate students’ cognitive development of exercise physiology laboratory concepts. The course core is the two independent research projects that students, working in small groups, complete during the last 9 wk of the semester. Student groups develop their own research question and hypothesis, design the experiment, collect and analyze the data, and report their findings to the rest of the class using presentation software. To help with success of the research projects, students are taken through a series of guided-inquiry laboratory activities during the initial 6 wk of the semester to develop laboratory skills and an understanding of the scientific process. Observations of student behaviors reflected a high level of enthusiasm and engagement in laboratory activities. Surveys, journal entries, and interviews indicated that students felt empowered by having ownership in their projects, which may be the key reason for the success of this model.
Xanthine derivatives without PDE effect stimulate voltage-activated chloride conductance of toad skin
Authors: Nagel Wolfram , Katz Uri
Published: December 2017

The effect of xanthine derivatives on the voltage-activated Cl− conductance ( G Cl) of amphibian skin was analyzed. 3-Isobutyl-1-methylxanthine (IBMX) and the recently synthesized xanthine derivatives 3,7-dimethyl-1-propyl xanthine (X-32) and 3,7-dimethyl-1-isobutyl xanthine (X-33), which lack inhibitory effects on phosphodiesterases in CHO and Calu-3 cells, increased voltage-activated G Cl without effect on baseline conductance at inactivating voltage. Half-maximal stimulation of G Cl occurred at 108 ± 9 μM for X-32 and X-33 after apical or basolateral application. The stimulation of G Cl, which occurs only in the presence of Cl− in the mucosal solution, is caused by a shift of the voltage sensitivity to lower clamp potentials and an increase of the maximally activated level. Furosemide reversed both the shift of sensitivity and the increase in magnitude. These patterns are fundamentally different from those seen after application of membrane-permeant, nonmetabolized analogs of cAMP, and they indicate that the xanthines stimulate G Cl directly. This notion is strengthened by the lack of influence on intracellular cAMP content, which is consistent with the observations in CHO and Calu-3 cells. We propose that the xanthine derivatives increase the voltage sensitivity of a regulative component in the conductive Cl− pathway across amphibian skin.
Separation of active and passive components of short-range stiffness of muscle
Authors: Morgan D. L.
Published: December 2017

The short-range stiffness of smoothly but submaximally contracting isometric soleus muscles of anesthetised cats was measured by applying small fast stretches. The ratio of isometric tension to stiffness was plotted against tension over a wide range of muscle lengths and stimulus rates. The results fitted a straight line well, as predicted from crossbridge theory, showing the stiffness to be a function of tension only, independent of the combination of length and stimulus rate used to generate the tension. The major deviation from this line was attributed to incomplete fusion at low frequencies of stimulation. Values believed to be tendon compliance and crossbridge tension per unit of stiffness were found from the graph, and the tendon compliance correlated with the maximum muscle tension. Shortening the tendon by attaching nearer to the muscle changed the results in a manner consistent with the theory, provided that appropriate precautions were taken against slippage.
Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis
Authors: Blaustein M. P.
Published: December 2017

An attempt is made to elucidate the cellular mechanisms which may account for the well-documented correlation between sodium metabolism and peripheral vascular resistance. As a starting point, the evidence that the Na electrochemical gradient across the vascular smooth muscle cell plasma membrane (sarcolemma) plays an important role in cell calcium regulation is reviewed. Because there is significant resting tension (“tone”) in most resistance vessels, the ionized Ca2+ level ([Ca2+]1) in the smooth muscle fibers in these vessels must be maintained above the contraction threshold. Consequently, the Ca transport system in the sarcolemma, presumably an Na-Ca exchange mechanism, must be set so as to hold [Ca2+]1 at this suprathreshold level. Any change in the Na gradient will then be reflected as a change in [Ca2+]1 and, therefore, in steady vessel wall tension and peripheral resistance. The correlation between Na metabolism and hypertension could then be accounted for if a circulating agent, perhaps the “natriuretic hormone,” affects the Na gradient (across the sarcolemma) and, therefore, [Ca2+]1 and tension.
Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells
Authors: Randles J. , Kimmich G. A.
Published: December 2017

Phloretin and theophylline each exert an immediate inhibitory effect on the Na+-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na+-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na+-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an elevation of intracellular Na+. Other agents which elevate cell Na+ also inhibit Na+-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na+, the inhibitory effect on Na+-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na+-dependent sugar carrier by cellular Na+. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na+-dependent transport systems.
Cellular augmentation of polymorphonuclear leukocyte chemotaxis
Authors: Takeuchi A. , Persellin R. H.
Published: December 2017

The density of neutrophils influences the number of cells that will respond to a chemoattractant, endotoxin-activated serium. When fewer than 3 x 10(5) polymorphonuclear leukocytes (PMN) were placed in the top compartment of a modified Boyden chemotaxis chamber, the cellular response was weak. Complete membrane penetration by activated neutrophils rarely was observed. When this number of PMN was exceeded, however, both the number of cells and the percentage of neutrophils responding to the leukoattractant increased. The density of cells required for effective chemotactic response to occur was such that intimate cell-to-cell contact was suggested. This indicated that PMN exerted a kinetic influence upon one another. Extracts of disrupted PMN induced an otherwise insufficient number of neutrophils to respond to the chemotactic stimulus. The active component was isolated in the cytoplasmic fraction (postcentrifugation, 100,000 x g, 60 min) of PMN, but was not present in other subcellular fractions. This cytoplasmic augmentor of chemotaxis (CACh) increased random mobility of neutrophils, but was not, itself, a chemotactic factor. These findings suggest that PMN cooperate in their response to a leukotactic stimulus.
The generation of electric currents in cardiac fibers by Na/Ca exchange
Authors: Mullins L. J.
Published: December 2017

The presence of a detectable Ca current during the excitation of a cardiac fiber implies that the Ca lost during the resting interval of the duty cycle must also be detectable. Ca outward movement appears to be effected by Na/Ca exchange when more Na enters than Ca leaves per cycle, thus making the mechanism electrogenic. Since Na/Ca exchange can move Ca either inward or outward depending on the direction of the electrochemical gradient for Na, a potential exists where there is no electric current generated by the Na/Ca exchange mechanism, i.e., a reversal potential ER. Cardiac fibers appear to have a reversal potential that is about midway between their resting membrane potential and their plateau. Carrier currents both inward and outward are therefore generated during cardiac action potentials. The implications of the conditions stated above are explored.
Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria
Authors: Winder W. W.
Published: December 2017

Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process.
Potassium permeability of embryonic avian heart cells in tissue culture
Authors: Horres C. R. , Aiton J. F. , Lieberman M.
Published: December 2017

The relationship between the external potassium concentration ([K]o) and membrane permeability has been reexamined using a tissue-cultured preparation of embryonic chick heart cells in which diffusional limitations are minimal. The unidirectional K efflux and electrochemical gradients were determined as a function of [K]o, and the results showed that potassium permeability was constant within the range of 1-20 mM [K]o. Membrane potentials were obtained in K-free solutions and correlated with 42K efflux and intracellular ion content measurements under the same conditions. In contrast to preparations of the intact embryonic chick heart, 42K efflux does not decrease in K-free media. Simulations of tracer measurements at reduced [K]o from naturally occurring cardiac muscle indicate that the experimentally observed decrease in 42K efflux could result from diffusional limitations. This observation, when coupled with the experimental results, suggests that the effect of low [K]o on membrane permeability in homeothermic preparations of cardac muscle should be reevaluated.
Blood:bone disequilibrium. III. Linkage between cell energetics and Ca fluxes
Authors: Neuman W. F. , Neuman M. W. , Myers C. R.
Published: December 2017

Specially designed Ussing chambers were used for the quantitation of fluxes of Ca2+ and lactate ions to and from viable calvaria taken from 2- to 3-day-old rat pups and young adult mice. The latter in vitro support Ca2+ levels comparable to plasma levels in vivo. The effects of various metabolic inhibitors and parathyroid hormone were studied. The results support previous findings that Ca influx into bone is a passive concentration-dependent process not significantly affected by alterations in the energy status of the bone cells. In large measure, the efflux from bone also appears to be passive. However, significant alterations in the calcium levels supported by efflux from bone were observed as acute effects of metabolic inhibitors. Part of the metabolically derived efflux may be attributed to acid production (aerobic glycolysis). However, part must be ascribed to cellular activities not yet defined.
Cow red blood cells. I. Effect of purines, pyrimidines, and nucleosides in bovine red cell glycolysis
Authors: Seider M. J. , Kim H. D.
Published: December 2017

Cow red cells, under in vitro incubation conditions, exhibit a comparatively low glycolytic rate of 0.56 +/- 0.05 micromol/(ml cells.h), with a ratio of lactate formed to glucose consumed of 1.58. It has been found that this low glycolytic rate can be stimulated 50--60% above the basal level in the presence of a variety of purine and pyrimidine compounds including adenosine, inosine, adenine, hypoxanthine, xanthine, and uracil. In contrast, calf red cells, which have a much higher glycolytic rate, display no discernible response to these agents. In attempts to elucidate the mechanism by which this stimulation takes place, both glucose transport and glycolytic enzyme activities were determined in the presence of these stimulators. Glucose influx in cow red cells, measured using the glucose analog 3-O-methyl-glucose, exhibits both a low Km of 117 microM and a Vmax of 0.38 micromol/(ml cells.min), and is unaltered in the presence of adenosine. On the other hand, hexokinase, which in normal hemolysates of cow red cells has an activity of 0.49 +/- 0.03 micromol/(g Hb.min). was found to be stimulated to 0.73 micromol/(g Hb.min) in the presence of adenine. Both pyruvate kinase and phosphofructokinase were unaffected by this compound. These data suggest that certain purines and pyrimidine compounds may exert their stimulatory effect on hexokinase activity, resulting in an augmentation of cow red cell glycolysis.
Cow red blood cells. II. Stimulation of bovine red cell glycolysis by plasma
Authors: Seider M. J. , Kim H. D.
Published: December 2017

Cow red cell glycolysis, which can be stimulated by a variety of purines and pyrimidines, was also found to be elevated by its own plasma. Dialyzed or charcoal-treated plasma could no longer stimulate glycolysis, suggesting that the stimulating factors may be purines or pyrimidines. Determination of purines or pyrimidines in plasma revealed the presence of xanthine (0.31 muM), hypoxanthine (0.60 muM), and adenosine (0.05 muM), as well as unknown compounds. A physiologic level of hypoxanthine, with or without xanthine and adenosine approximating their concentrations in plasma, resulted in the stimulation of cow red cell glycolytic rate by 16% (P less than 0.01). These findings suggest that plasma-borne purines may act on cow red cells in concert with as yet unidentified factors. Moreover, exchanging calf and cow plasmas produced no stimulatory effect on either calf or cow red cell glycolysis, suggesting that a) calf red cells lack some of the cellular components that respond to this stimulator and, b) only cow plasma contains this specific stimulator. In other species, including dog, cat, rabbit, rat, guinea pig, and human, stimulation of glycolysis by plasma was not observed.
Uptake and metabolism of [3H]norepinephrine in uterine nerves of pregnant guinea pig
Authors: Alm P. , Owman C. , Sjoberg N. O. , Thorbert G.
Published: December 2017

Myometrial tissue slices from virgin, pregnant (uni- or bilateral pregnancy), and puerperal animals were incubated in media containing [3H]norepinephrine ([3H]NE), and the neuronal and extraneuronal uptake was estimated. The metabolic fate of [3H]NE was elucidated by the chromatographic separation of [3H]NE, [3H]normetanephrine and 3H-labeled acid metabolites. An early and extensive reduction in both total and neuronal uptakes occurred in the myometrial regions surrounding the fetuses, and at term pregnancy no neuronal [3H]NE uptake at all was found in tissue slices from the fetus-containing horns. Concomitantly, the fraction of unchanged [3H]NE decreased with a corresponding increment in its metabolites. Similar changes, though less extensive, also occurred in the empty horn in unilateral pregnancy. The total amount of neuronal uptake in the cervix seemed unchanged compared to virgin animals. Earlier and present data support the following suggestion that in uterine horns harboring fetuses, an extensive axonal degeneration occurs; in those devoid of fetuses (unilateral pregnancy), the nerve terminals are to a great extent structurally intact, but functionally damaged. Recovery of the pregnancy-induced impairment of the adrenergic nerve plexus is slow and incomplete.
Length-dependent activation of in situ canine skeletal muscle
Authors: Lambert C. R. , Gladden L. B. , Stainsby W. N.
Published: December 2017

This study was designed to assess the contribution of length-dependent activation to the peak isometric twitch tension developed and the maximal rate of tension development (dP/dt) of in situ canine skeletal muscle. Length-developed tension and length-dP/dt relationships were generated for the dog gastrocnemius-plantaris muscle group at three different levels of inotropic state as determined by stimulation frequency. These relationships were then normalized with respect to maximal developed tension and maximal dP/dt and the normalized curves were superimposed for comparison. At progressively shorter muscle lengths the augmentation of tension production by a given increment in inotropic state was greater as measured by either developed tension or dP/dt. Thus, a given change in muscle length produced a greater change in performance in less potentiated muscles. These findings are similar to those from studies of isolated cardiac muscle and illustrate the lack of independence between activational state and muscle length for in situ skeletal muscle.