bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a medical emergency team follow‐up programme on patients discharged from the medical intensive care unit to the general ward: a single‐centre experience
Authors: Choi Sunhui , Lee Jinmi , Shin Yujung , Lee JuRy , Jung JiYoung , Han Myongja , Son JeongSuk , Jung YounKyung , Lee Soon‐Haeng , Hong Sang‐Bum , Huh Jin‐Won
Published: December 2015

Rationale, aims and objectives

The aim of this study was to analyse the effects of the follow‐up programme implemented by the Asan Medical Center Medical Emergency Team (MET).

Method

A quasi‐experimental pre–post intervention design was used, retrospectively reviewed. The follow‐up programme includes respiratory care, regular visits and communication between the attending doctors and MET nurse for patients discharged from the medical intensive care unit (MICU) to the general ward. This programme has been implemented since February 2013. Outcomes of patients before and at 1 year after the introduction of the programme were retrospectively reviewed.

Results

A total of 1229 patients were enrolled and divided two groups (Before, n = 624; After the introduction of the programme, n = 625). Forty‐six patients (3.7%) were readmitted to the ICU within 72 hours, and there was no significant difference found between the two groups (3.7% versus 3.7%, P = 0.996). Respiratory distress was the most common reason for readmission (67.4%). Cardiac arrest developed in four (0.6%) Before patients; whereas, no cardiac arrest occurred in the After group (0.0%, P = 0.062) cases. A total of 223 patients were discharged to the step‐down units. The SOFA (sequential organ failure assessment) score was significantly higher in the step‐down unit patients than general ward patients (4.9 ± 2.8 versus 6.2 ± 3.1, P = 0.000). In the analysis restricted to patients discharged to step‐down units, unplanned ICU readmissions significantly decreased in the After group (9.3% versus 2.6%, P = 0.034).

Conclusions

The implementation of the MET follow‐up programme did not change the rate of ICU readmission and cardiac arrest; however, its introduction was associated with the reduced ICU readmission of the high‐risk patient populations discharged to the step‐down unit.
Regulation of cyclic AMP response element‐binding protein during neuroglial interactions
Authors: Qin LiMei , Bouchard Ron , Pugazhenthi Subbiah
Published: December 2015

Communications between neurons and glial cells play an important role in regulating homeostasis in the central nervous system. cAMP response element‐binding protein (CREB), a transcription factor, is down‐regulated by neurotoxins, which are known to be released by activated glial cells. To determine the role of CREB signaling in neuroglial interactions, we used three neuroglial coculture models consisting of human neuroprogenitor cell (NPC)‐derived neurons and human microglia. Conditioned medium from the Abeta (Aβ)‐activated microglia decreased CREB phosphorylation and brain‐derived neurotrophic factor promoter activity (47%), whereas the same medium induced (p < 0.01) the promoter of CXCL10, a chemokine, in NPC‐derived neuron‐rich cultures. These effects were reversed when microglia were exposed to Aβ in the presence of minocycline, an anti‐inflammatory agent. The expression of CREB targets, including brain‐derived neurotrophic factor, synapsin‐1, and BIRC3 decreased by 50–65% (p < 0.01) in neurons isolated by laser capture microdissection in close proximity of microglia in neuroglial mixed cultures. Neuronal survival actively modulated microglial behavior when neurons and microglia were cocultured side‐by‐side on semicircles of ACLAR membrane. Neuronal injury, caused by the over‐expression of dominant negative form of CREB, exacerbated Aβ‐mediated microglial activation, whereas CREB over‐expression resulted in decreased microglial activation. Decreases in the levels of neuronal markers were observed when NPCs were differentiated in the presence of proinflammatory cytokines IL‐1β, tumor necrosis factor α, or IL‐6. Instead, the NPCs differentiated into a glial phenotype, and these effects were more pronounced in the presence of tumor necrosis factor α. Our findings suggest that CREB down‐regulation is an important component of defective neuroglial communications in the brain during neuroinflammation.

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Neuroglial interactions were examined using coculture models of human neuroprogenitor cell‐derived neurons and microglia isolated from human fetal brain. A novel coculture model of neurons and microglia cultured on ACLAR membranes in the same dish was also included. In this model, over‐expression of the dominant negative mutant form of the transcription factor CREB in neurons induced neuronal apoptosis and microglial activation whereas expression of the wild type form of CREB resulted in protection of neurons and suppressed microglial activity, thereby suggesting that neurons play an active role in neuroglial interactions.
Development of Real‐time RT‐PCR Assays for Detection and Quantification of Pineapple Mealybug Wilt‐associated Viruses‐1
Authors: Chang Kai‐Wei , Ho Tsing‐Fen , Lin Yu‐Chang , Kuan Cheng‐Ping
Published: December 2015

Pineapple mealybug wilt‐associated virus‐1 (PMWaV‐1) is a major causative agent for pineapple disease. A real‐time, one‐step reverse transcription (RT)–polymerase chain reaction (PCR) assay using TaqMan probes was developed for the detection of PMWaV‐1. Real‐time RT‐PCR, targeting the amplification of heat‐shock protein 70 homolog (hsp70 h) gene fragment, was highly specific and capable of distinguishing PMWaV‐1 from PMWaV‐2 and PMWaV‐3, which are two other common virus species in pineapple plants. Sensitivity assay revealed that real‐time RT‐PCR was approximately 100‐ to 1000‐fold more sensitive than standard one‐step RT‐PCR, when total RNA of infected plant and PMWaV‐1 hsp70 h transcript were used, respectively. This real‐time RT‐PCR assay is rapid, specific and sensitive, which can be used for PMWaV‐1 diagnosis as well as surveillance.
A simple estimation of ideal profile of essential amino acids and metabolizable energy for growing Japanese quail
Authors: Mehri M. , Ghazaghi M. , Bagherzadeh‐Kasmani F. , Rokouei M.
Published: December 2015

An experiment was conducted to determine apparent metabolizable energy (AME) and amino acid requirements of growing Japanese quail based on ideal protein concept using artificial neural network and desirability function (D‐ANN). Seven‐day‐old quail chicks were assigned to nine experimental diets based on central composite design (CCD) containing five levels of AME (2809–3091 kcal/kg) and CP (19–24.8% of diet). The ratio of lysine (Lys) to CP was set at 0.053 among all treatments, and remaining essential amino acids (EAA) were adjusted to Lys. The experimental data of CCD were fitted to D‐ANN model to compute the optimal values for independent variables. The optimal values of inputs including AME, CP, digestible Lys (dLys), methionine (dMet), total sulphur amino acids (dTSAA), threonine (dThr), tryptophan (dTrp), isoleucine (dIle), valine (dVal) and arginine (dArg) for maximizing gain and minimizing feed conversion ratio were estimated at 2865 kcal/kg, 25, 1.32, 0.55, 0.88, 0.84, 0.20, 0.75, 1.04 and 1.45% of diet, respectively, with D (desirability function) = 0.94. The corresponding optimal amounts of amino acids based on total amino acids were 1.42, 0.59, 0.95, 0.90, 0.22, 0.81, 1.12 and 1.56% of diet respectively. The ideal pattern of essential amino acids to Lys was as follows: dMet: dLys = 0.42, dTSAA: dLys = 0.67, dThr: dLys = 0.64, dTrp: dLys = 0.15, dIle: dLys = 0.57, dVal: dLys = 0.79 and dArg: dLys = 1.09. The results of this study showed that amino acid requirements of modern quails might be higher than those reported by NRC.
A pharmacokinetic and residual study of sulfadiazine/trimethoprim in mandarin fish (Siniperca chuatsi) with single‐ and multiple‐dose oral administrations
Authors: Wang W. , Luo L. , Xiao H. , Zhang R. , Deng Y. , Tan A. , Jiang L.
Published: December 2015

A pharmacokinetic and tissue residue study of sulfadiazine combined with trimethoprim (SDZ/TMP = 5/1) was conducted in Siniperca chuatsi after single‐ (120 mg/kg) or multiple‐dose (an initial dose of 120 mg/kg followed by a 5‐day consecutive dose of 60 mg/kg) oral administrations at 28 °C. The absorption half‐life (t1/2α), elimination half‐life (t1/2β), volume of distribution (Vd/F), and the total body clearance (ClB/F) for SDZ and TMP were 4.3 ± 1.7 to 6.3 ± 1.8 h and 2.4 ± 1.0 to 3.9 ± 0.9 h, 25.9 ± 4.5 to 53.0 ± 5.6 h and 11.8 ± 3.5 to 17.1 ± 3.4 h, 2.34 ± 0.78 to 3.67 ± 0.99 L/kg and 0.39 ± 0.01 to 1.33 ± 0.57 L/kg, and 0.03 ± 0.01 to 0.06 ± 0.01 L/kg·h and 0.02 ± 0.01 to 0.05 ± 0.01 L/kg·h, respectively, after the single dose. The elimination half‐life (t1/2β) and mean residue time (MRT) for SDZ and TMP were 68.8 ± 7.8 to 139.8 ± 12.3 h and 34.0 ± 5.5 to 56.1 ± 6.8 h, and 99.3 ± 6.1 to 201.7 ± 11.5 h and 49.1 ± 3.5 to 81.0 ± 5.1 h, respectively, after the multiple‐dose administration. The daily oral SDZ/TMP administration might cause a high tissue concentration and long t1/2β, thereby affecting antibacterial activity. The withdrawal time for this oral SDZ/TMP formulation (according to the accepted guidelines in Europe for maximum residue limits, <0.1 mg/kg of tissues for sulfonamides, and <0.05 mg/kg for TMP) should not be <36 days for fish.
Genome‐wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome
Authors: Mahurkar S. , Polytarchou C. , Iliopoulos D. , Pothoulakis C. , Mayer E. A. , Chang L.
Published: December 2015

Background

Irritable bowel syndrome (IBS) is a stress‐sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well‐studied in IBS. We performed a pilot study investigating genome‐wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits.

Methods

Twenty‐seven IBS patients (59% women; 10 IBS‐diarrhea, 8 IBS‐constipation, 9 IBS‐mixed) and 23 age‐ and sex‐matched HCs were examined. DNA methylation from peripheral blood mononuclear cells (PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non‐GI symptoms were measured using validated questionnaires. Associations were tested using non‐parametric methods.

Key Results

Genome‐wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions (DMPs) (mean difference ≥10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)‐Spondin (SSPO), glutathione‐S‐transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing. Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).

Conclusions & Inferences

This study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies.
An evaluation of new and established methods to determine T‐DNA copy number and homozygosity in transgenic plants.
Authors: Głowacka Katarzyna , Kromdijk Johannes , Leonelli Lauriebeth , Niyogi Krishna K. , Clemente Tom E. , Long Stephen P.
Published: December 2015

Stable transformation of plants is a powerful tool for hypothesis testing. A rapid and reliable evaluation method of the transgenic allele for copy number and homozygosity is vital in analysing these transformations. Here the suitability of Southern blot analysis, thermal asymmetric interlaced (TAIL‐)PCR, quantitative (q)PCR and digital droplet (dd)PCR to estimate T‐DNA copy number, locus complexity and homozygosity were compared in transgenic tobacco. Southern blot analysis and ddPCR on three generations of transgenic offspring with contrasting zygosity and copy number were entirely consistent, whereas TAIL‐PCR often underestimated copy number. qPCR deviated considerably from the Southern blot results and had lower precision and higher variability than ddPCR. Comparison of segregation analyses and ddPCR of T1 progeny from 26 T0 plants showed that at least 19% of the lines carried multiple T‐DNA insertions per locus, which can lead to unstable transgene expression. Segregation analyses failed to detect these multiple copies, presumably because of their close linkage. This shows the importance of routine T‐DNA copy number estimation. Based on our results, ddPCR is the most suitable method, because it is as reliable as Southern blot analysis yet much faster. A protocol for this application of ddPCR to large plant genomes is provided.
Electrophysiological measurement of information flow during visual search
Authors: Cosman Joshua D. , Arita Jason T. , Ianni Julianna D. , Woodman Geoffrey F.
Published: December 2015

The temporal relationship between different stages of cognitive processing is long debated. This debate is ongoing, primarily because it is often difficult to measure the time course of multiple cognitive processes simultaneously. We employed a manipulation that allowed us to isolate ERP components related to perceptual processing, working memory, and response preparation, and then examined the temporal relationship between these components while observers performed a visual search task. We found that, when response speed and accuracy were equally stressed, our index of perceptual processing ended before both the transfer of information into working memory and response preparation began. However, when we stressed speed over accuracy, response preparation began before the completion of perceptual processing or transfer of information into working memory on trials with the fastest reaction times. These findings show that individuals can control the flow of information transmission between stages, either waiting for perceptual processing to be completed before preparing a response or configuring these stages to overlap in time.
RegData: A numerical database on industry‐specific regulations for all United States industries and federal regulations, 1997–2012
Authors: Al‐Ubaydli Omar , McLaughlin Patrick A.
Published: December 2015

We introduce RegData, formerly known as the Industry‐specific Regulatory Constraint Database. RegData annually quantifies federal regulations by industry and regulatory agency for all federal regulations from 1997–2012. The quantification of regulations at the industry level for all industries is without precedent. RegData measures regulation for industries at the two, three, and four‐digit levels of the North American Industry Classification System. We created this database using text analysis to count binding constraints in the wording of regulations, as codified in the Code of Federal Regulations, and to measure the applicability of regulatory text to different industries. We validate our measures of regulation by examining known episodes of regulatory growth and deregulation, as well as by comparing our measures to an existing, cross‐sectional measure of regulation. Researchers can use this database to study the determinants of industry regulations and to study regulations’ effects on a massive array of dependent variables, both across industries and time.
THE ACTION OF PITUITARY EXTRACTS ON INTESTINAL MUSCLE
Authors: Macdonald A. D.
Published: December 2015

Doubt is thrown on the commonly held view that the pituitary gland contains a general stimulant of plain muscle fibres, since for the isolated intestine there is no evidence of action in such concentration nor of such tissue specificity as would justify that belief.

The expenses of this research were defrayed by a grant from the Earl of Moray Fund of the University of Edinburgh.
ON AMPHIBIAN RETINAL CURRENTS
Authors: Jolly W. A.
Published: December 2015

The amphibian isolated eyeball mounted in the usual way in a moist dark chamber furnished with a camera shutter, in an oxygen atmosphere, was stimulated by flashes of light, 40 σ in duration, from equal areas in different regions of the spectrum and the responses recorded by the string galvanometer.

The maximum response in the case of the initial positive deflection B of the electroretinogram was found to lie in the dark‐adapted eye in the neighbourhood of 6350, and the maximum of the secondary elevation C in the neighbourhood of 5360 A.U.

Oscillations on the curve at a slow rate (below 3 per second) are described.

By experimental alterations of the condition of adaptation of the eye it is possible to conclude that the oscillation phenomenon, the B summit, and the dip between the B and C summits are together dependent on one retinal process, the C summit on another. The relations of the preliminary negative deflection A are undecided.
ACETYLCHOLINE ACTION ON THE PULMONARY VASCULAR BED OF THE DOG AND ITS MODIFICATION BY ADRENALINE AND BY ERGOTOXINE
Authors: Foggie P.
Published: December 2015

In isolated lungs of the dog under negative pressure ventilation and perfused at constant volume inflow with defibrinated blood, it has been found that:

1. In non‐nicotinised preparations adrenaline tends to suppress or reverse the rise in pulmonary arterial pressure produced by large doses of acetylcholine.

2. In fully nicotinised preparations, ergotoxine partially or wholly suppresses, or reverses the pulmonary arterial pressure rise produced by large doses of acetylcholine.

I wish to express my thanks to Professor I. de Burgh Daily and to Miss Catherine O. Hebb for helpful advice, and to the Moray Endowment Committee for defraying part of the cost of the research.
OBSERVATIONS RELATING TO CARDIAC HYPERTROPHY IN THE RABBIT: ITS PRODUCTION BY ARTERIO‐VENOUS ANASTOMOSIS
Authors: Drury Alan N. , Wightman K. J. R.
Published: December 2015

The anastomosis of the right carotid artery into the external jugular vein leads within a short time to cardiac hypertrophy and dilatation.

In the auricles the hypertrophy is considerable, the weights being on occasions four times that of the normal auricle. Both auricles share equally in the hypertrophy.

In the ventricles the hypertrophy is not so great, the weights seldom being greater than twice the normal. The right ventricle shows a slightly greater hypertrophy than the left.

The change of pressure in the right auricle upon closing the anastomosis indicates that the input into the heart is increased.

When the anastomosis is closed, the venous pressure in the veins leading to the superior vena cava falls, but rises in those leading to the inferior vena cava.

I wish to express my thanks to Dr. T. D. Day and Miss G. Plaut for their help in the histological study of the hearts.
THE INFLUENCE OF NERVES AND DRUGS ON SECRETION BY THE SMALL INTESTINE AND AN INVESTIGATION OF THE ENZYMES IN INTESTINAL JUICE
Authors: Wright R. D. , Jennings M. A. , Florey H. W. , Lium R.
Published: December 2015

1. Stimulation of the vagus nerves in decerebrate or decapitate cats causes a secretion from the duodenum which comes principally from the Brunner's gland area.

2. No clear evidence has been obtained that vagal stimulation causes secretion from the jejunum or ileum.

3. Cutting the greater splanchnic nerves in the thorax causes secretion from the duodenum, but not from the lower levels of the small intestine.

4. Cutting all the preganglionic sympathetic fibres causes secretion from all the small intestine.

5. The ganglia of the solar plexus exert an inhibitory influence on secretion after section of the preganglionic fibres.

6. The subcutaneous administration of eserine causes secretion from all the small intestine.

7. The concomitant administration of eserine and acetylcholine may cause extreme damage to the intestinal mucosa.

8. Stimulation of the Nervi Erigentes has no influence on the secretion of the small intestine.

9. Histamine has no influence on the secretion of the small intestine.

10. Certain anæsthetics abolish or considerably reduce secretory activity produced by the above methods.

11. Atropine also abolishes it.

12. Confirmation has been obtained of the presence of a secretory hormone acting on the first part of the duodenum in cats. A similar hormone has been shown to be present in pigs. In dogs, innervated fistulæ cease to secrete after 24 hours' starvation and recommence soon after feeding.

13. Duodenal secretion obtained experimentally contains amylase and enterokinase. It does not contain protease or peptidase. It sometimes contains traces of invertase and lipase, but their digestive power is insignificant.

14. The duodenal secretions of five different species of animal and of both denervated and innervated fistulæ have the same digestive properties.

15. In a few experiments no differences were found between the digestive properties of secretion from the duodenum and from other levels of the small intestine.

16. Juices from the same level of the small intestine secreted in response to different stimuli show differences in digestive properties which are due to cells and not to differences in the secreted fluid.

Dr. E. Chain has kindly advised on the conduct of the enzyme investigations. We are glad to acknowledge the technical help of J. Kent and A. Sale. We are indebted to the Government Grants Committee of the Royal Society and to the Nuffield Trust for grants towards expenses. One of us (R. D. W.) was also in receipt of a personal grant from the Nuffield Trust.
ABSORPTION FROM THE JOINT CAVITY
Authors: Adkins E. W. O. , Davies D. V.
Published: December 2015

1. Removal of true solutions, colloidal solutions and fine suspensions from the joint cavity into the subsynovial tissues occurs comparatively rapidly. The rate is proportional to the size of the particle under consideration.

2. The mechanism of this removal is obscure. The experiments in this paper suggest a predominantly physical process, although an active rôle for the synovial cells has not been excluded.

The mechanism of further removal of substances from the subsynovial tissues varies with the size of particle.

(a) Small particles, e.g. true solutions, enter both capillaries and lymphatics with ease. Most are removed in the blood‐stream.

(b) Small colloidal particles, e.g. Congo red, enter both blood capillaries and lymphatics, but with greater difficulty.

(c) Above a certain critical size, probably in the neighbourhood of the globulin molecule, removal by both these routes ceases, with the exception of small quantities which enter lymphatic vessels but are retained in the regional lymphatic glands.

(d) Still larger particles, e.g. 100 m. µ and over, have no route of egress from the subsynovial tissues.

We wish to express our gratitude to Professor H. A. Harris for his stimulating interest. Our thanks are also due to Mr. N. W. Pirie and Mr. R. Markham for their help and advice, and to Mr. J. A. F. Fozzard and Miss R. Ernest for technical assistance.
THE PROBLEM OF THE MOULT IN THE CASTRATED BROWN LEGHORN FOWL
Authors: Greenwood Alan W. , Burns Marca
Published: December 2015

From the observations that have been recorded here on the shedding of feathers from the plumage of fowls it can be concluded that capons do not behave in the same way as normal males and females. They exhibit a tendency, to an appreciable extent, to cast feathers in the winter period, a season of the year when normal birds retain their feathering.

With the onset of spring an intensification of the moulting process sets in and feather loss reaches its maximum in the May‐June period, and this may be taken as the appearance of a true moult in such birds. Females, on the other hand, characteristically enter the moult much later in the year—autumn and early winter—as determined by the cessation of egg production and coincident casting of feathers. In normal males, although no accurate determination of moulting phenomena has so far been made, casual observations over a number of years suggest that they tend to moult at a time intermediate between that shown by castrates and females respectively.

The data discussed lend support to the hypothesis previously put forward by Greenwood that in the fowl reproductive activity inhibits the onset of the moult, and only when this activity ceases, or continues at a lower level, can the casting and renewing of feathers occur.

The investigation failed to provide evidence in support of the conclusion of Benoit [1929] that the capon does not exhibit a true annual moult, although agreement is reached with him on the point that feathers continue to grow and are replaced throughout the whole year. The contention of Pézard [1918] that capons behave as normal males received no confirmation, and the view of Zawadowsky [1922] that castrated males moult twice a year was not borne out, neither by reference to the total number of feathers shed by these birds in the course of a full year nor by the rate of feather shedding. His explanation of the phenomena would only be valid if confusion had arisen with regard to the moult as it affected one particular region only, the neck, an area which, even in normal birds, may exhibit a double moult annually.

A further point of interest which was brought out in this study is the appearance of distinct and characteristic rhythms in feather casting in various regions of the plumage. It has been suggested tentatively that an explanation of this may be found by attributing to the expression of a causal relationship the known sensitivity of certain feather types to thyroid stimulation with the variable character of the moult as it affects certain regions. Among many workers Giacomini [1924] and Zawadowsky [1925] have shown that a generalised moult may be obtained in birds by feeding a heavy single dose of thyroid substance. Moulting of the plumage follows as a direct result of hypophysectomy in birds [Hill, Corkhill and Parkes, 1924], but while the primary factor here may be the removal of the pituitary gland it is significant that the new feathers subsequently growing in indicated by their colour and structure a marked inactivity of the thyroid glands.
REVIEW ARTICLE THE DORSAL HORN OF THE SPINAL CORD
Authors: Brown A. G.
Published: December 2015

Recent advances in techniques, especially the intraneuronal injection of the enzyme horseradish peroxidase, have led to a new era in our understanding of spinal cord structure and function. Input to the cord is precisely organized: the primary afferent fibres from different types of receptors distribute their anatomically specific collaterals to particular parts of the dorsal horn, afferent fibres from the skin lay down a precise somatotopic map, input to the dorsal horn from descending systems is also distributed in a localized way. The neurones of the dorsal horn are varied in both structure and function, even so some quite specific cell types can be identified and the dendritic trees may respect laminar boundaries as determined cytoarchitectonically (although the majority of neurones have dendrites that cut across these boundaries). The output pathways from the dorsal horn are many and various, but again they arise from cells in definite parts of the dorsal horn. The dorsal horn must be considered as a well‐organized, and complex, part of the central nervous system. It cannot be considered as a structural or functional unit but is made up of many interacting parts that process input from the primary afferent fibres, from other levels of the spinal cord and from many descending pathways from the brain.
SENSITIVITY OF TOUCH CORPUSCLES IN VITAMIN A‐DEFICIENT RATS
Authors: Hamann W. C. , Lee N. B.
Published: December 2015

Fifty percent of a population of thirty weanling rats were fed a vitamin A‐deficient diet. The remaining 50% were fed a control diet. In comparison with the control group, the rate of growth started to slow down in the vitamin A‐deficient animals around day 33. Single unit recordings were made from sensory nerve fibres supplying slowly adapting type I cutaneous mechano‐receptors (touch corpuscles). Touch corpuscles were stimulated repetitively with low force mechanical stimuli. Receptors in vitamin A‐deficient animals showed clearly reduced nervous responses compared with receptors in control animals. Most receptors remained responsive even after prolonged repetitive stimulation.
BILIRUBIN EXCRETION FOLLOWING FEEDING OR THE INFUSION OF GLUCOSE IN PONIES
Authors: Canning Jane F.
Published: December 2015

Bile flow, during feeding and fasting, was studied in three ponies in which catheters, maintained in the bile duct over 1–2 months, drained all bile continuously. During experiments bile was returned to the small intestine, via a second catheter, by means of a small pump which also measured bile flow rates. The mean±S.E. of the mean rate of bile flow in fed ponies with an intact enterohepatic circulation of bile salts was 1·33±0·10 ml/kg. h, n = 13; mean±S.E. of the mean concentration of bilirubin in bile was 10·82±0·91 mg/dl, n = 13. The effect on bile flow and bilirubin excretion in bile of a standard feed lasting 2 h was compared with that of an intraduodenal or intravascular 2 h infusion of glucose (50 g/h) before and after a short period of fasting (approximately 2 d). Prior to the fast, bile flow and bilirubin excretion in bile rose by 38·5 and 39·0% respectively following a feed. Glucose infused intravascularly or intraduodenally did not alter bilirubin excretion. Following a two day fast, bilirubin excretion in bile rose 72·7% to 136·5% following feeding and 65·2% to 120·3% when glucose was infused either intravascularly or intraduodenally. A correlation between plasma glucose and bilirubin excretion in bile was observed when the pony was fed or glucose infused intraduodenally. When glucose was infused intravascularly a correlation was only observed in a single experiment in which glucose was infused over 10 h at the lower rate of 24 g/h. It appears that an infusion of glucose can mimic the effects of a feed on bilirubin excretion in bile following a short fast, but not preceding it.
PERMEABILITY OF CANINE SUBMANDIBULAR GLANDS TO BLOOD‐BORNE HORSERADISH PEROXIDASE: EFFECTS OF TRANSIENT DUCTAL OBSTRUCTION DURING SECRETION
Authors: Garrett J. R. , Klinger A. H. , Parsons P. A.
Published: December 2015

Outflow obstruction of the submandibular duct, for a short period during parasympathetic secretion, caused an increase in glandular permeability to horseradish peroxidase. Higher frequencies of parasympathetic nerve stimulation during the obstructive period induced greater increases in the permeability. It is likely that the intraluminal distensions had disrupted some tight junctions and so permitted a greater paracellular leakiness. The damage tended to induce ballooning between striated ductal cells, similar to the appearances observed by Emmelin, Garrett & Gjörstrup (1977a) when sympathetic secretion was accompanied by myoepithelial contraction against a raised outflow pressure.

The present results have been compared with experimental data from other workers and give support to the idea that tight junctions can behave in a sieve‐like manner towards the back‐diffusion of molecules across them.

This work indicates that there is a great need for care in permeability studies. It is possible that some permeability changes observed by other workers may have been the consequences of physical damage between cells. Our findings reinforce the need for morphological assessment of the glands after permeability experiments. In man it is likely that naturally occurring or artificially induced obstructive events may at times create similar permeability changes and these may enable protective substances to pass from the blood to the saliva. This affords possible explanation for such phenomena as the therapeutic value that often accrues from sialography and the efficacy of many different antibiotics in obstructive sialadenitis, despite the fact that most antibiotics do not normally permeate to the saliva.
Factors regulating quiescent stem cells: insights from the intestine and other self‐renewing tissues
Authors: Richmond Camilla A. , Shah Manasvi S. , Carlone Diana L. , Breault David T.
Published: December 2015

Long‐lived and self‐renewing adult stem cells (SCs) are essential for homeostasis in a wide range of tissues and can include both rapidly cycling and quiescent (q)SC populations. Rapidly cycling SCs function principally during normal tissue maintenance and are highly sensitive to stress, whereas qSCs exit from their quiescent state in response to homeostatic imbalance and regenerative pressure. The regulatory mechanisms underlying the quiescent state include factors essential for cell cycle control, stress response and survival pathways, developmental signalling pathways, and post‐transcriptional modulation. Here, we review these regulatory mechanisms citing observations from the intestine and other self‐renewing tissues.

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Regulation of calcium fluxes in rat pancreatic islets: dissimilar effects of glucose and of sodium ion accumulation.
Authors: Herchuelz A , Malaisse W J
Published: December 2015

1. Removal of extracellular K+ provoked a dramatic increase in 43Ca efflux from pancreatic islets prelabelled in the presence of glucose. Such an increase in 45Ca efflux was preceded by a modest and transient reduction in 45Ca efflux. The increase in 45Ca efflux was reduced when the islets were perifused either in the presence of glucose 16 . 7 mM or in the absence of extracellular Ca2+. It was abolished when the islets were perifused in the absence of extracellular Na+. 2. When the islets had been prelabelled in the absence as distinct from presence of glucose, the increase in 45Ca efflux observed on removal of extracellular K+ was of smaller amplitude. It was completely abolished when, in addition, Ca2+ was replaced by Co2+ in the perifusate. 3. Veratridine also provoked a dramatic increase in 45Ca efflux. This increase was slightly reduced when the perifusate contained glucose 5 . 6 mM and markedly reduced in the absence of extracellular Ca2+. 4. Both the removal of extracellular K+ or addition of veratridine had little or no effect on insulin release in the absence of glucose. A significant increase in insulin release was observed, however, in the presence of glucose. The increase in insulin release, due to removal of extracellular K+, was completely abolished at low extracellular Na+ concentration. Such as ionic manipulation failed to affect veratridine‐induced insulin release. Tetrodotoxin failed to inhibit glucose‐stimulated insulin release. 5. It is concluded that Na+ accumulation in islet cells due to either veratridine or removal of extracellular K+ provokes the release of Ca2+ from intracellular stores but fails to reproduce the effect of glucose to reduce 45Ca efflux and to stimulate insulin release.
Appearance of calcium action potentials in crayfish slow muscle fibres under conditions of low intracellular pH.
Authors: Moody W
Published: December 2015

1. The intracellular pH (pHi) of crayfish slow flexor muscle fibres was measured using recessed‐tip pH micro‐electrodes. To study the electrophysiological effects of intracellular acidification, pHi was lowered to values between the normal 7 . 2 and 6 . 3 by removal of external NH4Cl after a 20‐‐30 min exposure. 2. During intracellular acidification, the fibres became capable of generating all‐or‐none Ca action potentials, rather than the normal small graded responses; no change in resting potential or input resistance accompanied this change in excitability. 3. All‐or‐none spikes appeared at pHi = 6 . 4‐‐6 . 5. The spikes disappeared when pHi was increased again following the addition of 10 mM‐bicarbonate to the external solution. CO2‐saturated saline, which decreased pHi to 6 . 4, also caused the appearance of all‐or‐none action potentials. 4. The appearance of action potentials was correlated with a decrease in delayed rectification as pHi fell, as indicated by the response to depolarizing current pulses and by constant‐current I‐‐V plots in solutions in which all Ca ions had been replaced by Co. 5. External tetraethylammonium (TEA), at concentrations which reproduced the pHi = 6 . 4 effects on the I‐‐V relation, also caused the appearance of all‐or‐none action potentials. 6. It is concluded that low pHi in these fibres partially blocks (or causes a depolarizing shift in the voltage dependence of) the voltage‐sensitive outward K current which normally shunts the inward Ca current and prevents the generation of action potentials.
Comparison of electromyogram spectra with force spectra during human elbow tremor.
Authors: Matthews P B , Muir R B
Published: December 2015

1. The tremor that develops when the elbow is flexed against a spring attached at the wrist has been analysed by determining the ‘power’ spectrum of the demodulated surface e.m.g. recorded from two of the active muscles, biceps and brachioradialis. This was compared with the corresponding force spectrum obtained by analysis of the force developed at the fixed end of the spring (normally one of stiffness 2.8 N/mm); this force is directly proportional to the movement at the wrist. 2. When the subject was maintaining a high target force (100‐160 N), with the aid of a visual display, the tremor was large with a large sharply tuned peak in the force spectrum and there was a clear peak at the same frequency in the e.m.g. spectrum. The coherence (gamma) between the force peak and the corresponding e.m.g. peak typically had a value of 0.95 or above, indicating a high degree of correlation. 3. On developing the same target force against a rigid restraint (70 N/mm) the peak in the force spectrum was absent or very much smaller and less sharply tuned. More particularly, the tremor‐related peak seen in the e.m.g. spectrum under compliant conditions was no longer present under rigid conditions. 4. At low target forces (20‐40 N) with compliant loading there was a small peak in the force spectrum but no peak could be detected in the e.m.g. spectrum. With increasing target force the mechanical tremor increased considerably and a peak progressively emerged from above the background level in the e.m.g. spectrum, accompanied by the development of a corresponding peak in the coherence spectrum. Thus the difference in detectability of peaks in the e.m.g. and force spectra might simply result from differences in the background ‘noise’ level of the two types of spectra. 5. Changing the spring stiffness in the range 0.7‐12.5 N/mm altered the frequency of the mechanically recorded tremor by 1.5‐2 Hz and the peak in the e.m.g. spectrum shifted in approximate correspondence. 6. The findings support the view that the tremor seen with compliant loading of the arm is due to the stretch reflex. In addition, this work should help define the conditions under which spectral analysis of the gross e.m.g. is of practical utility.
Motoneurone projection patterns in embryonic chick limbs following partial deletions of the spinal cord.
Authors: Lance‐Jones C , Landmesser L
Published: December 2015

1. Several anterior segments of the lumbosacral spinal cord were deleted in a series of St. 15‐16 chick embryos, which is prior to the birthdate of the motoneurones and to limb bud formation. Deleted segments did not regenerate and therefore some muscles were deprived of their normal source of innervation. 2. The projection pattern of motoneurones in remaining lumbosacral segments was assessed electrophsiologically (St. 30‐36) and by orthograde and retrograde labelling of motoneurones with horseradish peroxidase (St. 24‐36) from the time that axons first enter the limb until after the normal motoneurone cell death period. 3. The projection pattern of remaining segments was not altered by the deletion. At no time did inappropriate segments innervate muscles or regions of the primary muscle mass which had had their enter innervation source removed by the deletion, although they often innervated immediately adjacent regions. 4. The pathways taken by remaining motoneurones both in the plexus and muscle nerves were not different from their normal control pattern. From the time that axons first reached the base of the limb, there was no evidence that they compensated for missing spinal nerves by projecting down inappropriate pathways. 5. With respect to pathway selection, we can conclude that axons are normally not excluded from certain pathways by interactions with other axons, nor do they interact amongst each other in distributing themselves to all available pathways. 6. We can also conclude that once axons enter a muscle or muscle mass, they are not kept within appropriate regions by competition with axons that normally occupy adjacent regions. In summary we can exclude both the process of competition and a timed outgrowth mechanism as playing a major role in the development of specific motor connexions in the chick hind limb. 7. Muscles totally deprived of their innervation by the deletion underwent cleavage, became contractile and appeared to differentiate normally until St. 20. However by St. 35 they had become extremely atrophic. 8. In some cases following the deletion of part of a motoneurone pool, the number of motoneurones per unit of cord in the remaining pool at St. 35‐36 was significantly greater than control values. Since these motoneurones were located in the position (both rostro‐caudal and transverse) of the control motoneurone pool, we conclude that we were able to rescue some of the neurones that would normally have died during the motoneurone cell death period (St. 30‐35).
The effect of vasopressin on renal tubular 22Na efflux in the rat.
Authors: Fejes‐Tóth G , Szénási G
Published: December 2015

1. Paired tracer microinjections of [3H]inulin and 22Na were performed at late proximal and early distal puncture sites in water diuresis and during vasopressin‐induced antidiuresis in anaesthetized rats. Vasopressin caused a sixfold increase in Na and a fourfold increase in K excretion without significant changes in renal haemodynamics. 2. 22Na‐recovery from late proximal injections increased nearly fivefold (from 0.98+/‐ 0.16 to 4.76 +/‐ 0.66%, P less than 0.001). A significant correlation could be detected between changes in sodium excretion and changes in late proximal 22Na recovery. Vasopressin had no significant effect on 22Na recovery from early distal injections. 3. These results suggest that vasopressin inhibits active salt reabsorption within the loop of Henle.
Mechanism of action of vasoactive intestinal polypeptide on myometrial smooth muscle of rabbit and guinea‐pig.
Authors: Bolton T B , Lang R J , Ottesen B
Published: December 2015

1. The action of vasoactive intestinal peptide (VIP) on the electrical and mechanical activity of strips of longitudinal myometrial smooth muscle from rabbits and guinea‐pigs treated with oestradiol was studied in the sucrose‐gap apparatus. 2. In myometrial strips which spontaneously exhibited regular contractions, or which were induced to contract rhythmically to the application of oxytocin, VIP reduced both the frequency and the force of contraction. 3. Contractions were associated with bursts of action potential discharge. In guinea‐pig, the membrane potential reached its most negative value shortly following a burst and a slow decay of negativity followed ("generator potential'). VIP inhibited the decay of this negativity and increased the duration of the period between bursts. In rabbit myometrical strips, electrical discharges occurred less regularly but VIP also had an inhibitory action. The inhibitory action of VIP was not affected by the beta‐adrenoreceptor blocker propranolol, by tetrodotoxin, or by apamin. 4. Using the double sucrose‐gap apparatus, bursts of action potentials and contractions were elicited with depolarizing electrical pulses in the absence of oxytocin. Changes in membrane resistance were also estimated by eliciting hyperpolarizing electrotronic potentials. VIP hyperpolarized the membrane and inhibited contractions as depolarizing pulses now failed to reach threshold for action potential discharge or fewer action potentials were discharged. A small (about 10%) reduction in membrane resistance was freqeuently observed during the hyperpolarization. 5. If a single action potential was elicited in the presence of VIP, the tension generated by the muscle was less than in its absence. 6. In a calcium‐free high‐potassium (126 mM) solution, readmitting calcium produced contraction; VIP inhibited this contraction. Activation of beta‐receptors by means of isoprenaline had a similar effect but unlike isoprenaline the action of VIP was not blocked by propranolol. 7. It is suggested that the primary action of VIP is on the calcium economy of the myometrial smooth muscle cell, possibly to accelerate sequestration and/or extrusion of calcium from the cell. In some way this is associated with inhibition of the generator potential, hyperpolarization, and with a small increase in permeability of the membrane to potassium.
Plasma proteins in fetal sheep brain: blood‐brain barrier and intracerebral distribution.
Authors: Dziegielewska K M , Evans C A , Lorscheider F L , Malinowska D H , Møllgård K , Reynolds M L , Saunders N R
Published: December 2015

1. Plasma proteins have been demonstrated to be present in early fetal sheep brain in amounts which cannot be accounted for by blood contamination. 2. The distribution of alpha‐fetoprotein, albumin, fetuin, alpha 1‐antitrypsin and transferrin has been studied by immunoassay of extracts from brain homogenates and by immunoperoxidase histochemistry of fetal brains between 37 and 125 days gestation (term is 150 days). 3. At 35 days gestation fetuin and albumin were quantitatively the most important proteins in fetal brain, both as estimated by extraction and by immunohistochemistry. Both of these proteins, and also alpha‐fetoprotein and alpha 1‐antitrypsin, declined considerably in amount by 60 days gestation. After 60 days the concentrations of albumin and alpha‐fetoprotein were not significantly different from that due to blood contamination and only occasional cells could be demonstrated by immunohistochemistry. Fetuin and alpha 1‐antitrypsin were present in reduced but significant amounts at least up to 125 days gestation. 4. The immunohistochemical results showed that considerable numbers of immature neurones were stained for some plasma proteins. Fetuin positive cells predominated both in terms of the larger number of cells which stained at 35‐40 days gestation and in the persistence of positive cells up to 125 days gestation. Numerous cells in the neuroependymal layer and in several layers of the developing cortical plate were positive, especially early in gestation. Only a few transferrin or alpha 1‐antitrypsin positive cells were observed. 5. Permeability of the blood‐brain barrier to sheep or human serum albumin (labelled with 125I) was tested in 60 day fetal sheep by intravenous injection and estimation of brain radioactivity at 3 or 6 hr with allowance for blood contamination. Only a very small (but significant) penetration of protein was detected. Unlike penetration of protein into c.s.f. at the same age, it did not reach its natural steady state in brain. 6. It is concluded that the blood‐brain barrier to protein is well developed in the immature fetal sheep but that developing neurones probably acquire certain plasma proteins directly from the c.s.f. when they are differentiating in the neuroependyma. The subsequent distribution of plasma protein positive cells in different brain regions is suggested to be due to the migration of developing neurones for the neuroependyma although the possibility of local synthesis of plasma proteins has not been excluded.