bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of global changes on the climatic niche of the tick Ixodes ricinus inferred by species distribution modelling
Authors: Porretta Daniele , Mastrantonio Valentina , Amendolia Sara , Gaiarsa Stefano , Epis Sara , Genchi Claudio , Bandi Claudio , Otranto Domenico , Urbanelli Sandra
Published: September 2013

Background

Global climate change can seriously impact on the epidemiological dynamics of vector-borne diseases. In this study we investigated how future climatic changes could affect the climatic niche ofIxodes ricinus(Acari, Ixodida), among the most important vectors of pathogens of medical and veterinary concern in Europe.

Methods

Species Distribution Modelling (SDM) was used to reconstruct the climatic niche ofI. ricinus, and to project it into the future conditions for 2050 and 2080, under two scenarios: a continuous human demographic growth and a severe increase of gas emissions (scenario A2), and a scenario that proposes lower human demographic growth than A2, and a more sustainable gas emissions (scenario B2). Models were reconstructed using the algorithm of “maximum entropy”, as implemented in the softwareMaxent3.3.3e; 4,544 occurrence points and 15 bioclimatic variables were used.

Results

In both scenarios an increase of climatic niche of about two times greater than the current area was predicted as well as a higher climatic suitability under the scenario B2 than A2. Such an increase occurred both in a latitudinal and longitudinal way, including northern Eurasian regions (e.g. Sweden and Russia), that were previously unsuitable for the species.

Conclusions

Our models are congruent with the predictions of range expansion already observed inI. ricinusat a regional scale and provide a qualitative and quantitative assessment of the future climatically suitable areas forI. ricinusat a continental scale. Although the use of SDM at a higher resolution should be integrated by a more refined analysis of further abiotic and biotic data, the results presented here suggest that under future climatic scenarios most of the current distribution area ofI. ricinuscould remain suitable and significantly increase at a continental geographic scale. Therefore disease outbreaks of pathogens transmitted by this tick species could emerge in previous non-endemic geographic areas. Further studies will implement and refine present data toward a better understanding of the risk represented byI. ricinusto human health.
α5β1 integrin induces the expression of noncartilaginous procollagen gene expression in articular chondrocytes cultured in monolayers
Authors: Tanaka Nobuho , Ikeda Yasuko , Yamaguchi Tetsuo , Furukawa Hiroshi , Mitomi Hiroyuki , Nakagawa Takumi , Tohma Shigeto , Fukui Naoshi
Published: September 2013

Introduction

Articular chondrocytes undergo an obvious phenotypic change when cultured in monolayers. During this change, or dedifferentiation, the expression of type I and type III procollagen is induced where normal chondrocytes express little type I and type III procollagen. In this study, we attempted to determine the mechanism(s) for the induction of such procollagen expression in dedifferentiating chondrocytes.

Methods

All experiments were performed using primary-cultured human articular chondrocytes under approval of institutional review boards. Integrin(s) responsible for the induction of type I and type III procollagen expression were specified by RNAi experiments. The signal pathway(s) involved in the induction were determined by specific inhibitors and RNAi experiments. Adenovirus-mediated experiments were performed to identify a small GTPase regulating the activity of integrins in dedifferentiating chondrocytes. The effect of inhibition of integrins on dedifferentiation was investigated by experiments using echistatin, a potent disintegrin. The effect of echistatin was investigated first with monolayer-cultured chondrocytes, and then with pellet-cultured chondrocytes.

Results

In dedifferentiating chondrocytes, α5β1 integrin was found to be involved in the induction of type I and type III procollagen expression. The induction was known to be mediated by v-akt murine thymoma viral oncogene homolog (AKT) signaling. Among the three AKT isoforms, AKT1 seemed to be most involved in the signaling. Elated RAS viral (r-ras) oncogene homolog (RRAS) was considered to regulate the progression of dedifferentiation by modulating the affinity and avidity of α5β1 integrin to ligands. Echistatin inhibited dedifferentiation of monolayer-cultured chondrocytes. Furthermore, the matrix formed by pellet-cultured chondrocytes more closely resembled that of normal cartilage compared with the controls.

Conclusions

The result of this study has shown, for the first time, that α5β1 integrin may be responsible for the induction of non-cartilaginous collagen expression in chondrocytes undergoing dedifferentiation. Again, this study has shown that the inhibition of ligand ligation to integrins may be an effective strategy to inhibit phenotypic change of cultured chondrocytes, and to improve the quality of matrix synthesized by primary cultured chondrocytes.
Skeletal muscle predicts ventilator-free days, ICU-free days, and mortality in elderly ICU patients
Authors: Moisey Lesley L , Mourtzakis Marina , Cotton Bryan A , Premji Tahira , Heyland Daren K , Wade Charles E , Bulger Eileen , Kozar Rosemary A ,   for the Nutrition and Rehabilitation Investigators Consortium (NUTRIC)
Published: September 2013

Introduction

As the population ages, the number of injured elderly is increasing. We sought to determine if low skeletal muscle mass adversely affected outcome in elderly patients following trauma.

Methods

Patients ≥ 65 years of age with an admission abdominal computed tomography scan and requiring intensive care unit (ICU) stay at a Level I trauma center in 2009–2010 were reviewed. Muscle cross-sectional area at the 3rd lumbar vertebra was quantified and muscle index, a normalized measure of muscle mass, was calculated and related to clinical parameters including ventilator-free days, ICU-free days, and mortality. Using previously established sex-specific, muscle index cut-points, patients were then categorized as sarcopenic or non-sarcopenic and differences in clinical outcomes between these two groups were also compared. We also examined muscle index as a continuous variable relative to the same clinical outcomes.

Results

There were 149 severely injured elderly patients (median age 79 years) enrolled in this study of which 71% were sarcopenic. Of the patients who were sarcopenic, 9% were underweight, 44% normal weight, and 47% overweight/obese as per body mass index (BMI) classifications. The overall mortality rate was 27% and univariate analysis demonstrated higher mortality among those who were sarcopenic (32% vs. 14%, P = 0.018). After controlling for age, sex, and injury severity, multiple logistic regression demonstrated that increased muscle index was significantly associated with decreased mortality (OR per unit muscle index = 0.93, 95% CI: 0.875-0.997, P = 0.025). In addition, multivariate linear regression showed that sarcopenia, but not muscle index, was associated with decreased ventilator-free (P = 0.004) and ICU-free days (P = 0.002). Neither BMI, serum albumin nor total adipose tissue on admission were indicative of survival, ventilator-free or ICU-free days.

Conclusions

Sarcopenia is highly prevalent in the elderly population with traumatic injuries. Traditional measures of nutritional assessment, such as BMI and serum albumin, do not accurately predict outcome in the injured elderly. Sarcopenia, however, represents a potential new predictor for mortality, discharge disposition, and ICU utilization. Measurement of muscularity allows for the early identification of at-risk patients who may benefit from aggressive and multidisciplinary nutritional and rehabilitative strategies.
Safety Monitoring of Railway Tunnel Construction Using FBG Sensing Technology
Authors: Ye X.W. , Ni Y.Q. , Yin J.H.
Published: September 2013

In comparison with above-ground structures, the investigation of underground space structures still faces great challenges because of the extremely complicated constitutive relationships of the soils or rocks. Implementation of structural health monitoring (SHM) systems on the underground structures such as tunnels commencing from the construction stage may be of help in understanding their operational behaviors and long-term trends. This paper explores the application of the fiber Bragg grating (FBG) sensing technology for safety monitoring during railway tunnel construction. An FBG-based temperature monitoring system is first developed for real-time temperature measurement of the frozen soils during freezing construction of a metro-tunnel cross-passage. Through in-situ deployment of FBG-based liquid-level sensors, the subgrade settlement of a segment of a high-speed rail line is then monitored in an automatic manner during construction of an undercrossing tunnel. The field results indicate that the FBG sensors are robust and reliable in perceiving temperature and strain variations even in harsh environments.
Management Development in Small Firms: Understanding the Learning Dilemma for Small Business Managers
Authors: Tell Joakim , Gabrielsson Jonas
Published: September 2013

In this study, we link discussions about management development in small firms to the work environment of small business managers. In particular, our aim is to examine management development as an experiential process carried out in daily managerial practice. Using structured observations of managerial work, we found that small business managers operate in work environments with rich opportunities for learning. However, we also found that various and unexpected interruptions and problems typically fragment their workdays. In addition, such managers lack peer support and guidance and have few external interactions and little internal communication. As a result, small business managers find themselves in a learning dilemma that, in the long run, may limit their creativity and innovation. Based on these empirical findings, we draw conclusions about support for work-based management development in small firms.
Applying Principles of Innovation to Curriculum Revision
Authors: O'Keefe Robert
Published: September 2013

This paper expresses the author's point of view that principles and concepts traditionally identified with Industrial Innovation can be productively applied to activities that are related to the creation of new courses and to the revisions of existing courses that comprise academic programs. The author outlines a proven market based method for successful curricular revision. The approach outlined is derived directly from the traditional stages associated with the innovation process. In support of the viewpoint expressed in this paper, the author makes reference to several classic articles and includes relevant references to his own published work.
Cyrface: An interface from Cytoscape to R that provides a user interface to R packages
Authors: Gonçalves Emanuel , Saez-Rodriguez Julio
Published: September 2013

There is an increasing number of software packages to analyse biological experimental data in theRenvironment. In particular,Bioconductor, a repository of curated R packages, is one of the most comprehensive resources for bioinformatics and biostatistics. The use of these packages is increasing, but it requires a basic understanding of the R language, as well as the syntax of the specific package used. The availability of user graphical interfaces for these packages would decrease the learning curve and broaden their application.   Here, we present aCytoscapeplug-in termedCyrfacethat allowsCytoscapeplug-ins to connect to any function and package developed inR.Cyrfacecan be used to runRpackages from within theCytoscapeenvironment making use of a graphical user interface. Moreover, it links the R packages with the capabilities of Cytoscape and its plug-ins, in particular network visualization and analysis. Cyrface’s utility has been demonstrated for two Bioconductor packages (CellNOptR and DrugVsDisease), and here we further illustrate its usage by implementing a workflow of data analysis and visualization. Download links, installation instructions and user guides can be accessed from theCyrfacehomepage (http://www.ebi.ac.uk/saezrodriguez/cyrface/).
Staging Authenticity
Authors: Leistra-Jones Karen
Published: September 2013

Joseph Joachim, Johannes Brahms, and other members of their circle were important figures in the ascendancy of the Werktreue paradigm of performance in the second half of the nineteenth century. This article explores the ways in which their approach to Werktreue intersected with a broader ideal of “authentic” subjectivity. An authentic performer, according to this ideal, would be true to himself or herself, absorbed in the music, oblivious of the audience, and restrained in gestures and overall expressivity. I examine how these musicians performed authenticity in different types of self-representation, including autobiographical writings, portraits, and musical performances. Furthermore, I explore the connection between the subjectivity modeled in their performances and the aesthetic ideology of nonprogrammatic instrumental music. Concerns about authenticity played an important role in the struggle over the ownership of the Austro-German musical tradition; debates about which performers were “authentic” often hinged on the question of who could claim the cultural and spiritual aptitude necessary to inhabit the thoughts of master composers. In this context, the performative strategies associated with authenticity also evoked social codes associated with gender, nationality, and race during a period in which participation in Germanic culture was being conceived of in increasingly exclusive terms.
Spreading the Gospel of Singbewegung
Authors: Berger Anna Maria Busse
Published: September 2013

From 1931 to 1939, Franz Rietzsch, a German missionary, worked with the Nyakyusa in Tanganyika. He differed from most other missionaries in two respects: first, he was invested in the German Singbewegung, a movement that played a central role in the revival of early-music performance and scholarship; and second, he had a background in comparative musicology, which shared the ideals of the early-music movement by emphasizing authenticity and musical universals. Rietzsch observed that the tonal system of the Wanyakyusa is derived from overtones over one fundamental and set out to write music for the service in what he called “African style.” Yet even though his settings use the pentatonic system of the Nyakyusa, they sound as if they were written in the early fifteenth century. Rietzsch's story sits at the intersection of three seemingly distinct but surprisingly connected worlds in the 1920s and 1930s: that of the founders of comparative musicology; that of interwar Protestant missionaries; and that of the scholars and musicians working on early Euro-pean music. All three searched for the origins of music in an authentic mode and feared that hybrid forms of music (African-European or old music played in too modern a way) would be inauthentic.
The islet ghrelin cell
Authors: Wierup Nils , Sundler Frank , Heller R Scott
Published: September 2013

The islets of Langerhans are key regulators of glucose homeostasis and have been known as a structure for almost one and a half centuries. During the twentieth century several different cell types were described in the islets of different species and at different developmental stages. Six cell types with identified hormonal product have been described so far by the use of histochemical staining methods, transmission electron microscopy, and immunohistochemistry. Thus, glucagon-producing α-cells, insulin-producing β-cells, somatostatin-producing δ-cells, pancreatic polypeptide-producing PP-cells, serotonin-producing enterochromaffin-cells, and gastrin-producing G-cells have all been found in the mammalian pancreas at least at some developmental stage. Species differences are at hand and age-related differences are also to be considered. Eleven years ago a novel cell type, the ghrelin cell, was discovered in the human islets. Subsequent studies have shown the presence of islet ghrelin cells in several animals, including mouse, rat, gerbils, and fish. The developmental regulation of ghrelin cells in the islets of mice has gained a lot of interest and several studies have added important pieces to the puzzle of molecular mechanisms and the genetic regulation that lead to differentiation into mature ghrelin cells. A body of evidence has shown that ghrelin is an insulinostatic hormone, and the potential for blockade of ghrelin signalling as a therapeutic avenue for type 2 diabetes is intriguing. Furthermore, ghrelin-expressing pancreatic tumours have been reported and ghrelin needs to be taken into account when diagnosing pancreatic tumours. In this review article, we summarise the knowledge about islet ghrelin cells obtained so far.
Molecular Phylogeography of a Human Autosomal Skin Color Locus Under Natural Selection
Authors: Canfield Victor A , Berg Arthur , Peckins Steven , Wentzel Steven M , Ang Khai Chung , Oppenheimer Stephen , Cheng Keith C
Published: September 2013

Divergent natural selection caused by differences in solar exposure has resulted in distinctive variations in skin color between human populations. The derived light skin color allele of the SLC24A5 gene, A111T, predominates in populations of Western Eurasian ancestry. To gain insight into when and where this mutation arose, we defined common haplotypes in the genomic region around SLC24A5 across diverse human populations and deduced phylogenetic relationships between them. Virtually all chromosomes carrying the A111T allele share a single 78-kb haplotype that we call C11, indicating that all instances of this mutation in human populations share a common origin. The C11 haplotype was most likely created by a crossover between two haplotypes, followed by the A111T mutation. The two parental precursor haplotypes are found from East Asia to the Americas but are nearly absent in Africa. The distributions of C11 and its parental haplotypes make it most likely that these two last steps occurred between the Middle East and the Indian subcontinent, with the A111T mutation occurring after the split between the ancestors of Europeans and East Asians.
Dissecting Genome-Wide Association Signals for Loss-of-Function Phenotypes in Sorghum Flavonoid Pigmentation Traits
Authors: Morris Geoffrey P , Rhodes Davina H , Brenton Zachary , Ramu Punna , Thayil Vinayan Madhumal , Deshpande Santosh , Hash C Thomas , Acharya Charlotte , Mitchell Sharon E , Buckler Edward S , Yu Jianming , Kresovich Stephen
Published: September 2013

Genome-wide association studies are a powerful method to dissect the genetic basis of traits, although in practice the effects of complex genetic architecture and population structure remain poorly understood. To compare mapping strategies we dissected the genetic control of flavonoid pigmentation traits in the cereal grass sorghum by using high-resolution genotyping-by-sequencing single-nucleotide polymorphism markers. Studying the grain tannin trait, we find that general linear models (GLMs) are not able to precisely map tan1-a, a known loss-of-function allele of the Tannin1 gene, with either a small panel (n = 142) or large association panel (n = 336), and that indirect associations limit the mapping of the Tannin1 locus to Mb-resolution. A GLM that accounts for population structure (Q) or standard mixed linear model that accounts for kinship (K) can identify tan1-a, whereas a compressed mixed linear model performs worse than the naive GLM. Interestingly, a simple loss-of-function genome scan, for genotype-phenotype covariation only in the putative loss-of-function allele, is able to precisely identify the Tannin1 gene without considering relatedness. We also find that the tan1-a allele can be mapped with gene resolution in a biparental recombinant inbred line family (n = 263) using genotyping-by-sequencing markers but lower precision in the mapping of vegetative pigmentation traits suggest that consistent gene-level resolution will likely require larger families or multiple recombinant inbred lines. These findings highlight that complex association signals can emerge from even the simplest traits given epistasis and structured alleles, but that gene-resolution mapping of these traits is possible with high marker density and appropriate models.
Hydromechanical behaviour of a volcanic ash
Authors: FERRARI A. , EICHENBERGER J. , LALOUI L.
Published: September 2013

This paper presents experimental analysis and numerical modelling aimed at improved understanding and prediction of the hydromechanical behaviour of volcanic ash at various states of saturation. Results from a comprehensive experimental programme are presented in order to characterise the response of the material in terms of matric suction and confining stress changes. The evolution of the yield stress at different suction levels has been quantified. The volumetric response with suction variations allowed the analysis of the collapse-upon-wetting behaviour. Water retention and permeability are also addressed. Tests results are used to calibrate a constitutive model based on the effective stress concept extended to partially saturated conditions. The ability of the model to reproduce and anticipate the ash behaviour is tested with an articulated stress path.
Habitat connectivity shapes urban arthropod communities: the key role of green roofs
Authors: Braaker S. , Ghazoul J. , Obrist M. K. , Moretti M.
Published: September 2013

The installation of green roofs, defined here as rooftops with a shallow soil cover and extensive vegetation, has been proposed as a possible measure to mitigate the loss of green space caused by the steady growth of cities. However, the effectiveness of green roofs in supporting arthropod communities, and the extent to which they facilitate connectivity of these communities within the urban environment is currently largely unknown. We investigated the variation of species community composition (β diversity) of four arthropod groups with contrasting mobility (Carabidae, Araneae, Curculionidae, and Apidae) on 40 green roofs and 40 extensively managed green sites on the ground in the city of Zurich, Switzerland. With redundancy analysis and variation partitioning, we (1) disentangled the relative importance of local environmental conditions, the surrounding land cover composition, and habitat connectivity on species community composition, (2) searched for specific spatial scales of habitat connectivity for the different arthropod groups, and (3) discussed the ecological and functional value of green roofs in cities. Our study revealed that on green roofs community composition of high‐mobility arthropod groups (bees and weevils) were mainly shaped by habitat connectivity, while low‐mobility arthropod groups (carabids and spiders) were more influenced by local environmental conditions. A similar but less pronounced pattern was found for ground communities. The high importance of habitat connectivity in shaping high‐mobility species community composition indicates that these green roof communities are substantially connected by the frequent exchange of individuals among surrounding green roofs. On the other hand, low‐mobility species communities on green roofs are more likely connected to ground sites than to other green roofs. The integration of green roofs in urban spatial planning strategies has great potential to enable higher connectivity among green spaces, so that eventually even communities of low‐mobility species become connected. Furthermore, improving the design of green roofs (composition and configuration of vegetation and soil types) could enhance the ecological value, particularly for low‐mobility species.
Exercise Program-Induced Mood Improvement and Improved Eating in Severely Obese Adults
Authors: Annesi James J. , Tennant Gisèle A.
Published: September 2013

Background:

Using a practical setting, this study aimed to test exercise and nutrition interventions' effects on negative mood, self-regulation, and self-efficacy to control eating; and to assess the ability of mood change to predict changes in eating behavior, while accounting for changes in self-regulation and self-efficacy.

Methods:

Severely obese adults participated in a cognitive-behavioral exercise support treatment paired with either nutrition education ( n = 140) or cognitive-behavioral methods applied to improved eating ( n = 146). They were assessed on measures of overall negative mood, self-regulatory skill usage, self-efficacy to control eating when negative moods are present, and fruit and vegetable consumption at baseline and Week 26.

Results:

Significant improvements in each psychosocial variable and fruit and vegetable intake were found. Improved mood significantly predicted fruit and vegetable consumption change, R2 = 0.12, P < 0.001. Entry of changes in self-regulation and self-efficacy into the multiple regression equation significantly strengthened the variance explained, R2 = 0.18, P < 0.001.

Discussion:

Findings suggest that exercise-induced improvements in mood improve eating behaviors, with increases in self-regulation and self-efficacy adding to this effect.
Researching with Young Children: Considering Issues of Ethics and Engagement
Authors: MacDonald Amy
Published: September 2013

When conducting research with young children it is important to consider not only the data which have been produced as a result of the research, but also the research process itself. This article presents a parallel analysis of data which has been articulated elsewhere from a three-year study of children's understandings about measurement. This article considers the overarching methodological issues which arose from the study and implications for the ways in which the data should be viewed. Specific points for discussion which emerged during this research are: ethical considerations; notions of shared perspectives, recurring images, and socially-constructed images; the perceived ‘reality’ of the events depicted; differences between children's perspectives and adults' perspectives; the risk of intervention; and the competence of children in the research process.
Recognising the Ethical Implications of the Use of Photography in Early Childhood Educational Settings
Authors: Quinn Suzanne M. Flannery , Manning John P.
Published: September 2013

This article examines the use of photography within the profession of early childhood education (including teacher education) and provides a post-structural critique of its use in light of ethical implications, particularly with regard to power relations between the various stakeholders, including children, their families, teachers, schools, school administrations, and state (or national) departments of education. This examination takes a critical stance with regard to photography by recognising the importance of creating a space for considering the benefits and costs of practices with regard to values, such as human agency, respect, dignity, democracy, inclusivity, honesty, and duty. These values form the basis of the critique in which we present a discussion of key questions with regard to specific ethical dilemmas in practice. Suggestions for democratic dialogue amongst stakeholders are provided.
Confirmation of Impaired Early Insulin Response to Glycemic Stimulus in Nonobese Mild Diabetics
Authors: Fujita Yoshikuni , Herron Arthur L , Seltzer Holbrooke S
Published: September 2013

The initial insulin responses of nonobese normal subjects and mild diabetics were analyzed during and after five-minute and twominute infusions of 0.5 gm. per kilogram of glucose by vein. It was found that the two-minute injection elicited faster and significantly higher absolute hormonal output in both normals and diabetics, and that on both tests the normal subjects secreted significantly more insulin than did the mild diabetics. Comparison of respective “insulinogenic indexes” (net insulin output per unit of glycemic stimulus) showed that the corrected early insulin responses were in fact the same on both the five-minute and two-minute tests in normal subjects, and also in mild diabetics; but that the corrected insulin output was still twice as great in control subjects on both tests. It was also found that obese mild diabetics had significantly greater absolute insulin responses to both the five-minute and two-minute glucose injections than did their nonobese counterparts. These findings reconfirm that the earliest clinically recognizable state of diabetes mellitus is characterized by an impaired initial insulin secretory response to glycemic stimulus. They also indicate that valid interpretations of the influence of mild diabetes per se on the early insulin response can only be drawn from data obtained in nonobese individuals.
Effect of Intracisternal Insulin on Plasma Glucose and Insulin in the Dog
Authors: Woods Stephen C , Porte Daniel
Published: September 2013

The intracisternal administration of insulin (0.2 U./kg.) to anesthetized dogs resulted in an increase of arterial immunoreactive insulin and a decrease of plasma glucose relative to a control injection. The arterial responses were significantly attenuated when the insulin was administered to the cisternum of subdiaphragmatically vagotomized dogs. When cerebrospinal fluid glucose was lowered by injecting pneumococcal neuraminidase intracisternally, no peripheral hyperinsulinemia resulted, indicating that increased spinal fluid insulin and its consequent increase of glucose uptake, rather than decreased spinal fluid glucose, is necessary to elicit the vagally mediated insulin secretion and hypoglycemia. It is hypothesized that increased spinal fluid insulin causes an increased glucose uptake of some glucoregulatory area of the brain and that the elicited reflex is vagally mediated pancreatic insulin secretion.
Effect of Adrenergic Agents on Postgastrectomy Hypoglycemia
Authors: Leichter Steven B , Permutt M Alan
Published: September 2013

Reactive hypoglycemia was documented in ten postgastrectomy patients by a control oral glucose tolerance test (OGTT). Nine patients experienced nausea, flushing, and fatigue during the first hour of the test. Neuroglycopenic or adrenergic symptoms of hypoglycemia occurred in eight patients two to five hours after oral glucose. The oral administration of phenylephrine elixir, 15 mg., thirty minutes before a repeat OGTT, significantly raised thelowest plasma glucose from 37.5 ± 2.8 mg./dl. to 45.2 ± 3.8 mg./dl. (p < 0.05) but did not affect the occurrence of either the early or the late symptoms. In contrast, propranolol, 10 mg., raised the lowest plasma glucose from 37.5 ± 2.8 mg./dl. to 57 ± 5.2 mg./dl. (p < 0.02) and prevented the occurrence of early and late symptoms. Neither peak nor total plasma insulin levels were affected by either drug. The rate of glucose utilization, as determined by intravenous glucose tolerance tests, did not significantly change after the oral administration of either drug. It is concluded that propranolol ameliorated the symptoms and chemical hypoglycemia after oral glucose and merits more detailed study as a long-term therapy for this disorder.
Comparison of Alpha- and Beta-Cell Secretory Responses in Islets Isolated with Collagenase and in the Isolated Perfused Pancreas of Rats
Authors: Norfleet William T , Pagliara Anthony S , Haymond Morey W , Matschinsky Franz
Published: September 2013

The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system.

The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic.
Gastric Inhibitory Polypeptide: Its Physiologic Release and Insulinotropic Action in the Dog
Authors: Pederson Raymond A , Schubert Harold E , Brown John C
Published: September 2013

Studies were carried out in conscious dogs in which the immunoreactive gastric inhibitory polypeptide (IR-GIP) response to graded doses of oral fat (triglycerides) and glucose was investigated. The IR-GIP response to the doses of triglycerides used was greater and more prolonged than the response to the glucose loads employed. In addition, the relative insulinotropic potencies of exogenous porcine GIP and IR-GIP released by fat as against those released by oral glucose were assessed. When glucose was administered by the oral route, the immunoreactive insulin (IRI) response was magnified above the IRI response to a comparable intravenous glucose load. The serum IRI response to oral glucose was accompanied by a concomitant rise in serum IR-GIP levels, suggesting a causal relationship. IR-GIP released by oral fat was shown to augment the IRI response to an intravenous glucose load, resulting in an improvement of glucose tolerance. Fat-released IR-GIP augmented IRI levels to a lessor degree than either oral glucose or an infusion of porcine GIP.
Capillaries of South African Diabetics: IV. Relation to Retinopathy
Authors: Yodaiken Ralph E , Menefee Max , Seftel Harold C , Kew M C , McClaren M J
Published: September 2013

The muscle capillaries of diabetic subjects, with and without retinopathy, have been measured. The groups with retinopathy had significantly thicker laminae than those without the fundal changes. No significant difference was found between the group with proliferative retinopathy and the group with nonproliferative retinopathy. The focal and segmental nature of the basal lamina thickening was confirmed by the increasing standard deviation of the measurements within and among capillaries. This study also confirms the fact that, at least for muscle capillaries, an apparent relationship exists between the thickness of the basal lamina of these vessels and the presence of clinical retinopathy.
Growth Hormone Kinetics in Diabetic Patients
Authors: Navalesi R , Pilo A , Vigneri R , Del Chicca M G , Lenzi A , Cecchetti P
Published: September 2013

Several reports have shown that average plasma GH concentrations in insulin-treated and in juvenile diabetics are elevated in respect to normal values: these findings have been alternatively attributed to an increased pituitary GH secretion or to a lower GH catabolism induced by the disease.

To reinvestigate the problem we studied GH kinetics in twentyfour diabetics using 125I-GH. The patients were all normal in body weight and their fasting blood sugar did not exceed 190 mg. per 100 ml.; fourteen normal subjects were included as a control group.

After single injection of the tracer, the plasma disappearance curve of labeled hormone was obtained. Starting from this curve, metabolic clearance rate (MCR), fractional catabolic rate (FCR), initial distribution volume (IDV), and total distribution volume (TDV) were computed; MCR and plasma concentration of endogenous GH in plasma samples were used to estimate the amount of hormone irreversibly lost during the experiment (IHL240).

The major points that result from the comparison of the values obtained in diabetic patients with those in the normal group are: MCR values in diabetics do not differ from those found in normals (63.6 ± 19.6 and 64.6 ± 24.3 ml./min./m.2 respectively*). The higher plasma concentrations of endogenous GH in diabetics together with a normal MCR, yield hormone loss values (IHL240) significantly larger than normal (46.4 ± 29.5 μg/240 min. as compared to 23.7 ± 24.5) thus indicating that an increased GH secretion is present in diabetics.

TDV, fairly constant in normals, (5.8 ± 0.9 L./m.2) tends to decrease in diabetic patients as the disease progresses; in fact the values of TDV are significantly reduced (P<0.005) in long-term diabetics (>10 yrs. of disease) while TDV of short-term diabetics (<10 yrs.) does not differ from the normal value (4.6 ± 1.16 L./m.2 and 5.8 ± 0.9 L./m.2, respectively).
Progestogen-induced Diabetes in the Dog
Authors: Sloan J M , Oliver I M
Published: September 2013

The development of diabetes in a small percentage of female beagles receiving large doses of synthetic progestogen for one year is described. The abnormalities in blood sugar and plasma insulin responses to oral glucose arising during induction of diabetes are presented.

After a two-year period of diabetes, two animals were examined histologically. Lesions in the kidney and retina, similar to early lesions associated with human diabetic nephropathy and retinopathy, were present. Histologic changes related to the diabetes were also seen in the pancreas and pituitary. The means of induction of the diabetes is discussed. The study supports the view that the dog is a useful species in which to study the long-term pathology of diabetes.
Pituitary Responsiveness to Luteinizing Hormone-releasing Hormone in Insulin-dependent Diabetes Mellitus
Authors: Distiller Larry A , Sagel Julius , Morley John E , Seftel H C
Published: September 2013

Impaired fertility and menstrual disturbances are common in diabetes mellitus. In order to study the effect of diabetes on gonadotropin secretion by the pituitary gland, twenty premenopausal diabetic females and seven diabetic males were investigated using luteinizing hormone-releasing hormone (LH-RH). Although the gonadotropes responded to LH-RH in the patients studied, a relative impairment was apparent when compared to normal matched control groups. In the female diabetic patients there was no difference in the gonadotropin responses obtained in those with oligomenorrhea or amenorrhea when compared to those with normal menses. A significant inverse relationship was found between the maximum rise in plasma luteinizing hormone and the fasting plasma glucose. These findings suggest an influence of glucose metabolism on pituitary gonadotropin function. However, the reduced gonadotropin response is unlikely to be the sole cause of the abnormal gynecologic function.
Electrical and Secretory Manifestations of Glucose and Amino Acid Interactions in Rat Pancreatic Islets
Authors: Pace Caroline S , Stillings Susan N , Hover Barbara A , Matschinsky Franz M
Published: September 2013

Interactions between glucose and amino acids in rat pancreatic islets were studied by recording the intracellular membrane potential and spike discharges from single islet cells and by measuring insulin release from the isolated perfused pancreas. It was found that L-isoleucine requires the presence of basal glucose (5 mM) in Order to increase spike discharge from islet cells and depolarize the cell membrane. Similarly basal glucose is needed for insulin release by L-isoleucine. A physiological mixture of twenty amino acids also required the presence of basal glucose in order to increase spike activity and insulin release. In contrast to L-isoleucine the amino acid mixture did not depolarize the β-cells. Iodoacetate, at concentrations previously shown to block glycolysis completely, did not interfere with any of these permissive actions of glucose, nor did iodoacetate alter the well known electrical manifestations of high levels of glucose itself (i.e. depolarization and increased spike discharge).

These data show that glucose plays a pre-eminent role as regulator of islet cell function, governing the efficacy of amino acids as β-cells stimulants. The results are most easily interpreted if one assumes that glycolysis is not required for glucose to exert its action.
Diabetic Retinopathy and the Fibrinolytic System
Authors: Aimér Lars-Olof , Pandolfi Maurizio , Nilsson Inga Marie , Siveden Malmo
Published: September 2013

We found that patients with long-standing (>10 years) diabetes who have not developed retinopathy had a significantly higher and almost normal fibrinolytic response to venous occlusion and also a higher spontaneous fibrinolytic activity than those who had developed retinopathy. In the latter, the low fibrinolytic activity of the blood was, however, not correlated to a low plasminogen activator activity of the vessel walls. Although generally lower than in controls, the activator activity of the vessel walls in the retinopathy group tended to be higher than in the rest, and in fact those with only minor vascular changes (microaneurysms) had a significantly higher activity than the other diabetics. The fibrinogen and alpha2-macroglobulin levels were higher in the retinopathy group. Thus multiple abnormalities of the fibrinolytic system were found to be related to diabetic microangiopathy.
Prevention of Hypoglycemic Attacks by Propranolol in a Patient Suffering from Insulinoma
Authors: Blum I , Down M , Laron Z , Atsmon A
Published: September 2013

An insulinoma was diagnosed in a fifty-seven-year-old woman suffering from frequent hypoglycemic attacks. Propranolol—a beta-adrenergic blocker—in a dose of 80 mg. per day effectively prevented recurrent hypoglycemic attacks. It also corrected the basal hyperinsulinemia as well as the increased insulin secretion which results from stimulation with glucose or arginine.
Comparison of the Value of the Two- and One-hour Glucose Levels of the Oral GTT in the Diagnosis of Diabetes in Pima Indians
Authors: Rushforth Norman B , Bennett Peter H , Steinberg Arthur G , Miller Max
Published: September 2013

In many population and screening studies of diabetes, the onehour glucose level of the GTT has been used to define the diabetic status of subjects. The one-hour postglucose load determination has been preferred over the two-hour value by many investigators primarily because of convenience and justified on the basis of the high correlation between the two values.

Venous plasma glucose levels, one and two hours after a 75-gm. carbohydrate load, were determined on over 1,600 Pima Indians. In most sex and age groups, the frequency distributions of both the one-hour and two-hour glucose levels were clearly bimodal. By the logarithms of the glucose values these distributions were consistent with a model of two overlapping Gaussian distributions. The data indicate that for the Pima the amount of overlap of the distributions was greater for the one-hour than for the two-hour values. For each sex and decade the probabilities of misclassification of a normal as “hyperglycemic” and vice versa were smaller for the two-hour than for the one-hour values. Such misclassifications for the two-hour levels averaged 6.6 per cent and 11.6 per cent for the one-hour levels.

The reproducibility of the GTT taken one to three weeks apart in a sample of ninety-nine Puna Indians showed that the two-hour level was superior to the one-hour level as measured by the mean values of the absolute difference between log GTT levels for test and retest values. The one-hour measurements also gave more disagreements between the classifications of diabetic status than the two-hour test values.

If a single measure of glucose tolerance is to be selected for the diagnosis of diabetes among Pima Indians, these data provide a mathematical rationale for preferring the two-hour level to the one-hour determination.
Basal and Postprotein Insulin and Glucagon Levels During a High and Low Carbohydrate Intake and Their Relationships to Plasma Triglycerides
Authors: Fujita Yoshikuni , Gotto Antonio M , Unger Roger M
Published: September 2013

The effects of acute and chronic differences in the carbohydrate content of the diet on plasma insulin, glucagon, insulin-glucagon molar ratio (I/G), and triglycerides were studied. Acute effects were studied by varying the carbohydrate content of a single test meal, while chronic effects were determined by varying the carbohydrate content of the diet for a week. A test meal containing 0.6 gm. of gelatin per kilogram plus 0.6 gm. per kilogram of glucose resulted in much higher levels of insulin and I/G (p<0.005), lower glucagon levels (p<0.05), and slightly higher triglycerides (N.S.) than did a meal of 1.2 gm. per kilogram of gelatin alone. One week of a 12-gm. carbohydrate, 2870-calorie diet lowered insulin (p<0.001), I/G (p<0.05), and triglycerides (p<0.001) and increased glucagon (N.S.), whereas a 390-gm. carbohydrate, 2784-calorie intake significantly increased insulin, I/G, and triglycerides (p<0.005) and lowered glucagon (p<0.02) within two days; even greater changes in hormones were observed on a 510-gm. carbohydrate intake. Of those patients in whom a high carbohydrate intake induced a triglyceride rise of at least 40 mg. per deciliter, a significant correlation between the change in I/G and the change in triglycerides was noted (r=0.82; p<0.01). The results are compatible with but do not prove the proposal that pancreatic α and β cells play a mediating role in carbohydrate induction of hyperlipidemia.
Gluconeogenesis from Alanine in Normal Postabsorptive Man: Intrahepatic Stimulatory Effect of Glucagon
Authors: Chiasson J L , Liljenquist J E , Sinclair-Smith B C , Lacy W W
Published: September 2013

Although the stimulatory effect of glucagon on gluconeogenesis has been well demonstrated in certain systems in vitro, this effect has never been established in man. The present study was undertaken, therefore, to determine whether glucagon could stimulate gluconeogenesis from alanine in normal fasting man. Glucagon might stimulate this process by increasing the hepatic alanine uptake and/or by shunting the extracted alanine within the liver into the gluconeogenic pathway. In order to be able to examine these two aspects of gluconeogenesis, we combined the hepatic veinbrachial artery catheterization technic with an isotopic infusion of alanine-14C. Alanine-14C specific activity was measured in whole blood and plasma by use of a rapid chromatographic technic. Since plasma contributed 93 per cent of the alanine extracted by the splanchnic bed with a specific activity three times that of the red blood cells, plasma alanine specific activity was used to study the conversion of alanine to glucose. A constant infusion of alanine-14C achieved a relatively stable arterial specific activity by forty minutes. The administration of glucagon by constant infusion (15–50 ng./kg./min.) had no effect on the splanchnic extraction of alanine. Net splanchnic glucose-14C production, however, doubled during the glucagon infusion, and the conversion of alanine to glucose increased from 30 ± 2 to 58 ± 9 μmol/min. These data (1) demonstrate that in normal man fasted twelve to fourteen hours, glucagon at supraphysiblogic levels can double the rate of gluconeogenesis from alanine and (2) indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extracted alanine toward new glucose formation rather than by increasing the hepatic extraction of alanine.