Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer anorexia-cachexia syndrome: cytokines and neuropeptides

Purpose of reviewCancer anorexia-cachexia syndrome is observed in 80% of patients in the advanced stages of cancer and is a strong independent risk factor for mortality. Numerous cytokines produced by tumor and immune cells, interacting with the neuropeptidergic system, mediate the cachectic effect of cancer. Since there is currently no effective pharmacological treatment and the anorexia-cachexia syndrome continues to be defined biochemically, we review the role of cytokines and neuropeptides in this process. Recent findingsCurrently data suggest that cancer anorexia-cachexia syndrome results from a multifactorial process involving many mediators, including hormones (e.g. leptin), neuropeptides (e.g. neuropeptide Y, melanocortin, melanin-concentrating hormone and orexin) and cytokines (e.g. interleukin 1, interleukin 6, tumor necrosis factor α and interferon γ). It is likely that close interrelation among these mediators exists in the hypothalamus, decreasing food intake and leading to cachexia. SummaryIn the pathogenesis of cancer anorexia, cytokines play a pivotal role influencing the imbalance of orexigenic and anorexigenic circuits that regulate the homeostatic loop of body-weight regulation, leading to cachexia. Interfering pharmacologically with cytokine expression or neural transduction of cytokine signals can be an effective therapeutic strategy in anorectic patients before they develop cancer anorexia-cachexia syndrome.
An anti‐inflammatory role for interleukin‐11 in established murine collagen‐induced arthritis

Interleukin‐11 (IL‐11) is a cytokine belonging to the IL‐6 family which has both pro‐ and anti‐inflammatory potential. Like IL‐6 it can diminish tumour necrosis factor‐α and IL‐1 production, and augment immunoglobulin synthesis. We have explored the immunomodulatory effects of IL‐11 treatment in mice in a model of inflammatory autoimmune joint disease, collagen‐induced arthritis (CIA). Recombinant human IL‐11 was administered at various doses to DBA/1 mice after the onset of CIA. IL‐11 treatment caused a significant reduction in the clinical severity of established CIA, which was associated with protection from joint damage, as assessed by histology. Although there was a suggestion at high doses of IL‐11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL‐11 treatment on anti‐CII antibody levels. Similarly, the acute‐phase reactant serum amyloid P was only elevated in mice receiving very high doses (50–100 μg/day) of IL‐11. Endogenous IL‐11 was abundantly produced in synovial membrane cultures derived from CII‐immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cytokine is spontaneously produced in the inflammatory response in CIA. The results presented here demonstrate an anti‐arthritic immunoregulatory role for IL‐11 in murine CIA, and suggest that IL‐11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.
Cardiopulmonary effects of sevoflurane, compared with halothane, enflurane, and isoflurane, in dogs.

OBJECTIVE To evaluate cardiopulmonary effects of sevoflurane (Sevo), compared with halothane (Hal), enflurane (Enf), and isoflurane (Iso). ANIMALS 24 healthy Beagles, randomly assigned to 4 groups of 6 dogs each. PROCEDURE Dogs under spontaneous ventilation were anesthetized with Sevo, Hal, Enf, or Iso. After minimum elveolar concentration (MAC) of each anesthetic was determined, anesthesia was maintained at light (1 MAC), moderate surgical (1.5 MAC), and deep (2 MAC), stages and cardiopulmonary variables at conscious state (baseline) and each anesthesia stage were measured. RESULTS In dogs of the Sevo group, heart rate increased significantly from the baseline value at all anesthesia stages. Systemic vascular resistance during Sevo anesthesia decreased gradually with increasing anesthesia stage, which was accompanied by dose-dependent decreases in systolic, mean, and diastolic arterial blood pressures. At 1.5 and 2 MAC Sevo, stroke index decreased slightly but significantly from the baseline value; however, cardiac index was unchanged because of the significant increase in heart rate. Respiratory rate decreased significantly at 2 MAC from that at 1 MAC Sevo. Tidal volume and dead space-to-tidal volume ratio were unchanged at all anesthesia stages of Sevo, resulting in significantly decreased expired and alveolar ventilation at 2 MAC, compared with values at 1 and 1.5 MAC Sevo. PaCO2 increased and pHa decreased significantly, depending on anesthesia stage; PaO2, increased significantly from baseline values, and remained constant because of inhalation of 100% O2. CONCLUSION Cardiovascular effects of Sevo were greater than those of Hal, similar to those of Iso, and less than those of Enf. Respiratory effects of Sevo were similar to those of Iso at all anesthesia stages, greater than those of Hal at 2 MAC, and less than those of Enf at 1.5 and 2 MAC. Up to the moderate surgical anesthesia stage, Sevo can be used safely in dogs undergoing spontaneous ventilation.
Brain Evoked Responses, a Bioassay for Central Actions of Adrenocorticotropin (ACTH 1-39) and Corticotropin Releasing Hormone (CRH) in Humans

Blood borne hormones of the hypothalamus-pituitary-adrenal (HPA) axis form an afferent humoral system modulating a great variety of brain functions. In humans, bioassays consistently reflecting central nervous system actions have not been developed, so far. The present experiments are part of a series of studies which have been conducted to demonstrate the afferent influences of ACTH and CRH on brain activity by recording of auditory event-related brain potentials (ERPs) in healthy human subjects. In a double-blind within-subject comparison in 12 healthy male students, influences of 4 U ACTH and 100 micrograms CRH (infused within 2 h; the infusion starting 1 h prior to ERP recordings) were compared with the effects of a placebo infusion. Influences of the hormones were tested for the early, brain stem generated ERP components (BAEPs) and for the late components of the ERP associated with cortical stimulus processing. ACTH and CRH showed no consistent effect on BAEPs. ACTH, but not CRH, significantly reduced amplitudes of late ERP components, in particular, the Nd and P3 components which are considered signs of selective attention. These results are consistent with findings from previous studies demonstrating impaired ERP signs of selective attention in humans after administration of the 4-10 fragment of ACTH which lacks the peripheral adrenocorticotropic activity. Together with these foregoing studies, results from the present experiments further establish ERP methodology as a sensitive bioassay for CNS actions of hormones in humans.
Investigation of the Action Patterns of Pectinmethylesterase Isoforms through Kinetic Analyses and NMR Spectroscopy

Well characterized pectin samples were incubated with cell wall-bound and -solubilized pure isoforms of pectinmethylesterase from mung bean hypocotyls (Vigna radiata). Both enzyme activity and average product structure were determined at intervals along the deesterification pathway at pH 5.6 and 7.6. The latter analyses were performed by 13C NMR spectroscopy, and the degree of esterification was probed by both13C NMR and potentiometric measurements. A dichotomy was observed in the behavior of the α and γ isoforms when compared with that of the β isoenzyme. Ideal blockwise deesterification mechanisms reproduced the experimental average structures (methylester distribution) throughout the course of the reaction. In the case of the α and γ isoforms, a single chain mechanism associated with a free carboxyl group at the second nearest neighbor position could be postulated at pH 5.6, whereas some multiple attack character was required to reproduce the data at pH 7.6. Several mechanisms that differed from the preceding ones were compatible with the data for the β isoform at the two pH values. Both the nature of the polysaccharides produced in these reactions and the role of pectinmethylesterase in the cell wall-stiffening process along the growth gradient are discussed.
Modélisation du langage naturel appliquée à la reconnaissance de l'écriture manuscrite en-ligne

L'evolution de la societe de l'Information avec les concepts d'ubiquite, de nomadisme, d'acces a l'information sans discontinuer, en tous lieux et en tous temps, et si possible avec le minimum d'efforts pour l'utilisateur impose de repenser les interfaces de communication. En effet, dans ces situations, la plupart du temps, le clavier n'apporte pas les solutions de confort attendu. L'utilisation de commandes gestuelles, et en particulier de l'ecriture manuscrite, se revele etre aujourd'hui une alternative credible pour ces nouveaux systemes communicants (assistant numerique, ardoise electronique, etc. ). Les performances des syste��mes de reconnaissance actuels sont encore bien inferieures a celles de l'humain notamment dans la prise en compte d'informations contextuelles d'ordre linguistique. Les travaux que nous presentons dans ce manuscrit s'inscrivent dans un cadre industriel (CIFRE) et visent a ameliorer le systeme de reconnaissance de l'ecriture manuscrite nomme MyScript Builder, developpe par la societe Vision Objects. Dans un tel systeme, la prise en compte des proprietes du langage constitue un element cle. C'est l'objectif central de ce travail pour lequel encore peu de contributions sont disponibles. Nous avons cherche a concevoir, developper et tester des modeles de langage les plus efficaces possibles pour un systeme de reconnaissance de l'ecriture manuscrite en-ligne. Plusieurs types de contraintes etaient a satisfaire. En articulier, il fallait veiller au compromis taille/performance, mais aussi envisager la portabilite de la methode afin de pouvoir la generaliser a differentes langues. Ainsi, nous avons privilegie une approche probabiliste basee sur des n-classes pour traiter les langues naturelles. Nous avons experimente de nombreuses techniques de classification basees sur differentes methodes d'exploration de l'espace de recherche et se basant sur un critere de nature contextuelle ou syntaxique. Par ailleurs, des modeles structurels appeles lexiques d'expressions, ont ete etudies pour traiter des entites linguistiques specifiques. Ces modeles ont fait l'objet d'experimentations poussees pour evaluer les ameliorations apportees au systeme de reconnaissance MyScript Builder. Sur des phrases appartenant a 13 langues differentes, le taux d'erreur a ete diminue de 30 %en moyenne a l'aide de modeles n-classes par rapport a une version ne comportant qu'un simple lexique. Les lexiques d'expressions s'averent particulierement performants puisque le nombre d'erreurs de reconnaissance est reduit de moitie.
Identification of RanBP2‐ and Kinesin‐Mediated Transport Pathways with Restricted Neuronal and Subcellular Localization

Ran‐binding proteins, karyopherins, and RanGTPase mediate and impart directionality to nucleocytoplasmic transport processes. This biological process remains elusive in neurons. RanBP2 has been localized at the nuclear pore complexes and is very abundant in the neuroretina. RanBP2 mediates the assembly of a large complex comprising RanGTPase, CRM1/exportin‐1, importin‐β, KIF5‐motor proteins, components of the 19S cap of the 26S proteasome, ubc9 and opsin. Here, we show RanBP2 is abundant in the ellipsoid compartment of photoreceptors and RanGTPase‐positive particles in cytoplasmic tracks extending away from the nuclear envelope of subpopulations of ganglion cells, suggesting RanBP2's release from nuclear pore complexes. KIF5C and KIF5B are specifically expressed in a subset of neuroretinal cells and differentially localize with RanBP2 and importin‐β in distinct compartments. The C‐terminal domains of KIF5B and KIF5C, but not KIF5A, associate directly with importin‐β in a RanGTPase‐dependent fashion in vivo and in vitro, indicating importin‐β is an endogenous cargo for a subset of KIF5s in retinal neurons. The KIF5 transport pathway is absent from the myoid region of a topographically distinct subclass of blue cones and the distribution of kinesin‐light chains is largely distinct from its KIF5 partners. Altogether, the results identify the existence of neuronal‐ and subtype‐specific kinesin‐mediated transport pathways of importin‐β‐bound cargoes to and/or from RanBP2 and indicate RanBP2 itself may also constitute a scaffold carrier for some of its associated partners. The implications of these findings in protein kinesis and pathogenesis of degenerative neuropathies are discussed.
Psychologically Speaking: A Book of Quotations

Includes quotations from: Woody Allen, Aristotle, Jane Austen, Alan Bennett, Tony Blair, William Blake, Michael Caine, Charles Darwin, Richard Dawkins, Charles Dickens, Albert Einstein, George Eliot, E.M. Forster, Anna Freud, Sigmund Freud, Ernest Hemingway, Aldous Huxley, William James, Carl Jung, D.H. Lawrence, Roger McGough, Karl Marx, Friedrich Nietzsche, George Orwell, Camille Paglia, Dorothy Parker, Raj Persaud, Jean Piaget, Steven Pinker, Dennis Potter, Will Self, Vikram Seth, William Shakespeare, George Bernard Shaw, Margaret Thatcher, Peter Ustinov, Kurt Vonnegut, Lev Vygotsky, Irvine Welsh, Oscar Wilde, Virginia Woolf and many others.
Anti‐cancer properties of anthraquinones from rhubarb

Rhubarb has been used as a traditional Chinese medicine since ancient times and today it is still present in various herbal preparations. In this review the toxicological and anti‐neoplastic potentials of the main anthraquinones from Rhubarb, Rheum palmatum, will be highlighted. It is interesting to note that although the chemical structures of various anthraquinones in this plant are similar, their bioactivities are rather different. The most abundant anthraquinone of rhubarb, emodin, was capable of inhibiting cellular proliferation, induction of apoptosis, and prevention of metastasis. These capabilities are reported to act through tyrosine kinases, phosphoinositol 3‐kinase (PI3K), protein kinase C (PKC), NF‐kappa B (NF‐κB), and mitogen‐activated protein kinase (MAPK) signaling cascades. Aloe‐emodin is another major component in rhubarb found to have anti‐tumor properties. Its anti‐proliferative property has been demonstrated to be through the p53 and its downstream p21 pathway. Our recent proteomic study also suggests that the molecular targets of these two anthraquinones are different. However, both components were found to be able to potentiate the anti‐proliferation of various chemotherapeutic agents. Rhein is the other major rhubarb anthraquinone, although less well studied. This compound could effectively inhibit the uptake of glucose in tumor cells, caused changes in membrane‐associated functions and led to cell death. Interestingly, all three major rhubarb anthraquinones were reported to have in vitro phototoxic. This re‐evaluation of an old remedy suggests that several bioactive anthraquinones of rhubarb possess promising anti‐cancer properties and could have a broad therapeutic potential. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 609–630, 2007
Effects of Three‐Dimensional Culturing on Osteosarcoma Cells Grown in a Fibrous Matrix: Analyses of Cell Morphology, Cell Cycle, and Apoptosis

Osteosarcoma cells were cultured in stirred tank bioreactors with either a fibrous matrix or nonporous microcarriers to study the environmental effects on cell growth, morphology, cell cycle, and apoptosis. Cell cycle and apoptosis were analyzed using flow cytometry and visualized using confocal laser scanning microscopy and fluorescence microscopy. The three‐dimensional (3‐D) fibrous culture had better cell growth and higher metabolic rates than the two‐dimensional (2‐D) microcarrier culture because cells in the fibrous matrix were protected from shear stress and had lower apoptosis and cell death even under suboptimal conditions (e.g., nutrient depletion). The polyester fibrous matrix used in this study also exhibited the capability of selectively retaining viable and nonapoptotic cells and disposing apoptotic and nonviable cells. Consequently, very few apoptotic cells were found in the fibrous matrix even in the long‐term (1 month) T‐flask culture. In the continuous culture with packed fibrous matrixes for cell support, most cells were arrested in the G1/G0 phase after 4 days. Decreasing the dissolved oxygen level from 60 to 10% air saturation did not significantly change cell cycle and apoptosis, which remained low at ∼15%. These results could explain why the fibrous bed bioreactor had good long‐term stability and was advantageous for production of non‐growth‐associated proteins by animal cell cultures.
Inzidenz und Letalität häufiger neonataler Erkrankungen beim Fohlen während der ersten 10 Tage post natum in einer Veterinärklinik

Zusammenfassung Ziel der Studie war, durch Auswertung von Patientendaten die Häufigkeit und Letalität von Fohlenerkrankungen in den ersten 10 Tagen nach der Geburt darzustellen. Material und Methode: Über einen Zeitraum von 6 Jahren wurden die Patientendaten von 393 Fohlen ausgewertet, die innerhalb der ersten 10 Tage post natum in einer Klinik vorgestellt wurden. Ermittelt wurden Art und Anzahl der Erkrankungen, das Geschlecht der betroffenen Fohlen und die Letalitätsrate. Ergebnisse: Unter den insgesamt 28 Krankheitsbildern waren Systemic Inflammatory Response Syndrome (SIRS), Mekoniumobstipation und Bronchopneumonie am häufigsten diagnostiziert worden. Die Letalität für SIRS lag bei 41,8 %, für Mekoniumobstipation bei 29,7 % und für Bronchopneumonie bei 37,9 %. Der durchschnittliche Todeszeitpunkt betrug bei SIRS 4,2 ± 2,9 Tage, bei Mekoniumobstipation 4,6 ± 3,2 Tage und bei Bronchopneumonie 5,2 ± 3,5 Tage post natum. Schlussfolgerung und klinische Relevanz: Anhand der Datenerhebung kann die Häufigkeit und damit die Bedeutung einzelner Krankheitsbilder abgeleitet werden. Die Angaben zur Letalität helfen, Aussagen zur Prognose der häufigsten neonatalen Fohlenerkrankungen nach Erstuntersuchung zu treffen.
A Comparison of the Effects of Selective Increases in Peripheral or Portal insulin on Hepatic Glucose Production in the Conscious Dog

We investigated the mechanisms by which peripheral or portal insulin can independently alter liver glucose production. Isotopic ([3-3H]glucose) and arteriovenous difference methods were used in conscious overnight-fasted dogs. A pancreatic clamp (somatostatin plus basal insulin and basal glucagon infusions) was used to control the endocrine pancreas. After a 40-min basal period, a 180-min experimental period followed in which selective increases in peripheral (PERI group, n = 5) or portal-vein (PORT group, n = 5) insulin were induced. In control dogs (CONT group, n = 10), insulin was not increased. Glucagon levels were fixed in all studies, and basal euglycemia was maintained by peripheral glucose infusion in the two experimental groups. In the PERI group, arterial insulin rose from 36 ± 12 to 120 ± 12 pmol/l, while portal insulin was unaltered. In the PORT group, portal insulin rose from 108 ± 42 to 192 ± 42 pmol/l, while arterial insulin was unaltered. Neither arterial nor portal insulin changed from basal in the CONT group. With a selective rise in peripheral insulin, the net hepatic glucose output (NHGO; basal, 11.8 ± 0.7 µmol · kg−1 · min−1) did not change initially (11.8 ± 2.1 µmol · kg−1 · min−1, 30 min after the insulin increase), but eventually fell (P < 0.05) to 6.1 ± 0.9 µmol · kg−1 · min−1 (last 30 min). With a selective rise in portal insulin, NHGO dropped quickly (P < 0.05) from 10.0 ± 0.9 to 5.6 ± 0.6 µmol · kg−1 · min−1 (30 min after the insulin increase) and eventually reached 3.1 ± 1.1 µmol x kg−1 · min−1 (last 30 min). When insulin levels were not increased (CONT group), NHGO dropped progressively from 10.1 ± 0.6 to 8.3 ± 0.6 µmol · kg−1 · min−1 (last 30 min). Conclusions drawn from the net hepatic glucose balance data were confirmed by the tracer data. Net hepatic gluconeogenic substrate uptake (three carbon precursors) fell 2.0 µmol · kg−1 · min−1 in the PERI group, but rose 1.2 µmol · kg−1 · min−1 in the PORT group and 1.2 µmol · kg−1 · min−1 in the CONT group. A selective 84 pmol/l rise in arterial insulin was thus associated with a fall in NHGO of ∼ 50%, which took 1 h to manifest. Conversely, a selective 84 pmol/l rise in portal insulin was associated with a 50% fall in NHGO, which occurred quickly (15 min). From the control data, it is evident that in either case ∼ 30% of the fall in NHGO was due to a drift down in baseline and that 70% was due to the rise in insulin. In conclusion, an increment in portal insulin had a rapid inhibitory effect on NHGO, caused by the suppression of glycogenolysis, while an equal increment in arterial insulin produced an equally potent but slower effect that resulted from a small increase in hepatic sinusoidal insulin, from a suppression of gluconeogenic precursor uptake by the liver, and from a redirection of glycogenolytic carbon to lactate rather than glucose.
Generation of Mice Expressing Only the Long Form of the Prolactin Receptor Reveals That Both Isoforms of the Receptor Are Required for Normal Ovarian Function1

ABSTRACT Prolactin (PRL), a pleiotropic hormone essential for maintenance of corpus luteum (CL) function and pregnancy, transduces its signal through two types of receptors, a short form (PRLR-S) and a long form (PRLR-L). Both types of receptors are expressed in the CL, yet their individual roles are not well defined. We have shown previously that female transgenic mice expressing only PRLR-S display total infertility characterized by defective follicular development and early degeneration of CL, suggesting that expression of PRLR-L is a prerequisite for normal follicular development and maintenance of CL. To determine whether PRLR-L alone is the sole receptor required to maintain normal CL formation, differentiation, and progesterone secretion, we generated two transgenic mice which express only PRLR-L, either ubiquitously (Tg-RL) or in a CL-specific manner (CL-RL). To generate CL-specific expression, we used the HSD17B7 promoter. We found both transgenic mice models cycled normally, displayed no apparent defect in follicular development, and had normal ovulation rates. The STAT5 signaling pathway, considered essential for luteinization and progesterone production, was activated by PRL in both transgenic mice models. However, soon after mating, Tg-RL and CL-RL mice showed early regression of CL, lack of progesterone production, and implantation failure that rendered them totally infertile. Embryo transfer studies demonstrated no embryo abnormalities, and supplementation with progesterone rescued implantation failure in these mice. Close observation revealed lack of luteinization and reduced expression of proteins involved in progesterone biosynthesis despite normal levels of LHCGR (LH-R), ESR1 (ER-alpha), CEBPB (C/EBP-beta) and CDKN1B (p27), proteins essential for luteinization. However, we found VEGFA, a key regulator of angiogenesis and vascularization, to be dramatically reduced in both Tg-RL and CL-RL mice. We also found collagen IV, a marker for the basal lamina of endothelial cells, aberrantly expressed and a discordant organization of endothelial cells in CL. Although luteinization did not occur in vivo, granulosa cells isolated from these mice luteinized in culture. Taken together, these results suggest that a vascularization defect in the CL may be responsible for lack of luteinization, progesterone production, and infertility in mice expressing only PRLR-L. This investigation therefore demonstrates that in contrast to earlier presumptions that PRLR-L alone is able to support normal CL formation and function, both isoforms of the PRL receptor are required in the CL for normal female fertility.