bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell activation, from atopy to asthma: more a paradox than a paradigm
Authors: El Biaze M. , Boniface S. , Koscher V. , Mamessier E. , Dupuy P. , Milhe F. , Ramadour M. , Vervloet D. , Magnan A. 
Published: August 2003

During the last 15 years, it was largely shown that allergic inflammation was orchestrated by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. Indeed, Th2 activation was shown to be necessary to induce allergic sensitization in animal models. In humans, a Th2 skewing was shown in atopic children soon after birth. In asthma, descriptive studies showed that Th2 cells were more numerous in patients than in controls. In addition, during specific allergen stimulation, an increase of Th2 cells was described in most cases. According to this Th2 paradigm, it was proposed that early avoidance of microbial exposure could explain the increase of atopic diseases seen in the last 20 years in developed countries, as the ‘hygiene hypothesis’. Recently, it was proposed that early exposure to lipopolysaccharide (LPS) could be protective against atopic diseases.However, it is well established that exposure to LPS can induce asthma symptoms, both in animals and humans, although it induces a Th1 inflammatory response. In addition, most infections induce asthma exacerbations and Th1 responses. Recently, some studies have showed that some Th1 cells were present in asthmatic patients, which could be related to bronchial hyperreactivity.There is therefore an ‘infectious paradox’ in asthma, which contributes to show that the Th2 paradigm is insufficient to explain the whole inflammatory reaction of this disease. We propose that the Th2paradigm is relevant to atopy and inception of asthma albeit a Th1 activation would account at least in part for bronchial hyperreactivity and asthma symptoms.
Receptor Activity Modifying Protein 2 Distribution in the Rat Central Nervous System and Regulation by Changes in Blood Pressure
Authors: Stachniak T. J. E. , Krukoff T. L. 
Published: August 2003

AbstractThe neuropeptide, adrenomedullin, acts in the central nervous system (CNS) to regulate blood pressure, at least partly through an adrenomedullin receptor which is composed of receptor activity modifying protein 2 (RAMP‐2) and calcitonin receptor‐like receptor (CRLR). We used in situ hybridization to localize RAMP‐2 mRNA throughout the brain, and we performed reverse transcription‐polymerase chain reaction to detect CRLR mRNA in the brain. We found that RAMP‐2 mRNA is expressed in numerous areas, including autonomic nuclei such as the paraventricular, supraoptic, arcuate and ventromedial nuclei, as well as the nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus. Many regions expressing RAMP‐2 mRNA also express low levels of CRLR mRNA. We examined changes in the mRNA expression of RAMP‐2 and preproadrenomedullin in the brain in response to blood pressure manipulations. Rats received intravenous infusions of nitroprusside or phenylephrine to decrease or increase blood pressure, respectively. Decreased blood pressure elicited an increase in RAMP‐2 mRNA expression in the NTS and a decrease in preproadrenomedullin mRNA expression in the paraventricular nucleus (PVN). Increased blood pressure elicited a decrease in RAMP‐2 mRNA expression in the PVN and NTS. The CNS distribution and modulation of adrenomedullin signalling components by changes in blood pressure provide anatomical and physiological evidence for a homeostatic role for adrenomedullin in the brain.
Evidence That Gonadotropin‐Releasing Hormone II Is Not a Physiological Regulator of Gonadotropin Secretion in Mammals
Authors: Gault P. M. , Maudsley S. , Lincoln G. A. 
Published: August 2003

AbstractGonadotropin‐releasing hormone (GnRH)‐II stimulates luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH‐II receptor expressed on gonadotropes. This study used two selective GnRH‐I receptor antagonists to test the alternative hypothesis that GnRH‐II acts through the GnRH‐I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor‐relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS‐7 cells transfected with either mammalian GnRH‐I and GnRH‐II receptors and, in vivo, potently antagonized the gonadotropin‐releasing effect of a single injection of 250 ng GnRH‐I in our sexually inactive sheep model. In a series of studies in sheep, antide (i) blocked the acute LH response to a single injection of GnRH‐II (20 µg antide: 10 µg GnRH‐II); (ii) blocked both the acute, pulsatile LH response and the FSH priming response to 2‐hourly injections of GnRH‐II over 36 h (100 µg antide/8 h: 4 µg GnRH‐II/2 h); and (iii) chronically blocked both the pulsatile LH response and the marked FSH priming response to 4‐hourly injections of GnRH‐II over 10 days (75 µg antide/8 h: 4 µg GnRH‐II/4 h). In two final experiments, the GnRH‐I antagonist 135‐18, shown previously to agonize the mammalian GnRH‐II receptor, blocked the gonadotropin‐releasing effects of GnRH‐I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH‐II (250 ng) failed to alter the LH‐releasing effect of GnRH‐I (50–500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH‐II decapeptide is a native regulator of the gonadotrope in mammals.
Palatable Solutions During Paradoxical Sleep Deprivation: Reduction of Hypothalamic‐Pituitary‐Adrenal Axis Activity and Lack of Effect on Energy Imbalance
Authors: Suchecki D. , Antunes J. , Tufik S. 
Published: August 2003

AbstractParadoxical sleep deprivation (PSD) induces increased energy expenditure in rats, insofar as rats eat more but loose weight throughout the deprivation period. In the present study, rats were offered water, saccharin or sucrose to drink during the deprivation period, since it has been proposed that carbohydrates reduce the hypothalamic‐pituitary‐adrenal (HPA) axis response to stress. Rats were submitted to the flower pot technique for 96 h. During the PSD period, they were weighed daily and food and fluid intake was assessed twice a day. At the end of the PSD period, rats were killed and plasma concentrations of glucose, adrenocorticotropic hormone (ACTH) and corticosterone were assayed. Compared to their control counterparts, all paradoxical sleep‐deprived rats consumed more food, but lost weight. Paradoxical sleep‐deprived rats given sucrose drank more than their control counterparts (especially in the light phase of the light/dark cycle). Paradoxical sleep‐deprived rats showed increased food intake during all periods throughout the experiment, with peak intake during the dark phase and nadir during the light phase of the light/dark cycle. All paradoxical sleep‐deprived rats showed lower glucose plasma levels than control rats and increased relative adrenal weight. However, when given saccharin or sucrose, paradoxical sleep‐deprived rats showed lower concentrations of ACTH and corticosterone than their water‐provided counterparts, indicating that palatable fluids were capable of lowering HPA axis activation produced by PSD. The fact that PSD induced energy imbalance regardless of the relative attenuation of the HPA axis activity produced by saccharin or sucrose suggests that the HPA axis may play only a secondary role in this phenomenon, and that other mechanisms may account for this effect. The data also suggest that supply of palatable fluids can be an additional modification to reduce the stress of the flower pot method.
Early Expression of Chicken Gonadotropin‐Releasing Hormone‐1 in the Developing Chick
Authors: Witkin J. W. , Dao D. , Livne I. , Dunn I. C. , Zhou X. L. , Pula K. , Silverman A. J. 
Published: August 2003

AbstractGonadotropin‐releasing hormone (GnRH), which is essential for reproductive function, is made by neurones that migrate from the nasal region into the brain during early embryonic development. This migration begins in chick when the olfactory pit is formed. This is approximately the time that GnRH neurones can be detected immunocytochemically. The present study investigated (i) how early in development the GnRH gene is expressed and (ii) the sites of its expression. Accordingly, reverse transcriptase‐polymerase chain reaction (PCR) and in situ hybridization were performed on chick embryos before gastrulation up until the stage by which GnRH neurones have begun to migrate into the central nervous system. Primers were made to the 5′‐ and 3′‐UTR region of the message for cGnRH‐I, the form of the peptide that is essential for reproductive function in the chicken. PCR product was found in all stages and the sequences of products from all stages were identical. Thus, the GnRH gene is expressed continuously throughout embryonic development. In situ hybridization with a digoxygenin labelled riboprobe revealed staining along the primitive streak immediately before gastrulation. In later stages, cGnRH‐I gene expression was seen in association with the anterior neural ridge. The expression was subsequently restricted to a narrow, clearly defined region, which is associated with the presumptive nasal cavity and olfactory placode. Later, GnRH neurones could be seen in their migratory routes by both in situ hybridization and immunocytochemistry. Expression of the GnRH gene has been described in preimplantation stages in mammals and there is evidence that the neuropeptide plays a role in formation and maintenance of the placenta. What role (if any) it may play in early avian development remains unknown. The demonstration of sites of GnRH expression during the early period of neurulation suggests that GnRH neurones arise before olfactory placode formation.
µ‐Opioid Receptor Modulates Peptide Release From Rat Neurohypophysial Terminals By Inhibiting Ca2+ Influx
Authors: Ortiz‐Miranda S. I. , Dayanithi G. , Coccia V. , Custer E. E. , Alphandery S. , Mazuc E. , Treistman S. , Lemos J. R. 
Published: August 2003

AbstractThe activation of opioid receptors in neurones of the central nervous system leads to a variety of effects including the modulation of diuresis and parturition, processes that are directly controlled by the hypothalamic–neurohypophysial system (HNS). The effects of µ‐opioid receptor activation on peptide release, voltage‐gated Ca2+ currents and intracellular calcium levels ([Ca2+]i) were studied in isolated nerve terminals of the HNS. The µ‐receptor agonist, DAMGO ([d‐Ala2,N‐Me‐Phe4,Gly5‐ol]‐enkephalin) inhibited high K+‐induced peptide release in a dose‐dependent manner, with oxytocin release being more sensitive to block than vasopressin release at all concentrations tested. The addition of the µ‐receptor antagonist CTOP (d‐Phe‐Cys‐Tyr‐d‐Trp‐Orn‐Thr‐Pen‐Thr amide) was able to overcome the inhibitory effects of DAMGO. By contrast to previous results, voltage‐gated Ca2+ currents were sensitive to blockage by DAMGO and this inhibition was also prevented by CTOP. Furthermore, [Ca2+]i measurements with Fura‐2 corroborated the inhibition by DAMGO of calcium entry and its reversal by the µ‐receptor antagonist in these nerve terminals. Thus, the decrease in neuropeptide release, particularly for oxytocin, induced by the activation of µ‐opioid receptors in neurohypophysial terminals is mediated, at least in part, by a corresponding decrease in Ca2+ entry due to the inhibition of voltage‐gated Ca2+ channels.
Diversity, taxonomy and evolution of medium‐chain dehydrogenase/reductase superfamily
Authors: Riveros‐Rosas Héctor , Julián‐Sánchez Adriana , Villalobos‐Molina Rafael , Pardo Juan Pablo , Piña Enrique 
Published: August 2003

A comprehensive, structural and functional, in silico analysis of the medium‐chain dehydrogenase/reductase (MDR) superfamily, including 583 proteins, was carried out by use of extensive database mining and the blastp program in an iterative manner to identify all known members of the superfamily. Based on phylogenetic, sequence, and functional similarities, the protein members of the MDR superfamily were classified into three different taxonomic categories: (a) subfamilies, consisting of a closed group containing a set of ideally orthologous proteins that perform the same function; (b) families, each comprising a cluster of monophyletic subfamilies that possess significant sequence identity among them and might share or not common substrates or mechanisms of reaction; and (c) macrofamilies, each comprising a cluster of monophyletic protein families with protein members from the three domains of life, which includes at least one subfamily member that displays activity related to a very ancient metabolic pathway. In this context, a superfamily is a group of homologous protein families (and/or macrofamilies) with monophyletic origin that shares at least a barely detectable sequence similarity, but showing the same 3D fold.The MDR superfamily encloses three macrofamilies, with eight families and 49 subfamilies. These subfamilies exhibit great functional diversity including noncatalytic members with different subcellular, phylogenetic, and species distributions. This results from constant enzymogenesis and proteinogenesis within each kingdom, and highlights the huge plasticity that MDR superfamily members possess. Thus, through evolution a great number of taxa‐specific new functions were acquired by MDRs. The generation of new functions fulfilled by proteins, can be considered as the essence of protein evolution. The mechanisms of protein evolution inside MDR are not constrained to conserve substrate specificity and/or chemistry of catalysis. In consequence, MDR functional diversity is more complex than sequence diversity.MDR is a very ancient protein superfamily that existed in the last universal common ancestor. It had at least two (and probably three) different ancestral activities related to formaldehyde metabolism and alcoholic fermentation. Eukaryotic members of this superfamily are more related to bacterial than to archaeal members; horizontal gene transfer among the domains of life appears to be a rare event in modern organisms.
Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier
Authors: Gatto Cheryl L. , Walker Barbara J. , Lambert Stephen 
Published: August 2003

Nodes of Ranvier are specialized, highly polarized axonal domains crucial to the propagation of saltatory action potentials. In the peripheral nervous system, axo–glial cell contacts have been implicated in Schwann cell (SC) differentiation and formation of the nodes of Ranvier. SC microvilli establish axonal contact at mature nodes, and their components have been observed to localize early to sites of developing nodes. However, a role for these contacts in node formation remains controversial.
Using a myelinating explant culture system, we have observed that SCs reorganize and polarize microvillar components, such as the ezrin-binding phosphoprotein 50 kD/regulatory cofactor of the sodium-hydrogen exchanger isoform 3 (NHERF-1), actin, and the activated ezrin, radixin, and moesin family proteins before myelination in response to inductive signals. These components are targeted to the SC distal tips where live cell imaging reveals novel, dynamic growth cone–like behavior. Furthermore, localized activation of the Rho signaling pathway at SC tips gives rise to these microvillar component–enriched “caps” and influences the efficiency of node formation.
The Neurotrophins Nerve Growth Factor, Brain-derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4 Are Survival and Activation Factors for Eosinophils in Patients with Allergic Bronchial Asthma
Authors: Nassenstein Christina , Braun Armin , Erpenbeck Veit Johannes , Lommatzsch Marek , Schmidt Stephanie , Krug Norbert , Luttmann Werner , Renz Harald , Virchow Johann Christian 
Published: August 2003

Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma.
Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
CSF-induced and HIV-1–mediated Distinct Regulation of Hck and C/EBPβ Represent a Heterogeneous Susceptibility of Monocyte-derived Macrophages to M-tropic HIV-1 Infection
Authors: Komuro Iwao , Yokota Yasuko , Yasuda Sachiko , Iwamoto Aikichi , Kagawa Kiyoko S. 
Published: August 2003

Granulocyte/macrophage colony-stimulating factor (GM-CSF)–induced monocyte-derived macrophages (GM-MΦ) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MΦ) produce a large amount of HIV-1. M-MΦ express a high level of Hck and a large isoform of C/EBPβ, and HIV-1 infection increases the expression of Hck but not of C/EBPβ. GM-MΦ express a high level of C/EBPβ and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPβ but decreases that of Hck.
Treatment of M-MΦ with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPβ and inhibits the viral replication. Treatment of GM-MΦ with a moderate amount of AS-C/EBPβ not only inhibits the expression of the small isoform of C/EBPβ preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1–mediated distinct regulation of Hck and small isoform of C/EBPβ represent the heterogeneous susceptibility of tissue MΦ to HIV-1 infection, and the regulation of Hck and C/EBPβ are closely related and these two molecules affect one another.
The changing sources of new mortgage debt
Authors: Talbot Richard 
Published: August 2003

A much clearer understanding is needed of the forces driving the current upsurge in the mortgage market and of the key factors contributing to the exceptional growth of mortgage indebtedness. It would then be easier to judge whether the widely‐expected downswing in mortgage lending will be reasonably limited and gradual, or more pronounced and protracted.This paper, by Richard Talbot, develops an appropriate analytical framework and model that traces the composition of incremental mortgage borrowing over the period since the mid‐1980s. Estimates have been compiled for the various elements of additional borrowing using data from the Survey of Mortgage Lenders and the Bank of England back to 1993, and other statistics on the earlier composition of bank approvals and building society advances.This analysis of the debt aggregation process suggests that, at the level of the individual household, people simply will be unable, and indeed unwilling, to go on absorbing the relatively large amounts of incremental debt implied by many medium‐term forecasts for mortgage lending.
Stress during pregnancy is associated with developmental outcome in infancy
Authors: Huizink Anja C. , Robles de Medina Pascale G. , Mulder Eduard J.H. , Visser Gerard H.A. , Buitelaar Jan K. 
Published: August 2003

Background: Animal studies show that prenatal maternal stress may be related to cognitive impairments in offspring. Therefore, we examined whether psychological and endocrinologic measures of stress during human pregnancy predicted developmental outcome of the infant at 3 and 8 months.Method: Self‐report data about daily hassles and pregnancy‐specific anxiety and salivary cortisol levels were collected in 170 nulliparous women in early, mid‐ and late pregnancy in a prospective design, in which healthy infants born at term were followed up after birth.Results: High levels of pregnancy‐specific anxiety in mid‐pregnancy predicted lower mental and motor developmental scores at 8 months (p < .05). High amounts of daily hassles in early pregnancy were associated with lower mental developmental scores at 8 months (p < .05). Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months (p < .05 and p < .005, respectively) and motor development at 8 months (p < .01). On average a decline of 8 points on the mental and motor development scale was found. All results were adjusted for a large number of covariates.Conclusion: Stress during pregnancy appears to be one of the determinants of delay in motor and mental development in infants of 8 months of age and may be a risk factor for later developmental problems. Further systematic follow‐up of the present sample is needed to determine whether these delays are transient, persistent or even progressive.
The role of the clinician: three‐year predictive value of parents’, teachers’, and clinicians’ judgment of childhood psychopathology
Authors: Ferdinand Robert F. , Hoogerheide Kirsten N. , Van Der Ende Jan , Visser Jeroen Heijmens , Koot Hans M. , Kasius Marianne C. , Verhulst Frank C. 
Published: August 2003

Background: The present study investigated the differential predictive value of parents’, teachers’, and clinicians’ reports of psychopathology for poor outcome in children referred to a child psychiatric outpatient clinic.Method: A referred sample (N = 96), aged 6 to 12 years at initial assessment, was followed up after a mean interval of 3.2 years. Data on parent‐ and teacher‐reported problem behavior (Child Behavior Checklist and Teacher's Report Form), and clinician‐reported observations and self‐reports during a semi‐structured clinical interview (SCICA), were linked to outcome measures assessed with a parent questionnaire, including outpatient and inpatient treatment at Time 2, parent's wish for professional help for the child, school problems, and police/judicial contacts.Results: Information from all three informants (clinicians, parents, and teachers) predicted measures of poor outcome after three years. Clinicians’ ratings on the SCICA predicted all five outcome measures. Independent of CBCL and TRF scores, SCICA scores predicted parental wish for help and inpatient treatment.Conclusions: The present study was the first to report that clinician's ratings of self‐reported and observed behaviors in a semi‐structured interview (SCICA) make an important unique contribution to the multi‐axial assessment of problem behaviors.