bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mobility group 1 B‐box mediates activation of human endothelium
Authors: Treutiger C. J. , Mullins G. E. , Johansson A.‐S. M. , Rouhiainen A. , Rauvala H. M. E. , Erlandsson‐Harris H. , Andersson U. , Yang H. , Tracey K. J. , Andersson J. , Palmblad J. E. W. 
Published: September 2003

Abstract Treutiger CJ, Mullins GE, Johansson A‐SM, Rouhiainen A, Rauvala HME, Erlandsson‐Harris H, Andersson U, Yang H, Tracey KJ, Andersson J, Palmblad JEW (Center for Infectious Medicine; Center for Inflammation and Haematology Research; Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden, Finnish Red Cross Blood Transfusion Service; Institute of Biotechnology, University of Helsinki; Helsinki, Finland, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden and North Shore‐Long Island Jewish Research Institute, NY, USA). High mobility group 1 B‐box mediates activation of human endothelium. J Intern Med 2003; 254: 375–385.Objectives. Severe sepsis and septic shock is a consequence of a generalized inflammatory systemic response because of an invasive infection that may result in acute organ dysfunction. Mortality is high despite access to modern intensive care units. The nuclear DNA binding protein high mobility group 1 (HMGB1) protein has recently been suggested to act as a late mediator of septic shock via its function as a macrophage‐derived pro‐inflammatory cytokine (J Exp Med 2000; 192: 565, Science1999; 285: 248). We investigated the pro‐inflammatory activities of the A‐box and the B‐box of HMGB1 on human umbilical venular endothelial cells (HUVEC).Design. The HUVEC obtained from healthy donors were used for experiments. Recombinant human full‐length HMGB1, A‐box and B‐box were cloned by polymerase chain reaction (PCR) amplification from a human brain quick‐clone cDNA. The activation of HUVEC was studied regarding (i) upregulation of adhesion molecules, (ii) the release of cytokines and chemokines, (iii) the adhesion of neutrophils to HUVEC, (iv) the activation of signalling transduction pathways and (v) the involvement of the receptor for advanced glycation end‐products (RAGE).Results. The full‐length protein and the B‐box of HMGB1 dose‐dependently activate HUVEC to upregulate adhesion molecules such as ICAM‐1, VCAM‐1 and E‐selectin and to release IL‐8 and G‐CSF. The activation of HUVEC could be inhibited to 50% by antibodies directed towards the RAGE. HMGB1‐mediated HUVEC stimulation resulted in phosphorylation of the ELK‐1 signal transduction protein and a nuclear translocation of p65 plus c‐Rel, suggesting that HMGB1 signalling is regulated in endothelial cells through NF‐κB.Conclusions. The HMGB1 acts as a potent pro‐inflammatory cytokine on HUVEC and the activity is mainly mediated through the B‐box of the protein. HMGB1 may be a key factor mediating part of the pro‐inflammatory response occurring in septic shock and severe inflammation.
Lesions of the Diagonal Band of Broca Enhance Drinking in the Rat
Authors: Sullivan M. J. , Cunningham J. T. , Mazzella D. , Allen A. M. , Nissen R. , Renaud L. P. 
Published: September 2003

AbstractThis study examined the role of the diagonal band of Broca (DBB) in drinking behaviour and vasopressin release. Adult male rats were anaesthetized (pentobarbital 50 mg/kg) and received DBB injections of either ibotenic acid (0.5 µl of 5 µg/µl) or vehicle (0.5 µl of phosphate‐buffered saline). Although baseline drinking and urine output were not affected, drinking to 30% polyethylene glycol (MW 8000; 1 ml/100 g s.c.) and angiotensin II (0, 1.5 and 3.0 mg/kg s.c.) were significantly increased in ibotenic acid in phosphate‐buffered saline (DBBX) rats. Drinking to hypertonic saline (0.9, 4 and 6%; 1 ml/100 g), and water deprivation were not significantly affected. DBBX rats had significantly lower basal heart rates than controls but the cardiovascular responses to infusions of angiotensin II (100 ng/kg/min i.v. for 45 min) were not affected. DBBX rats had significantly higher basal vasopressin, but angiotensin‐stimulated vasopressin release was not significantly different. Although the DBB is not involved in basal water intake, it is involved in dipsogenic responses to hypovolemic stimuli and possibly basal autonomic function and basal vasopressin release.
Corticotropin‐Releasing Factor Type‐1 Receptor mRNA is Not Induced in Mouse Hypothalamus By Either Stress or Osmotic Stimulation
Authors: Imaki T. , Katsumata H. , Konishi S.‐I. , Kasagi Y. , Minami S. 
Published: September 2003

AbstractIn rats, acute stress substantially increases corticotropin‐releasing factor (CRF) type 1 receptor (CRFR‐1) mRNA expression in the paraventricular nucleus (PVN) and osmotic stimulation induces both CRF and CRFR‐1 mRNA in magnocellular PVN and supraoptic nucleus (SON). However, these phenomena have not been analysed in other species. We compared CRF and CRFR‐1 expression in rat and mouse hypothalamus. Male C57BL/6 mice and Wistar rats were exposed to acute restraint stress for 3 h, or to hypertonic saline ingestion for 7 days. Restraint stress increased CRF and c‐fos mRNA expression in both rat and mouse PVN. CRFR‐1 mRNA was barely detectable in controls, whereas restraint stress substantially increased CRFR‐1 mRNA in rat PVN, but not in mouse. Hypertonic saline ingestion induced CRF mRNA in magnocellular PVN and SON of the rat, but did not alter CRF mRNA levels in mouse hypothalamus. CRFR‐1 mRNA was also induced in magnocellular PVN and SON of the rat in response to osmotic stimulation, but not in mouse. Immunohistochemistry demonstrated that CRFR‐1‐like immunoreactivity (ir) was distributed within parvocellular and magnocellular PVN of mouse and rat. CRFR‐1‐ir in rat PVN was increased by acute stress and osmotic stimulation. By contrast, these treatments did not alter CRFR‐1‐ir in mouse PVN. Combined immunohistochemistry and in situ hybridization revealed that CRFR‐1‐ir was most frequently colocalized to CRF in mouse PVN, whereas only a small percentage of oxytocin and vasopressin‐producing cells coexpressed CRFR‐1‐ir. These results indicate that (i) by contrast to rats, neither acute stress nor osmotic stimulation induces CRFR‐1 mRNA expression in the mouse PVN; (ii) osmotic stimulation does not alter CRF mRNA expression in parvocellular and magnocellular neurones of mouse PVN; and (iii) acute stress increases c‐fos and CRF mRNA to a similar degree in mouse and rat PVN. Thus, differences may exist between mouse and rat in the regulation of CRF and CRFR‐1 gene expression in hypothalamus following stress and osmotic stimulation.
Influence of Monoamines on Differentiating Gonadotropin‐Releasing Hormone Neurones in Foetal Mice
Authors: Pronina T. , Ugrumov M. , Calas A. , Seif I. , Tramu G. 
Published: September 2003

AbstractThis study evaluated the influence of monoamines, serotonin (5‐hydroxytryptamine, 5‐HT) and noradrenaline, on differentiating gonadotropin‐releasing hormone (GnRH)‐producing neurones in foetal mice. The differentiation and migration of GnRH neurones were compared in Tg8 mice (the knocked‐out gene encoding monoamine oxidase A) with increased levels of 5‐HT and noradrenaline and in C3H mice with normal metabolism of monoamines in C3H mice. To achieve this, immunocytochemistry for GnRH combined with quantitative and semiquantitative image analysis were employed. GnRH neurones in foetuses at the 18th embryonic day were detected in the forebrain along the trajectory of their migration from the olfactory bulbs to the hypothalamic retrochiasmatic region. The total number of GnRH neurones in the forebrain in knockout mice was significantly lower compared to C3H mice, suggesting an inhibiting influence of monoamines on the proliferation of precursor cells. The fraction of GnRH neurones in the caudal part of the trajectory of their migration in Tg8 mice exceeded significantly those in C3H foetuses, whereas there was a reverse in the rostral part of the trajectory. These data suggest that an excess of 5‐HT and noradrenaline served to accelerate the GnRH neurone migration in Tg8 mice. Moreover, an excess of 5‐HT and noradrenaline provided a minor effect on the area and optical density of GnRH neurones (i.e. on GnRH neurone differentiation). Thus, an excess of 5‐HT and noradrenaline appears to inhibit the proliferation of the precursor cells of GnRH neurones and stimulates the GnRH neurone migration to the place of their final location in the septo‐preoptic region.
Histamine and Prostaglandin Interaction in Regulation of Oxytocin and Vasopressin Secretion
Authors: Knigge U. , Kjær A. , Kristoffersen U. , Madsen K. , Toftegaard C. , Jørgensen H. , Warberg J. 
Published: September 2003

AbstractProstaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose‐dependently stimulated by intracerebroventricular infusion of 1 or 5 µg of PGE1, PGE2 or PGF2α, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2α. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four‐ and two‐fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose‐dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2α interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.
Long‐Term Effects of Ciliary Neurotrophic Factor on the Survival of Vasopressin Magnocellular Neurones in the Rat Supraoptic Nucleus In Vitro
Authors: Rusnak M. , House S. B. , Gainer H. 
Published: September 2003

AbstractThe use of hypothalamic organotypic cultures for the long‐term study of mechanisms in magnocellular neurones (MCNs) of the hypothalamic‐neurohypophysial system has been limited by the relatively poor maintenance of the vasopressin MCNs in vitro. Recent studies have shown that addition of ciliary neurotrophic factor (CNTF) to the media significantly reduced the apoptosis of both oxytocin and vasopressin MCNs. Here, we studied various temporal factors in the CNTF treatment that can influence the efficacy of MCN survival. Immunohistochemistry was used to identify and count surviving vasopressin and oxytocin MCNs in the supraoptic nucleus (SON) in hypothalamic slices cultured in the presence of CNTF (10 ng/ml media) for various time intervals, and in situ hybridization for vasopressin mRNA was used to evaluate the vasopressin mRNA gene expression in the SON under the same conditions. The presence of CNTF in the medium for 10 days produced a maximal increase in the survival of vasopressin MCNs (by 11‐fold) and in the survival of oxytocin‐MCNs (by approximately four‐fold) over controls. These effects persisted for an additional 7–10 days even in the absence of CNTF. The ability of CNTF to increase survival of the MCNs or increase vasopressin mRNA levels in the SON required that the CNTF be present during the initial 7–10 days of culture. CNTF failed to rescue vasopressin or oxytocin MCNs when added to the media only for the last 7 days of a total of 14 days in vitro. Similar results were observed when SON vasopressin mRNA levels were measured. These results indicate that the presence of CNTF is required at the outset to rescue the vasopressin and oxytocin MCN from axotomy induced apoptosis, and that, after 10 days in CNTF, the MCNs no longer require the CNTF for survival.
Kinase‐Dependent Regulation of the Secretion of Thyrotrophin and Luteinizing Hormone By Glucocorticoids and Annexin 1 Peptides
Authors: John C. D. , Christian H. C. , Morris J. F. , Flower R. J. , Solito E. , Buckingham J. C. 
Published: September 2003

AbstractOur previous studies have identified a role for annexin 1 (ANXA1), a protein produced by the pituitary folliculostellate cells, as a paracrine/juxtacrine mediator of the acute regulatory effects of glucocorticoids on the release of adrenocorticotropic hormone and other pituitary hormones. In the present study, we focused on the secretion of thyroid stimulating hormone (TSH) and luteinizing hormone (LH) and used a battery of ANXA1‐derived peptides to identify the key domains in the ANXA1 molecule that are critical to the inhibition of peptide release. In addition, as ANXA1 is a substrate for protein kinase C (PKC) and tyrosine kinase, we examined the roles of these kinases in the manifestation of the ANXA1‐dependent inhibitory actions of dexamethasone on TSH and LH release. Dexamethasone suppressed the forskolin‐induced release of TSH and LH from rat anterior pituitary tissue in vitro. Its effects were mimicked by human recombinant ANXA1 (hrANXA1) and a truncated protein, ANXA11‐188. ANXA1Ac2−26, also suppressed stimulated peptide release but it lacked both the potency and the efficacy of the parent protein. Shorter N‐terminal ANXA1 sequences were without effect. The PKC inhibitor PKC19‐36 abolished the inhibitory actions of dexamethasone on the forskolin‐evoked release of TSH and LH; it also attenuated the inhibitory actions of ANXA1Ac2−26. Similar effects were produced by annexin 5 (ANXA5) which sequesters PKC in other systems. By contrast, the tyrosine kinase inhibitors, p60v‐src (137–157) and genistein, had no effect on the secretion of TSH or LH alone or in the presence of forskolin and/or dexamethasone. Dexamethasone caused the translocation of a tyrosine‐phosphorylated species of ANXA1 to the surface of pituitary cells. The total amount of ANXA1 exported from the cells in response to the steroid was unaffected by tyrosine kinase blockade. However, the degree of tyrosine‐phosphorylation of the exported protein was markedly reduced by genistein. These results suggest that (i) the ANXA1‐dependent inhibitory actions of dexamethasone on the release of TSH and LH require PKC and sequences in the N‐terminal domain of ANXA1, but are independent of tyrosine kinase, and (ii) while dexamethasone induces the cellular exportation of a tyrosine‐phosphorylated species of ANXA1, tyrosine phosphorylation per se is not critical to the steroid‐induced passage of ANXA1 across the membrane.
DNA Microarray Analyses of Circadian Timing: The Genomic Basis of Biological Time
Authors: Duffield G. E. 
Published: September 2003

AbstractMany aspects of physiology and behaviour are organized around a daily rhythm, driven by an endogenous circadian clock. Studies across numerous taxa have identified interlocked autoregulatory molecular feedback loops which underlie circadian organization in single cells. Until recently, little was known of (i) how the core clock mechanism regulates circadian output and (ii) what proportion of the cellular transcriptome is clock regulated. Studies using DNA microarray technology have addressed these questions in a global fashion and identified rhythmically expressed genes in numerous tissues in the rodent (suprachiasmatic nucleus, pineal gland, liver, heart, kidney) and immortalized fibroblasts, in the head and body ofDrosophila, in the fungusNeurosporaand the higher plantArabidopsis. These clock controlled genes represent 0.5–9% of probed genes, with functional groups covering a broad spectrum of cellular pathways. There is considerable tissue specificity, with only approximately 10% rhythmic genes common to at least one other tissue, principally consisting of known clock genes. The remaining common genes may constitute genes operating close to the clock mechanism or novel core clock components. Microarray technology has also been applied to understand input pathways to the clock, identifying potential signalling components for clock resetting in fibroblasts, and elucidating the temperature entrainment mechanism inNeurospora. This review explores some of the common themes found between tissues and organisms, and focuses on some of the striking connections between the molecular core oscillator and aspects of circadian physiology and behaviour. It also addresses the limitations of the microarray technology and analyses, and suggests directions for future studies.
Photoperiod Alters the Time Course of Brain Cyclooxygenase‐2 Expression in Siberian Hamsters
Authors: Bilbo S. D. , Quan N. , Prendergast B. J. , Bowers S. L. , Nelson R. J. 
Published: September 2003

AbstractFever is initiated by activation of the arachidonic acid cascade and the biosynthesis of prostaglandins within the brain. Inducible cyclooxygenase (COX‐2) is a rate‐limiting enzyme in prostaglandin synthesis, and the number of blood vessels expressing COX‐2 correlates with elevated body temperature following peripheral lipopolysaccharide (LPS). Despite its importance in host defense, fever is energetically expensive and we hypothesized that fever may be limited by available metabolic resources. During winter, when competing metabolic demands are constrained by low temperatures and food availability, it was predicted that fever duration would be reduced in seasonally breeding Siberian hamsters (Phodopus sungorus). We measured LPS‐induced COX‐2 expression in blood vessels of hamsters to test whether photoperiodic alterations in fever duration are centrally mediated, or whether they reflect changes in peripheral modulation of body temperature. Hamsters housed in long, ‘summer‐like’ or short, ‘winter‐like’ day lengths for 10 weeks were injected with LPS, and brains were collected 2, 4, or 8 h later. COX‐2 expression was comparably increased in long‐ and short‐day hamsters by 2 h and 4 h post‐LPS; however, short‐day hamsters exhibited significantly fewer COX‐2‐positive cells and blood vessels by 8 h post‐LPS compared to long‐day hamsters, corresponding with reduced fever duration in short‐day hamsters. Cortisol concentrations increased more than two‐fold in short‐day compared to long‐day hamsters by 4 h; this increase may have contributed to the decrease in COX‐2 expression observed by 8 h in short days. We conclude that short photoperiods significantly altered the time course of central COX‐2 protein expression in hamsters in a manner consistent with reduced fever duration.
Central Nervous System Receptors Involved in Mediating the Inhibitory Action of Neuropeptide Y on Luteinizing Hormone Secretion in the Male Rhesus Monkey (Macaca mulatta)
Authors: Shahab M. , Balasubramaniam A. , Sahu A. , Plant T. M. 
Published: September 2003

AbstractAn earlier finding that gonadotropin‐releasing hormone (GnRH) secretion may be triggered prematurely in the juvenile male monkey by central administration of 1229U91, a Y1 receptor antagonist, contributed to our current hypothesis that neuropeptide Y (NPY) is a major component of the brake that holds pulsatile GnRH release in check during prepubertal development in primates. However, 1229U91 is also a Y4 receptor agonist, and the present study was conducted to further examine the role of the Y1 receptor in mediating the putative inhibitory action of NPY on GnRH release. Agonadal juvenile and postpubertal male monkeys were implanted with i.v. and i.c.v. cannulae to gain continuous access to the venous and cerebroventricular circulations without sedation. Luteinizing hormone (LH) secretion was measured to provide an indirect index of GnRH release. The specific Y1 antagonists, VD‐11 (476 µg; n = 4) and isopropyl 3‐chloro‐5‐[1‐({6‐[2‐(5‐ethyl‐4‐methyl‐1,3‐thiazol‐2‐yl)ethyl]‐4‐morpholin‐4‐ylpyridin‐2‐yl}amino)ethyl]phenylcarbamate (Compound A, 300 µg; n = 4), did not mimic the stimulatory action of 1229U91 on GnRH secretion in the juvenile male monkey. Additionally, neither NPY (200 µg; n = 2), a general Y receptor agonist, nor rPP (100 µg; n = 4), a Y4 agonist, mimicked the action of 1229U91 in stimulating GnRH release. Moreover, previous exposure of the hypothalamus of juvenile monkeys (n = 5) to NPY (660 µg) failed to block 1229U91‐induced (200 µg) GnRH release. However, the action of NPY (364 µg) in inhibiting GnRH release postpubertally was attenuated by 1229U91 (300 µg). We conclude that, although the action of exogenous NPY to suppress GnRH release from the postpubertal hypothalamus appears to be mediated, at least in part, by the Y1 receptor, the existence of a Y1 receptor pathway inhibitory to GnRH release in the prepubertal hypothalamus remains to be substantiated.
Short‐Photoperiod Exposure Reduces Vasopressin (V1a) Receptor Binding But Not Arginine‐Vasopressin‐Induced Flank Marking in Male Syrian Hamsters
Authors: Caldwell H. K. , Albers H. E. 
Published: September 2003

AbstractIn Syrian hamsters, socially relevant information is communicated with a form of scent marking known as flank marking. There is substantial evidence that arginine‐vasopressin acting on V1a vasopressin receptors (V1aR) in the medial preoptic‐anterior hypothalamic continuum (MPOA‐AH) regulates the expression of flank marking. Previous studies have shown that the expression of flank marking is also influenced by the circulating concentrations of gonadal hormones. In hamsters housed in long ‘summer‐like’ photoperiods (i.e. >12.5 h of light/day), castration reduces flank marking and administration of testosterone restores precastration levels of flank marking. When exposed to short ‘winter‐like’ photoperiods (i.e. <12.5 h of light/day), hamsters undergo gonadal regression and the circulating levels of testosterone decline. Surprisingly, flank marking induced during social encounters is not reduced in hamsters exposed to short photoperiods despite the low circulating concentrations of testosterone. In the present study, it was hypothesized that reductions in testosterone, caused by exposure to short photoperiod, would not reduce the ability of vasopressin to stimulate flank marking by its actions in the MPOA‐AH. The amount of flank marking induced by vasopressin injected into the MPOA‐AH did not significantly differ between hamsters housed in long and short photoperiods; however, short photoperiod‐exposed males had significantly less V1aR binding in the MPOA than long photoperiod‐exposed males. These results support the hypothesis that the sensitivity of the MPOA‐AH to vasopressin is not reduced in short photoperiod‐exposed males, despite decreases in serum testosterone. However, by contrast to our predictions, short photoperiod‐exposed males have significantly reduced V1aR binding in the MPOA‐AH compared to long photoperiod‐exposed males.