bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay Between Superantigens and Immunoreceptors
Authors: Petersson K. , Forsberg G. , Walse B. 
Published: March 2004

AbstractSuperantigens (SAGs) cause a massive T‐cell proliferation by simultaneously binding to major histocompatibility complex (MHC) class II on antigen‐presenting cells and T‐cell receptors (TCRs) on T cells. These T‐cell mitogens can cause disease in host, such as food poisoning or toxic shock. The best characterized groups of SAGs are the bacterial SAGs secreted by Staphylococcus aureus and Streptococcus pyogenes. Despite a common overall three‐dimensional fold of these SAGs, they have been shown to bind to MHC class II in different ways. Recently, it has also been shown that SAGs have individual preferences in their binding to the TCRs. They can interact with various regions of the variable β‐chain of TCRs and at least one SAG seems to bind to the α‐chain of TCRs. In this review, different subclasses of SAGs are classified based upon their binding mode to MHC class II, and models of trimolecular complexes of MHC–SAG–TCR molecules are described in order to reveal and understand the complexity of SAG‐mediated T‐cell activation.
Human Miscarriage is Associated with Increased Number of CD26+ Decidual Lymphocytes
Authors: Sehmsdorf U. S. , Zenclussen A. C. , Arck P. , Hertwig K. , Joachim R. A. , Klapp B. , Hildebrandt M. O. 
Published: March 2004

AbstractDipeptidyl peptidase‐IV (DPP‐IV, CD26), a serine protease with broad distribution in mammalian tissues and known activity in serum, participates in T‐cell activation and promotes a Th1‐like cytokine response. Previous data on murine abortion indicate that DPP‐IV may play a critical role in pregnancy failure by inducing a Th1 local response. Here, we investigated the possible participation of DPP‐IV in the onset of human spontaneous abortion (SA).The systemic (peripheral blood) and local (decidua) percentages of CD4+, CD8+, CD26+ and CD56+ cells as well as the number of Th1 lymphocytes (CCR5+ cells) were assessed in samples from women after SAs (n = 20) and from women with normally progressing pregnancies (NPs) (n = 27) using flow cytometry and immunohistochemistry. We further measured the DPP‐IV activity and concentrations of Th1 (interferon‐γ and tumour necrosis factor‐α), Th2 [interleukin‐4 (IL‐4), IL‐10] and Th3 (transforming growth factor‐β2) cytokines in serum samples.We could not find any difference in the number of CD4+, CD8+, CD26+, CD26+/CD4+ or CD8+/CD26+ blood cells between NP and SA patients. No differences in the Th1, Th2 or Th3 cytokine levels could be observed between both groups. However, the percentages of decidual CD26+ lymphocytes as well as the number of decidual Th1 cells were significantly higher in SA samples compared to samples from patients with NP.Our data support the hypothesis that CD26+ decidual lymphocytes with DPP‐IV activity may play a critical role in SAs, as previously suggested in an abortion mice model. This abortive effect may be mediated by enhancing the levels of Th1 abortogenic cytokines only locally.
Immunization of Saimiri sciureus Monkeys with Plasmodium falciparum Merozoite Surface Protein‐3 and Glutamate‐Rich Protein Suggests that Protection is Related to Antibody Levels
Authors: Carvalho L. J. M. , Oliveira S. G. , Theisen M. , Alves F. A. , Andrade M. C. R. , Zanini G. M. , Brígido M. C. O. , Oeuvray C. , Póvoa M. M. , Muniz J. A. P. C. , Druilhe P. , Daniel‐Ribeiro C. T. 
Published: March 2004

AbstractThe immunogenicity and protective efficacy of various antigen‐adjuvant formulations derived either from the merozoite‐surface protein‐3 (MSP‐3) or the glutamate‐rich protein (GLURP) of Plasmodium falciparum were evaluated in Saimiri sciureus monkeys. These proteins were selected for immunogenicity studies based primarily on their capacity of inducing an antibody‐dependent cellular inhibition effect on parasite growth. Some of the S. sciureus monkeys immunized with MSP‐3212−380‐AS02 or GLURP27−500‐alum were able to fully or partially control parasitaemia upon an experimental P. falciparum [Falciparum Uganda Palo Alto (FUP‐SP) strain] blood‐stage infection, and this protection was related to the prechallenge antibody titres induced. The data are indicative that MSP‐3 and GLURP can induce protective immunity against an experimental P. falciparum infection using adjuvants that are acceptable for human use and this should trigger further studies with those new antigens.
Circulating CD4+CD25+ and CD4+CD25– T Cells in Myasthenia Gravis and in Relation to Thymectomy
Authors: Huang Y.‐M. , Pirskanen R. , Giscombe R. , Link H. , Lefvert A.‐K. 
Published: March 2004

AbstractStudies in experimental animal models of human autoimmune diseases have revealed that CD4+CD25+ T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto‐aggressive immunity. Myasthenia gravis (MG) is the best‐characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4+CD25+ versus CD4+CD25– cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4+CD25+ cells. CD4+CD25high cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4+CD25high cells were similar in MG patients irrespective of treatment with thymectomy. CD4+CD25+ cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4+CD25– cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)‐DR‐positive cells. In both MG patients and HCs, CD4+CD25+ cells also contained a high proportion of CD95‐expressing cells as possible evidence of apoptosis‐proneness. Upon stimulation with anti‐CD3/CD28 monoclonal antibodies, CD4+CD25+ cells responded more vigorously than CD4+CD25– cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4+CD25– cells are mainly naïve T cells, in non‐thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA‐DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4+CD25+ cells in MG, nor is the proportion of CD4+CD25+ cells influenced by thymectomy.
Long‐Term Modulation By Postnatal Oxytocin of the α2‐Adrenoceptor Agonist Binding Sites in Central Autonomic Regions and the Role of Prenatal Stress
Authors: Díaz‐Cabiale Z. , Olausson H. , Sohlström A. , Agnati L. F. , Narváez J. A. , Uvnäs‐Moberg K. , Fuxe K. 
Published: March 2004

AbstractThe aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life‐long effects on the α2‐agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the α2‐agonist [3H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of α2‐agonist binding sites in the NTS and in the hypothalamus. The Kd value of the α2‐agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food‐restricted dams, oxytocin treatment produced a significant increase of the Bmax values in the hypothalamus and the amygdala and the Kd value of the α2‐agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin‐induced increase of regional α2‐adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central α2‐adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of α2‐adrenoceptor signalling in adulthood may contribute to the anti‐stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in α2‐adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the α2‐agonist binding sites in the hypothalamus and the amygdala.
Plasma Vasopressin Concentrations and Fos Protein Expression in the Supraoptic Nucleus Following Osmotic Stimulation or Hypovolaemia in the Ovariectomized Rat: Effect of Oestradiol Replacement
Authors: Hartley D. E. , Dickson S. L. , Forsling M. L. 
Published: March 2004

AbstractThe set points for vasopressin release in response to increasing plasma osmolality and hypovolaemia alter with reproductive status. Here, we studied stimulated vasopressin release following ovariectomy and oestrogen replacement, neuronal activity being measured in terms of immediate early gene expression. Observations were carried out on three groups of female Sprague‐Dawley rats. The first group were ovariectomized. The second group were given a subcutaneous oestrogen implant (20 µg/ml oestradiol‐17β) at the time of ovariectomy. The final group were left intact and observations performed at oestrus. Two weeks after ovariectomy, vascular cannulae were implanted under anaesthesia and at least 48 h allowed for recovery before hormone release was stimulated by infusion of 1.5 m NaCl for 90 min, or hypovolaemia induced by the removal of 10 mg/kg body weight taken in 1‐ml aliquots. Blood pressure was monitored, and blood samples were taken for determination of packed cell volume and plasma vasopressin and osmolality. After a minimum of 48 h, the challenge was repeated, the rats anaesthetized, and perfused with 4% paraformaldehyde. Brain sections were processed for immunocytochemical detection of Fos protein. Vasopressin release in response to both stimuli was reduced in ovariectomized compared to intact rats and the response could be substantially restored by oestradiol replacement. The number of Fos positive cells in the supraoptic nucleus of oestrogen‐replaced rats was significantly higher than in the ovariectomized group and not statistically different from the intact group.
DAMGO Suppresses Both Excitatory and Inhibitory Synaptic Transmission in Supraoptic Neurones of Mouse Hypothalamic Slice Preparations
Authors: Honda E. , Ono K. , Inenaga K. 
Published: March 2004

AbstractOpioid effects on synaptic transmission in the mouse supraoptic nucleus (SON) were investigated using whole‐cell, patch‐clamp techniques. The µ‐opioid receptor agonist, [d‐Ala2, N‐Me‐Phe4, Gly5‐ol]‐enkephalin (DAMGO) decreased the amplitude of both evoked excitatory postsynaptic currents (eEPSCs) and inhibitory postsynaptic currents (eIPSCs), and also decreased the frequency of both miniature EPSCs and IPSCs without effect on the amplitude. The selective µ‐opioid receptor antagonist, d‐Phe‐Cys‐Tyr‐D‐Trp‐Orn‐Thr‐Pen‐Thr‐NH2, and the nonselective antagonist naloxone, antagonized these inhibitory effects. The application of DAMGO suppressed the amplitude of both the first and second evoked postsynaptic currents with a paired‐pulse stimulus protocol, but increased the paired‐pulse ratios (second ePSC/first ePSC). DAMGO induced neither inward nor outward currents, and had no significant changes in either glutamate‐ or GABA‐induced currents. When compared with the relatively selective κ‐ and δ‐opioid receptor agonists dynorphin and [D‐Pen2, D‐Pen5]‐enkephalin, DAMGO showed the most potent inhibitory effects on evoked and miniature postsynaptic currents. Taken together, these results imply that DAMGO strongly suppresses the release of glutamate and GABA via µ‐opioid receptors in the mouse SON, and support the involvement of presynaptic regulation by opioids in the control of magnocellular neurosecretory neurones.
Intracellular Calcium Increase and Somatodendritic Vasopressin Release by Vasopressin Receptor Agonists in the Rat Supraoptic Nucleus: Involvement of Multiple Intracellular Transduction Signals
Authors: Sabatier N. , Shibuya I. , Dayanithi G. 
Published: March 2004

AbstractVasopressin neurones of the supraoptic nucleus are autoregulated by vasopressin released from their soma and dendrites. Vasopressin binds to specific autoreceptors to trigger an influx of Ca2+, and this response involves both phospholipase C (PLC) and adenylate cyclase (AC) pathways that, in the periphery, are activated by V1 (V1a and V1b)‐ and V2‐type receptors. To investigate the pathways involved in the [Ca2+]i response, [Ca2+]i measurements were made on freshly dissociated neurones using Fura‐2 microspectrofluorimetry, and vasopressin release was measured from isolated supraoptic nuclei. The [Ca2+]i increase and vasopressin release induced by the V1a agonist were strongly inhibited by a PLC blocker, an IP3 receptor antagonist, and a PKC blocker. An AC inhibitor did not affect the V1a response, while PKA inhibitors significantly reduced the V1a‐induced [Ca2+]i and release responses. The [Ca2+]i increase and vasopressin release elicited by the V2 agonist were attenuated not only by AC pathway blockers, but also by PLC inhibitors. Surprisingly, the V1b agonist showed no [Ca2+]i or vasopressin release response. In conclusion, the V1a agonist activates both PLC and AC pathway, confirming the functional expression of a V1a vasopressin receptor on vasopressin neurones. The V2 agonist activation of both PLC and AC pathways could result from an action on the PLC‐linked unknown receptor, and/or the AC‐linked dual angiotensin II‐vasopressin receptor.
Leptin‐Mediated Effects of Undernutrition or Fasting on Luteinizing Hormone and Growth Hormone Secretion in Ovariectomized Ewes Depend on the Duration of Metabolic Perturbation
Authors: Henry B. A. , Goding J. W. , Tilbrook A. J. , Dunshea F. R. , Blache D. , Clarke I. J. 
Published: March 2004

AbstractWe aimed to determine the importance of leptin in the regulation of luteinizing hormone (LH) and growth hormone (GH) secretion in ovariectomized (OVX) ewes. Lean and fat sheep were produced by dietary manipulation over 8 months and were then fasted for 32 h. Plasma concentrations of glucose, insulin and leptin were higher in the fat group. Fasting decreased plasma concentrations of glucose and insulin and increased concentrations of nonesterified fatty acids (NEFA) in fat and lean ewes, but leptin concentrations were reduced in the fat group only. Plasma GH concentrations were higher in the lean group and LH concentrations were lower; there was no effect of fasting. These data suggested that long‐term changes in plasma leptin concentrations might affect LH and GH secretion, but acute changes with fasting had no effect. OVX ewes of normal body weight were fasted for 72 h with or without intracerebroventricular (i.c.v.) infusion of leptin (4 µg/h), achieving similar metabolic effects to the 32 h fast. The 72‐h fast increased LH pulse amplitude, mean GH and cortisol concentrations, but these changes were corrected towards normal by leptin treatment. Thus, leptin could attenuate fasting‐induced alterations in the secretion of LH, GH and cortisol. Finally, we food‐restricted OVX ewes for 4 months (lean), leading to a 20‐kg reduction in body weight. Plasma concentrations of leptin and insulin were decreased, and plasma GH concentrations increased, but there was no effect on plasma concentrations of LH, glucose or NEFA. Icv infusion of leptin did not affect any endocrine or metabolic parameter in these ewes. In summary, maintenance of a lean or fat condition for a prolonged period (8 months) or an extended fasting (72 h) can affect LH and GH secretion, but short‐term food restriction (4 months) affected only GH secretion and short‐term fasting (32 h) had no effect on either LH or GH secretion. This is in spite of altered plasma leptin concentrations in all circumstances studied. Although leptin treatment can restore plasma concentrations of LH, GH and cortisol towards normal in sheep fasted for 72 h, some other factor(s) must signal to the brain to cause shifts in neuroendocrine function in other conditions where nutritional/metabolic status is altered.
Acute Carbon Dioxide Exposure in Healthy Adults: Evaluation of a Novel Means of Investigating the Stress Response
Authors: Kaye J. , Buchanan F. , Kendrick A. , Johnson P. , Lowry C. , Bailey J. , Nutt D. , Lightman S. 
Published: March 2004

AbstractAcute hypercapnia was studied to assess its potential as a noninvasive and simple test for evoking neuroendocrine, cardiovascular and psychological responses to stress in man. A single breath of four concentrations of carbon dioxide (CO2), 5%, 25%, 35% and 50%, was administered to nine healthy volunteers in a randomized, single‐blind fashion. Although no adverse effects occurred, most subjects were unable to take a full inspired vital capacity breath of 50% CO2. In response to the remaining exposures, subjective and somatic symptoms of anxiety increased in a dose‐dependent manner. Unlike 5% and 25% CO2, 35% CO2stimulated significant adrenocorticotropic hormone and noradrenaline release at 2 min and cortisol and prolactin release at 15 min following inhalation. This same dose also provoked a significant bradycardia that was followed by an acute pressor response. No significant habituation of psychological, hypothalamic‐pituitary‐adrenal (HPA) or cardiovascular responses following 35% CO2was seen when this dose was repeated after 1 week. A single breath of 35% CO2safely and reliably produced sympathetic and HPA axis activation and should prove a useful addition to currently available laboratory tests of the human stress response.
Androgen Inhibits, While Oestrogen Enhances, Restraint‐Induced Activation of Neuropeptide Neurones in the Paraventricular Nucleus of the Hypothalamus
Authors: Lund T. D. , Munson D. J. , Haldy M. E. , Handa R. J. 
Published: March 2004

AbstractThe hormonal response to stress is enhanced by oestrogen but inhibited by androgens. To determine underlying changes in activity of neuropeptide neurones in the paraventricular nucleus of the hypothalamus (PVN), we examined the effect of oestrogen and androgen treatment on restraint‐induced c‐fos mRNA, corticotropin‐releasing hormone (CRH) heteronuclear RNA, and arginine vasopressin hnRNA expression in the PVN. Male rats were gonadectomized and injected with oestradiol benzoate (EB) or dihydrotestosterone propionate (DHTP; s.c., daily for 4 days). Rats were stressed by restraint for 10 min or 30 min before killing. Other rats were stressed for 30 min and then returned to their home cage for 20 min before killing. Corticosterone and adrenocorticotropic hormone responses to restraint stress were significantly greater in EB‐treated rats and lower in DHTP‐treated rats at the 30‐min timepoint compared to controls. c‐fos mRNA increases following stress were augmented by EB but inhibited by DHTP. CRH hnRNA expression increased significantly in the PVN in response to restraint stress, and this increase was augmented by EB treatment, but decreased by DHTP treatment. Vasopressin hnRNA expression was also increased in response to stress, and this increase was attenuated by DHTP. These findings indicate that gonadal hormones influence the reactivity of the hypothalamic‐pituitary adrenal axis to stress.
Roles of Corticotropin‐Releasing Factor, Neuropeptide Y and Corticosterone in the Regulation of Food Intake In Xenopus laevis
Authors: Crespi E. J. , Vaudry H. , Denver R. J. 
Published: March 2004

AbstractIn mammals, hypothalamic control of food intake involves counterregulation of appetite by anorexigenic peptides such as corticotropin‐releasing factor (CRF), and orexigenic peptides such as neuropeptide Y (NPY). Glucocorticoids also stimulate food intake by inhibiting CRF while facilitating NPY actions. To gain a better understanding of the diversity and evolution of neuroendocrine feeding controls in vertebrates, we analysed the effects of CRF, NPY and glucocorticoids on food intake in juvenile Xenopus laevis. We also analysed brain CRF and NPY mRNA content and plasma corticosterone concentrations in relation to nutritional state. Intracerebroventricular (i.c.v.) injection of ovine CRF suppressed food intake while CRF receptor antagonist αhelical CRF(9–41) significantly increased food intake relative to uninjected and placebo controls. By contrast, i.c.v. injection of frog NPY and short‐term corticosterone treatment increased food intake. Semi‐quantitative reverse transcription‐polymerase chain reaction analyses showed that CRF and NPY mRNA fluctuated with food intake in the brain region containing the mid‐posterior hypothalamus, pretectum, and optic tectum: CRF mRNA decreased 6 h after a meal and remained low through 31 days of food deprivation; NPY mRNA content also decreased 6 h after a meal, but increased to prefeeding levels by 24 h. Plasma corticosterone concentration increased 6 h after a meal, returned to prefeeding levels by 24 h, and did not change with prolonged food deprivation. This postprandial increase in plasma corticosterone may be related to the subsequent increase in plasma glucose and body water content that occurs 24 h postfeeding. Overall, our data support the conclusion that, similar to other vertebrates, CRF is anorexigenic while NPY is orexigenic in X. laevis, and CRF secretion modulates food intake in the absence of stress by exerting an inhibitory tone on appetite. Furthermore, the stress axis is activated in response to food intake, but in contrast to mammals and birds is not activated during periods of food deprivation.
Modelling the Pituitary Response to Luteinizing Hormone‐Releasing Hormone
Authors: Scullion S. , Brown D. , Leng G. 
Published: March 2004

AbstractThe pituitary response to luteinizing hormone‐releasing hormone (LHRH) is steroid‐dependent and varies throughout the reproductive cycle, but the rapid rise in pituitary sensitivity on the day of the ovulation‐inducing LH surge is due to a ‘self‐priming’ effect of exposure to LHRH that results in a potentiation of pituitary responsiveness 35–40 min later. The expression of this effect is itself steroid‐dependent, and is most marked on pro‐oestrus. Here, a model of LHRH‐induced LH release was developed to incorporate the changes in pituitary sensitivity observed throughout the reproductive cycle. LH release is based on the Law of Mass Action, and a component related to self‐priming is included in the model, incorporating the delay between initial exposure and potentiation of responsiveness and an upper maximum to the achievable level of priming. Where possible, model parameters were obtained from biological values, otherwise they were optimized to fit an experiment performed in vivo. These parameters were then used to test the model against other experimental data obtained both in vivo and in vitro. The model provided a good fit to the in vivo data but the in vitro experimental data required a change in one parameter, the upper limit of priming. We conclude that this model of the pituitary release mechanism can simulate the changes in pituitary responsiveness throughout the reproductive cycle. We suggest that substitution of this model in a previous model of the LHRH pulse generator could allow more appropriate tests of the LHRH pulse generator model.