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Dean C. Norman - One of the best experts on this subject based on the ideXlab platform.
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Effect of Age on Fever Response to Recombinant Interleukin-6 in a Murine Model
The journals of gerontology. Series A Biological sciences and medical sciences, 1995Co-Authors: Denver Miller, Thomas T. Yoshikawa, Dean C. NormanAbstract:BACKGROUND A blunted or absent Fever Response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile Response to recombinant IL-6 (rIL-6) using a well-defined murine model. METHODS Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes. RESULTS A dose-Response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature Response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes. CONCLUSIONS Our findings confirm that IL-6 has a role in the pathogenesis of Fever and that aging alters the febrile Response to rIL-6.
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Effect of age on Fever Response to recombinant tumor necrosis factor alpha in a murine model.
Journal of gerontology, 1991Co-Authors: Denver Miller, Steven C. Castle, Thomas T. Yoshikawa, Dean C. NormanAbstract:Certain elderly humans show a blunted Fever Response to infection. A study was designed using a murine model to assess the influence of age on the febrile Response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of Fever; (b) aging alters significantly the febrile Response; and (c) a mechanism of this age-related blunted febrile Response may involve TNF alpha.
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Fever Response in elderly nursing home residents: are the older truly colder?
Journal of the American Geriatrics Society, 1991Co-Authors: Steven C. Castle, Dean C. Norman, Michael W. Yeh, Denver Miller, Thomas T. YoshikawaAbstract:OBJECTIVE To test the hypothesis that many nursing home residents with an apparently blunted Fever Response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" Fever Response (Tmax less than 101 degrees F). Of the 25 "blunted" Fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of Fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections.
Denver Miller - One of the best experts on this subject based on the ideXlab platform.
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Effect of Age on Fever Response to Recombinant Interleukin-6 in a Murine Model
The journals of gerontology. Series A Biological sciences and medical sciences, 1995Co-Authors: Denver Miller, Thomas T. Yoshikawa, Dean C. NormanAbstract:BACKGROUND A blunted or absent Fever Response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile Response to recombinant IL-6 (rIL-6) using a well-defined murine model. METHODS Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes. RESULTS A dose-Response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature Response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes. CONCLUSIONS Our findings confirm that IL-6 has a role in the pathogenesis of Fever and that aging alters the febrile Response to rIL-6.
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Effect of age on Fever Response to recombinant tumor necrosis factor alpha in a murine model.
Journal of gerontology, 1991Co-Authors: Denver Miller, Steven C. Castle, Thomas T. Yoshikawa, Dean C. NormanAbstract:Certain elderly humans show a blunted Fever Response to infection. A study was designed using a murine model to assess the influence of age on the febrile Response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of Fever; (b) aging alters significantly the febrile Response; and (c) a mechanism of this age-related blunted febrile Response may involve TNF alpha.
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Fever Response in elderly nursing home residents: are the older truly colder?
Journal of the American Geriatrics Society, 1991Co-Authors: Steven C. Castle, Dean C. Norman, Michael W. Yeh, Denver Miller, Thomas T. YoshikawaAbstract:OBJECTIVE To test the hypothesis that many nursing home residents with an apparently blunted Fever Response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" Fever Response (Tmax less than 101 degrees F). Of the 25 "blunted" Fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of Fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections.
Tamas Bartfai - One of the best experts on this subject based on the ideXlab platform.
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single cell transcriptomics of hypothalamic warm sensitive neurons that control core body temperature and Fever Response signaling asymmetry and an extension of chemical neuroanatomy
Pharmacology & Therapeutics, 2011Co-Authors: James Eberwine, Tamas BartfaiAbstract:We report on an 'unbiased' molecular characterization of individual, adult neurons, active in a central, anterior hypothalamic neuronal circuit, by establishing cDNA libraries from each individual, electrophysiologically identified warm sensitive neuron (WSN). The cDNA libraries were analyzed by Affymetrix microarray. The presence and frequency of cDNAs were confirmed and enhanced with Illumina sequencing of each single cell cDNA library. cDNAs encoding the GABA biosynthetic enzyme Gad1 and of adrenomedullin, galanin, prodynorphin, somatostatin, and tachykinin were found in the WSNs. The functional cellular and in vivo studies on dozens of the more than 500 neurotransmitters, hormone receptors and ion channels, whose cDNA was identified and sequence confirmed, suggest little or no discrepancy between the transcriptional and functional data in WSNs; whenever agonists were available for a receptor whose cDNA was identified, a functional Response was found. Sequencing single neuron libraries permitted identification of rarely expressed receptors like the insulin receptor, adiponectin receptor 2 and of receptor heterodimers; information that is lost when pooling cells leads to dilution of signals and mixing signals. Despite the common electrophysiological phenotype and uniform Gad1 expression, WSN transcriptomes show heterogeneity, suggesting strong epigenetic influence on the transcriptome. Our study suggests that it is well-worth interrogating the cDNA libraries of single neurons by sequencing and chipping.
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Interleukin‐1 System: Receptors, Ligands, and ICE in the Brain and Their Involvement in the Fever Response
Annals of the New York Academy of Sciences, 1998Co-Authors: Katarina Alheim, Tamas BartfaiAbstract:The ligands and the receptors of the interleukin 1 (IL-1) system constitute a highly inducible set of proteins whose expression in infection and inflammation is of key importance in the host defense. The IL-1 system participates in the stimulation of the immune system, the neuroendocrine system, and the neuroimmune system. The major soluble and secreted agonist of the system, IL-1 beta, has been studied by mutational and transgenic approaches. Furthermore, involvement of the signal-transducing type I IL-1 receptor (IL-1RI), in Fever and other Responses, has been studied by null mutation technique. We describe the inducible expression of the two agonists, IL-1 alpha (31 kDa and 17 kDa) and IL-1 beta (17 kDa) and of the IL-1 receptor subtypes IL-1RI and IL-1RII in the brain and in the adrenals (as well as in the pituitary cell line AtT20). We also describe an additional member of the IL-1 family: the IL-1 receptor antagonist (IL-1ra), an endogenous antagonist to IL-1 alpha and IL-1 beta. Furthermore, the IL-1 beta-converting enzyme (ICE) and its differential regulation and expression in brain and adrenals is also discussed. Fever is a systemic Response to intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection of IL-1 alpha or IL-1 beta. IL-1 beta-induced Fever can be blocked by IL-1ra pretreatment. The Fever Response seems to be mediated via the IL-1RI as inferred from studies with receptor subtype-specific mutants of IL-1 beta and from studies in IL-1RI knock-out (IL-1RI KO) mice. IL-1 beta knock-out mice showed a hyperresponsive Fever to both IL-1 agonists, IL-1 alpha and IL-1 beta, as well as to LPS.
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Interleukin (IL)-6 gene expression in the central nervous system is necessary for Fever Response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice.
The Journal of experimental medicine, 1996Co-Authors: Z Chai, S Gatti, C Toniatti, Valeria Poli, Tamas BartfaiAbstract:Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the Fever Response has not yet been clarified. The purpose of this study was to determine the role of IL-6 in the Fever Response by making use of mice carrying a null mutation in the IL-6 gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg), respectively, failed to evoke Fever Response in IL-6-deficient mice, whereas the same doses of LPS and rmIL-1 beta caused Fever Response in wild-type mice. The Fever Response could be induced in the IL-6-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse), whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to produce Fever Response in the IL-6-deficient mice. These results suggest that central IL-6 is a necessary component of the Fever Response to both endogenous (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream from both peripheral and central IL-1 beta.
Thomas T. Yoshikawa - One of the best experts on this subject based on the ideXlab platform.
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Effect of Age on Fever Response to Recombinant Interleukin-6 in a Murine Model
The journals of gerontology. Series A Biological sciences and medical sciences, 1995Co-Authors: Denver Miller, Thomas T. Yoshikawa, Dean C. NormanAbstract:BACKGROUND A blunted or absent Fever Response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile Response to recombinant IL-6 (rIL-6) using a well-defined murine model. METHODS Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes. RESULTS A dose-Response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature Response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes. CONCLUSIONS Our findings confirm that IL-6 has a role in the pathogenesis of Fever and that aging alters the febrile Response to rIL-6.
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Effect of age on Fever Response to recombinant tumor necrosis factor alpha in a murine model.
Journal of gerontology, 1991Co-Authors: Denver Miller, Steven C. Castle, Thomas T. Yoshikawa, Dean C. NormanAbstract:Certain elderly humans show a blunted Fever Response to infection. A study was designed using a murine model to assess the influence of age on the febrile Response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of Fever; (b) aging alters significantly the febrile Response; and (c) a mechanism of this age-related blunted febrile Response may involve TNF alpha.
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Fever Response in elderly nursing home residents: are the older truly colder?
Journal of the American Geriatrics Society, 1991Co-Authors: Steven C. Castle, Dean C. Norman, Michael W. Yeh, Denver Miller, Thomas T. YoshikawaAbstract:OBJECTIVE To test the hypothesis that many nursing home residents with an apparently blunted Fever Response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" Fever Response (Tmax less than 101 degrees F). Of the 25 "blunted" Fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of Fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections.
Quentin J. Pittman - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of Fever At Near Term: Is Interleukin‐6–STAT3 Signalling Altered?
Journal of neuroendocrinology, 2006Co-Authors: E.-m. Harré, Abdeslam Mouihate, Quentin J. PittmanAbstract:Pregnant rats in late gestation show a reduced Fever Response after stimulation with lipopolysaccharide (LPS). This can result from either an increased action of endogenous antipyretics or a reduction in the production or action of endogenous pyrogens. Nonpregnant rats given LPS release interleukin (IL)-6, which causes nuclear translocation of the signal transducer and activator of transcription 3 (STAT3) in the vascular organ of the lamina terminalis (OVLT), followed by a significant increase in core body temperature. The present study investigated whether the reduced Fever Response in near-term pregnant rats is associated with a reduced nuclear STAT3 Response. Rats at gestation day 15 (G15), gestation day 21 (G21, near term) and at lactation day 5 (L5) were injected with LPS (50 microg/kg, i.p.) or vehicle. Only near-term pregnant rats responded with an attenuated body temperature during the Fever Response. Immunohistological analysis indicated no significant difference in nuclear STAT3 in the OVLT of the different animal groups 2 h after LPS. Measurement of total and phosphorylated STAT3 protein in the OVLT with semiquantitative western blot revealed no significant differences of this protein among these immune challenged animal groups. IL-6 concentrations were also similar at G15, G21 and L5 2 h after injection of LPS. These results lead to the conclusion that the attenuation of the Fever Response at near-term pregnancy is not associated with a reduced amount of nuclear STAT3 in the OVLT, indicating a maintained IL-6-STAT3 signalling pathway in the OVLT.
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Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways
American journal of physiology. Regulatory integrative and comparative physiology, 2005Co-Authors: Abdeslam Mouihate, E.-m. Harré, Shaun Ellis, Quentin J. PittmanAbstract:Near-term pregnant rats show a suppressed Fever Response to LPS that is associated with reduced induction of cyclooxygenase (COX)-2 in the hypothalamus. The objective of this study is to explore wh...
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Suppression of Fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus
American journal of physiology. Regulatory integrative and comparative physiology, 2002Co-Authors: Abdeslam Mouihate, M. S. Clerget-froidevaux, Kazuhiro Nakamura, Manabu Negishi, John L. Wallace, Quentin J. PittmanAbstract:The Fever Response is blunted at near term. As the enzyme cyclooxygenase-2 (COX-2) plays a critical role in Fever development, we measured its expression in rat hypothalamus during pregnancy and la...