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Mark R Green - One of the best experts on this subject based on the ideXlab platform.
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cisplatin vinblastine and Hydrazine Sulfate in advanced non small cell lung cancer a randomized placebo controlled double blind phase iii study of the cancer and leukemia group b
Journal of Clinical Oncology, 1994Co-Authors: Michael P Kosty, Stewart B Fleishman, James E Herndon, K Coughlin, Alice B Kornblith, A Scalzo, J C Morris, Joanne E Mortimer, Mark R GreenAbstract:PURPOSETo assess the chemotherapy regimen of cisplatin, vinblastine, and Hydrazine Sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study.PATIENTS AND METHODSBetween July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either Hydrazine Sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of Hydrazine Sulfate on nutritional status, performance status, and quality of life was also assessed.RESULTSAnalysis of 266 eligible patients showed a median survival duration of 7.78 months for the...
David C. Morrison - One of the best experts on this subject based on the ideXlab platform.
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Hydrazine Sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
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Hydrazine Sulfate protects d galactosamine sensitized mice against endotoxin and tumor necrosis factor cachectin lethality evidence of a role for the pituitary
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
Richard Silverstein - One of the best experts on this subject based on the ideXlab platform.
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Hydrazine Sulfate Protects D-Galactosamine-sensitized Mice against Endotoxin and Tumor Necrosis Factor/Cachectin Lethality: Evidence of a Role for the Pituitary
2013Co-Authors: Richard Silverstein, B R Turley, Catherine A Christofl&apos, Donald C Johnson, David C MorrisontAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects ofendotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the n-galactosamine model with an increase in the endotoxin LD5o of approximately four orders of magnitude. Elimination of the pretreatment period, or administration ofan additional dose ofD-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect ofHydrazine Sulfate on the plasma levels ofphosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mic
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Hydrazine Sulfate protection against endotoxin lethality : analysis of effects on expression of hepatic cytokine genes and an acute-phase gene
Microbial Pathogenesis, 1992Co-Authors: Richard Silverstein, Glen K. AndrewsAbstract:Abstract Hydrazine Sulfate (HS) pretreatment protects mice against the lethal effects of bacterial endotoxin lipopolysaccharide (LPS) through mechanisms yet to be established. The liver was examined as a model organ to determine HS effects on (a) LPS activation of leukocyte (Kupffer cell) interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) genes and (b) subsequent cytokine-mediated induction of the acute-phase response as measured by hepatic metallo-thionein (MT) gene expression. The utility of this model was documented by in situ hybridization which showed that acute induction by LPS of the IL-1β gene occurred in cells found in liver sinusoids, consistent with Kupffer cells, whereas induction of the MT gene occurred in hepatocytes. The cell specific expression of these genes was further verified by Northern blot hybridization to LPS-treated liver RNA which showed that the LPS-mediated increase in hepatic cytokine mRNA levels, unlike that of MT, was not prevented by d -galactosamine ( d -GaIN) treatment. Northern blot hybridization established that HS pretreatment did not block the acute induction of hepatic cytokine mRNAs (IL-1β and TNF-α) by LPS nor did it induce these cytokine mRNAs in the absence of LPS. Northern blot hybridization further established that HS did not prevent LPS-mediated activation of hepatocyte MT gene expression. Thus, HS does not prevent LPS from activating liver leukocytes. These results also suggest that HS pretreatment neither prevents the general release of cytokines from LPS activated leukocytes nor the general induction of acute-phase protein gene expression in hepatocytes. Therefore, it is unlikely that HS protection against LPS-mediated lethality entails a global down-regulation of LPS-mediated inflammatory events.
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Hydrazine Sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
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Hydrazine Sulfate protects d galactosamine sensitized mice against endotoxin and tumor necrosis factor cachectin lethality evidence of a role for the pituitary
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
Michael P Kosty - One of the best experts on this subject based on the ideXlab platform.
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cisplatin vinblastine and Hydrazine Sulfate in advanced non small cell lung cancer a randomized placebo controlled double blind phase iii study of the cancer and leukemia group b
Journal of Clinical Oncology, 1994Co-Authors: Michael P Kosty, Stewart B Fleishman, James E Herndon, K Coughlin, Alice B Kornblith, A Scalzo, J C Morris, Joanne E Mortimer, Mark R GreenAbstract:PURPOSETo assess the chemotherapy regimen of cisplatin, vinblastine, and Hydrazine Sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study.PATIENTS AND METHODSBetween July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either Hydrazine Sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of Hydrazine Sulfate on nutritional status, performance status, and quality of life was also assessed.RESULTSAnalysis of 266 eligible patients showed a median survival duration of 7.78 months for the...
D C Johnson - One of the best experts on this subject based on the ideXlab platform.
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Contribution of tumor necrosis factor-alpha and glucocorticoid in Hydrazine Sulfate-mediated protection against endotoxin lethality.
Circulatory shock, 1994Co-Authors: D C Johnson, M. A. Freudenberg, Fenglan Jia, J. C. Gonzalez, C. Galanos, D. C. Morrison, R. SilversteinAbstract:Hydrazine Sulfate pretreatment has previously been shown in our laboratory to protect normal mice against endotoxin and D-galactosamine-sensitized mice against both exogenous tumor necrosis factor (TNF) and endotoxin. An intact pituitary is required for manifestation of the protective effects. Further, we have demonstrated that Hydrazine Sulfate pretreatment specifically modulates the TNF response to lipopolysaccharide (LPS) in mouse macrophages in vitro. This in vivo study was performed to test whether a reduced TNF response and/or increased glucocorticoid response may contribute to Hydrazine Sulfate protection against LPS-induced lethality in vivo. The results presented here establish that Hydrazine Sulfate pretreatment selectively attenuates circulating TNF levels following LPS challenge. Moreover, adrenalectomy abrogates Hydrazine Sulfate protection but does not prevent Hydrazine Sulfate attenuation of circulating TNF levels in response to LPS. Hydrazine Sulfate-mediated protection is, however, restored permissively by corticosterone. Thus, the mechanism by which Hydrazine Sulfate protects against LPS lethality in adrenalectomized mice includes TNF modulation in response to endotoxin, as well as a pivotal requirement for glucocorticoid.
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Hydrazine Sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
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Hydrazine Sulfate protects d galactosamine sensitized mice against endotoxin and tumor necrosis factor cachectin lethality evidence of a role for the pituitary
Journal of Experimental Medicine, 1991Co-Authors: Richard Silverstein, C A Christoffersen, D C Johnson, B R Turley, David C. MorrisonAbstract:In previously published studies, we had demonstrated that Hydrazine Sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same Hydrazine Sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of Hydrazine Sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of Hydrazine Sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of Hydrazine Sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after Hydrazine Sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by Hydrazine Sulfate. Although Hydrazine Sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by Hydrazine Sulfate. We conclude that Hydrazine Sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the Hydrazine Sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine Sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.
