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Majid Mokhtari - One of the best experts on this subject based on the ideXlab platform.
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Oxaliplatin-Induced Renal Tubular Vacuolization:
The Annals of pharmacotherapy, 2014Co-Authors: Ali Yaghobi Joybari, Samaneh Sarbaz, Payam Azadeh, S. Abbas Mirafsharieh, Ali Rahbari, Maryam Farasatinasab, Majid MokhtariAbstract:Objective: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. Case Summary: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of
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oxaliplatin induced renal tubular Vacuolization
Annals of Pharmacotherapy, 2014Co-Authors: Ali Yaghobi Joybari, Samaneh Sarbaz, Payam Azadeh, Ali Rahbari, Maryam Farasatinasab, Abbas S Mirafsharieh, Majid MokhtariAbstract:Objective: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. Case Summary: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of <1% schistocytes in the peripheral blood smear stood against the diagnosis of immune-mediated hemolytic anemia or hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Renal biopsy was consistent with interstitial nephritis with tubular Vacuolization in favor of drug-induced renal injury. Based on the Naranjo Probability Scale, the likelihood of oxaliplatin-induced renal injury in this c...
Roger W. Byard - One of the best experts on this subject based on the ideXlab platform.
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Basal Vacuolization in Renal Tubular Epithelial Cells at Autopsy and Their Relation to Ketoacidosis
Journal of forensic sciences, 2017Co-Authors: Chong Zhou, Andrea J. Yool, Roger W. ByardAbstract:Basal Vacuolization of renal tubular epithelial cells is a useful postmortem marker for ketoacidosis. To investigate its incidence and relationship to the severity of ketoacidosis, 158 autopsy cases with elevated β-hydroxybutyrate (>1 mmol/L) over a 7-year-period were retrospectively reviewed. Sixty-eight cases (43%) exhibited basal Vacuolizations (vitreous β-hydroxybutyrate: 1.16–29.35 mmol/L, mean 10.28 mmol/L), and 90 cases (57%) did not (vitreous β-hydroxybutyrate: 1.03–13.7 mmol/L, mean 2.84 mmol/L). Quantitative analysis revealed on average a fourfold elevation in β-hydroxybutyrate in cases with basal Vacuolizations compared to those without; 10.3% of cases with β-hydroxybutyrate concentrations between 1.01 and 2.00 mmol/L had basal Vacuolizations, and this incidence increased to 33.3% with concentrations between 4.01 and 6.00 mmol/L. A marked increase in incidence to >70% was observed with concentrations >6.00 mmol/L, and basal vacuoles were invariably present (100%) with concentrations >14.01 mmol/L. This study demonstrates that basal Vacuolizations are a sensitive marker for significant ketoacidosis and reaffirms its use as an indicator for likely cases of fatal ketoacidosis at autopsy.
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The Etiology of Basal Vacuolizations in Renal Tubular Epithelial Cells Evaluated in an Isolated Perfused Kidney Model.
Journal of forensic sciences, 2016Co-Authors: Chong Zhou, Andrea J. Yool, Roger W. ByardAbstract:To determine whether basal lipid Vacuolization characteristic of ketoacidosis could be induced with short-term hypertriglyceridemia, adult Sprague Dawley rat kidneys were perfused in an isolated perfused kidney model with, and without, 11.3 mM (10 g/L) of triglycerides in Krebs-Henseleit buffer, for 1 and 2 h (n = 5/group). Additional treatments included perfusion with triglycerides with 20 mM of β-hydroxybutyrate and 2 mM of acetoacetate (n = 5) and perfusion with triglycerides with 70 mM of glucose (n = 1). Basal Vacuolization was produced in all groups, but differed in morphology to that reported in postmortem studies. There was no further increase in Vacuolization after 2 h of perfusion compared to 1 h (p = 0.24), and the addition of ketones did not alter the morphology or extent of Vacuolization. This study using an ex vivo model has confirmed that isolated hypertriglyceridemia is sufficient to cause basal lipid Vacuolization in renal tubular epithelial cells, but with different morphology to vacuoles observed in lethal ketoacidosis at autopsy.
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Septic Ketoacidosis-A Potentially Lethal Entity with Renal Tubular Epithelial Vacuolization.
Journal of forensic sciences, 2016Co-Authors: Chong Zhou, Roger W. ByardAbstract:Fatal ketoacidosis due to diabetes mellitus, alcoholism, and starvation may produce characteristic basal Vacuolization of renal tubular epithelial cells (RTEC). Septic ketoacidosis has recently been recognized clinically as a distinct condition in which septicemia can lead to elevation of ketones and various anions unrelated to diabetes mellitus, alcoholism, or caloric deprivation. We report four lethal cases with significantly elevated vitreous ketones secondary to sepsis and/or severe localized infection in individuals with no history of diabetes mellitus, alcoholism, or starvation. Three of four cases exhibited typical basal Vacuolization of RTEC. We suggest that septic ketoacidosis is an appropriate cause of death in the forensic setting where sepsis or severe localized infection is found with significant ketoacidosis (β-hydroxybutyrate > 5 mmol/L)-in the absence of diabetes mellitus, alcoholism, starvation, or other states associated with accelerated ketogenesis. The finding of basal Vacuolization of RTEC in such cases provides morphological support for the underlying metabolic derangement.
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Lethal hypothermia in an animal model, not associated with basal renal epithelial Vacuolization
Journal of forensic and legal medicine, 2013Co-Authors: Chong Zhou, Andrea J. Yool, Fiona Bright, Calle Winskog, Roger W. ByardAbstract:A rodent model was used to evaluate the association between hypothermia and basal Vacuolization in renal tubular epithelial cells. 28 Sprague Dawley rats were anaesthetized in non-stressful conditions and placed two at a time into a cooling chamber. Body core temperatures dropped to a minimum of 7e10 � C, causing death under anaesthesia at times varying from 120 to 240 min. The animals were then subjected to necropsy; the kidneys were removed and placed in 10% buffered formalin. Examination of haematoxylin and eosin-stained renal sections failed to reveal basal Vacuolization of renal tubular epithelial cells in any of the 28 animals. In this model, no evidence of subnuclear lipid Vacuolization of renal tubular cells could be demonstrated despite significant and eventually lethal hypothermia. These results lend support to the hypothesis that the basal Vacuolization in hypothermia may be a manifestation of a more complex pathophysiological pathway rather than being due simply to low body core temperatures.
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Basal renal tubular epithelial cell Vacuolization and alcoholic ketoacidosis.
Journal of forensic sciences, 2011Co-Authors: Chong Zhou, Roger W. ByardAbstract:Subnuclear renal tubular epithelial cell Vacuolization is a marker for diabetic ketoacidosis. Whether it is because of hyperglycemia or of ketoacidosis is unclear. To examine the effect of ketoacidosis on renal cells in isolation, five cases of lethal alcoholic ketoacidosis without hyperglycemia were examined (vitreous humor β-hydroxybutyrate: 6.42-8.75 mM, mean 7.66 mM; and glucose: 0.1-4.2 mM, mean 1.46 mM). Microscopic examination of the kidneys revealed basal vacuoles in three cases (60%). Seven control cases with acute alcohol toxicity without ketoacidosis (blood alcohol: 0.18-0.43%, mean 0.31%; and β-hydroxybutyrate: 0.12-0.42 mM, mean 0.21 mM) did not have these changes. In this study, basal epithelial Vacuolization was found only in cases with significant ketoacidosis. Although the numbers are small, the finding of basal renal tubular epithelial Vacuolization in normoglycemic cases with elevated β-hydroxybutyrate levels provide further evidence that disordered lipid metabolism may be involved in the pathogenesis of this phenomenon.
Tongsheng Chen - One of the best experts on this subject based on the ideXlab platform.
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TAXOL INDUCES CELL DEATH WITH CYTOPLASM Vacuolization IN PARAPTOSIS-LIKE BUT NOT ONCOSIS FASHION IN ASTC-a-1 CELLS
Journal of Innovative Optical Health Sciences, 2013Co-Authors: Ying-yao Quan, Chaoyang Wang, Xiao-ping Wang, Tongsheng ChenAbstract:Recently, we found that high concentration of taxol (70 μM) induced cell death with cytoplasm Vacuolization, the typical characteristic of both paraptosis and oncosis, in human lung carcinoma (ASTC-a-1) cells. This report was designed to further determine the form of taxol-induced cell death with cytoplasm Vacuolization. It is generally considered that the cytoplasm Vacuolization in oncosis due to the swelling of endoplasmic reticulum (ER), mitochondria, lysosomes and nuclei occurs after the loss of mitochondrial membrane potential (ΔΨm). However, flow cytometry (FCM) analysis showed that taxol-induced cytoplasm Vacuolization preceded the loss of ΔΨm. Moreover, taxol treatment did not induce the collapse of microtubule, the typical characteristic of oncosis. These data demonstrated that taxol-induced cell death with cytoplasm Vacuolization is not oncosis. FCM analysis by Annexin V-FITC/PI apoptosis detection kit further demonstrated that taxol-induced cell death with cytoplasm Vacuolization is not apoptosis. In conclusion, in combination with our recent in vitro and in vivo data, this report further demonstrates that high concentration of taxol induces cell death with cytoplasm Vacuolization in paraptosis-like but not oncosis fashion.
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Intratumoral injection of taxol in vivo suppresses A549 tumor showing cytoplasmic Vacuolization.
Journal of cellular biochemistry, 2012Co-Authors: Chaoyang Wang, Tongsheng ChenAbstract:Based on our recent in vitro studies, this report was designed to explore the mechanism by which high concentration of taxol (70 µM) induced paraptosis-like cell death in human lung carcinoma (A549) cells, and to evaluate the therapeutic efficacy of taxol using A549 tumor-bearing mice in vivo. Exposure of cells to taxol induced time-dependent cytotoxicity and cytoplasmic Vacuolization without the involvement of Bax, Bak, Mcl-1, Bcl-XL, and caspase-3. Although taxol treatment induced activating transcription factor 6 (ATF6) cleavage indicative of endoplasmic reticulum (ER) stress, silencing ATF6 by shATF6 did not prevent taxol-induced both cytotoxcity and cytoplasmic Vacuolization, suggesting that taxol-induced cytoplasmic Vacuolization and cell death were not due to ER stress. Moreover, taxol-treated cells did not show DNA fragmentation and loss of mitochondrial membrane potential, the typical characteristics of apoptosis. In addition, taxol-induced cytoplasmic Vacuolization did not show the cellular lysis, the characteristics of oncosis, and positive of β-galactosidase, the characteristic of senescence, indicating that taxol induced paraptosis-like cell death is neither oncosis nor senescence. Moreover, our in vivo data showed that intratumoral injection of taxol (50 mg/kg) in A549 tumor xenograft mice on day 1 and day 19 potently suppressed tumor growth showing significant ER Vacuolization without toxicity. In conclusion, high concentration of taxol exhibits a significant anticancer activity by inducing paraptosis-like cell death in vitro and in vivo, without significant toxicity, suggesting a promising therapeutic strategy for apoptosis-resistance cancer by inducing ER Vacuolization.
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Reactive oxygen species (ROS) is not a promotor of taxol-induced cytoplasmic Vacuolization
Biophotonics and Immune Responses IV, 2009Co-Authors: Qingrui Sun, Tongsheng ChenAbstract:we have previously reported that taxol, a potent anticancer agent, induces caspase-independent cell death and cytoplasmic Vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. However, the mechanisms of taxol-induced cytoplasmic Vacuolization are poorly understood. Reactive oxygen species (ROS) has been reported to be involved in the taxol-induced cell death. Here, we employed confocal fluorescence microscopy imaging to explore the role of ROS in taxol-induced cytoplasmic Vacuolization. We found that ROS inhibition by addition of N-acetycysteine (NAC), a total ROS scavenger, did not suppress these Vacuolization but instead increased Vacuolization. Take together, our results showed that ROS is not a promotor of the taxol-induced cytoplasmic Vacuolization.
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Taxol induces caspase-independent cytoplasmic Vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells.
Cancer letters, 2008Co-Authors: Tongsheng Chen, Xiao-ping Wang, Lei Sun, Longxiang Wang, Da Xing, Martin S. MokAbstract:High concentration of taxol was found to induce programmed cell death (PCD) and cytoplasm Vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. To elucidate the relationship between the PCD and cytoplasm Vacuolization, confocal fluorescence microscopy was performed on the cytoplasm Vacuolization, endoplasmic reticulum (ER) and mitochondria swelling after taxol treatment in living cells. erRFP plasmid was used to probe the ER distribution, and SCAT3 plasmid was used to monitor the caspase-3 activation in living cells. Our results showed that taxol induced concentration-dependent and caspases-independent cytoplasm Vacuolization and cell death through ER and mitochondria swelling. Live confocal imaging of ASTC-a-1 cells stably expressing SCAT3 further verified that taxol-induced cytoplasm Vacuolization and cell death was caspase-3-independent. In conclusion, we found for the first time that taxol induces a paraptosis-like PCD in the ASTC-a-1 cells by cytoplasm Vacuolization due to the swelling of both ER and mitochondria without activating the caspase enzymes.
Daniel Dimaio - One of the best experts on this subject based on the ideXlab platform.
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sv40 polyomavirus activates the ras mapk signaling pathway for Vacuolization cell death and virus release
Viruses, 2020Co-Authors: Nasim Motamedi, Xaver Sewald, Yong Luo, Walther Mothes, Daniel DimaioAbstract:Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, in viral transcription and DNA replication, and in cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to release of progeny polyomaviruses. We previously showed that cytoplasmic Vacuolization, a characteristic late cytopathic effect of SV40 infection, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here, we show that, late during infection, SV40 activates a signaling cascade in permissive monkey CV-1 cells involving Ras, Rac1, MKK4, and JNK to stimulate SV40-specific cytoplasmic Vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits Vacuolization, lysis, and virus release, even though high-level intracellular virus replication occurs. Identification of this pathway for SV40-induced Vacuolization and virus release provides new insights into the late steps of non-enveloped virus infection.
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sv40 polyomavirus activates the ras mapk signaling pathway for Vacuolization cell death and virus release
bioRxiv, 2018Co-Authors: Nasim Motamedi, Xaver Sewald, Yong Luo, Walther Mothes, Daniel DimaioAbstract:Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, viral transcription and DNA replication, and cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to polyomavirus release. We previously showed that cytoplasmic Vacuolization, a characteristic late cytopathic effect of SV40, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here we show that late during infection, SV40 activates a signaling cascade in permissive CV-1 monkey cells involving Ras, Rac1, MKK4 and JNK to induce SV40-specific cytoplasmic Vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits Vacuolization, lysis and virus release, even though high-level intracellular virus replication occurs. The identification of this pathway for SV40-induced Vacuolization and virus release provides new insights into the late steps of non-enveloped virus infection and reveals potential drug targets for the treatment of diseases caused by these viruses.
Ali Yaghobi Joybari - One of the best experts on this subject based on the ideXlab platform.
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Oxaliplatin-Induced Renal Tubular Vacuolization:
The Annals of pharmacotherapy, 2014Co-Authors: Ali Yaghobi Joybari, Samaneh Sarbaz, Payam Azadeh, S. Abbas Mirafsharieh, Ali Rahbari, Maryam Farasatinasab, Majid MokhtariAbstract:Objective: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. Case Summary: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of
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oxaliplatin induced renal tubular Vacuolization
Annals of Pharmacotherapy, 2014Co-Authors: Ali Yaghobi Joybari, Samaneh Sarbaz, Payam Azadeh, Ali Rahbari, Maryam Farasatinasab, Abbas S Mirafsharieh, Majid MokhtariAbstract:Objective: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. Case Summary: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of <1% schistocytes in the peripheral blood smear stood against the diagnosis of immune-mediated hemolytic anemia or hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Renal biopsy was consistent with interstitial nephritis with tubular Vacuolization in favor of drug-induced renal injury. Based on the Naranjo Probability Scale, the likelihood of oxaliplatin-induced renal injury in this c...
