March 11th, 2010 / No Comments » / by Johnston DL, Bains T, Mandel K, Klaassen R, Halton J
Fatal Neurotoxicity in a Patient With Down Syndrome Treated With Chemotherapy, Irradiation, Stem Cell Transplant, and Clofarabine.
J Pediatr Hematol Oncol. 2010 Mar 1;
Authors: Johnston DL, Bains T, Mandel K, Klaassen R, Halton J
Clofarabine is an effective therapy of pediatric patients with relapsed acute lymphoblastic leukemia (ALL). We present a child with Down syndrome who had received previous chemotherapy, cranial radiation, and a stem cell transplant with total body irradiation for her acute lymphoblastic leukemia. She subsequently relapsed and was treated with clofarabine. After her third course, she had a stroke that was felt to be secondary to dehydration and radiation vasculitis. After her subsequent course of clofarabine, she developed fatal neurotoxicity.
PMID: 20216234 [PubMed - as supplied by publisher]
Posted in: J Pediatr Hematol Oncol
March 6th, 2010 / No Comments » / by Kuhnt LA, Jennings RN, Brawner WR, Hathcock JT, Carreno AD, Johnson CM
Magnetic resonance imaging of radiation-induced thymic atrophy as a model for pathologic changes in acute feline immunodeficiency virus infection.
J Feline Med Surg. 2009 Dec;11(12):977-84
Authors: Kuhnt LA, Jennings RN, Brawner WR, Hathcock JT, Carreno AD, Johnson CM
The development of a protocol to reproducibly induce thymic atrophy, as occurs in feline immunodeficiency virus (FIV) infection and other immunosuppressive diseases, and to consistently estimate thymic volume, provides a valuable tool in the search of innovative and novel therapeutic strategies. Magnetic resonance imaging (MRI) using the short tau inversion recovery (STIR) technique, with fat suppression properties, was determined to provide an optimized means of locating, defining, and quantitatively estimating thymus volume in young cats. Thymic atrophy was induced in four, 8-10-week-old kittens with a single, directed 500 cGy dose of 6 MV X-rays from a clinical linear accelerator, and sequential MR images of the cranial mediastinum were collected at 2, 7, 14, and 21 days post irradiation (PI). Irradiation induced a severe reduction in thymic volume, which was decreased, on average, to 47% that of normal, by 7 days PI. Histopathology confirmed marked, diffuse thymic atrophy, characterized by reduced thymic volume, decreased overall cellularity, increased apoptosis, histiocytosis, and reduced distinction of the corticomedullary junction, comparable to that seen in acute FIV infection. Beginning on day 7 PI, thymic volumes rebounded slightly and continued to increase over the following 14 days, regaining 3-35% of original volume. These findings demonstrate the feasibility and advantages of using this non-invasive, in vivo imaging technique to measure and evaluate changes in thymic volume in physiologic and experimental situations. All experimental protocols in this study were approved by the Institutional Animal Care and Use Committee (IACUC) at Auburn University.
PMID: 19540785 [PubMed - indexed for MEDLINE]
Posted in: Uncategorized
March 6th, 2010 / No Comments » / by Kuhnt LA, Jennings RN, Brawner WR, Hathcock JT, Carreno AD, Johnson CM
Magnetic resonance imaging of radiation-induced thymic atrophy as a model for pathologic changes in acute feline immunodeficiency virus infection.
J Feline Med Surg. 2009 Dec;11(12):977-84
Authors: Kuhnt LA, Jennings RN, Brawner WR, Hathcock JT, Carreno AD, Johnson CM
The development of a protocol to reproducibly induce thymic atrophy, as occurs in feline immunodeficiency virus (FIV) infection and other immunosuppressive diseases, and to consistently estimate thymic volume, provides a valuable tool in the search of innovative and novel therapeutic strategies. Magnetic resonance imaging (MRI) using the short tau inversion recovery (STIR) technique, with fat suppression properties, was determined to provide an optimized means of locating, defining, and quantitatively estimating thymus volume in young cats. Thymic atrophy was induced in four, 8-10-week-old kittens with a single, directed 500 cGy dose of 6 MV X-rays from a clinical linear accelerator, and sequential MR images of the cranial mediastinum were collected at 2, 7, 14, and 21 days post irradiation (PI). Irradiation induced a severe reduction in thymic volume, which was decreased, on average, to 47% that of normal, by 7 days PI. Histopathology confirmed marked, diffuse thymic atrophy, characterized by reduced thymic volume, decreased overall cellularity, increased apoptosis, histiocytosis, and reduced distinction of the corticomedullary junction, comparable to that seen in acute FIV infection. Beginning on day 7 PI, thymic volumes rebounded slightly and continued to increase over the following 14 days, regaining 3-35% of original volume. These findings demonstrate the feasibility and advantages of using this non-invasive, in vivo imaging technique to measure and evaluate changes in thymic volume in physiologic and experimental situations. All experimental protocols in this study were approved by the Institutional Animal Care and Use Committee (IACUC) at Auburn University.
PMID: 19540785 [PubMed - indexed for MEDLINE]
Posted in: J Feline Med Surg
March 4th, 2010 / No Comments » / by Lee HJ, Kim JS, Song MS, Seo HS, Yang M, Kim JC, Jo SK, Shin T, Moon C, Kim SH
Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation.
J Vet Sci. 2010 Mar;11(1):81-3
Authors: Lee HJ, Kim JS, Song MS, Seo HS, Yang M, Kim JC, Jo SK, Shin T, Moon C, Kim SH
This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
PMID: 20195069 [PubMed - in process]
Posted in: J Vet Sci
March 4th, 2010 / No Comments » / by Lee HJ, Kim JS, Song MS, Seo HS, Yang M, Kim JC, Jo SK, Shin T, Moon C, Kim SH
Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation.
J Vet Sci. 2010 Mar;11(1):81-3
Authors: Lee HJ, Kim JS, Song MS, Seo HS, Yang M, Kim JC, Jo SK, Shin T, Moon C, Kim SH
This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
PMID: 20195069 [PubMed - in process]
Posted in: Uncategorized
February 26th, 2010 / No Comments » / by Triantopoulou C, Delis S, Dervenis C
Imaging Evaluation Of Post-Pancreatitis Infection.
Infect Disord Drug Targets. 2010 Feb 1;10(1):15-20
Authors: Triantopoulou C, Delis S, Dervenis C
Acute pancreatitis affects around 40 per 100.000 of the general population and 20-30% of attacks are severe. Mortality is usually associated to septic multiorgan dysfunction syndrome caused by secondary infection of pancreatic or peripancreatic necrosis. The diagnosis of acute pancreatitis is generally based on clinical and laboratory findings. However CT is the imaging technique of choice for detecting complications. Patients with complicated pancreatitis require multiple follow-up examinations. Substitution of US or MRI for CT in certain cases would reduce the radiation dose considerably. Complicated pseudocysts and other pancreatic collections may contain solid debris, which is best depicted by MRI. Abscesses are suggested when gas is present in a pancreatic or peripancreatic collection. MRI can reveal air-fluid levels or large pockets of gas, but CT is more sensitive for small gas collections. US or CT-guided percutaneous drainage of pancreatic abscesses or infected collections is a useful therapeutic approach in acute cases obviating the need for unnecessary surgery. On the other hand infected necrosis can not be successfully treated percutaneously due to its thicker consistency. In this review, the role of different imaging modalities in the evaluation of post-pancreatitis infection as well as in the treatment planning will be discussed.
PMID: 20180754 [PubMed - as supplied by publisher]
Posted in: Infect Disord Drug Targets
February 26th, 2010 / No Comments » / by Clementz MA, Chen Z, Banach BS, Wang Y, Sun L, Ratia K, Baez-Santos YM, Wang J, Takayama J, Ghosh AK, Li K, Mesecar AD, Baker SC
Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-like Proteases.
J Virol. 2010 Feb 24;
Authors: Clementz MA, Chen Z, Banach BS, Wang Y, Sun L, Ratia K, Baez-Santos YM, Wang J, Takayama J, Ghosh AK, Li K, Mesecar AD, Baker SC
Coronaviruses encode multifunctional proteins that are critical for viral replication and blocking the innate immune response to viral infection. One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB)/deISGylating activities, and antagonizes the induction of type I interferon (IFN). Here, we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism. We found that NL63 PLP2 deconjugated ubiquitin (Ub) and ISG15 from cellular substrates and processed both lysine-48 and lysine-63 linked polyubiquitin chains. This PLP2 DUB activity was dependent on an intact catalytic cysteine residue. We demonstrated that, in contrast to PLP2 DUB activity, PLP2-mediated interferon antagonism did not require enzymatic activity. Furthermore, addition of an inhibitor that blocks coronavirus protease/DUB activity did not abrogate interferon antagonism. These results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity. Overall, these results demonstrate the multifunctional nature of the coronavirus PLP domain as a viral protease, DUB/deISGylase, and IFN antagonist and suggest that these independent activities may provide multiple targets for antiviral therapies.
PMID: 20181693 [PubMed - as supplied by publisher]
Posted in: J Virol
February 26th, 2010 / No Comments » / by Clementz MA, Chen Z, Banach BS, Wang Y, Sun L, Ratia K, Baez-Santos YM, Wang J, Takayama J, Ghosh AK, Li K, Mesecar AD, Baker SC
Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-like Proteases.
J Virol. 2010 Feb 24;
Authors: Clementz MA, Chen Z, Banach BS, Wang Y, Sun L, Ratia K, Baez-Santos YM, Wang J, Takayama J, Ghosh AK, Li K, Mesecar AD, Baker SC
Coronaviruses encode multifunctional proteins that are critical for viral replication and blocking the innate immune response to viral infection. One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB)/deISGylating activities, and antagonizes the induction of type I interferon (IFN). Here, we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism. We found that NL63 PLP2 deconjugated ubiquitin (Ub) and ISG15 from cellular substrates and processed both lysine-48 and lysine-63 linked polyubiquitin chains. This PLP2 DUB activity was dependent on an intact catalytic cysteine residue. We demonstrated that, in contrast to PLP2 DUB activity, PLP2-mediated interferon antagonism did not require enzymatic activity. Furthermore, addition of an inhibitor that blocks coronavirus protease/DUB activity did not abrogate interferon antagonism. These results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity. Overall, these results demonstrate the multifunctional nature of the coronavirus PLP domain as a viral protease, DUB/deISGylase, and IFN antagonist and suggest that these independent activities may provide multiple targets for antiviral therapies.
PMID: 20181693 [PubMed - as supplied by publisher]
Posted in: Uncategorized
February 24th, 2010 / No Comments » / by Wolbarst AB, Wiley AL, Nemhauser JB, Christensen DM, Hendee WR
Medical response to a major radiologic emergency: a primer for medical and public health practitioners.
Radiology. 2010 Mar;254(3):660-77
Authors: Wolbarst AB, Wiley AL, Nemhauser JB, Christensen DM, Hendee WR
There are several types of serious nuclear or radiologic emergencies that would require a specialized medical response. Four scenarios of great public health, economic, and psychologic impact are the detonation of a nuclear weapon, the meltdown of a nuclear reactor, the explosion of a large radiologic dispersal device ("dirty bomb"), or the surreptitious placement of a radiation exposure device in a public area of high population density. With any of these, medical facilities that remain functional may have to deal with large numbers of ill, wounded, and probably contaminated people. Special care and/or handling will be needed for those with trauma, blast injuries, or thermal burns as well as significant radiation exposures or contamination. In addition, radiologists, nuclear medicine specialists, and radiation oncologists will be called on to perform a number of diverse and critically important tasks, including advising political and public health leaders, interfacing with the media, managing essential resources, and, of course, providing medical care. This article describes the medical responses needed following a radiologic or nuclear incident, including the symptoms of and specific treatments for acute radiation syndrome and other early health effects. (c) RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090330/-/DC1.
PMID: 20177084 [PubMed - in process]
Posted in: Radiology
February 24th, 2010 / No Comments » / by Wolbarst AB, Wiley AL, Nemhauser JB, Christensen DM, Hendee WR
Medical response to a major radiologic emergency: a primer for medical and public health practitioners.
Radiology. 2010 Mar;254(3):660-77
Authors: Wolbarst AB, Wiley AL, Nemhauser JB, Christensen DM, Hendee WR
There are several types of serious nuclear or radiologic emergencies that would require a specialized medical response. Four scenarios of great public health, economic, and psychologic impact are the detonation of a nuclear weapon, the meltdown of a nuclear reactor, the explosion of a large radiologic dispersal device ("dirty bomb"), or the surreptitious placement of a radiation exposure device in a public area of high population density. With any of these, medical facilities that remain functional may have to deal with large numbers of ill, wounded, and probably contaminated people. Special care and/or handling will be needed for those with trauma, blast injuries, or thermal burns as well as significant radiation exposures or contamination. In addition, radiologists, nuclear medicine specialists, and radiation oncologists will be called on to perform a number of diverse and critically important tasks, including advising political and public health leaders, interfacing with the media, managing essential resources, and, of course, providing medical care. This article describes the medical responses needed following a radiologic or nuclear incident, including the symptoms of and specific treatments for acute radiation syndrome and other early health effects. (c) RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090330/-/DC1.
PMID: 20177084 [PubMed - in process]
Posted in: Radiology
