BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment. METHODS: Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC. RESULTS: Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence. CONCLUSION: Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.
Adult* ; BK Virus ; Cystitis* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; JC Virus ; Recurrence

Mutations in the p53 tumor suppressor gene have been shown to be one of the most common genetic abnormalities in human cancers. Loss of p53 tumor suppressor gene function can occur through gene mutation or interaction with early proteins of oncogenic viruses such as E6 protein of human papillomaviruses(HPV). We studied 24 squamous cell carcinomas of the larynx(20) and hypopharynx(4) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exon 5 through 8 of the p53 gene were examined using polymerase chain reaction-direct sequencing methods. HPV detection was done using polymerase chain reaction amplification with HPV L1 consensus primer. HPV type was determined by the same method using HPV-16 and -18 type-specific E6 primers. The results were as follows: 1) Eight of 24 tumors(33%) had p53 mutations, one of which had 2 mutational sites. All cases of which had p53 mutations or HPV DNA detection were larynx cancer. 2) p53 genetic alteration in larynx cancer included seven missense mutations resulting in single amino acid substitutions, one nonsense mutation encoding a stop codon and one silent mutation. Six of 9(66.7%) mutations occurred in two distinct regions of the genes, codon 245-248(3 mutations) and codon 283-294(3 mutations). 3) The p53 mutational spectrum observed was characterized by G to T transversion(4 of 9), T to A transversion(2 of 9), C to A transversion(1 of 9), G to A transition(1 of 9) and C to T transition(1 of 9). 4) HPV DNA was detected in 3 of 24(12.5%) tumors. According to the type of HPV DNA, HPV-16 was detected in 1 case and HPV non-16, -18 was detected in 2 cases, one of which had p53 mutation. 5) There was no relationship between p53 mutations or HPV DNA detection and clinicopathologic parameters. These results suggest that p53 mutations may play an important role in carcinogenesis of laryngeal cancer. Further study is necessary to clarify the role of p53 mutation and oncogenic HPV infection on clinical outcome of laryngeal cancer.
Amino Acid Substitution ; Carcinogenesis ; Carcinoma, Squamous Cell ; Codon ; Codon, Nonsense ; Codon, Terminator ; Consensus ; DNA* ; Exons ; Genes, p53* ; Genes, Tumor Suppressor ; Human papillomavirus 16 ; Humans* ; Laryngeal Neoplasms ; Larynx* ; Mutation, Missense ; Oncogenic Viruses ; Pharyngeal Neoplasms* ; Pharynx* ; Polymerase Chain Reaction

BACKGROUND: Hemorrhagic cystitis(HC), a common complication of bone marrow transplantation(BMT), is known to be associated with toxic metabolites of chemotherapy drugs or reactivation of primary virus infections. In this study, we evaluated the association between polyomaviruria and HC in BMT patients. METHODS: Urine specimens of 29 patients with HC after BMT were requested for the detection of polyomavirus by culture and polyomerase chain reaction(PCR). Several clinical parameters were analyzed in relations to the presence of polyomaviruria. For comparison, 19 patients without HC after BMT were involved in this study. RESULTS: Overall, 45 of 558 patients developed HC after BMT, and the incidence of HC was estimated to be 8.1%. Patients group showed significantly high prevalence of BK viruria compared with control group by PCR(72.4% vs 31.6%, P = 0.005). In patients group, BK virus was isolated in 44.8%(13/29) by culture and detected in 72.4%(21/29) by PCR. Results of both methods were agreed in 65.5%(19/29). JC virus was detected in 6.9%(2/29) by PCR. Sex, conditioning regimen, graft-versus-host disease(GVHD), onset time after BMT and duration of hematuria did not show any statistically significant differences between the two groups based on the presence of BK viruria by PCR. CONCLUSIONS: High prevalence of BK viruria in HC patients after BMT suggests the possible association between BK virus and HC. However, we could not find any significant clinical parameters in association with BK viruria.
BK Virus ; Bone Marrow Transplantation ; Bone Marrow* ; Cystitis* ; Drug Therapy ; Hematuria ; Humans ; Incidence ; JC Virus ; Polymerase Chain Reaction ; Polyomavirus ; Prevalence

OBJECTIVES: To evaluate the effect of glutathione(GSH) on lead induced modulation of nitric oxide(NO) synthesis, and to examine how lead modulates NO production in macrophages. METHODS: This study was observed in a culture of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that was induced by the Abelson murine leukemia virus. The compounds investigated were lead chloride, N-acetyl-cystein(NAC), and Buthionine Sulfoximine(BSO). RESUJLTS: ATP synthesis in RAW 264.7 cells was unchanged by each lead concentration exposure in a dose dependent manner. The NO synthesis was decreased when exposed to lead(PbCl2) concentration 0.5 micro M. The presence of 300 micro M NAC, used as a pretreatment in the culture medium, caused the recovery of the lead induced decrease in NO synthesis, but in the presence of 300 micro M BSO as a pretreatment, there was no recoverey. Pretreatment with NAC and BSO had no affect on ATP synthesis at any of the lead concentrations used. CONCLUSIONS: These results indicated that GSH has a protective effect toward lead toxicity, and suggested that the inhibition of NO production in macrophage due to lead toxicity may be related to cofactors of iNOS (inducible nitric oxide synthase)
Abelson murine leukemia virus ; Acetylcysteine ; Adenosine Triphosphate ; Animals ; Buthionine Sulfoximine ; Glutathione* ; Macrophages ; Mice ; Nitric Oxide

OBJECTIVES: To evaluate the effect of glutathione(GSH) on lead induced modulation of nitric oxide(NO) synthesis, and to examine how lead modulates NO production in macrophages. METHODS: This study was observed in a culture of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that was induced by the Abelson murine leukemia virus. The compounds investigated were lead chloride, N-acetyl-cystein(NAC), and Buthionine Sulfoximine(BSO). RESUJLTS: ATP synthesis in RAW 264.7 cells was unchanged by each lead concentration exposure in a dose dependent manner. The NO synthesis was decreased when exposed to lead(PbCl2) concentration 0.5 micro M. The presence of 300 micro M NAC, used as a pretreatment in the culture medium, caused the recovery of the lead induced decrease in NO synthesis, but in the presence of 300 micro M BSO as a pretreatment, there was no recoverey. Pretreatment with NAC and BSO had no affect on ATP synthesis at any of the lead concentrations used. CONCLUSIONS: These results indicated that GSH has a protective effect toward lead toxicity, and suggested that the inhibition of NO production in macrophage due to lead toxicity may be related to cofactors of iNOS (inducible nitric oxide synthase)
Abelson murine leukemia virus ; Acetylcysteine ; Adenosine Triphosphate ; Animals ; Buthionine Sulfoximine ; Glutathione* ; Macrophages ; Mice ; Nitric Oxide

The genomic diversity of Avian leukosis virus subgroup J (ALV-J) was investigated in an experimentally infected chicken. ALV-J variants in tissues from four different organs of the same bird were re-isolated in DF-1 cells, and their gp85 gene was amplified and cloned. Ten clones from each organ were sequenced and compared with the original inoculum strain, NX0101. The minimum homology of each organ ranged from 96.7 to 97.6%, and the lowest homology between organs was only 94.9%, which was much lower than the 99.1% homology of inoculum NX0101, indicating high diversity of ALV-J, even within the same bird. The gp85 mutations from the left kidney, which contained tumors, and the right kidney, which was tumor-free, had higher non-synonymous to synonymous mutation ratios than those in the tumor-bearing liver and lungs. Additionally, the mutational sites of gp85 gene in the kidney were similar, and they differed from those in the liver and lung, implying that organ- or tissue-specific selective pressure had a greater influence on the evolution of ALV-J diversity. These results suggest that more ALV-J clones from different organs and tissues should be sequenced and compared to better understand viral evolution and molecular epidemiology in the field.
Animals ; Avian Leukosis Virus* ; Avian Leukosis* ; Birds ; Chickens* ; Clone Cells ; Kidney ; Liver ; Lung ; Molecular Epidemiology ; Silent Mutation

The first clinical infections with polyomavirus (PV) were demonstrated in 1971, when BK virus was isolated from the urine after a kidney transplant recipient and JC virus from the brain of a patient who died of progressive multifocal leukoencephalopathy. Polyomavirus-associated nephropathy (PVAN) has become an important cause of allograft dysfunction and loss in kidney transplantation since first recognized in kidney transplant recipient with PVAN in 1995. Most cases of PVAN are caused by polyomavirus hominis type 1, known as BK virus and arise while the patient in on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Significant progress has been made, particularly in the area of diagnostic methods for PV, facilitating diagnosis, screening and monitoring of PV infection. Definitive diagnosis of PVAN requires allograft kidney biopsy. Immunologic control of PV replication can be achieved by reducing, switching, and discontinuing of the immunusuppressive agents. Cidofovir and leflunomide are used empirically in the treatment of PVAN. However, these antiviral agents are not approved for PVAN. Recently, investigational use at low-dose cidofovir (0.25~0.33 mg/kg intravenously biweekly) without probenecid should be considered for the treatment of cases refractory to decreasedmaintenance immunosuppression. PVAN had a serious consequence of kidney transplantation that increasingly cause for chronic allograft kidney loss. Despite reduction in immuo-suppression, allograft kidney loss occurred in 46% of transplant recipients with PVAN. PVAN recurred in 15% of retransplantations compared with 5% of primary kidney transplantations. However, retransplantation is not contraindicated for transplant recipient in whom a first allograft kidney lost due to PVAN. Recently, preemptive retransplantation can be considered in patients with allograft loss due to PVAN.
Adrenal Cortex Hormones ; Allografts ; Antiviral Agents ; Biopsy ; BK Virus ; Brain ; Diagnosis ; Humans ; Immunosuppression ; JC Virus ; Kidney ; Kidney Transplantation* ; Leukoencephalopathy, Progressive Multifocal ; Mass Screening ; Polyomavirus ; Probenecid ; Tacrolimus ; Transplantation

BACKGROUND: Reactivation of the polyomavirus and the use of conditioning regimen may be the causes of hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). However, there are only a few reports on the clinical characteristics of viral reactivation in HC following HSCT in Korea, especially in pediatric population.METHODS: 51 patients who received HSCT in Ajou University Hospital from January 2006 to June 2012 were investigated retrospectively. 16 patients were diagnosed with HC following HSCT and were enrolled in this study. Confirmation of polyomavirus was done by polymerase chain reaction (PCR) method.RESULTS: Out of the 16 patients diagnosed with HC following HSCT, there were 5 early type HC patients and 11 late type HC patients. Positive PCR results for the BK virus (BKV) and the JC virus were found on 13 and 5 patients, respectively. 4 patients showed positive results for both viruses. For the late type HC, there were 10 patients with positive PCR results for the BKV. Cyclophosphamide was used in 33 patients, and 13 patients eventually developed HC. There was no statistical significance between the incidence of hematuria and the reactivation of the BKV or the conditioning regimens. Most patients were treated conservatively but 4 patients who showed severe hematuria or poor general condition received intravenous cidofovir. After the infusion of cidofovir, hematuria disappeared on average of 65 days and the BKV was undetectable on average of 53 days.CONCLUSION: In our study, activation of the BKV was common in patients who were diagnosed with HC following HSCT. All patients recovered from HC with conservative management and the BKV became undetectable in the majority of patients who were treated with intravenous cidofovir.
BK Virus ; Cyclophosphamide ; Cystitis ; Cytosine ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Hematuria ; Humans ; Incidence ; JC Virus ; Korea ; Organophosphonates ; Polymerase Chain Reaction ; Polyomavirus ; Retrospective Studies

The Bcr-Abl oncogene is produced by the reciprocal translocation between c-Abl gene on chromosome 9 and the Bcr gene on chromosome 22 in human genome. The encoded Bcr-Abl fusion protein is responsible for the pathogenesis of certain human leukemias. Abelson murine leukemia virus (A-MuLV) is a retrovirus that could lead to transformation of B lymphocyte in mice, and v-Abl is the oncogene of A-MuLV. Abl oncoproteins (such as Bcr-Abl and v-Abl) play critical roles in tumorigenesis of certain cell types. Several signal transduction pathways, including JAK/STAT/Pim, PI3K/AKT/mTOR and RAS/RAF/MEK signaling pathway, are involved in Abl-mediated tumorigenesis. In addition, Abl-mediated tumorigenesis is associated with mutation or abnormal modification of key signal molecules as well as dysregulation of some critical long noncoding RNAs (lncRNAs). Here, we review the molecular mechanisms by which Abl oncogenes activate three major signaling pathways, and provide a scientific basis for therapy of Abl oncoprotein-induced tumors.
Abelson murine leukemia virus ; Animals ; Cell Transformation, Neoplastic ; Fusion Proteins, bcr-abl ; Genes, abl ; Humans ; Phosphatidylinositol 3-Kinases

In order to clarify Avian leukosis virus (ALV) characteristics from Chinese native chicken breeds, three ALV JS11C1, JS11C2 and JS11C3 were isolated from Chinese native breed "luhua" by inoculation of DF1 cell culture and detection of p27 antigen. Using PCR amplification of env gene, the amplified gp85 genes were analyzed and compared to all six chicken ALV subgroups reported. The gp85 genes of these three viruses were 1 005bp in length and encoded 335 amino acids, and the gp37 genes were 609bp and encoded 203 amino acids. The homology of gp85 among these three isolated strains was 91.9%-97.0%. Comparing to 18 stains of subgroup A, B, C, D, E published in GenBank, the homology was only in the range of 77.7%-84.6%, significantly lower than the gp85 homology observed within the common chicken subgroups A (88.2%-98.5%), B (91.6%-98.8%), and E (97.9%-99.4%). The gp85 homology compared with subgroup J was only 34.2%-36.5%. These results suggested that three isolated strains from Chinese native breed "luhua" belong to a new subgroup different from all six known subgroups from Chickens, and thus designated as subgroup K.
Animals ; Avian Leukosis ; virology ; Avian Leukosis Virus ; classification ; genetics ; isolation & purification ; metabolism ; Breeding ; Chickens ; genetics ; virology ; Molecular Sequence Data ; Phylogeny ; Poultry Diseases ; virology ; Viral Envelope Proteins ; genetics ; metabolism