Sample records for polyomavirus jcv late
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Human polyomavirus JCV late leader peptide region contains important regulatory elements
International Nuclear Information System (INIS)
Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh; Khalili, Kamel; Safak, Mahmut
2006-01-01
Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader
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Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.
2003-01-01
OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.
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JC Polyomavirus (JCV and Monoclonal Antibodies: Friends or Potential Foes?
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Roberta Antonia Diotti
2013-01-01
Full Text Available Progressive multifocal leukoencephalopathy (PML is a demyelinating disease of the central nervous system (CNS, observed in immunodeficient patients and caused by JC virus ((JCV, also called JC polyomavirus (JCPyV. After the HIV pandemic and the introduction of immunomodulatory therapy, the PML incidence significantly increased. The correlation between the use of natalizumab, a drug used in multiple sclerosis (MS, and the PML development of particular relevance. The high incidence of PML in natalizumab-treated patients has highlighted the importance of two factors: the need of PML risk stratification among natalizumab-treated patients and the need of effective therapeutic options. In this review, we discuss these two needs under the light of the major viral models of PML etiopathogenesis.
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Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses
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Eileen M. Geoghegan
2017-10-01
Full Text Available Summary: Progressive multifocal leukoencephalopathy (PML is a lethal brain disease caused by uncontrolled replication of JC polyomavirus (JCV. JCV strains recovered from the brains of PML patients carry mutations that prevent the engagement of sialylated glycans, which are thought to serve as receptors for the infectious entry of wild-type JCV. In this report, we show that non-sialylated glycosaminoglycans (GAGs can serve as alternative attachment receptors for the infectious entry of both wild-type and PML mutant JCV strains. After GAG-mediated attachment, PML mutant strains engage non-sialylated non-GAG co-receptor glycans, such as asialo-GM1. JCV-neutralizing monoclonal antibodies isolated from patients who recovered from PML appear to block infection by preventing the docking of post-attachment co-receptor glycans in an apical pocket of the JCV major capsid protein. Identification of the GAG-dependent/sialylated glycan-independent alternative entry pathway should facilitate the development of infection inhibitors, including recombinant neutralizing antibodies. : Geoghegan et al. show that JC polyomavirus strains that cause brain disease infect cells via a pathway involving a heparin-like attachment receptor and a non-sialylated co-receptor. Candidate therapeutic human monoclonal antibodies neutralize by blocking co-receptor engagement. Keywords: polyomavirus, JC, BK, SV40, progressive multifocal leukoencephalopathy, PML, monoclonal antibody, mAb, virus entry, receptor
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Modulation of PML protein expression regulates JCV infection
International Nuclear Information System (INIS)
Gasparovic, Megan L.; Maginnis, Melissa S.; O'Hara, Bethany A.; Dugan, Aisling S.; Atwood, Walter J.
2009-01-01
JC virus (JCV) is a human polyomavirus that infects the majority of the human population worldwide. It is responsible for the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy. JCV binds to cells using the serotonin receptor 5-HT 2A R and α(2-6)- or α(2-3)-linked sialic acid. It enters cells using clathrin-dependent endocytosis and traffics to the early endosome and possibly to the endoplasmic reticulum. Viral DNA is then delivered to the nucleus where transcription, replication, and assembly of progeny occur. We found that the early regulatory protein large T antigen accumulates in microdomains in the nucleus adjacent to ND-10 or PML domains. This observation prompted us to explore the role of these domains in JCV infection. We found that a reduction of nuclear PML enhanced virus infection and that an increase in nuclear PML reduced infection. Infection with JCV did not directly modulate nuclear levels of PML but our data indicate that a host response involving interferon beta is likely to restrict virus infection by increasing nuclear PML.
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Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.
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Jennifer Gordon
Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases
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Bag3-induced autophagy is associated with degradation of JCV oncoprotein, T-Ag.
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Ilker Kudret Sariyer
Full Text Available JC virus, JCV, is a human neurotropic polyomavirus whose replication in glial cells causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML. In addition, JCV possesses oncogenic activity and expression of its transforming protein, large T-antigen (T-Ag, in several experimental animals induces tumors of neural origin. Further, the presence of JCV DNA and T-Ag have been repeatedly observed in several human malignant tissues including primitive neuroectodermal tumors and glioblastomas. Earlier studies have demonstrated that Bag3, a member of the Bcl-2-associated athanogene (Bag family of proteins, which is implicated in autophagy and apoptosis, is downregulated upon JCV infection of glial cells and that JCV T-Ag is responsible for suppressing the activity of the BAG3 promoter. Here, we investigated the possible impact of Bag3 on T-Ag expression in JCV-infected human primary glial cells as well as in cells derived from T-Ag-induced medulloblastoma in transgenic animals. Results from these studies revealed that overexpression of Bag3 drastically decreases the level of T-Ag expression by inducing the autophagic degradation of the viral protein. Interestingly, this event leads to the inhibition of JCV infection of glial cells, suggesting that the reduced levels of T-antigen seen upon the overexpression of Bag3 has a biological impact on the viral lytic cycle. Results from protein-protein interaction studies showed that T-Ag and Bag3 physically interact with each other through the zinc-finger of T-Ag and the proline rich domains of Bag3, and this interaction is important for the autophagic degradation of T-Ag. Our observations open a new avenue of research for better understanding of virus-host interaction by investigating the interplay between T-Ag and Bag3, and their impact on the development of JCV-associated diseases.
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Bag3-induced autophagy is associated with degradation of JCV oncoprotein, T-Ag.
Sariyer, Ilker Kudret; Merabova, Nana; Patel, Prem Kumer; Knezevic, Tijana; Rosati, Alessandra; Turco, Maria C; Khalili, Kamel
2012-01-01
JC virus, JCV, is a human neurotropic polyomavirus whose replication in glial cells causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition, JCV possesses oncogenic activity and expression of its transforming protein, large T-antigen (T-Ag), in several experimental animals induces tumors of neural origin. Further, the presence of JCV DNA and T-Ag have been repeatedly observed in several human malignant tissues including primitive neuroectodermal tumors and glioblastomas. Earlier studies have demonstrated that Bag3, a member of the Bcl-2-associated athanogene (Bag) family of proteins, which is implicated in autophagy and apoptosis, is downregulated upon JCV infection of glial cells and that JCV T-Ag is responsible for suppressing the activity of the BAG3 promoter. Here, we investigated the possible impact of Bag3 on T-Ag expression in JCV-infected human primary glial cells as well as in cells derived from T-Ag-induced medulloblastoma in transgenic animals. Results from these studies revealed that overexpression of Bag3 drastically decreases the level of T-Ag expression by inducing the autophagic degradation of the viral protein. Interestingly, this event leads to the inhibition of JCV infection of glial cells, suggesting that the reduced levels of T-antigen seen upon the overexpression of Bag3 has a biological impact on the viral lytic cycle. Results from protein-protein interaction studies showed that T-Ag and Bag3 physically interact with each other through the zinc-finger of T-Ag and the proline rich domains of Bag3, and this interaction is important for the autophagic degradation of T-Ag. Our observations open a new avenue of research for better understanding of virus-host interaction by investigating the interplay between T-Ag and Bag3, and their impact on the development of JCV-associated diseases.
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Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.
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Ilker Kudret Sariyer
Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to
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High prevalence of human polyomavirus JC VP1 gene sequences in pediatric malignancies.
Shiramizu, B; Hu, N; Frisque, R J; Nerurkar, V R
2007-05-15
The oncogenic potential of human polyomavirus JC (JCV), a ubiquitous virus that establishes infection during early childhood in approximately 70% of the human population, is unclear. As a neurotropic virus, JCV has been implicated in pediatric central nervous system tumors and has been suggested to be a pathogenic agent in pediatric acute lymphoblastic leukemia. Recent studies have demonstrated JCV gene sequences in pediatric medulloblastomas and among patients with colorectal cancer. JCV early protein T-antigen (TAg) can form complexes with cellular regulatory proteins and thus may play a role in tumorigenesis. Since JCV is detected in B-lymphocytes, a retrospective analysis of pediatric B-cell and non-B-cell malignancies as well as other HIV-associated pediatric malignancies was conducted for the presence of JCV gene sequences. DNA was extracted from 49 pediatric malignancies, including Hodgkin disease, non-Hodgkin lymphoma, large cell lymphoma and sarcoma. Polymerase chain reaction (PCR) was conducted using JCV specific nested primer sets for the transcriptional control region (TCR), TAg, and viral capsid protein 1 (VP1) genes. Southern blot analysis and DNA sequencing were used to confirm specificity of the amplicons. A 215-bp region of the JCV VP1 gene was amplified from 26 (53%) pediatric tumor tissues. The JCV TCR and two JCV gene regions were amplified from a leiomyosarcoma specimen from an HIV-infected patient. The leiomyosarcoma specimen from the cecum harbored the archetype strain of JCV. Including the leiomyosarcoma specimen, three of five specimens sequenced were typed as JCV genotype 2. The failure to amplify JCV TCR, and TAg gene sequences in the presence of JCV VP1 gene sequence is surprising. Even though JCV TAg gene, which is similar to the SV40 TAg gene, is oncogenic in animal models, the presence of JCV gene sequences in pediatric malignancies does not prove causality. In light of the available data on the presence of JCV in normal and cancerous
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Molecular Epidemiology of Human Polyomavirus JC in the Biaka Pygmies and Bantu of Central Africa
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Sylvester C Chima
1998-09-01
Full Text Available Polyomavirus JC (JCV is ubiquitous in humans and causes a chronic demyelinating disease of the central nervous system , progressive multifocal leukoencephalopathy which is common in AIDS. JCV is excreted in urine of 30-70% of adults worldwide. Based on sequence analysis of JCV complete genomes or fragments thereof, JCV can be classified into geographically derived genotypes. Types 1 and 2 are of European and Asian origin respectively while Types 3 and 6 are African in origin. Type 4, a possible recombinant of European and African genotypes (1 and 3 is common in the USA. To delineate the JCV genotypes in an aboriginal African population, random urine samples were collected from the Biaka Pygmies and Bantu from the Central African Republic. There were 43 males and 25 females aged 4-55 years, with an average age of 26 years. After PCR amplification of JCV in urine, products were directly cycle sequenced. Five of 23 Pygmy adults (22% and four of 20 Bantu adults (20% were positive for JC viruria. DNA sequence analysis revealed JCV Type 3 (two, Type 6 (two and one Type 1 variant in Biaka Pygmies. All the Bantu strains were Type 6. Type 3 and 6 strains of JCV are the predominant strains in central Africa. The presence of multiple subtypes of JCV in Biaka Pygmies may be a result of extensive interactions of Pygmies with their African tribal neighbors during their itinerant movements in the equatorial forest.
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Association between the JC polyomavirus infection and male infertility.
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Manola Comar
Full Text Available In recent years the incidence of male infertility has increased. Many risk factors have been taken into consideration, including viral infections. Investigations into viral agents and male infertility have mainly been focused on human papillomaviruses, while no reports have been published on polyomaviruses and male infertility. The aim of this study was to verify whether JC virus and BK virus are associated with male infertility. Matched semen and urine samples from 106 infertile males and 100 fertile males, as controls, were analyzed. Specific PCR analyses were carried out to detect and quantify large T (Tag coding sequences of JCV and BKV. DNA sequencing, carried out in Tag JCV-positive samples, was addressed to viral protein 1 (VP1 coding sequences. The prevalence of JCV Tag sequences in semen and urine samples from infertile males was 34% (72/212, whereas the BKV prevalence was 0.94% (2/212. Specifically, JCV Tag sequences were detected in 24.5% (26/106 of semen and 43.4% (46/106 of urine samples from infertile men. In semen and urine samples from controls the prevalence was 11% and 28%, respectively. A statistically significant difference (p<0.05 in JCV prevalence was disclosed in semen and urine samples of cases vs. controls. A higher JC viral DNA load was detected in samples from infertile males than in controls. In samples from infertile males the JC virus type 2 strain, subtype 2b, was more prevalent than ubiquitous type 1. JCV type 2 strain infection has been found to be associated with male infertility. These data suggest that the JC virus should be taken into consideration as an infectious agent which is responsible for male infertility.
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JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.
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Emilie Sundqvist
2014-04-01
Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and
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Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation
International Nuclear Information System (INIS)
Orba, Yasuko; Sunden, Yuji; Suzuki, Tadaki; Nagashima, Kazuo; Kimura, Takashi; Tanaka, Shinya; Sawa, Hirofumi
2008-01-01
The human Polyomavirus JC virus (JCV) utilizes cellular proteins for viral replication and transcription in the host cell nucleus. These cellular proteins represent potential targets for antiviral drugs against the JCV. In this study, we examined the antiviral effects of the pharmacological cyclin-dependent kinase (cdk) inhibitor R-Roscovitine, which has been shown to have antiviral activity against other viruses. We found that Roscovitine significantly inhibited the viral production and cytopathic effects of the JCV in a JCV-infected cell line. Roscovitine attenuated the transcriptional activity of JCV late genes, but not early genes, and also prevented viral replication via inhibiting phosphorylation of the viral early protein, large T antigen. These data suggest that the JCV requires cdks to transcribe late genes and to replicate its own DNA. That Roscovitine exhibited antiviral activity in JCV-infected cells suggests that Roscovitine might have therapeutic utility in the treatment of progressive multifocal leukoencephalopathy (PML)
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Ryschkewitsch, C F; Friedlaender, J S; Mgone, C S; Jobes, D V; Agostini, H T; Chima, S C; Alpers, M P; Koki, G; Yanagihara, R; Stoner, G L
2000-07-01
The peopling of the Pacific was a complex sequence of events that is best reconstructed by reconciling insights from various disciplines. Here we analyze the human polyomavirus JC (JCV) in Highlanders of Papua New Guinea (PNG), in Austronesian-speaking Tolai people on the island of New Britain, and in nearby non-Austronesian-speaking Baining people. We also characterize JCV from the Chamorro of Guam, a Micronesian population. All JCV strains from PNG and Guam fall within the broad Asian group previously defined in the VP1 gene as Type 2 or Type 7, but the PNG strains were distinct from both genotypes. Among the Chamorro JCV samples, 8 strains (Guam-1) were like the Type 7 strains found in Southeast Asia, while nine strains (Guam-2) were distinct from both the mainland strains and most PNG strains. We identified three JCV variants within Papua New Guinea (PNG-1, PNG-2 and PNG-3), but none of the Southeast Asian (Type 7) strains. PNG-1 strains were present in all three populations (Highlanders and the Baining and Tolai of New Britain), but PNG-2 strains were restricted to the Highlanders. Their relative lack of DNA sequence variation suggests that they arose comparatively recently. The single PNG-3 strain, identified in an Austronesian-speaking Tolai individual, was closely related to the Chamorro variants (Guam-2), consistent with a common Austronesian ancestor. In PNG-2 variants a complex regulatory region mutation inserts a duplication into a nearby deletion, a change reminiscent of those seen in the brains of progressive multifocal leukoencephalopathy patients. This is the first instance of a complex JCV rearrangement circulating in a human population.
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Adami, G R; Marlor, C W; Barrett, N L; Carmichael, G G
1989-01-01
Polyomavirus late mRNA molecules contain multiple, tandem copies of a noncoding 57-base "late leader" exon at their 5' ends. This exon is encoded only once in the genome. Leader multiplicity arises from leader-leader splicing in giant primary transcripts, which are the result of multiple circuits of the viral genome by RNA polymerase II. We have been interested in learning more about the role of the leader exon in late viral gene expression. We recently showed that an abbreviated-leader mutan...
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Hradsky, Ondrej; Copova, Ivana; Zarubova, Kristyna; Durilova, Marianna; Nevoral, Jiri; Maminak, Miroslav; Hubacek, Petr; Bronsky, Jiri
2015-11-01
Young age and thiopurine therapy are risk factors for lymphoproliferative disease among patients with inflammatory bowel disease (IBD). The aims of this study were to evaluate the prevalence of seropositivity for the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) among children and adolescents with IBD, to assess the viral load of EBV, CMV, and BK and JC polyomaviruses (BKV, JCV) in these patients, and to assess the influence of different therapeutic regimens on seroprevalence and viral load. Children who had been followed in our center were tested for EBV, CMV, BKV, and JCV in a cross-sectional study. One hundred and six children were included who had Crohn's disease (68%), ulcerative colitis (29%), and unclassified IBD (3%). We found that 64% of patients were EBV seropositive. The proportion of EBV seropositive patients increased during childhood. Azathioprine therapy (p = 0.003) was associated with EBV seropositivity in a multiple logistic regression model, after adjusting for gender, age, and disease activity at determination. We found a significant association between the number of polymerase chain reaction copies and infliximab dose (p = 0.023). We did not find any significant association between CMV serology and CMV, BKV, or JCV viral load, or any other therapeutic regimen or clinical characteristics. Treatment with azathioprine appears to be a risk factor for early EBV seropositivity in children with IBD, and the infliximab dose was associated with a higher EBV viral load.
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Ling, Paul D.; Lednicky, John A.; Keitel, Wendy A.; Poston, David G.; White, Zoe S.; Peng, RongSheng; Liu, Zhensheng; Mehta, Satish K.; Pierson, Duane L.; Rooney, Cliona M.;
2003-01-01
Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (Por=40 years old (P.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.
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Jérôme T J Nicol
Full Text Available Phylogenetic analyses based on the major capsid protein sequence indicate that Merkel cell polyomavirus (MCPyV and chimpanzee polyomaviruses (PtvPyV1, PtvPyV2, and similarly Trichodysplasia spinulosa-associated polyomavirus (TSPyV and the orangutan polyomavirus (OraPyV1 are closely related. The existence of cross-reactivity between these polyomaviruses was therefore investigated. The findings indicated serological identity between the two chimpanzee polyomaviruses investigated and a high level of cross-reactivity with Merkel cell polyomavirus. In contrast, cross-reactivity was not observed between TSPyV and OraPyV1. Furthermore, specific antibodies to chimpanzee polyomaviruses were detected in chimpanzee sera by pre-incubation of sera with the different antigens, but not in human sera.
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International Nuclear Information System (INIS)
Gee, Gretchen V.; Manley, Kate; Atwood, Walter J.
2003-01-01
JC virus (JCV) is a common human polyomavirus that infects 70-80% of the population worldwide. In immunosuppressed individuals, JCV infects oligodendrocytes and causes a fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). The tropism of JCV is restricted to oligodendrocytes, astrocytes, and B lymphocytes. Several mechanisms may contribute to the restricted tropism of JCV, including the presence or absence of cell-type-specific transcription and replication factors and the presence or absence of cell-type-specific receptors. We have established a system to investigate cellular factors that influence viral tropism by selecting JCV-resistant cells from a susceptible glial cell line (SVG-A). SVG-A cells were subjected to several rounds of viral infection using JC virus (M1/SVEΔ). A population of resistant cells emerged (SVGR2) that were refractory to infection with the Mad-4 strain of JCV, the hybrid virus M1/SVEΔ, as well as to the related polyomavirus SV40. SVGR2 cells were as susceptible as the SVG-A cells to infection with an unrelated amphotropic retrovirus. The stage at which these cells are resistant to infection was investigated and the block appears to be at early viral gene transcription. This system should ultimately allow us to identify glial specific factors that influence the tropism of JCV
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W. Yang; E.L. Beaudoin; L. Lu; R.A. Du Pasquier (Renaud); M.J. Kuroda; R.A. Willemsen (Ralph); I.J. Koralnik; R.P. Junghans
2007-01-01
textabstractProgressive multifocal leukoencephalopathy (PML) is a deadly brain disease caused by the polyomavirus JC (JCV). The aim of this study is to develop 'designer T cells' armed with anti-JCV TCR-based chimeric immune receptors (CIRs) by gene modification for PML immunotherapy. Two T cell
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Vilkin, Alex; Niv, Yaron
2011-04-01
Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.
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A novel polyomavirus from the nasal cavity of a giant panda (Ailuropoda melanoleuca).
Qi, Dunwu; Shan, Tongling; Liu, Zhijian; Deng, Xutao; Zhang, Zhihe; Bi, Wenlei; Owens, Jacob Robert; Feng, Feifei; Zheng, Lisong; Huang, Feng; Delwart, Eric; Hou, Rong; Zhang, Wen
2017-10-27
Polyomaviruses infect a wide variety of mammalian and avian hosts with a broad spectrum of outcomes including asymptomatic infection, acute systemic disease, and tumor induction. Viral metagenomics and general PCR methods were used to detected viral nucleic acid in the samples from a diseased and healthy giant pandas. A novel polyomavirus, the giant panda polyomavirus 1 (GPPyV1) from the nasal cavity of a dead giant panda (Ailuropoda melanoleuca) was characterized. The GPPyV1 genome is 5144 bp in size and reveals five putative open-reading frames coding for the classic small and large T antigens in the early region, and the VP1, VP2 and VP3 capsid proteins in the late region. Phylogenetic analyses of the large T antigen of the GPPyV1 indicated GPPyV1 belonged to a putative new species within genus Deltapolyomavirus, clustering with four human polyomavirus species. The GPPyV1 VP1 and VP2 clustered with genus Alphapolyomavirus. Our epidemiologic study indicated that this novel polyomavirus was also detected in nasal swabs and fecal samples collected from captive healthy giant pandas. A novel polyomavirus was detected in giant pandas and its complete genome was characterized, which may cause latency infection in giant pandas.
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International Nuclear Information System (INIS)
Verma, Saguna; Ziegler, Katja; Ananthula, Praveen; Co, Juliene K.G.; Frisque, Richard J.; Yanagihara, Richard; Nerurkar, Vivek R.
2006-01-01
Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML
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Chattaraj, S; Bera, N K; Dutta, C; Bhattacharjee, S
2015-01-01
Human polyomavirus JC (JCV) is a widespread human virus with profound pathogenic potential. A study was undertaken to quantify JCV load in urine and peripheral blood samples of immunocompetent, apparently healthy tribal individuals of North-Eastern part of West Bengal, India for the first time. One hundred and thirteen samples of urine or blood were collected from different tribal groups of this region. For the quantitative estimation of the viral load in each sample, real-time polymerase chain reaction method using the SYBR Green dye was employed. The viral load estimated was found in the range between 3.5 × 102 and 2.12 × 106 copies/ml of samples having a mean and median viral copy numbers of 8.67 × 105 and 9.19 × 105 copies/ml of sample respectively. The mean viral DNA load in urine samples of the studied immunocompetent population was found to be higher than that found in a study conducted in the USA, but lower than similar groups of Italy and healthy adult women in the USA. However when compared with median values of viral DNA loads in urine samples of immunocompetent human subjects of Kuwait, Portugal, and Switzerland the observed viral DNA load was found to be substantially higher.
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Directory of Open Access Journals (Sweden)
Nelly Scuda
Full Text Available Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated, to greater or lesser extent, with human disease and cancer. Currently, twelve polyomaviruses are known to circulate within the human population. To further examine the diversity of human polyomaviruses, we have utilized a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of nonhuman primate (NHP polyomavirus species, followed by polyomavirus-specific serological analysis of human sera. Using this approach we identified twenty novel NHP polyomaviruses: nine in great apes (six in chimpanzees, two in gorillas and one in orangutan, five in Old World monkeys and six in New World monkeys. Phylogenetic analysis indicated that only four of the nine chimpanzee polyomaviruses (six novel and three previously identified had known close human counterparts. To determine whether the remaining chimpanzee polyomaviruses had potential human counterparts, the major viral capsid proteins (VP1 of four chimpanzee polyomaviruses were expressed in E. coli for use as antigens in enzyme-linked immunoassay (ELISA. Human serum/plasma samples from both Côte d'Ivoire and Germany showed frequent seropositivity for the four viruses. Antibody pre-adsorption-based ELISA excluded the possibility that reactivities resulted from binding to known human polyomaviruses. Together, these results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses.
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Scuda, Nelly; Madinda, Nadege Freda; Akoua-Koffi, Chantal; Adjogoua, Edgard Valerie; Wevers, Diana; Hofmann, Jörg; Cameron, Kenneth N.; Leendertz, Siv Aina J.; Couacy-Hymann, Emmanuel; Robbins, Martha; Boesch, Christophe; Jarvis, Michael A.; Moens, Ugo; Mugisha, Lawrence; Calvignac-Spencer, Sébastien; Leendertz, Fabian H.; Ehlers, Bernhard
2013-01-01
Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated, to greater or lesser extent, with human disease and cancer. Currently, twelve polyomaviruses are known to circulate within the human population. To further examine the diversity of human polyomaviruses, we have utilized a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of nonhuman primate (NHP) polyomavirus species, followed by polyomavirus-specific serological analysis of human sera. Using this approach we identified twenty novel NHP polyomaviruses: nine in great apes (six in chimpanzees, two in gorillas and one in orangutan), five in Old World monkeys and six in New World monkeys. Phylogenetic analysis indicated that only four of the nine chimpanzee polyomaviruses (six novel and three previously identified) had known close human counterparts. To determine whether the remaining chimpanzee polyomaviruses had potential human counterparts, the major viral capsid proteins (VP1) of four chimpanzee polyomaviruses were expressed in E. coli for use as antigens in enzyme-linked immunoassay (ELISA). Human serum/plasma samples from both Côte d'Ivoire and Germany showed frequent seropositivity for the four viruses. Antibody pre-adsorption-based ELISA excluded the possibility that reactivities resulted from binding to known human polyomaviruses. Together, these results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses. PMID:23818846
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Analysis of JC virus DNA replication using a quantitative and high-throughput assay
Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.
2015-01-01
Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. PMID:25155200
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Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection
Directory of Open Access Journals (Sweden)
Margarita-Maria Panou
2018-03-01
Full Text Available BK polyomavirus (BKPyV; hereafter referred to as BK causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF attachment protein (α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.
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Directory of Open Access Journals (Sweden)
Luiz Henrique da Silva Nali
2014-12-01
Full Text Available Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML. The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between the risks and the benefits of the treatment. Hence, strategies for monitor JCV-positive patients undergoing Natalizumab treatment are deeply necessary. To illustrate it, we monitored JCV/DNA in blood and urine of a patient receiving Natalizumab for 12 months. We also bring to discussion the effectiveness of the current methods used for risk evaluation, and the real implications of viral reactivation.
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Merkel cell polyomavirus and Merkel cell carcinoma.
DeCaprio, James A
2017-10-19
Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).
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Identification of a Second Raccoon-Associated Polyomavirus.
Geoghegan, Eileen M; Welch, Nicole L; Yabsley, Michael J; Church, Molly E; Pesavento, Patricia A; Buck, Christopher B
2017-06-29
Raccoon polyomavirus 1 (RacPyV1) is the suspected cause of an outbreak of fatal brain tumors among raccoons ( Procyon lotor ) in the western United States. Spleen samples from Georgia raccoons were screened for polyomaviruses. Although RacPyV1 was not detected, a previously unknown polyomavirus, which we designate RacPyV2, was identified and sequenced. Copyright © 2017 Geoghegan et al.
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Analysis of JC virus DNA replication using a quantitative and high-throughput assay
International Nuclear Information System (INIS)
Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.
2014-01-01
Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication
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Analysis of JC virus DNA replication using a quantitative and high-throughput assay
Energy Technology Data Exchange (ETDEWEB)
Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Gagnon, David [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Gjoerup, Ole [Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111 (United States); Archambault, Jacques [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Bullock, Peter A., E-mail: Peter.Bullock@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States)
2014-11-15
Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication.
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International Nuclear Information System (INIS)
Tada, Hiroomi; Lashgari, M.; Amini, S.; Khalili, K.; Rappaport, J.; Wong-Staal, F.
1990-01-01
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCV L , in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle in glial cells by stimulating JCV gene expression. The results suggest a mechanism for the relatively high incidence of PML in AIDS patients than in other immunosuppressive disorders. Furthermore, the findings indicate that the HIV-1 regulatory protein tat may stimulate other viral and perhaps cellular promoters, in addition to its own
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O'Neill, F J; Gao, Y; Xu, X
1993-11-01
The DNAs of polyomaviruses ordinarily exist as a single circular molecule of approximately 5000 base pairs. Variants of SV40, BKV and JCV have been described which contain two complementing defective DNA molecules. These defectives, which form a bipartite genome structure, contain either the viral early region or the late region. The defectives have the unique property of being able to tolerate variable sized reiterations of regulatory and terminus region sequences, and portions of the coding region. They can also exchange coding region sequences with other polyomaviruses. It has been suggested that the bipartite genome structure might be a stage in the evolution of polyomaviruses which can uniquely sustain genome and sequence diversity. However, it is not known if the regulatory and terminus region sequences are highly mutable. Also, it is not known if the bipartite genome structure is reversible and what the conditions might be which would favor restoration of the monomolecular genome structure. We addressed the first question by sequencing the reiterated regulatory and terminus regions of E- and L-SV40 DNAs. This revealed a large number of mutations in the regulatory regions of the defective genomes, including deletions, insertions, rearrangements and base substitutions. We also detected insertions and base substitutions in the T-antigen gene. We addressed the second question by introducing into permissive simian cells, E- and L-SV40 genomes which had been engineered to contain only a single regulatory region. Analysis of viral DNA from transfected cells demonstrated recombined genomes containing a wild type monomolecular DNA structure. However, the complete defectives, containing reiterated regulatory regions, could often compete away the wild type genomes. The recombinant monomolecular genomes were isolated, cloned and found to be infectious. All of the DNA alterations identified in one of the regulatory regions of E-SV40 DNA were present in the recombinant
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Directory of Open Access Journals (Sweden)
Imajoh Masayuki
2012-06-01
Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9, another lymphotropic polyomavirus, in Japanese CLL cases. Findings We found that 9/27 CLL cases (33.3 % were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. Conclusions This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.
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Prevalence of JC virus in Chinese patients with colorectal cancer.
Directory of Open Access Journals (Sweden)
Xiaozhou Mou
Full Text Available BACKGROUND: JCV is a DNA polyomavirus very well adapted to humans. Although JCV DNA has been detected in colorectal cancers (CRC, the association between JCV and CRC remains controversial. In China, the presence of JCV infection in CRC patients has not been reported. Here, we investigated JCV infection and viral DNA load in Chinese CRC patients and to determine whether the JCV DNA in peripheral blood (PB can be used as a diagnostic marker for JCV-related CRC. METHODOLOGY/PRINCIPAL FINDINGS: Tumor tissues, non-cancerous tumor-adjacent tissues and PB samples were collected from 137 CRC patients. In addition, 80 normal colorectal tissue samples from patients without CRC and PB samples from 100 healthy volunteers were also harvested as controls. JCV DNA was detected by nested PCR and glass slide-based dot blotting. Viral DNA load of positive samples were determined by quantitative real-time PCR. JCV DNA was detected in 40.9% (56/137 of CRC tissues at a viral load of 49.1 to 10.3×10(4 copies/µg DNA. Thirty-four (24.5% non-cancerous colorectal tissues (192.9 to 4.4×10(3 copies/µg DNA and 25 (18.2% PB samples (81.3 to 4.9×10(3 copies/µg DNA from CRC patients were positive for JCV. Tumor tissues had higher levels of JCV than non-cancerous tissues (P = 0.003 or PB samples (P<0.001. No correlation between the presence of JCV and demographic or medical characteristics was observed. The JCV prevalence in PB samples was significantly associated with the JCV status in tissue samples (P<0.001. Eleven (13.8% normal colorectal tissues and seven (7.0% PB samples from healthy donors were positive for JCV. CONCLUSIONS/SIGNIFICANCE: JCV infection is frequently present in colorectal tumor tissues of CRC patients. Although the association between JCV presence in PB samples and JCV status in tissue samples was identified in this study, whether PB JCV detection can serve as a marker for JCV status of CRC requires further study.
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A novel pulmonary polyomavirus in alpacas (Vicugna pacos).
Dela Cruz, Florante N; Li, Linlin; Delwart, Eric; Pesavento, P A
2017-03-01
Viral metagenomic analysis detected a novel polyomavirus in a 6-month old female alpaca (Vicugna pacos) euthanized after a diagnosis of disseminated lymphosarcoma. The viral genome was fully sequenced, found to be similar to other polyomaviruses in gene architecture and provisionally named Alpaca polyomavirus or AlPyV. Viral nucleic acid was detected by PCR in venous blood, spleen, thymus, and lung. AlPyV phylogenetically clustered in the "Wuki" group of PyVs, which includes WU and KI polyomaviruses, commonly found in human respiratory samples. In an ISH analysis of 17 alpaca necropsies, 7 had detectable virus within the lung. In animals without pneumonia, probe hybridization was restricted to the nuclei of scattered individual bronchiolar epithelial cells. Three of the ISH positive alpacas had interstitial pneumonia of unknown origin, and in these animals there was viral nucleic acid detected in bronchiolar epithelium, type II pneumocytes, and alveolar macrophages. The pattern of AlPyV distribution is consistent with a persistent respiratory virus that has a possible role in respiratory disease. Copyright © 2017 Elsevier B.V. All rights reserved.
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Natural history of polyomaviruses in men: the HPV infection in men (HIM) study.
Hampras, Shalaka S; Giuliano, Anna R; Lin, Hui-Yi; Fisher, Kate J; Abrahamsen, Martha E; McKay-Chopin, Sandrine; Gheit, Tarik; Tommasino, Massimo; Rollison, Dana E
2015-05-01
Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa-associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study. Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction. MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03-4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01-6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively. MCPyV infection is highly prevalent in adults, with age and race being predisposing factors. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Miner, Andrew G; Patel, Rajiv M; Wilson, Deborah A; Procop, Gary W; Minca, Eugen C; Fullen, Douglas R; Harms, Paul W; Billings, Steven D
2015-04-01
Merkel cell carcinoma is a rare, highly aggressive cutaneous neuroendocrine carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in ∼95% of cases. In 2008, Merkel cell carcinoma was shown to be associated with a virus now known as Merkel cell polyomavirus in ∼80% of cases. Prognostic and mechanistic differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinoma may exist. There has been the suggestion that CK20-negative Merkel cell carcinomas less frequently harbor Merkel cell polyomavirus, but a systematic investigation for Merkel cell polyomavirus incidence in CK20-negative Merkel cell carcinoma has not been done. To test the hypothesis that Merkel cell polyomavirus is less frequently associated with CK20-negative Merkel cell carcinoma, we investigated 13 CK20-negative Merkel cell carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel cell polyomavirus. Ten of these (77%) were negative for Merkel cell polyomavirus and three (23%) were positive for Merkel cell polyomavirus. Merkel cell polyomavirus is less common in CK20-negative Merkel cell carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel cell carcinoma is mechanistically and prognostically unique.
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Upadhyay, Mohita; Vivekanandan, Perumal
2015-01-01
Papillomaviruses and polyomaviruses are small ds-DNA viruses infecting a wide-range of vertebrate hosts. Evidence supporting co-evolution of the virus with the host does not fully explain the evolutionary path of papillomaviruses and polyomaviruses. Studies analyzing CpG dinucleotide frequencies in virus genomes have provided interesting insights on virus evolution. CpG dinucleotide depletion has not been extensively studied among papillomaviruses and polyomaviruses. We sought to analyze the relative abundance of dinucleotides and the relative roles of evolutionary pressures in papillomaviruses and polyomaviruses. We studied 127 full-length sequences from papillomaviruses and 56 full-length sequences from polyomaviruses. We analyzed the relative abundance of dinucleotides, effective codon number (ENC), differences in synonymous codon usage. We examined the association, if any, between the extent of CpG dinucleotide depletion and the evolutionary lineage of the infected host. We also investigated the contribution of mutational pressure and translational selection to the evolution of papillomaviruses and polyomaviruses. All papillomaviruses and polyomaviruses are CpG depleted. Interestingly, the evolutionary lineage of the infected host determines the extent of CpG depletion among papillomaviruses and polyomaviruses. CpG dinucleotide depletion was more pronounced among papillomaviruses and polyomaviruses infecting human and other mammals as compared to those infecting birds. Our findings demonstrate that CpG depletion among papillomaviruses is linked to mutational pressure; while CpG depletion among polyomaviruses is linked to translational selection. We also present evidence that suggests methylation of CpG dinucleotides may explain, at least in part, the depletion of CpG dinucleotides among papillomaviruses but not polyomaviruses. The extent of CpG depletion among papillomaviruses and polyomaviruses is linked to the evolutionary lineage of the infected host. Our
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Polyomavirus – an emergent pathogen in transplant recipients
Directory of Open Access Journals (Sweden)
Juliana de Moura Montagner
2007-06-01
Full Text Available Medical centers that work with transplants often face opportunisticinfections that demand specific tools to make diagnosis. Theprevalence of latent polyomavirus infections is high, and the mostcommon site of latency of the most prevalent polyomavirus in humans,BK virus (BKV, is the renal tissue. Hence, renal transplanted patientsare particularly vulnerable to the damage caused by viral reactivationduring immunosupression. In such patients BKV is associated toureteral stenosis and/or BKV nephropathy, leading to progressivedysfunction and graft loss, often diagnosed as rejection. In other organsrecipients (namely lung, liver, heart and pancreas, BKN is also the mostimportant clinical manifestation, whereas in bone marrow recipients themost common is hemorrhagic cystitis. This review presents the viralbiology and discusses the pathophysiology of polyomavirus diseasesand the diagnostic efficacy of the laboratory tests available, guidingto the best strategy for assessment and monitoring of patients at riskor under specific treatment.
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Delwart, Eric; Kapusinszky, Beatrix; Pesavento, Patricia A; Estrada, Marko; Seguin, M Alexis; Leutenegger, Christian M
2017-07-20
We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses. Copyright © 2017 Delwart et al.
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Detection and characterization of two chimpanzee polyomavirus genotypes from different subspecies
I. Deuzing (Ilona); Z. Fagrouch (Zahra); M.J. Groenewoud (Marlous); H. Niphuis (Henk); I. Kondova (Ivanela); W. Bogers (Willy); E.J. Verschoor (Ernst)
2010-01-01
textabstractThe complete nucleotide sequences of three chimpanzee polyomavirus genetic variants were determined. Phylogenetic analysis indicated that the viruses form two different genotypes of ChPyV. Comparison with other primate polyomaviruses revealed a putative agnogene, and an unusually long
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Hill, Sarah C; Murphy, Aisling A; Cotten, Matthew; Palser, Anne L; Benson, Phillip; Lesellier, Sandrine; Gormley, Eamonn; Richomme, Céline; Grierson, Sylvia; Bhuachalla, Deirdre Ni; Chambers, Mark; Kellam, Paul; Boschiroli, María-Laura; Ehlers, Bernhard; Jarvis, Michael A; Pybus, Oliver G
2015-06-01
Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.
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Cai, X.; Chang, D.; Rottinghaus, S.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)
1994-01-01
Recombinant polyomavirus VP2 protein was expressed in Escherichia coli (RK1448), using the recombinant expression system pFPYV2. Recombinant VP2 was purified to near homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroelution, and Extracti-Gel chromatography. Polyclonal serum to this protein which reacted specifically with recombinant VP2 as well as polyomavirus virion VP2 and VP3 on Western blots (immunoblots) was produced. Purified VP2 was used to establish an in vitro protein-protein interaction assay with polyomavirus structural proteins and purified recombinant VP1. Recombinant VP2 interacted with recombinant VP1, virion VP1, and the four virion histones. Recombinant VP1 coimmunoprecipitated with recombinant VP2 or truncated VP2 (delta C12VP2), which lacked the carboxy-terminal 12 amino acids. These experiments confirmed the interaction between VP1 and VP2 and revealed that the carboxyterminal 12 amino acids of VP2 and VP3 were not necessary for formation of this interaction. In vivo VP1-VP2 interaction study accomplished by cotransfection of COS-7 cells with VP2 and truncated VP1 (delta N11VP1) lacking the nuclear localization signal demonstrated that VP2 was capable of translocating delta N11VP1 into the nucleus. These studies suggest that complexes of VP1 and VP2 may be formed in the cytoplasm and cotransported to the nucleus for virion assembly to occur.
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The oncogenic potential of BK-polyomavirus is linked to viral integration into the human genome.
Kenan, Daniel J; Mieczkowski, Piotr A; Burger-Calderon, Raquel; Singh, Harsharan K; Nickeleit, Volker
2015-11-01
It has been suggested that BK-polyomavirus is linked to oncogenesis via high expression levels of large T-antigen in some urothelial neoplasms arising following kidney transplantation. However, a causal association between BK-polyomavirus, large T-antigen expression and oncogenesis has never been demonstrated in humans. Here we describe an investigation using high-throughput sequencing of tumour DNA obtained from an urothelial carcinoma arising in a renal allograft. We show that a novel BK-polyomavirus strain, named CH-1, is integrated into exon 26 of the myosin-binding protein C1 gene (MYBPC1) on chromosome 12 in tumour cells but not in normal renal cells. Integration of the BK-polyomavirus results in a number of discrete alterations in viral gene expression, including: (a) disruption of VP1 protein expression and robust expression of large T-antigen; (b) preclusion of viral replication; and (c) deletions in the non-coding control region (NCCR), with presumed alterations in promoter feedback loops. Viral integration disrupts one MYBPC1 gene copy and likely alters its expression. Circular episomal BK-polyomavirus gene sequences are not found, and the renal allograft shows no productive polyomavirus infection or polyomavirus nephropathy. These findings support the hypothesis that integration of polyomaviruses is essential to tumourigenesis. It is likely that dysregulation of large T-antigen, with persistent over-expression in non-lytic cells, promotes cell growth, genetic instability and neoplastic transformation. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Examining Merkel Cell Polyomavirus Minor Capsid Proteins | Center for Cancer Research
Merkel cell polyomavirus (MCV or MCPyV) is a recently discovered member of the viral family Polyomaviridae. It is a skin-dwelling polyomavirus species that appears to cause a rare but highly lethal form of skin cancer called Merkel cell carcinoma (MCC). Despite MCC being uncommon, chronic MCV infection of human skin is widespread, and most infected people have no known
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Merkel cell polyomavirus infection and Merkel cell carcinoma.
Liu, Wei; MacDonald, Margo; You, Jianxin
2016-10-01
Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.
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Neu, Ursula; Wang, Jianbo; Macejak, Dennis; Garcea, Robert L; Stehle, Thilo
2011-07-01
The Karolinska Institutet and Washington University polyomaviruses (KIPyV and WUPyV, respectively) are recently discovered human viruses that infect the respiratory tract. Although they have not yet been linked to disease, they are prevalent in populations worldwide, with initial infection occurring in early childhood. Polyomavirus capsids consist of 72 pentamers of the major capsid protein viral protein 1 (VP1), which determines antigenicity and receptor specificity. The WUPyV and KIPyV VP1 proteins are distant in evolution from VP1 proteins of known structure such as simian virus 40 or murine polyomavirus. We present here the crystal structures of unassembled recombinant WUPyV and KIPyV VP1 pentamers at resolutions of 2.9 and 2.55 Å, respectively. The WUPyV and KIPyV VP1 core structures fold into the same β-sandwich that is a hallmark of all polyomavirus VP1 proteins crystallized to date. However, differences in sequence translate into profoundly different surface loop structures in KIPyV and WUPyV VP1 proteins. Such loop structures have not been observed for other polyomaviruses, and they provide initial clues about the possible interactions of these viruses with cell surface receptors.
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The polyomavirus BK agnoprotein co-localizes with lipid droplets
International Nuclear Information System (INIS)
Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David; Lorentz, Pascal; Rinaldo, Christine H.; Hirsch, Hans H.
2010-01-01
Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function.
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Hause, Ben M; Smith, Catherine; Bishop, Brian; Stewart, Chelsea; Simonson, Randy
2018-04-26
Metagenomic sequencing of pooled nasal swabs from pigs with unexplained respiratory disease identified a large number of reads mapping to a previously uncharacterized porcine polyomavirus. Sus scrofa polyomavirus 2 was most closely related to betapolyomaviruses frequently detected in mammalian respiratory samples. Copyright © 2018 Hause et al.
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International Nuclear Information System (INIS)
Zullo, J.; Stiles, C.D.; Garcea, R.L.
1987-01-01
The levels of c-myc, c-fos, and JE mRNAs accumulate in a biphasic pattern following infection of quiescent BALB/c 3T3 mouse cells with polyomavirus. Maximal levels of c-myc and c-fos mRNAs were seen within 1 hr and were nearly undetectable at 6 hr after infection. At 12 hr after infection mRNA levels were again maximal and remained elevated thereafter. Empty virions (capsids) and recombinant VP 1 protein, purified from Escherichia coli, induced the early but not the late phase of mRNA accumulation. Virions, capsids, and recombinant VP 1 protein stimulated [ 3 H]thymidine nuclear labeling and c-myc mRNA accumulation in a dose-responsive manner paralleling their affinity for the cell receptor for polyoma. The second phase of mRNA accumulation is regulated by the viral early gene products, as shown by polyomavirus early gene mutants and by a transfected cell line (336a) expressing middle tumor antigen upon glucocorticoid addition. These results suggest that polyomavirus interacts with the cell membrane at the onset of infection to increase the levels of mRNA for the cellular genes associated with cell competence for DNA replication, and subsequently these levels are maintained by the action of the early viral proteins
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Mazda, Monica E; Brosch, Jared R; Wiens, Andrea L; Bonnin, José M; Kamer, Aaron P; Mattson, David H; Snook, Riley J
2013-05-01
The development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab is a well-known potential risk. Diagnosis of PML can be confounded in patients with multiple sclerosis (MS) if new demyelinating lesions develop, and the sensitivity of existing diagnostic tests is less than ideal. In the case presented here, four samples of cerebrospinal fluid tested negative for John Cunningham virus (JCV) DNA by polymerase chain reaction, yet brain biopsy eventually proved positive by immunohistochemistry. A review of the limitations of existing clinical diagnostic tests is addressed, and we review the most recent literature on the proper management of natalizumab-treated MS patients.
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Progressive Multifocal Leukoencephalopathy [version 1; referees: 2 approved
Directory of Open Access Journals (Sweden)
Laura Adang
2015-12-01
Full Text Available Progressive multifocal leukoencephalopathy (PML is a devastating demyelinating disease with significant morbidity and mortality and no effective, targeted therapies. It is most often observed in association with abnormalities of cell-mediated immunity, in particular human immunodeficiency virus (HIV infection, but also occurs in association with lymphoproliferative diseases, certain immunosuppressive and immunomodulatory regimens, and other conditions. The etiologic agent of PML is a small, ubiquitous polyomavirus, the JC virus (JCV, also known as JCPyV, for which at least 50% of the adult general population is seropositive. PML results when JCV replicates within cerebral oligodendrocytes and astrocytes, leading to oligodendrocyte death and demyelination. Unfortunately, no treatments have been convincingly demonstrated to be effective, though some have been employed in desperation; treatment otherwise includes attempts to restore any immune system defect, such as the withdrawal of the causative agent if possible, and general supportive care.
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Brostoff, Terza; Dela Cruz, Florante N; Church, Molly E; Woolard, Kevin D; Pesavento, Patricia A
2014-11-01
Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by in situ hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells in vitro and in a mouse xenograft model. When tumor cells were cultured in vitro, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer. The natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of free-ranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in
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Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew
2017-07-01
We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1 rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.
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Phylodynamics of Merkel-cell polyomavirus and human polyomavirus 6: A long-term history with humans.
Torres, Carolina; Barrios, Melina Elizabeth; Cammarata, Robertina Viviana; Victoria, Matías; Fernandez-Cassi, Xavier; Bofill-Mas, Silvia; Colina, Rodney; Blanco Fernández, María Dolores; Mbayed, Viviana Andrea
2018-04-20
New human polyomaviruses have been described in the last years, including the Merkel-cell polyomavirus (MCPyV; Human polyomavirus 5) and the Human polyomavirus 6 (HPyV6). Although their infection is usually asymptomatic, in immunocompromised host can cause life-threatening pathologies, such as the Merkel cell carcinoma, an aggressive skin neoplasia associated to the MCPyV. Despite being prevalent viruses in population, epidemiological data from South America are scarce, as well as the characterization of the viral types circulating and their origin. The aims of this work were to describe MCPyV and HPyV6 from environmental samples with different geographical origin and to analyze their phylogenetic and evolutionary histories, particularly for MCPyV. Partial and complete genome sequences were obtained from sewage samples from Argentina, Uruguay and Spain. A total number of 87 sequences were obtained for MCPyV and 33 for HPyV6. Phylogenetic analysis showed that MCPyV sequences distributed according to their geographic origin in Europe/North America, Africa, Asia, South America and Oceania groups, suggesting that viral diversification might have followed human migrations across the globe. In particular, viruses from Argentina associated with Europe/North America and South America genotypes, whereas those from Uruguay and Spain also grouped with Africa genotype, reflecting the origin of the current population in each country, which could arrive not only during ancient human migration but also during recent migratory events. In addition, the South American group presented a high level of clusterization, showing internal clusters that could be related to specific locations, such as French Guiana and Brazil or the Southern region into South America, such as Argentina and Uruguay, suggesting a long term evolutionary process in the region. Additionally, in this work, we carried out the first analysis about the evolutionary history of MCPyV trough the integration of
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Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication
International Nuclear Information System (INIS)
Diaz, Jason; Wang, Xin; Tsang, Sabrina H.; Jiao, Jing; You, Jianxin
2014-01-01
Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells
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Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication
Energy Technology Data Exchange (ETDEWEB)
Diaz, Jason; Wang, Xin; Tsang, Sabrina H. [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Jiao, Jing [Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); You, Jianxin, E-mail: jianyou@mail.med.upenn.edu [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)
2014-07-08
Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells.
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Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus
International Nuclear Information System (INIS)
Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian
2014-01-01
A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC
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Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma
International Nuclear Information System (INIS)
Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke; Ito, Hideki; Shimonohara, Nozomi; Tsuji, Takahiro; Nakajima, Noriko; Suzuki, Yoshio; Matsuo, Koma; Nakagawa, Hidemi; Sata, Tetsutaro; Katano, Harutaka
2010-01-01
To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.
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Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus
Energy Technology Data Exchange (ETDEWEB)
Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian, E-mail: A.Whitehouse@leeds.ac.uk [School of Molecular and Cellular Biology and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom)
2014-06-27
A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.
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El-Cheikh, Jean; Fürst, Sabine; Casalonga, Francois; Crocchiolo, Roberto; Castagna, Luca; Granata, Angela; Oudin, Claire; Faucher, Catherine; Berger, Pierre; Sarran, Anthony; Blaise, Didier
2012-01-01
We report here the case of progressive multifocal leukoencephalopathy (PML) related to human polyomavirus JC (JCV) infection after an allogeneic transplantation with umbilical cord blood cells in 59-year-old woman with follicular Non Hodgkin lymphoma. She presented with dysphagia and weakness; magnetic resonance imaging demonstrated marked signal abnormality in the sub-cortical white matter of the left frontal lobe and in the posterior limb of the right internal capsule. Polymerase chain reaction (PCR) analysis of the cerebrospinal fluid (CSF) was positive for John Cunningham (JC) virus. JC viral DNA in the CSF was positive, establishing the diagnosis of PML. Brain biopsy was not done. Extensive investigations for other viral infections seen in immuno-compromised patients were negative. The patient's neurologic deficits rapidly increased throughout her hospital stay, and she died one month after the diagnosis. These findings could have practical implications and demonstrate that in patients presenting neurological symptoms and radiological signs after UCBT, the JCV encephalitis must be early suspected.
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Human exposure to bovine polyomavirus: a zoonosis
Energy Technology Data Exchange (ETDEWEB)
Parry, J V; Gardner, S D
1986-01-01
A competitive-type solid phase radioimmunoassay (RIA) was developed for the detection of antibody to bovine polyomavirus. Comparison of RIA and counter-immunoelectrophoresis (CIE) results on 273 cattle sera indicated that both techniques were detecting antibody of like specificity. Human sera from 256 blood donors, 219 people recently vaccinated against polio, rubella or rabies, 50 immunosuppressed patients and 472 people with various occupational exposure to cattle were tested for antibody to bovine polyomavirus, the foetal rhesus monkey kidney strain, (anti-FRKV) by RIA. Apart from one blood donor and one of 108 rabies vaccinees only those in close contact with cattle possessed anti-FRKV. Compared with 62 per cent seropositive in the natural hosts, cattle, 71 per cent of veterinary surgeons, 50 per cent of cattle farmers, 40 per cent of abattoir workers, 16 per cent of veterinary institute technical staff and 10 per cent of veterinary students were anti-FRKV positive. Our findings indicate that the theoretical hazard of FRKV infection from undetected contamination of current tissue culture derived vaccines may, in practice, be remote. Proposed wider use of primate kidney cells as substrates for new vaccines may increase this risk.
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JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants
DEFF Research Database (Denmark)
Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens
2014-01-01
sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast...
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International Nuclear Information System (INIS)
Shen, Peter S.; Enderlein, Dirk; Nelson, Christian D.S.; Carter, Weston S.; Kawano, Masaaki; Xing Li; Swenson, Robert D.; Olson, Norman H.; Baker, Timothy S.; Cheng, R. Holland; Atwood, Walter J.; Johne, Reimar; Belnap, David M.
2011-01-01
Avian polyomavirus (APV) causes a fatal, multi-organ disease among several bird species. Using cryogenic electron microscopy and other biochemical techniques, we investigated the structure of APV and compared it to that of mammalian polyomaviruses, particularly JC polyomavirus and simian virus 40. The structure of the pentameric major capsid protein (VP1) is mostly conserved; however, APV VP1 has a unique, truncated C-terminus that eliminates an intercapsomere-connecting β-hairpin observed in other polyomaviruses. We postulate that the terminal β-hairpin locks other polyomavirus capsids in a stable conformation and that absence of the hairpin leads to the observed capsid size variation in APV. Plug-like density features were observed at the base of the VP1 pentamers, consistent with the known location of minor capsid proteins VP2 and VP3. However, the plug density is more prominent in APV and may include VP4, a minor capsid protein unique to bird polyomaviruses.
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Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States.
Dela Cruz, Florante N; Giannitti, Federico; Li, Linlin; Woods, Leslie W; Del Valle, Luis; Delwart, Eric; Pesavento, Patricia A
2013-01-01
Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.
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Martin, M E; Piette, J; Yaniv, M; Tang, W J; Folk, W R
1988-01-01
The polyomavirus enhancer is composed of multiple DNA sequence elements serving as binding sites for proteins present in mouse nuclear extracts that activate transcription and DNA replication. We have identified three such proteins and their binding sites and correlate them with enhancer function. Mutation of nucleotide (nt) 5140 in the enhancer alters the binding site (TGACTAA, nt 5139-5145) for polyomavirus enhancer A binding protein 1 (PEA1), a murine homolog of the human transcription fac...
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In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection
Directory of Open Access Journals (Sweden)
Heidi Barth
2016-10-01
Full Text Available Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV. Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned.
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International Nuclear Information System (INIS)
Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer; Hirsch, Hans H.; Rinaldo, Christine Hanssen
2010-01-01
High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.
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Vandeven, Natalie; Nghiem, Paul
2016-07-01
Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (˜80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virus-negative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immune-based approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease.
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Church, Molly E; Estrada, Marko; Leutenegger, Christian M; Dela Cruz, Florante N; Pesavento, Patricia A; Woolard, Kevin D
2016-11-01
Polyomavirus infection often results in persistence of the viral genome with little or no virion production. However, infection of certain cell types can result in high viral gene transcription and either cytolysis or neoplastic transformation. While infection by polyomavirus is common in humans and many animals, major questions regarding viral persistence of most polyomaviruses remain unanswered. Specifically, identification of target cells for viral infection and the mechanisms polyomaviruses employ to maintain viral genomes within cells are important not only in ascribing causality to polyomaviruses in disease, but in understanding specific mechanisms by which they cause disease. Here, we characterize the cell of origin in raccoon polyomavirus (RacPyV)-associated neuroglial brain tumours as a neural stem cell. Moreover, we identify an association between the viral genome and the host cell bromodomain protein, BRD4, which is involved in numerous cellular functions, including cell cycle progression, differentiation of stem cells, tethering of persistent DNA viruses, and regulation of viral and host-cell gene transcription. We demonstrate that inhibition of BRD4 by the small molecule inhibitors (+)-JQ1 and IBET-151 (GSK1210151A) results in reduced RacPyV genome within cells in vitro, as well as significant reduction of viral gene transcripts LT and VP1, highlighting its importance in both maintenance of the viral genome and in driving oncogenic transformation by RacPyV. This work implicates BRD4 as a central protein involved in RacPyV neuroglial tumour cell proliferation and in the maintenance of a stem cell state.
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Merkel Cell Polyomavirus: A New DNA Virus Associated with Human Cancer.
MacDonald, Margo; You, Jianxin
2017-01-01
Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades. With the widespread infection of MCPyV and the increase in MCC diagnoses, it is critical to better understand the biology of MCPyV and its oncogenic potential. In this chapter, we summarize recent discoveries regarding MCPyV molecular virology, host cellular tropism, mechanisms of MCPyV oncoprotein-mediated oncogenesis, and current therapeutic strategies for MCPyV-associated MCC. We also present epidemiological evidence for MCPyV infection in HIV patients and links between MCPyV and non-MCC human cancers.
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Siqueira, Juliana D; Ng, Terry F; Miller, Melissa; Li, Linlin; Deng, Xutao; Dodd, Erin; Batac, Francesca; Delwart, Eric
2017-07-01
Over the past century, the southern sea otter (SSO; Enhydra lutris nereis) population has been slowly recovering from near extinction due to overharvest. The SSO is a threatened subspecies under federal law and a fully protected species under California law, US. Through a multiagency collaborative program, stranded animals are rehabilitated and released, while deceased animals are necropsied and tissues are cryopreserved to facilitate scientific study. Here, we processed archival tissues to enrich particle-associated viral nucleic acids, which we randomly amplified and deeply sequenced to identify viral genomes through sequence similarities. Anelloviruses and endogenous retroviral sequences made up over 50% of observed viral sequences. Polyomavirus, parvovirus, and adenovirus sequences made up most of the remaining reads. We characterized and phylogenetically analyzed the full genome of sea otter polyomavirus 1 and the complete coding sequence of sea otter parvovirus 1 and found that the closest known viruses infect primates and domestic pigs ( Sus scrofa domesticus), respectively. We tested archived tissues from 69 stranded SSO necropsied over 14 yr (2000-13) by PCR. Polyomavirus, parvovirus, and adenovirus infections were detected in 51, 61, and 29% of examined animals, respectively, with no significant increase in frequency over time, suggesting endemic infection. We found that 80% of tested SSO were infected with at least one of the three DNA viruses, whose tissue distribution we determined in 261 tissue samples. Parvovirus DNA was most frequently detected in mesenteric lymph node, polyomavirus DNA in spleen, and adenovirus DNA in multiple tissues (spleen, retropharyngeal and mesenteric lymph node, lung, and liver). This study describes the virome in tissues of a threatened species and shows that stranded SSO are frequently infected with multiple viruses, warranting future research to investigate associations between these infections and observed lesions.
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Activation of DNA damage repair pathways by murine polyomavirus
Energy Technology Data Exchange (ETDEWEB)
Heiser, Katie; Nicholas, Catherine; Garcea, Robert L., E-mail: Robert.Garcea@Colorado.edu
2016-10-15
Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling. ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble. -- Highlights: •Murine polyomavirus activates and recruits DNA damage repair (DDR) proteins to replication centers. •Large T-antigen mediates recruitment of DDR proteins to viral replication centers. •Inhibition or knockout of CHK1, CHK2, DNA-PK or H2AX do not affect viral titers. •Inhibition of ATR activity reduces viral titers, but not viral DNA accumulation.
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Virion assembly factories in the nucleus of polyomavirus-infected cells.
Directory of Open Access Journals (Sweden)
Kimberly D Erickson
Full Text Available Most DNA viruses replicate in the cell nucleus, although the specific sites of virion assembly are as yet poorly defined. Electron microscopy on freeze-substituted, plastic-embedded sections of murine polyomavirus (PyV-infected 3T3 mouse fibroblasts or mouse embryonic fibroblasts (MEFs revealed tubular structures in the nucleus adjacent to clusters of assembled virions, with virions apparently "shed" or "budding" from their ends. Promyelocytic leukemia nuclear bodies (PML-NBs have been suggested as possible sites for viral replication of polyomaviruses (BKV and SV40, herpes simplex virus (HSV, and adenovirus (Ad. Immunohistochemistry and FISH demonstrated co-localization of the viral T-antigen (Tag, PyV DNA, and the host DNA repair protein MRE11, adjacent to the PML-NBs. In PML⁻/⁻ MEFs the co-localization of MRE11, Tag, and PyV DNA remained unchanged, suggesting that the PML protein itself was not responsible for their association. Furthermore, PyV-infected PML⁻/⁻ MEFs and PML⁻/⁻ mice replicated wild-type levels of infectious virus. Therefore, although the PML protein may identify sites of PyV replication, neither the observed "virus factories" nor virus assembly were dependent on PML. The ultrastructure of the tubes suggests a new model for the encapsidation of small DNA viruses.
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The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors.
Hurdiss, Daniel L; Frank, Martin; Snowden, Joseph S; Macdonald, Andrew; Ranson, Neil A
2018-04-21
BK polyomavirus (BKV) causes polyomavirus-associated nephropathy and hemorrhagic cystitis in immunosuppressed patients. These are diseases for which we currently have limited treatment options, but potential therapies could include pre-transplant vaccination with a multivalent BKV vaccine or therapeutics which inhibit capsid assembly or block attachment and entry into target cells. A useful tool in such efforts would be a high-resolution structure of the infectious BKV virion and how this interacts with its full repertoire of cellular receptors. We present the 3.4-Å cryoelectron microscopy structure of native, infectious BKV in complex with the receptor fragment of GT1b ganglioside. We also present structural evidence that BKV can utilize glycosaminoglycans as attachment receptors. This work highlights features that underpin capsid stability and provides a platform for rational design and development of urgently needed pharmacological interventions for BKV-associated diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Directory of Open Access Journals (Sweden)
Mengding Qian
2009-06-01
Full Text Available The mechanisms by which receptors guide intracellular virus transport are poorly characterized. The murine polyomavirus (Py binds to the lipid receptor ganglioside GD1a and traffics to the endoplasmic reticulum (ER where it enters the cytosol and then the nucleus to initiate infection. How Py reaches the ER is unclear. We show that Py is transported initially to the endolysosome where the low pH imparts a conformational change that enhances its subsequent ER-to-cytosol membrane penetration. GD1a stimulates not viral binding or entry, but rather sorting of Py from late endosomes and/or lysosomes to the ER, suggesting that GD1a binding is responsible for ER targeting. Consistent with this, an artificial particle coated with a GD1a antibody is transported to the ER. Our results provide a rationale for transport of Py through the endolysosome, demonstrate a novel endolysosome-to-ER transport pathway that is regulated by a lipid, and implicate ganglioside binding as a general ER targeting mechanism.
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Avian Polyomavirus Genome Sequences Recovered from Parrots in Captive Breeding Facilities in Poland
Dayaram, Anisha; Piasecki, Tomasz; Chrząstek, Klaudia; White, Robyn; Julian, Laurel; van Bysterveldt, Katherine; Varsani, Arvind
2015-01-01
Eight genomes of avian polyomaviruses (APVs) were recovered and sequenced from deceased Psittacula eupatria, Psittacula krameri, and Melopsittacus undulatus from various breeding facilities in Poland. Of these APV-positive samples, six had previously tested positive for beak and feather disease virus (BFDV) and/or parrot hepatitis B virus (PHBV).
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NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.
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Directory of Open Access Journals (Sweden)
manon edekeyser
2015-06-01
Full Text Available In renal transplantation, BK-virus-associated nephropathy has emerged as a major complication, with a prevalence of 5–10% and graft loss in >50% of cases. BK-virus is a member of the Polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression, which suggests a critical role for virus-specific cellular immunity to control virus replication and prevent chronic disease. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BK-virus specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BK-virus-associated nephropathy.
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Polyomavirus and Naturally Occuring Neuroglial Tumors in Raccoons (Procyon Lotor).
Pesavento, Patricia A; Brostoff, Terza; Church, Molly E; Dela Cruz, Florante N; Woolard, Kevin D
2016-01-01
Polyomavirus (PyV) infections are widespread in human populations and, although generally associated with silent persistence, rarely cause severe disease. Among diseases convincingly associated with natural PyV infections of humans, there are remarkably different tissue tropisms and outcomes, including progressive multifocal leukoencephalopathy, transient or progressive nephropathy, and cancer. The variable character and unpredictable outcomes of infection attest to large gaps in our basic understanding of PyV biology. In particular, the rich history of research demonstrating the oncogenic potential of PyVs in laboratory animals begs the question of why cancer is not more often associated with infection. Raccoon polyomavirus (RacPyV), discovered in 2010, is consistently identified in neuroglial tumors in free-ranging raccoons in the western United States. Exposure to RacPyV is widespread, and RacPyV is detected in tissues of raccoons without tumors. Studying the relationship of RacPyV with its natural host is a unique opportunity to uncover cogent cellular targets and protein interactions between the virus and its host. Our hypothesis is that RacPyV, as an intact episome, alters cellular pathways within neural progenitor cells and drives oncogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Avian Polyomavirus Genome Sequences Recovered from Parrots in Captive Breeding Facilities in Poland.
Dayaram, Anisha; Piasecki, Tomasz; Chrząstek, Klaudia; White, Robyn; Julian, Laurel; van Bysterveldt, Katherine; Varsani, Arvind
2015-09-24
Eight genomes of avian polyomaviruses (APVs) were recovered and sequenced from deceased Psittacula eupatria, Psittacula krameri, and Melopsittacus undulatus from various breeding facilities in Poland. Of these APV-positive samples, six had previously tested positive for beak and feather disease virus (BFDV) and/or parrot hepatitis B virus (PHBV). Copyright © 2015 Dayaram et al.
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Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor
Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung
2014-01-01
In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.
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Progressive multifocal leukoencephalopathy. Epidemiology, clinical pictures, diagnosis and therapy
International Nuclear Information System (INIS)
Kishida, Shuji
2007-01-01
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of a ubiquitous polyomavirus JC (JCV). PML was for many years a rare disease occurring only in patients with underlying severe impaired immunity. Over the past three decades, the incidence of PML has significantly increased related to the AIDS (acquired immunodeficiency syndrome) pandemic and, more recently, to the growing use of immunosuppressive drugs. The clinical presentation of PML is variable with neurological symptoms corresponding to affected cerebral areas. Usually, the clinical outcome of patients with PML is poor with an inexorable progression to death within 6 months of symptom onset. Although PML usually requires a brain biopsy or autopsy for confirmation, radiological imaging and a demonstration of JCV-DNA in the CSF (cerebrospinal fluid) provide supportive evidence for the diagnosis. Although there is no proven effective therapy for PML, patients with HIV (human immunodeficeincy virus)-related PML may benefit significantly from HAART (highly active antiretroviral therapy). In this article the author reviews the epidemiology, especially in Japan, current challenges in the diagnosis and the treatment guidelines of patients with PML based on recent advances in the understanding of the JC virus biology. (author)
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International Nuclear Information System (INIS)
Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M.
2008-01-01
Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and
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Energy Technology Data Exchange (ETDEWEB)
Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. [Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany)
2008-12-15
Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and
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Energy Technology Data Exchange (ETDEWEB)
Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. (Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany))
2008-12-15
Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and
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Wu, Julie H; Simonette, Rebecca A; Nguyen, Harrison P; Doan, Hung Q; Rady, Peter L; Tyring, Stephen K
2016-03-01
Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS) are two proliferative cutaneous diseases caused by the Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) respectively. Recently, studies have elucidated a key role of the small tumor (sT) antigen in the proliferative pathogenic mechanisms of MCPyV and likely TSPyV. While both sT antigens have demonstrated a capacity in regulating cellular pathways, it remains unknown whether MCPyV and TSPyV sT antigens contribute similarly or differentially to cell proliferation. The present study aims to explore the proliferative potential of MCPyV and TSPyV sT antigens by investigating their regulatory effects on the retinoblastoma protein (pRb) tumor suppressor. Inducible cell lines expressing MCPyV sT or TSPyV sT were created using a lentiviral packaging system. Cellular proteins were extracted and subjected to SDS-PAGE followed by Western blot detection and densitometric analysis. Expression of TSPyV sT markedly enhanced the phosphorylation of pRb in Western blot experiments. In contrast, expression of MCPyV sT did not alter pRb phosphorylation under the same experimental conditions. Densitometric analysis revealed that TSPyV sT antigen expression nearly doubled the ratio of phosphorylated to total pRb (P<0.001, Student's T-test), while MCPyV sT antigen expression did not cause significant change in pRb phosphorylation status. Given that hyperphosphorylation of pRb is associated with dysregulation of the cell cycle, S-phase induction, and increased cell proliferation, our findings support an important role of TSPyV-mediated pRb deactivation in the development of TS. The observation that the pRb tumor suppressor is inactivated by TSPyV sT but not MCPyV sT provides further insights into the distinct pathobiological mechanisms of MCC and TS. Copyright © 2016 Elsevier B.V. All rights reserved.
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T cell recognition of large T and small T antigen in Merkel cell polyomavirus-associated cancer
DEFF Research Database (Denmark)
Hansen, Ulla Kring; Lyngaa, Rikke Birgitte; Straten, Per Thor
Merkel Cell Carcinoma is an aggressive human skin cancer induced by Merkel Cell Polyomavirus (MCPyV). MCPyV is commonly found in human, but the oncogenic transformation takes place during immunosuppression. Two mutation events allow the clonal integration of the viral genome into the host genome...
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Masson Regnault, Marie; Vigarios, Emmanuelle; Projetti, Fabrice; Herbault-Barres, Beatrice; Tournier, Emilie; Lamant, Laurence; Sibaud, Vincent
2017-11-01
Oral lichen planus (OLP) is a chronic inflammatory disease considered as a CD8+ T lymphocyte-mediated autoimmune reaction, which may be triggered by undetermined virus. Recent reports have described the detection of Merkel cell polyomavirus (MCPyV) DNA in oral samples from healthy patients and in patients with different forms of oral cancers. We therefore investigated in a prospective way whether MCPyV was detectable in oral lesions of patients with active OLP. Our preliminary results do not support the hypothesis that OLP may be triggered by MCPyV infection. Further studies are needed to evaluate the involvement of other human polyomaviruses in OLP pathogenesis. © 2017 Wiley Periodicals, Inc.
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Directory of Open Access Journals (Sweden)
Ugo Moens
2017-11-01
Full Text Available Human polyomavirus 9 (HPyV9 was originally detected in the serum of a renal transplant patient. Seroepidemiological studies showed that ~20–50% of the human population have antibodies against this virus. HPyV9 has not yet been associated with any disease and little is known about the route of infection, transmission, host cell tropism, and genomic variability in circulating strains. Recently, the HPyV9 variant UF-1 with an eight base-pair deletion, a thirteen base-pair insertion and with point mutations, creating three putative Sp1 binding sites in the late promoter was isolated from an AIDS patient. Transient transfection studies with a luciferase reporter plasmid driven by HPyV9 or UF1 promoter demonstrated that UF1 early and late promoters were stronger than HPyV9 promoters in most cell lines, and that the UF1 late promoter was more potently activated by HPyV9 large T-antigen (LTAg. Mutation of two Sp1 motifs strongly reduced trans-activation of the late UF1 promoter by HPyV9 LTAg in HeLa cells. In conclusion, the mutations in the UF1 late promoter seem to strengthen its activity and its response to stimulation by HPyV9 LTAg in certain cells. It remains to be investigated whether these promoter changes have an influence on virus replication and affect the possible pathogenic properties of the virus.
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Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G; Katz, Joshua P; Cheng, Jingwei; Akagi, Keiko; Thakuria, Manisha; Rabinowits, Guilherme; Wang, Linda C; Symer, David E; Pipas, James M; Harris, Reuben S; DeCaprio, James A
2017-01-03
Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors. Copyright © 2017 Starrett et al.
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Gabardi, S; Ramasamy, S; Kim, M; Klasek, R; Carter, D; Mackenzie, M R; Chandraker, A; Tan, C S
2015-08-01
Up to 20% of renal transplant recipients (RTR) will develop human BK polyomavirus (BKPyV) viremia. BKPyV viremia is a pre-requisite of polyomavirus-associated nephropathy (PyVAN). Risk of BKPyV infections increases with immunosuppression. Currently, the only effective therapy against PyVAN is reductions in immunosuppression, but this may increase the risk of rejection. In vitro data have shown that pravastatin dramatically decreased caveolin-1 expression in human renal proximal tubular epithelial cells (HRPTEC) and suppressed BKPyV infection in these cells. Based on these data, we postulated that statin therapy may prevent the progression of BKPyV viremia to PyVAN. A multicenter, retrospective study was conducted in adult RTR transplanted between July 2005 and March 2012. All patients with documented BKPyV viremia (viral load >500 copies/mL on 2 consecutive tests) were included. Group I consisted of patients taking a statin before the BKPyV viremia diagnosis (n = 32), and Group II had no statin exposure before or after the BKPyV viremia diagnosis (n = 36). The primary endpoint was the incidence of PyVAN. Demographic data, transplant characteristics, and the degree of immunosuppression (i.e., induction/maintenance therapies, rejection treatment) were similar between the groups, with the exception of more diabetics in Group I. The incidence of PyVAN was comparable between the 2 groups (Group I = 28.1% vs. Group II = 41.7%; P = 0.312). Despite the proven in vitro effectiveness of pravastatin preventing BKPyV infection in HRPTEC, statins at doses maximized for cholesterol lowering, in RTR with BKPyV viremia, did not prevent progression to PyVAN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Directory of Open Access Journals (Sweden)
Friederike Neumann
Full Text Available Merkel Cell Polyomavirus (MCPyV genomes are clonally integrated in tumor tissues of approximately 85% of all Merkel cell carcinoma (MCC cases, a highly aggressive tumor of the skin which predominantly afflicts elderly and immunosuppressed patients. All integrated viral genomes recovered from MCC tissue or MCC cell lines harbor signature mutations in the early gene transcript encoding for the large T-Antigen (LT-Ag. These mutations selectively abrogate the ability of LT-Ag to support viral replication while still maintaining its Rb-binding activity, suggesting a continuous requirement for LT-Ag mediated cell cycle deregulation during MCC pathogenesis. To gain a better understanding of MCPyV biology, in vitro MCPyV replication systems are required. We have generated a synthetic MCPyV genomic clone (MCVSyn based on the consensus sequence of MCC-derived sequences deposited in the NCBI database. Here, we demonstrate that transfection of recircularized MCVSyn DNA into some human cell lines recapitulates efficient replication of the viral genome, early and late gene expression together with virus particle formation. However, serial transmission of infectious virus was not observed. This in vitro culturing system allows the study of viral replication and will facilitate the molecular dissection of important aspects of the MCPyV lifecycle.
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Isolation and characterization of NIH 3T3 cells expressing polyomavirus small T antigen
International Nuclear Information System (INIS)
Noda, T.; Satake, M.; Robins, T.; Ito, Y.
1986-01-01
The polyomavirus small T-antigen gene, together with the polyomavirus promoter, was inserted into retrovirus vector pGV16 which contains the Moloney sarcoma virus long terminal repeat and neomycin resistance gene driven by the simian virus 40 promoter. This expression vector, pGVST, was packaged into retrovirus particles by transfection of PSI2 cells which harbor packaging-defective murine retrovirus genome. NIH 3T3 cells were infected by this replication-defective retrovirus containing pGVST. Of the 15 G418-resistant cell clones, 8 express small T antigen at various levels as revealed by immunoprecipitation. A cellular protein with an apparent molecular weight of about 32,000 coprecipitates with small T antigen. Immunofluorescent staining shows that small T antigen is mainly present in the nuclei. Morphologically, cells expressing small T antigen are indistinguishable from parental NIH 3T3 cells and have a microfilament pattern similar to that in parental NIH 3T3 cells. Cells expressing small T antigen form a flat monolayer but continue to grow beyond the saturation density observed for parental NIH 3T3 cells and eventually come off the culture plate as a result of overconfluency. There is some correlation between the level of expression of small T antigen and the growth rate of the cells. Small T-antigen-expressing cells form small colonies in soft agar. However, the proportion of cells which form these small colonies is rather small. A clone of these cells tested did not form tumors in nude mice within 3 months after inoculation of 10 6 cells per animal. Thus, present studies establish that the small T antigen of polyomavirus is a second nucleus-localized transforming gene product of the virus (the first one being large T antigen) and by itself has a function which is to stimulate the growth of NIH 3T3 cells beyond their saturation density in monolayer culture
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Comparing Effects of BK Virus Agnoprotein and Herpes Simplex-1 ICP47 on MHC-I and MHC-II Expression
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Michela Cioni
2013-01-01
Full Text Available Background. Among human polyomaviruses, only BK virus (BKV and JC virus (JCV encode an agnoprotein upstream of VP1 on the viral late transcript. BKV agnoprotein is abundantly expressed late in the viral life cycle, but specific cellular and humoral immune responses are low or absent. We hypothesized that agnoprotein might contribute to BKV immune evasion by downregulating HLA expression, similar to Herpes simplex virus-1 ICP47. Methods UTA-6 or primary human renal proximal tubular epithelial cells (RPTEC were co-transfected with plasmids constitutively expressing agnoprotein, or ICP47, and enhanced green-fluorescent protein (EGFP. EGFP-gated cells were analyzed for HLA-ABC and HLA-DR expression by flow cytometry. HLA-ABC and HLA-DR expression was also analyzed on UTA-6 bearing tetracycline-regulated agnoprotein or ICP47. Effects of agnoprotein on viral peptide-dependent T-cell killing were investigated using 51Cr release. Results. ICP47 downregulated HLA-ABC without affecting HLA-DR, whereas agnoprotein did not affect HLA-ABC or HLA-DR expression. Interferon-γ treatment increased HLA-ABC in a dose-dependent manner, which was antagonized by ICP47, but not by agnoprotein. In UTA-6 cells, agnoprotein expression did neither impair HLA-ABC or -DR expression nor peptide-specific killing impaired by HLA-matched T-cells. Conclusion. Unlike the HSV-1 ICP47, BKV agnoprotein does not contribute to viral immune evasion by down-regulating HLA-ABC, or interfere with HLA-DR expression or peptide-dependent T-cell cytotoxicity.
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DEFF Research Database (Denmark)
Fenton, Kristin Andreassen; Mjelle, Janne Erikke; Jacobsen, Søren
2008-01-01
) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis...... to the evolution of lupus nephritis in human SLE....
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Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.
2002-01-01
Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.
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DEFF Research Database (Denmark)
Lyngaa, Rikke; Pedersen, Natasja Wulff; Schrama, David
2014-01-01
Purpose: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with strong evidence of viral carcinogenesis. The association of MCC with the Merkel cell polyomavirus (MCPyV) may explain the explicit immunogenicity of MCC. Indeed, MCPyV-encoded proteins are likely targets for cytotoxic...
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Czech Academy of Sciences Publication Activity Database
Bouřa, E.; Liebl, D.; Spíšek, R.; Frič, Jan; Marek, M.; Štokrová, Jitka; Holáň, Vladimír; Forstová, J.
2005-01-01
Roč. 579, č. 29 (2005), s. 6549-6558 ISSN 0014-5793 R&D Projects: GA MZd(CZ) NC6957; GA ČR(CZ) GA204/03/0593 Institutional research plan: CEZ:AV0Z50520514 Keywords : mouse polyomavirus * empty artificial virus-like particle * dendritic cell activation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.415, year: 2005
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Lin, Shu-Xiang; Wang, Wei; Guo, Wei; Yang, Hong-Jiang; Ma, Bai-Cheng; Fang, Yu-Lian; Xu, Yong-Sheng
2017-07-01
To investigate the relationship of KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) with acute respiratory infection in children in Tianjin, China. A total of 3 730 nasopharyngeal secretions were collected from hospitalized children with acute respiratory infection in Tianjin Children's Hospital from January 2011 to December 2013. Viral nucleic acid was extracted, and virus infection (KIPyV and WUPyV) was determined by PCR. Some KIPyV-positive and WUPyV-positive PCR products were subjected to sequencing. Sequencing results were aligned with the known gene sequences of KIPyV and WUPyV to construct a phylogenetic tree. Amplified VP1 fragments of KIPyV were inserted into the cloning vector (PUCm-T) transformed into E. coli competent cells. Positive clones were identified by PCR and sequencing. The nucleotide sequences were submitted to GenBank. In addition, another seven common respiratory viruses in all samples were detected by direct immunofluorescence assay. In the 3 730 specimens, the KIPyV-positive rate was 12.14% (453/3 730) and the WUPyV-positive rate was 1.69% (63/3 730). The mean infection rate of KIPyV was significantly higher in June and July, while the mean infection rate of WUPyV peaked in February and March. Most of the KIPyV-positive or WUPyV-positive children were infections with KIPyV, WUPyV, and other respiratory viruses were observed in the children. The co-infection rate was 2.31% (86/3 730) and there were nine cases of co-infections with WUPyV and KIPyV. Thirty-five KIPyV-positive and twelve WUPyV-positive PCR products were sequenced and the alignment analysis showed that they had high homology with the known sequences (94%-100% vs 95%-100%). The VP1 gene sequences obtained from two KIPyV strains in this study were recorded in GenBank with the accession numbers of KY465925 and KY465926. For some children with acute respiratory infection in Tianjin, China, the acute respiratory infection may be associated with KIPyV and WUPy
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Nunes, Marta C.; Kuschner, Zachary; Rabede, Zelda; Madimabe, Richard; Van Niekerk, Nadia; Moloi, Jackie; Kuwanda, Locadiah; Rossen, John W.; Klugman, Keith P.; Adrian, Peter V.; Madhi, Shabir A.
2014-01-01
Background: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and -KI (KIPyV) and human
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Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation
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Cristina Costa
2012-03-01
Full Text Available Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN, possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens: in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0% and 12 (2.0% specimens from 40 (11.0% and 11 (10.4% patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2% and 58 (9.8% specimens from 67 (18.5% and 27 (25.5% patients, being the difference of incidence highly significant (p <0.0001 for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation.
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Seeking Standards for the Detection of Merkel Cell Polyomavirus and its Clinical Significance.
Eid, Mary; Nguyen, Jannett; Brownell, Isaac
2017-04-01
Merkel cell carcinoma is a rare skin cancer associated with Merkel cell polyomavirus in most cases. Prior studies associating Merkel cell carcinoma viral status with prognosis have inconsistent findings. Moshiri et al. used multimodal virus detection to determine that the 81% of patients with virus-positive Merkel cell carcinoma tumors had earlier stage disease and better outcomes relative to virus-negative cases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy.
LENUS (Irish Health Repository)
Lonergan, Roisin M
2012-02-01
Natalizumab therapy in multiple sclerosis has been associated with JC polyomavirus-induced progressive multifocal leucoencephalopathy. We hypothesized that natalizumab may also lead to reactivation of BK, a related human polyomavirus capable of causing morbidity in immunosuppressed groups. Patients with relapsing remitting multiple sclerosis treated with natalizumab were prospectively monitored for reactivation of BK virus in blood and urine samples, and for evidence of associated renal dysfunction. In this cohort, JC and BK DNA in blood and urine; cytomegalovirus (CMV) DNA in blood and urine; CD4 and CD8 T-lymphocyte counts and ratios in peripheral blood; and renal function were monitored at regular intervals. BK subtyping and noncoding control region sequencing was performed on samples demonstrating reactivation. Prior to commencement of natalizumab therapy, 3 of 36 patients with multiple sclerosis (8.3%) had BK viruria and BK reactivation occurred in 12 of 54 patients (22.2%). BK viruria was transient in 7, continuous in 2 patients, and persistent viruria was associated with transient viremia. Concomitant JC and CMV viral loads were undetectable. CD4:CD8 ratios fluctuated, but absolute CD4 counts did not fall below normal limits. In four of seven patients with BK virus reactivation, transient reductions in CD4 counts were observed at onset of BK viruria: these resolved in three of four patients on resuppression of BK replication. No renal dysfunction was observed in the cohort. BK virus reactivation can occur during natalizumab therapy; however, the significance in the absence of renal dysfunction is unclear. We propose regular monitoring for BK reactivation or at least for evidence of renal dysfunction in patients receiving natalizumab.
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Directory of Open Access Journals (Sweden)
T. Jaeger
2012-01-01
Full Text Available Merkel cell carcinoma is a rare, but highly malignant tumor of the skin with high rates of metastasis and poor survival. Its incidence rate rises and is currently about 0.6/100000/year. Clinical differential diagnoses include basal cell carcinoma, cyst, amelanotic melanoma, lymphoma and atypical fibroxanthoma. In this review article clinical, histopathological and immunhistochemical features of Merkel cell carcinoma are reported. In addition, the role of Merkel cell polyomavirus is discussed.
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Sahi, Helka; Sihto, Harri; Artama, Miia; Koljonen, Virve; Böhling, Tom; Pukkala, Eero
2017-01-17
We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel cell carcinoma (MCC). Merkel cell carcinoma cases diagnosed in 1978-2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03-1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09-1.80) and diabetic conditions (OR 1.51, 95% CI 1.03-2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel cell polyomavirus positivity is more common in MCC patients unafflicted by CID.
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Wu, Julie H; Simonette, Rebecca A; Nguyen, Harrison P; Rady, Peter L; Tyring, Stephen K
2016-06-01
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer associated with the Merkel cell polyomavirus (MCPyV). The MCPyV genome, which is clonally integrated in the majority of MCCs, encodes the regulatory small T (sT) antigen. Previously, reports have established MCPyV sT antigen as a potent oncogene capable of inducing cell transformation. In the current study, we demonstrate a distinct role for c-Jun hyperactivation in MCPyV sT antigen pathogenesis. As MCPyV sT antigen's association with aggressive cancer growth has been previously established, this finding may represent a potential therapeutic target for the treatment of MCCs.
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Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.
Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin
2018-02-15
Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel
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de Abreu Corrêa, Adriana; Carratala, Anna; Barardi, Celia Regina Monte; Calvo, Miquel; Bofill-Mas, Sílvia
2012-01-01
Viruses excreted by humans affect the commercial and recreational use of coastal water. Shellfish produced in contaminated waters have been linked to many episodes and outbreaks of viral gastroenteritis, as well as other food-borne diseases worldwide. The risk can be reduced by appropriate treatment following harvesting and by depuration. The kinetics of inactivation of murine norovirus 1 and human adenovirus 2 in natural and artificial seawater by free available chlorine was studied by quantifying genomic copies (GC) using quantitative PCR and infectious viral particles (PFU). Human JC polyomavirus Mad4 kinetics were evaluated by quantitative PCR. DNase or RNase were used to eliminate free genomes and assess potential viral infectivity when molecular detection was performed. At 30 min of assay, human adenovirus 2 showed 2.6- and 2.7-log10 GC reductions and a 2.3- and 2.4-log10 PFU reductions in natural and artificial seawater, respectively, and infectious viral particles were still observed at the end of the assay. When DNase was used prior to the nucleic acid extraction the kinetic of inactivation obtained by quantitative PCR was statistically equivalent to the one observed by infectivity assays. For murine norovirus 1, 2.5, and 3.5-log10 GC reductions were observed in natural and artificial seawater, respectively, while no viruses remained infectious after 30 min of contact with chlorine. Regarding JC polyomavirus Mad4, 1.5- and 1.1-log10 GC reductions were observed after 30 min of contact time. No infectivity assays were conducted for this virus. The results obtained provide data that might be applicable to seawater used in shellfish depuration. PMID:22773637
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Directory of Open Access Journals (Sweden)
Jaione Simon-Santamaria
Full Text Available Liver sinusoidal endothelial cells (LSECs are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min, and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed
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Infectious offspring: how birds acquire and transmit an avian polyomavirus in the wild.
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Jaime Potti
Full Text Available Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an 'upwards vertical' route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care.
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Using Merkel cell polyomavirus specific TCR gene therapy for treatment of Merkel cellcarcinoma
DEFF Research Database (Denmark)
Lyngaa, Rikke Birgitte; Pedersen, Natasja Wulff; Linnemann, C.
2016-01-01
T cell receptor gene-therapy has entered the clinic and shown potential for successful cancer treatment. However, the clinical evaluation has also highlighted the need for selection of truly cancerspecific targets. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with Mer......T cell receptor gene-therapy has entered the clinic and shown potential for successful cancer treatment. However, the clinical evaluation has also highlighted the need for selection of truly cancerspecific targets. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated...... with Merkel cell polyomavirus (MCPyV). Due to the clear viral correlation CD8+ T cells specific for viral epitopes could potentially form cancer-specific targets in MCC patients. We have identified MCPyV specific T cells using a high-throughput platform for T-cell enrichment and combinatorial encoding...
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Directory of Open Access Journals (Sweden)
Guan Yi-fu
2009-03-01
Full Text Available Abstract Background John Cunningham virus (JCV constitutes a family of polyoma viruses, which plays important roles in the progressive multifocal leukoencephalopathy (PML and tumorigenesis. However, no bibliometric investigation has been reported to guide the researchers and potential readers. Methods Papers were collected from database Sci-expanded and Pubmed until May 22, 2008. The highly-productive authors, institutes and countries, highly-cited authors and journals were ranked. The highly-cited articles were subjected to co-citation and chronological analysis with highly-frequent MeSH words for co-occurrence analysis. Results Until now, 1785 articles about JCV were indexed in Sci-expanded and 1506 in Pubmed. The main document type was original article. USA, Japan and Italy were the largest three producers about JCV. Temple University published 128 papers and ranked the top, followed by University of Tokyo. Khalili K and Yogo Y became the core authors due to more than 20 documents produced. Journal of Neurovirology published more than 15 papers and ranked the top. Padgett BL and Berger JR were the first two highly-cited authors. Journal of Virology and Journal of Neurovirology respectively ranked to the first two highly-cited journals. These top highly-cited articles were divided into 5 aspects: (1 The correlation between JC virus and tumors; (2 Causal correlation of JCV with PML; (3 Polyoma virus infection and its related diseases in renal-allograft recipients; (4 Detection of JCV antibody, oncogene and its encoding protein; (5 Genetics and molecular biology of JCV. The MeSH/subheadings were classified into five groups: (1 JCV and virus infectious diseases; (2 JCV pathogenicity and pathological appearance of PML; (3 JCV isolation and detection; (4 Immunology of JCV and PML; (5 JCV genetics and tumors. Conclusion JCV investigation mainly focused on its isolation and detection, as well as its correlation with PML and tumors. Establishment of
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Czech Academy of Sciences Publication Activity Database
Liebl, D.; Difato, F.; Horníková, L.; Mannová, P.; Štokrová, Jitka; Forstová, J.
2006-01-01
Roč. 80, č. 9 (2006), s. 4610-4622 ISSN 0022-538X R&D Projects: GA ČR(CZ) GA204/03/0593; GA MŠk(CZ) LC545 Institutional research plan: CEZ:AV0Z50520514 Keywords : Polyomavirus internalization and trafficking * Early endosomes * Dependence of infection on endosomal pH Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.341, year: 2006
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Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus.
Bononi, Ilaria; Mazzoni, Elisa; Pietrobon, Silvia; Manfrini, Marco; Torreggiani, Elena; Rossini, Marika; Lotito, Francesca; Guerra, Giovanni; Rizzo, Paola; Martini, Fernanda; Tognon, Mauro
2018-08-01
JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS inducing the PML, (ii) the kidney of transplant patients causing the organ rejection. Association between JCPyV, which is a small DNA tumor virus, and gliomas and colorectal carcinomas has been published. In the present investigation, we report on a new indirect ELISA with two specific synthetic peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2-100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1 K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a docking site for serum antibodies. Data from this innovative immunologic assay indicate that the overall prevalence of JCPyV-VP1 antibodies in healthy subjects is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a useful method to detect specific IgG antibodies against this virus, without cross-reactivity with the closely related SV40 and BKPyV polyomaviruses. © 2018 Wiley Periodicals, Inc.
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Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome.
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Yoakim, M; Hou, W; Liu, Y; Carpenter, C L; Kapeller, R; Schaffhausen, B S
1992-01-01
The binding of phosphatidylinositol-3-kinase to the polyomavirus middle T antigen is facilitated by tyrosine phosphorylation of middle T on residue 315. The pp85 subunit of phosphatidylinositol-3-kinase contains two SH2 domains, one in the middle of the molecule and one at the C terminus. When assayed by blotting with phosphorylated middle T, the more N-terminal SH2 domain is responsible for binding to middle T. When assayed in solution with glutathione S transferase fusions, both SH2s are ca...
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Directory of Open Access Journals (Sweden)
Lanzillo R
2014-10-01
Full Text Available Roberta Lanzillo,1 Raffaele Liuzzi,2 Luca Vallefuoco,3 Marcello Moccia,1 Luca Amato,1 Giovanni Vacca,1 Veria Vacchiano,1 Giuseppe Portella,3 Vincenzo Brescia Morra1 1Neurological Sciences Department, Federico II University, 2Institute of Biostructure and Bioimaging, National Research Council, 3Clinical Pathology Department, Federico II University, Naples, ItalyAbstract: Natalizumab-treated patients have a higher risk of developing progressive multifocal leukoencephalopathy. Exposure to John Cunningham virus (JCV is a prerequisite for PML (progressive multifocal leukoencephalopathy. To assess JCV exposure in multiple sclerosis patients, we performed a serological examination, obtained the antibody index, performed real-time polymerase chain reaction (PCR to detect JCV DNA in plasma and urine, and investigated the role of ultrasensitive C-reactive protein (usCRP as a possible biological marker of JCV reactivation. We retrospectively analyzed consecutive natalizumab-treated multiple sclerosis patients who underwent a JCV antibody test through a two-step enzyme-linked immunosorbent assay (STRATIFY test to the measure of serum usCRP levels, and to perform blood and urine JCV PCR. The studied cohort included 97 relapsing–remitting patients (60 women. Fifty-two patients (53.6% tested positive for anti-JCV antibodies. PCR showed JCV DNA in the urine of 30 out of 83 (36.1% patients and 28 out of 44 seropositive patients (63.6%, with a 6.7% false-negative rate for the STRATIFY test. Normalized optical density values were higher in urinary JCV DNA-positive patients (P<0.0001. Interestingly, the level of usCRP was higher in urinary JCV DNA-positive patients and correlated to the number of DNA copies in urine (P=0.028. As expected, patients' age correlated with JCV seropositivity and with JC viruria (P=0.02 and P=0.001, respectively. JC viruria was significantly correlated with a high JCV antibody index and high serum usCRP levels. We suggest that PCR and
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Directory of Open Access Journals (Sweden)
Galati Gaspare
2009-07-01
Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is
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Identification of a Polyomavirus microRNA Highly Expressed in Tumors
Chen, Chun Jung; Cox, Jennifer E.; Azarm, Kristopher; Wylie, Karen N.; Woolard, Kevin D.; Pesavento, Patricia A.; Sullivan, Christopher S.
2014-01-01
Polyomaviruses (PyVs) are associated with tumors including Merkel cell carcinoma (MCC). Several PyVs encode microRNAs (miRNAs) but to date no abundant PyV miRNAs have been reported in tumors. To better understand the function of the Merkel cell PyV (MCPyV) miRNA, we examined phylogenetically-related viruses for miRNA expression. We show that two primate PyVs and the more distantly-related raccoon PyV (RacPyV) encode miRNAs that share genomic position and partial sequence identity with MCPyV miRNAs. Unlike MCPyV miRNA in MCC, RacPyV miRNA is highly abundant in raccoon tumors. RacPyV miRNA negatively regulates reporters of early viral (T antigen) transcripts, yet robust viral miRNA expression is tolerated in tumors. We also identify raccoon miRNAs expressed in RacPyV-associated neuroglial brain tumors, including several likely oncogenic miRNAs (oncomiRs). This work describes the first PyV miRNA abundantly expressed in tumors and is consistent with a possible role for both host and viral miRNAs in RacPyV-associated tumors. PMID:25514573
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Bennett, R S; Gresko, A K; Nelson, J T; Murphy, B R; Whitehead, S S
2012-01-01
La Crosse virus (LACV) and Jamestown Canyon virus (JCV), family Bunyaviridae, are mosquito-borne viruses that are endemic in North America and recognized as etiologic agents of encephalitis in humans. Both viruses belong to the California encephalitis virus serogroup, which causes 70 to 100 cases of encephalitis a year. As a first step in creating live attenuated viral vaccine candidates for this serogroup, we have generated a recombinant LACV expressing the attachment/fusion glycoproteins of JCV. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV. For the M segment, the open reading frame (ORF) of LACV is replaced with that derived from JCV and is flanked by the untranslated regions of LACV. The resulting chimeric virus retained the same robust growth kinetics in tissue culture as observed for either parent virus, and the virus remains highly infectious and immunogenic in mice. Although both LACV and JCV are highly neurovirulent in 21 day-old mice, with 50% lethal dose (LD₅₀) values of 0.1 and 0.5 log₁₀ PFU, respectively, chimeric JCV/LACV is highly attenuated and does not cause disease even after intracerebral inoculation of 10³ PFU. Parenteral vaccination of mice with 10¹ or 10³ PFU of JCV/LACV protected against lethal challenge with LACV, JCV, and Tahyna virus (TAHV). The chimeric virus was infectious and immunogenic in rhesus monkeys and induced neutralizing antibodies to JCV, LACV, and TAHV. When vaccinated monkeys were challenged with JCV, they were protected against the development of viremia. Generation of highly attenuated yet immunogenic chimeric bunyaviruses could be an efficient general method for development of vaccines effective against these pathogenic viruses.
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Kwun, H J; Wendzicki, J A; Shuda, Y; Moore, P S; Chang, Y
2017-12-07
The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.
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Identification of viral infections in the prostate and evaluation of their association with cancer
Directory of Open Access Journals (Sweden)
Calderon-Cardenas German
2010-06-01
Full Text Available Abstract Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs, and human cytomegalovirus (HCMV infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV was identified in prostate tissue with a high prevalence observed in prostate cancer (PC patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q. Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0% cases and 4 (5.3% controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027 by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.
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Charlotte T A H Wetzels
Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.
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Zhu, Teng; Lu, Qing-Bin; Zhang, Shu-Yan; Wo, Ying; Zhuang, Lu; Zhang, Pan-He; Zhang, Xiao-Ai; Wei, Wei; Liu, Wei
2017-05-01
To explore the molecular epidemiology and clinical characteristics of Washington University polyomavirus (WUPyV) infection in pediatric patients with acute respiratory tract infections in China. A laboratory surveillance was performed to recruit pediatric patients with acute respiratory tract infections. WUPyV was detected using real-time PCR and complete genome was sequenced for randomly selected positive nasopharyngeal aspirate. Altogether 122 (7.5%) of 1617 children found to be infected with WUPyV and 88 (72.1%) were coinfected with other viruses during 2012-2015. The phylogenetic analysis showed that 14 strains from our study formed two new clusters (Id and IIIc) within the Branch I and Branch III, respectively. WUPyV is persistently circulating in China. Surveillance on WUPyV infection in wider areas and long persistence is warranted.
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Human glial chimeric mice reveal astrocytic dependence of JC virus infection
DEFF Research Database (Denmark)
Kondo, Yoichi; Windrem, Martha S; Zou, Lisa
2014-01-01
with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection...
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Czech Academy of Sciences Publication Activity Database
Adamec, T.; Palková, Zdena; Velková, K.; Štokrová, Jitka; Forstová, J.
2005-01-01
Roč. 5, 4-5 (2005), s. 331-340 ISSN 1567-1356 R&D Projects: GA ČR GA204/03/0593 Institutional research plan: CEZ:AV0Z5052915 Keywords : polyomavirus VP1 * Saccharomyces cerevisiae * heterologous expression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.477, year: 2005
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Beck, Rose C; Kohn, Debra J; Tuohy, Marion J; Prayson, Richard A; Yen-Lieberman, Belinda; Procop, Gary W
2004-03-01
We evaluated 2 methods, a LightCycler PCR assay and pyrosequencing for the detection of the JC polyoma virus (JCV) in fixed brain tissue of 10 patients with and 3 control patients without progressive multifocal leukoencephalopathy (PML). Nucleic acid extraction was performed after deparaffinization and proteinase K digestion. The LightCycler assay differentiates the BK virus (BKV), JCV, and SV40 using melt curve analysis. Conventional PCR was used with the same primers to generate products for pyrosequencing. Two sequencing primers were used that differentiate the polyoma viruses. Seven of 11 biopsies (1 patient had 2 biopsies) with PML were positive for JCV by real-time PCR and/or PCR/pyrosequencing. Three of 4 remaining biopsies were positive by real-time PCR but had melting points between JCV and SV40. The 4 specimens that were negative or atypical by LightCycler PCR were positive by traditional PCR, but 1 had an amplicon of lower molecular weight by gel electrophoresis. These were shown to represent JCV by at least 1 of the 2 pyrosequencing primers. The biopsies from patients without PML were PCR negative. Both the LightCycler and pyrosequencing assays are useful for confirming JCV in brain biopsies from patients with PML, but variant JCVs may require supplementary methods to confirm JCV infection.
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Shuda, Masahiro; Guastafierro, Anna; Geng, Xuehui; Shuda, Yoko; Ostrowski, Stephen M; Lukianov, Stefan; Jenkins, Frank J; Honda, Kord; Maricich, Stephen M; Moore, Patrick S; Chang, Yuan
2015-01-01
Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT and Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting.
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Paz, Sonia Patricia Castedo; Branco, Luciana; Pereira, Marina Alves de Camargo; Spessotto, Caroline; Fragoso, Yara Dadalti
2018-01-01
John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
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López-Bueno, Alberto; Mavian, Carla; Labella, Alejandro M; Castro, Dolores; Borrego, Juan J; Alcami, Antonio; Alejo, Alí
2016-10-01
Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought. Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae In the Mediterranean area, the gilthead sea bream (Sparus aurata), an important farmed
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Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort
DEFF Research Database (Denmark)
Olsson, Tomas; Achiron, Anat; Alfredsson, Lars
2013-01-01
JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody...... prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49...
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Directory of Open Access Journals (Sweden)
Christopher DeBoever
Full Text Available Primary central nervous system lymphomas (PCNSL have a dramatically increased prevalence among persons living with AIDS and are known to be associated with human Epstein Barr virus (EBV infection. Previous work suggests that in some cases, co-infection with other viruses may be important for PCNSL pathogenesis. Viral transcription in tumor samples can be measured using next generation transcriptome sequencing. We demonstrate the ability of transcriptome sequencing to identify viruses, characterize viral expression, and identify viral variants by sequencing four archived AIDS-related PCNSL tissue samples and analyzing raw sequencing reads. EBV was detected in all four PCNSL samples and cytomegalovirus (CMV, JC polyomavirus (JCV, and HIV were also discovered, consistent with clinical diagnoses. CMV was found to express three long non-coding RNAs recently reported as expressed during active infection. Single nucleotide variants were observed in each of the viruses observed and three indels were found in CMV. No viruses were found in several control tumor types including 32 diffuse large B-cell lymphoma samples. This study demonstrates the ability of next generation transcriptome sequencing to accurately identify viruses, including DNA viruses, in solid human cancer tissue samples.
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Molly E. Church
2016-06-01
Full Text Available Here we describe the methods for production of a recombinant viral capsid protein and subsequent use in an indirect enzyme linked immunosorbent assay (ELISA, and for use in production of a rabbit polyclonal antibody. These reagents were utilized in development and optimization of an ELISA, which established the extent of exposure of free ranging raccoons to a newly described polyomavirus (RacPyV [1]. Production of a polyclonal antibody has allowed for further characterization of RacPyV, including immunohistochemistry and immunocytochemistry techniques, in order to answer questions about pathogenesis of this virus.
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Directory of Open Access Journals (Sweden)
Norberto A. Sanjuán
2010-04-01
Full Text Available The family Polyomaviridae is composed of small, non-enveloped, double-stranded DNA viruses widely used to study cell transformation in vitro and tumor induction in vivo. The development of pilomatricomas in mice experimentally infected with polyomavirus led us to detect the viral major capsid protein VP-1 in human pilomatricomas. This tumor, even uncommon, is one of the most frequent benign hair follicle tumors in humans and is composed of proliferating matrix cells that undergo keratinization, and form cystic neoplasms. The detection of VP-1 was performed using the peroxidase-antiperoxidase technique in paraffin-embedded slides with a specific primary serum. Adjacent slides treated with normal rabbit serum as a primary were employed as internal control. Positive and negative controls were also employed as well as slides of lesions caused by human papillomavirus to rule out any unspecific cross-reactivity. In 4 out of 10 cases polyomavirus VP-1 was clearly detected in nuclei of human pilomatricomas proliferating cells, in a patchy pattern of distribution. The controls confirmed the specificity of the immunocytochemical procedure. These results could indicate either an eventual infection of the virus in already developed tumors or alternatively, a direct involvement of polyomavirus in the pathogenesis of some pilomatricomas. The recent discovery of a new human polyomavirus associated with Merkel cell carcinomas has been a strong contribution to better understand the pathogenesis of some human uncommon skin cancers. Hopefully the results reported in this work will encourage further research on the role of polyomavirus in other human skin neoplasms.La familia Poliomaviridae está compuesta por virus oncogénicos pequeños, no envueltos, con ADN de doble cadena. En un modelo experimental murino pudimos desarrollar pilomatricomas inducidos por la inoculación de virus polioma. Eso nos llevó a estudiar la posibilidad de que otro virus polioma
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Directory of Open Access Journals (Sweden)
Sonia Patricia Castedo Paz
2018-01-01
Full Text Available OBJECTIVES John Cunningham virus (JCV is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS and neuromyelitis optica (NMO. PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%. CONCLUSIONS The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
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Directory of Open Access Journals (Sweden)
Marta C Nunes
Full Text Available Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV, human rhinovirus (hRV, polyomavirus-WU (WUPyV and -KI (KIPyV and human coronaviruses (CoV-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI.Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B.At least one of these viruses were identified in 274 (53.0% of 517 and in 509 (54.0% of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7% and -uninfected children (32.0%, followed by CoV-OC43 (12.2% and hBoV (9.5% in HIV-infected; and by hBoV (13.3% and WUPyV (11.9% in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002 and CoV-OC43 (12.2% vs. 3.6%; p<0.001 were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children.We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a
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Lawatscheck, R.; Aleksaite, E.; Schenk, J.A.; Micheel, B.; Jandrig, B.; Holland, G.; Sasnauskas, K.; Gedvilaite, A.; Ulrich, R.G.
2007-01-01
We inserted the sequence of the carcinoembryonic antigen-derived T cell epitope CAP-1-6D (CEA) into different positions of the hamster polyomavirus major capsid protein VP1. Independently from additional flanking linkers, yeast-expressed VP1 proteins harboring the CEA insertion between VP1 amino acid residues 80 and 89 (site 1) or 288 and 295 (site 4) or simultaneously at both positions assembled to chimeric virus-like particles (VLPs). BALB/c mice immunized with adjuvant-free VLPs developed ...
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International Nuclear Information System (INIS)
Li, T.-C.; Takeda, Naokazu; Kato, Kenzo; Nilsson, Josefina; Xing Li; Haag, Lars; Cheng, R. Holland; Miyamura, Tatsuo
2003-01-01
The major structural protein of the human polyomavirus BK (BKV), VP1, was expressed by using recombinant baculoviruses. A large amount of protein with a molecular mass of about 42 kDa was synthesized and identified by Western blotting. The protein was detected exclusively in the nuclei by immunofluorescent analysis and it was released into culture medium. The expressed BKV VP1 protein was self-assembled into virus-like particles (BK-VLPs) with two different sizes (50 and 26 nm in diameter), which migrated into four different bands in CsCl gradient with buoyant densities of 1.29, 1.30, 1.33, and 1.35 g/cm 3 . The immunological studies on the BK-VLPs suggested that they have similar antigenicity with those of authentic BKV particles. Cryoelectron microscopy and 3D image analysis further revealed that the larger BK-VLPs were composed of 72 capsomers which all were pentamers arranged in a T = 7 surface lattice. This system provides useful information for detailed studies of viral morphogenesis and the structural basis for the antigenicity of BKV
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Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew
2017-04-11
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.
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Neumann, Friederike; Czech-Sioli, Manja; Dobner, Thomas; Grundhoff, Adam; Schreiner, Sabrina; Fischer, Nicole
2016-11-01
Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60-80 % of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available. Until recently, MCPyV replication could only be studied using a semi-permissive in vitro replication system (Neumann et al., 2011; Feng et al., 2011, Schowalter et al., 2011). MCPyV replication most likely depends on subnuclear structures such as promyelocytic leukemia protein nuclear bodies (PML-NBs), which are known to play regulatory roles in the infection of many DNA viruses. Here, we investigated PML-NB components as candidate host factors to control MCPyV DNA replication. We showed that PML-NBs change in number and size in cells actively replicating MCPyV proviral DNA. We observed a significant increase in PML-NBs in cells positive for MCPyV viral DNA replication. Interestingly, a significant amount of cells actively replicating MCPyV did not show any Sp100 expression. While PML and Daxx had no effect on MCPyV DNA replication, MCPyV replication was increased in cells depleted for Sp100, strongly suggesting that Sp100 is a negative regulator of MCPyV DNA replication.
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Directory of Open Access Journals (Sweden)
Norberto A. Sanjuan
2004-02-01
Full Text Available Los virus Polioma murinos provocan infecciones líticas en cultivos de células de ratón y transforman in vitro células de rata a través de la interacción de su oncogén mT con diversos reguladores celulares. Luego de su inoculación en ratones neonatos inducen neoplasias epiteliales y mesenquimáticas. Se ha propuesto que las cepas de polioma más oncogénicas son aquellas que previamente replican más en el ratón. Sin embargo, a nivel de una sola célula la infección lítica y la transformación deberían ser mutuamente excluyentes. En cada neoplasia han sido descriptos 3 tipos celulares según expresen el DNA viral solo o concomitantemente con la proteína mayor de la cápside VP1, o que no contengan DNA viral ni VP-1. En nuestro laboratorio detectamos la existencia de un cuarto tipo celular en las neoplasias, en el que se expresa la totalidad del genoma viral pero no ocurre el ensamblaje, probablemente por alteraciones en la fosforilación de VP-1. Se discuten los mecanismos de migración intracelular de Polioma, la diseminación en el ratón y los factores que podrían estar involucrados en la inducción de neoplasias o en la infección lítica inducidas por el virus.Murine polyomaviruses can produce lytic infections in mouse cell cultures or transform in vitro rat fibroblasts through a complex interaction with key cellular regulators. After infection of newborn mice, some strains of polyomavirus induce epithelial and mesenchymal tumors. It has been described that there is a direct relationship between viral dissemination in the mouse and tumor induction. However, at a single cell level lytic infection and transformation would not be able to coexist. The existence of 3 distinct cell populations in polyoma-induced tumors, classified according to the presence or absence of viral DNA and viral capsid protein VP-1 have been described. We have reported a fourth type of cell in the neoplasms, that can express the early and the late viral
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Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A
2017-06-15
Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.
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Detection of Merkel Cell Polyomavirus DNA in Serum Samples of Healthy Blood Donors
Mazzoni, Elisa; Rotondo, John C.; Marracino, Luisa; Selvatici, Rita; Bononi, Ilaria; Torreggiani, Elena; Touzé, Antoine; Martini, Fernanda; Tognon, Mauro G.
2017-01-01
Merkel cell polyomavirus (MCPyV) has been detected in 80% of Merkel cell carcinomas (MCC). In the host, the MCPyV reservoir remains elusive. MCPyV DNA sequences were revealed in blood donor buffy coats. In this study, MCPyV DNA sequences were investigated in the sera (n = 190) of healthy blood donors. Two MCPyV DNA sequences, coding for the viral oncoprotein large T antigen (LT), were investigated using polymerase chain reaction (PCR) methods and DNA sequencing. Circulating MCPyV sequences were detected in sera with a prevalence of 2.6% (5/190), at low-DNA viral load, which is in the range of 1–4 and 1–5 copies/μl by real-time PCR and droplet digital PCR, respectively. DNA sequencing carried out in the five MCPyV-positive samples indicated that the two MCPyV LT sequences which were analyzed belong to the MKL-1 strain. Circulating MCPyV LT sequences are present in blood donor sera. MCPyV-positive samples from blood donors could represent a potential vehicle for MCPyV infection in receivers, whereas an increase in viral load may occur with multiple blood transfusions. In certain patient conditions, such as immune-depression/suppression, additional disease or old age, transfusion of MCPyV-positive samples could be an additional risk factor for MCC onset. PMID:29238698
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Martens, I; Nilsson, S A; Linder, S; Magnusson, G
1989-05-01
The function of polyomavirus small T antigen in productive infection and in transformation was studied. Transfection of permissive mouse cells with mixtures of mutants that express only one type of T antigen showed that small T antigen increased large-T-antigen-dependent viral DNA synthesis approximately 10-fold. Under the same conditions, small T antigen was also essential for the formation of infectious virus particles. To analyze these activities of small T antigen, mutants producing protein with single amino acid replacements were constructed. Two mutants, bc1073 and bc1075, were characterized. Although both mutations led to the substitution of amino acid residues of more than one T antigen, the phenotype of both mutants was associated with alterations of the small T antigen. Both mutant proteins had lost their activity in the maturation of infectious virus particles. The bc1075 but not the bc1073 small T antigen had also lost its ability to stimulate viral DNA synthesis in mouse 3T6 cells. Finally, both mutants retained a third activity of small T antigen: to confer on rat cells also expressing middle T antigen the ability to grow efficiently in semisolid medium. The phenotypes of the mutants in these three assays suggest that small T antigen has at least three separate functions.
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Stakaitytė, Gabrielė; Nwogu, Nnenna; Dobson, Samuel J; Knight, Laura M; Wasson, Christopher W; Salguero, Francisco J; Blackbourn, David J; Blair, G Eric; Mankouri, Jamel; Macdonald, Andrew; Whitehouse, Adrian
2018-01-15
Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β 1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds
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Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.
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Jingwei Cheng
2017-10-01
Full Text Available Merkel cell carcinoma (MCC frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT and an intact Small T antigen (ST. While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.
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Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.
Cheng, Jingwei; Park, Donglim Esther; Berrios, Christian; White, Elizabeth A; Arora, Reety; Yoon, Rosa; Branigan, Timothy; Xiao, Tengfei; Westerling, Thomas; Federation, Alexander; Zeid, Rhamy; Strober, Benjamin; Swanson, Selene K; Florens, Laurence; Bradner, James E; Brown, Myles; Howley, Peter M; Padi, Megha; Washburn, Michael P; DeCaprio, James A
2017-10-01
Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.
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Directory of Open Access Journals (Sweden)
Sara Astegiano
2010-06-01
Full Text Available Introduction. Human polyomavirus BK (BKV is worldwide distributed, with a seroprevalence rate of 70–90% in the adults. Following primary infection, BK remains latent in the renourinary tract as the epidemiologically most relevant latency site, and in B cell, brain, spleen and probably other tissues. Reactivation may occur in both immunocompetent subjects and immunocompromised patients. In renal transplantation, in the context of intense immunosuppression, viral replication may determine BKV-associated nephropathy (BKVAN with interstitial nephritis and/or ureteral stenosis in 1–10% of the patients and leading to graft failure and return to haemodialysis in 30 to 80% of the cases (5. Screening of BKV replication represents the basic strategy to predict early the onset of BKVAN and may allow for earlier intervention with reduced allograft loss (3, 4. Nowadays, replication of BKV is monitored by quantification of BKV-DNA in serum and urine (2. The aim of this study was to evaluated the role of BKV VP1 mRNA in urine as a marker of viral replication in renal transplant recipients.
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Schneidewind, Laila; Neumann, Thomas; Knoll, Florian; Zimmermann, Kathrin; Smola, Sigrun; Schmidt, Christian Andreas; Krüger, William
2017-01-01
The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding. © 2017 S. Karger AG, Basel.
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Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko
2015-02-01
Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Christian Berrios
2016-11-01
Full Text Available Merkel cell polyomavirus (MCPyV is an etiological agent of Merkel cell carcinoma (MCC, a highly aggressive skin cancer. The MCPyV small tumor antigen (ST is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1. Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-κB and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-κB subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis.
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Leitz, Miriam; Stieler, Kristin; Grundhoff, Adam; Moll, Ingrid; Brandner, Johanna M; Fischer, Nicole
2014-10-01
Merkel cell carcinoma is a highly malignant skin cancer which predominantly occurs in elderly and immunocompromised persons. The identification of the Merkel cell polyomavirus (MCPyV) has inaugurated a new understanding of Merkel cell carcinoma pathogenesis. The frequent detection of the virus in Merkel cell carcinoma tissue (70-90%), its monoclonal integration in the tumor cells and the expression of viral oncogenes highly suggest that MCPyV is causally linked to the pathogenesis of the majority of Merkel cell cancer (MCC) cases. Using qualitative and quantitative PCR together with immunohistochemical staining this study aimed at characterizing the presence of MCPyV sequences and viral early gene expression in a cohort of MCC cases (n = 32) selected in Northern Germany. 40-57% of the cases were identified as MCPyV positive with 40.6% of the cases positive by immunohistochemical staining and 51.6-57.6% positive by PCR. Interestingly, in the majority (64%) of LT-Antigen positive tumors only 25-50% of tumor cells express LT-Antigen. These data are in accord with published studies describing heterogeneity in MCPyV viral loads and suggest that detection of MCPyV in Merkel cell carcinoma by PCR should be undertaken using multiple primer pairs. © 2013 Wiley Periodicals, Inc.
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Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme
2018-01-02
BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.
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Murdock, C C; Olival, Kevin J; Perkins, Susan L
2010-03-01
We collected blood-fed, snow-melt mosquitoes (Culicidae: Culiseta and Aedes) to describe the feeding patterns of potential mosquito vectors of Jamestown Canyon virus (JCV, Bunyaviridae: Orthobunyavirus). JCV is an arthropod-borne, zoonotic virus with deer as the primary amplifying host in western alpine ecosystems. We collected mosquitoes from natural resting areas, fiber pots, and carbon-dioxide baited miniature light traps in the Colorado Rocky Mountains in 2007. We conducted two polymerase chain reactions to amplify and sequence vertebrate DNA extracted from blood-fed mosquitoes, which yielded comparable, but not identical, results. Mammal-specific primers found mule deer (Odocoileus hemionus) and elk (Cervus elaphus canadensis) as the source of all bloodmeals. To determine if unamplified bloodmeals were from nonmammalian sources, we screened all samples with conserved vertebrate primers, which confirmed the initial polymerase chain reaction results, but also found porcupine (Erethizon dorsatum) and human (Homo sapiens) as additional bloodmeal sources. We consistently found that mule deer were the primary hosts for mosquitoes in this system. These results suggest that snow-melt mosquitoes, in particular A. cataphylla, may be important vectors in western JCV alpine systems and may also act as a bridge vector for JCV from cervid virus reservoirs to humans.
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Dubey, Divyanshu; Zhang, Yinan; Graves, Donna; DeSena, Allen D.; Frohman, Elliot; Greenberg, Benjamin
2015-01-01
A 51-year-old woman with relapsing–remitting multiple sclerosis (RRMS) and 3-year history of natalizumab use developed expressive aphasia. A brain magnetic resonance image (MRI) showed left frontotemporal and right parietal lesion with mild contrast enhancement and cerebrospinal fluid (CSF) was positive for John Cunningham virus (JCV) by polymerase chain reaction (PCR). The patient received five cycles of plasmapheresis followed by intravenous immunoglobulin. Despite this intervention, her speech deteriorated and she developed right hemiparesis. Upon referral to our institution, CSF quantitative JCV PCR was notable for 834 copies/ml. The patient was given an initial dose of 50,000 units of interleukin-2 (IL-2) subcutaneously (SQ) followed by 1 million units IL-2 SQ daily. Due to concern for immune reconstitution inflammatory syndrome (IRIS), the patient also received intravenous methylprednisone weekly. The regimen was tolerated well by the patient with no severe adverse effects. Clinically, the patient showed some improvement, and became more responsive and regained right lower extremity antigravity strength. After 12 weeks of IL-2 therapy, JCV quantitative PCR was notable for 31 copies/ml and the patient was more responsive. Due to persistence of JCV, IL-2 therapy was changed to mefloquine. At follow up after 6 months, the patient showed no clinical deterioration. PMID:27134676
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Yoakim, M; Hou, W; Liu, Y; Carpenter, C L; Kapeller, R; Schaffhausen, B S
1992-01-01
The binding of phosphatidylinositol-3-kinase to the polyomavirus middle T antigen is facilitated by tyrosine phosphorylation of middle T on residue 315. The pp85 subunit of phosphatidylinositol-3-kinase contains two SH2 domains, one in the middle of the molecule and one at the C terminus. When assayed by blotting with phosphorylated middle T, the more N-terminal SH2 domain is responsible for binding to middle T. When assayed in solution with glutathione S transferase fusions, both SH2s are capable of binding phosphorylated middle T. While both SH2 fusions can compete with intact pp85 for binding to middle T, the C-terminal SH2 is the more efficient of the two. Interaction between pp85 or its SH2 domains and middle T can be blocked by a synthetic peptide comprising the tyrosine phosphorylation sequence around middle T residue 315. Despite the fact that middle T can interact with both SH2s, these domains are not equivalent. Only the C-terminal SH2-middle T interaction was blocked by anti-SH2 antibody; the two SH2 fusions also interact with different cellular proteins. Images PMID:1380095
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Kuromi, Teruyuki; Matsushita, Michiko; Iwasaki, Takeshi; Nonaka, Daisuke; Kuwamoto, Satoshi; Nagata, Keiko; Kato, Masako; Akizuki, Gen; Kitamura, Yukisato; Hayashi, Kazuhiko
2017-11-01
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. Twenty-nineMCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. Polymerase chain reaction and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (PA. Only 2 mutations with amino acid changes were detected in MCPyV-negative MCCs only: 1 missense mutation in GLI1 exon 4 and 1 nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC. Copyright © 2017 Elsevier Inc. All rights reserved.
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Tracing Males From Different Continents by Genotyping JC Polyomavirus in DNA From Semen Samples.
Rotondo, John Charles; Candian, Tommaso; Selvatici, Rita; Mazzoni, Elisa; Bonaccorsi, Gloria; Greco, Pantaleo; Tognon, Mauro; Martini, Fernanda
2017-05-01
The human JC polyomavirus (JCPyV) is an ubiquitous viral agent infecting approximately 60% of humans. Recently, JCPyV sequences have been detected in semen samples. The aim of this investigation was to test whether semen JCPyV genotyping can be employed to trace the origin continent of males. Semen DNA samples (n = 170) from males of different Continents were investigated by PCR for the polymorphic JCPyV viral capsid protein 1 (VP1) sequences, followed by DNA sequencing. JCPyV sequences were detected with an overall prevalence of 27.6% (47/170). DNA sequencing revealed that European males carried JCPyV types 1A (71.4%), 4 (11.4%), 2B (2.9%), 2D1 (2.9%), and 3A (2.9%). Asians JCPyV type 2D1 (66.7%) and Africans JCPyV types 3A (33.3%) and 1A (33.3%). In 10.6% of males, two different JCPyV genotypes were detected, suggesting that the second JCPyV genotype was acquired in the destination country. This study indicates that the majority of semen samples found to be JCPyV-positive, were infected with the JCPyV genotype found in the geographic area of male origin. Therefore, semen JCPyV genotyping could be employed to trace the origin continent of males. Our findings could be applied to forensic investigations, in case of for instance sexual crimes. Indeed, JCPyV genotyping should enable investigators to make additional detailed profiling of the offender. J. Cell. Physiol. 232: 982-985, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Li, Long; Molberg, Kyle; Cheedella, Naga; Thibodeaux, Joel; Hinson, Stacy; Lucas, Elena
2018-01-01
Merkel cell carcinoma (MCC) is an aggressive skin tumor with a high tendency for metastases. We report a case of MCC initially presenting as axillary and pancreatic metastases. A 33-year-old HIV-positive Hispanic male presented with a history of a rapidly growing axillary mass. A needle core biopsy demonstrated an epithelioid neoplasm composed of small to medium-sized cells with high nuclear-cytoplasmic ratio, nuclear molding, and frequent mitotic figures. A subsequent PET scan revealed a 1.5 cm FDG avid mass in the pancreas. Endoscopic ultrasound-guided FNA of the pancreatic mass showed neoplastic cells with similar morphology to those of the axillary mass. The tumor cells were positive with pancytokeratin AE1/AE3, CK20, CD56, synatophysin, chromogranin, and Merkel cell polyomavirus (MCPyV). This case of MCC most likely originated from a resolved primary skin lesion drained by the involved axillary lymph node with subsequent metastases to the pancreas and distant lymph nodes. © 2017 Wiley Periodicals, Inc.
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Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.
Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro
2018-01-01
Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.
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Vahabpour, Rouhollah; Nasimi, Maryam; Naderi, Niloofar; Salehi-Vaziri, Mostafa; Mohajel, Nasir; Sadeghi, Farzin; Keyvani, Hossein; Monavari, Seyed Hamidreza
2017-04-01
The association of Merkel cell polyomavirus (MCP y V) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCP y V specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCP y V antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCP y V was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCP y V-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCP y V IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCP y V-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCP y V viral load among the groups ranged between 0.15 to 2.9 copies/10 3 cells (median, 1.9 copies/10 3 cells), with no significant difference between the studied populations (p value = 0.3).
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Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys
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Whitehead Stephen S
2011-03-01
Full Text Available Abstract Background Tahyna virus (TAHV is a human pathogen of the California encephalitis virus (CEV serogroup (Bunyaviridae endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV, fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. Results In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV, Jamestown Canyon virus (JCV, and Inkoo virus (INKV. By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Conclusions Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old
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Directory of Open Access Journals (Sweden)
Arun Kumar
Full Text Available The newly discovered Merkel Cell Polyomavirus (MCPyV resides in approximately 80% of Merkel cell carcinomas (MCC. Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL, suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs, using human bocavirus (HBoV VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.
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Directory of Open Access Journals (Sweden)
Motamedi Nasim
2012-09-01
Full Text Available Abstract Background The polyomaviruses WUPyV and KIPyV have been detected in various sample types including feces indicating pathogenicity in the gastrointestinal (GI system. However, quantitative viral load data from other simultaneously collected sample types are missing. As a consequence, primary replication in the GI system cannot be differentiated from swallowed virus from the respiratory tract. Here we present a retrospective quantitative longitudinal analysis in simultaneously harvested specimens from different organ sites of patients undergoing hematopoietic stem cell transplantation (HSCT. This allows the definition of sample types where deoxyribonucleic acid (DNA detection can be expected and, as a consequence, the identification of their primary replication site. Findings Viral DNA loads from 37 patients undergoing HSCT were quantified in respiratory tract secretions (RTS, stool and urine samples as well as in leukocytes (n = 449. Leukocyte-associated virus could not be found. WUPyV was found in feces, RTS and urine samples of an infant, while KIPyV was repeatedly detected in RTS and stool samples of 4 adult patients. RTS and stool samples were matched to determine the viral load difference showing a mean difference of 2.3 log copies/ml (p Conclusions The data collected in this study suggest that virus detection in the GI tract results from swallowed virus from the respiratory tract (RT. We conclude that shedding from the RT should be ruled out before viral DNA detection in the feces can be correlated to GI symptoms.
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DEFF Research Database (Denmark)
Turcan, Romeo V.
2016-01-01
literature on late globalization from sociocultural and economic perspectives. It illustrates in a vignette the character and features of late globalization observable in the withdrawal from foreign locations or deinternationalization of universities, as late globalizing entitis. The paper discusses...
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Arboviruses in North Dakota, 2003–2006
Anderson, John F.; Main, Andy J.; Armstrong, Philip M.; Andreadis, Theodore G.; Ferrandino, Francis J.
2015-01-01
To investigate arbovirus transmission in North Dakota, we collected and screened mosquitoes for viral infection by Vero cell culture assay. Seven viruses were isolated from 13 mosquito species. Spatial and temporal distributions of the important vectors of West Nile virus (WNV), Cache Valley virus, Jamestown Canyon virus (JCV), and trivittatus virus are reported. Snowshoe hare virus, Potosi virus, and western equine encephalomyelitis virus were also isolated. The risks of Culex tarsalis and Aedes vexans transmitting WNV to humans were 61.4% and 34.0% in 2003–2006, respectively, but in 2003 when the largest epidemic was reported, risks for Ae. vexans and Cx. tarsalis in Cass County were 73.6% and 23.9%, respectively. Risk of humans acquiring an infectious bite was greatest from about the second week of July through most of August. West Nile virus sequences were of the WN02 genotype. Most JCV strains belonged to a single clade of genetically related strains. Cache Valley virus and JCV were prevalent during August and early September and during July and August, respectively. PMID:25487728
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Cesaro, Simone; Dalianis, Tina; Hanssen Rinaldo, Christine; Koskenvuo, Minna; Pegoraro, Anna; Einsele, Hermann; Cordonnier, Catherine; Hirsch, Hans H
2018-01-01
To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Review of English literature and evidence-based recommendations by expert consensus. BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Late Carboniferous to Late Permian carbon isotope stratigraphy
DEFF Research Database (Denmark)
Buggisch, Werner; Krainer, Karl; Schaffhauser, Maria
2015-01-01
An integrated study of the litho-, bio-, and isotope stratigraphy of carbonates in the Southern Alps was undertaken in order to better constrain δ13C variations during the Late Carboniferous to Late Permian. The presented high resolution isotope curves are based on 1299 δ13Ccarb and 396 δ13Corg...
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Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function.
Korth, Johannes; Widera, Marek; Dolff, Sebastian; Guberina, Hana; Bienholz, Anja; Brinkhoff, Alexandra; Anastasiou, Olympia Evdoxia; Kribben, Andreas; Dittmer, Ulf; Verheyen, Jens; Wilde, Benjamin; Witzke, Oliver
2018-02-01
BK polyomavirus (BKPyV)-associated nephropathy (PyVAN) is a significant cause of premature renal transplant failure. High-level BKPyV viremia is predictive for PyVAN; however, low-level BKPyV viremia does not necessarily exclude the presence of PyVAN. As data are limited regarding whether or not low-level BKPyV viremia has an effect on intermediate-term graft outcome, this study analyzes the impact of low-level BKPyV viremia on intermediate-term graft function and outcome compared with high-level viremia and non-viremic patients. All renal transplant patients received follow-up examinations at the Department of Nephrology, University Hospital Essen. Patients were screened for BKPyV viremia and stratified into three groups according to their maximum BKPyV load in serum (low-level viremia, high-level viremia, and no viremia). In 142 of 213 (67%) patients, BKPyV was never detected in serum; 42 of 213 (20%) patients were found positive for low-level viremia (≤10 4 copies/mL); and 29 of 213 (13%) patients showed high-level viremia (>10 4 copies/mL). No significant differences regarding transplant function and graft failure were observed between patients without BKPyV viremia (delta estimated glomerular filtration rate [eGFR] +0.1 mL/min [month 1 vs last visit at month 44]) and patients with low-level BKPyV viremia (delta eGFR -1.7 mL/min). In patients with high-level viremia, transplant function was significantly restricted (delta eGFR -6.5 mL/min) compared with low-level viremia until the last visit at 44 ± 9.7 months after transplantation. Although the graft function and graft loss were worse in the high-level viremia group compared with no viremia (eGFR 37 vs 45 mL/min), the difference was not significant. High-level viremia was associated with impaired graft function. In contrast, low-level BKPyV viremia had no significant impact on intermediate-term graft function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland
2016-05-31
The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.
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Directory of Open Access Journals (Sweden)
Mathilda Eriksson
Full Text Available Virus-like particles (VLPs consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV VLPs carrying the entire human Prostate Specific Antigen (PSA (PSA-MPyVLPs for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs. Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4(+ and CD8(+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4(+ and CD8(+ cells with a low induction of anti-VLP antibodies.
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Soldatova, Irina; Prilepskaja, Terezie; Abrahamyan, Levon; Forstová, Jitka; Huérfano, Sandra
2018-03-31
The mechanism used by mouse polyomavirus (MPyV) overcomes the crowded cytosol to reach the nucleus has not been fully elucidated. Here, we investigated the involvement of importin α/β1 mediated transport in the delivery of MPyV genomes into the nucleus. Interactions of the virus with importin β1 were studied by co-immunoprecipitation and proximity ligation assay. For infectivity and nucleus delivery assays, the virus and its capsid proteins mutated in the nuclear localization signals (NLSs) were prepared and produced. We found that at early times post infection, virions bound importin β1 in a time dependent manner with a peak of interactions at 6 h post infection. Mutation analysis revealed that only when the NLSs of both VP1 and VP2/3 were disrupted, virus did not bind efficiently to importin β1 and its infectivity remarkably decreased (by 80%). Nuclear targeting of capsid proteins was improved when VP1 and VP2 were co-expressed. VP1 and VP2 were effectively delivered into the nucleus, even when one of the NLS, either VP1 or VP2, was disrupted. Altogether, our results showed that MPyV virions can use VP1 and/or VP2/VP3 NLSs in concert or individually to bind importins to deliver their genomes into the cell nucleus.
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Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin
2011-01-01
Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228
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Kervarrec, Thibault; Samimi, Mahtab; Gaboriaud, Pauline; Gheit, Tarik; Beby-Defaux, Agnès; Houben, Roland; Schrama, David; Fromont, Gaëlle; Tommasino, Massimo; Le Corre, Yannick; Hainaut-Wierzbicka, Eva; Aubin, Francois; Bens, Guido; Maillard, Hervé; Furudoï, Adeline; Michenet, Patrick; Touzé, Antoine; Guyétant, Serge
2018-05-01
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as "combined" or "conventional." Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of
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Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul
2017-04-01
Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Lateness to School Remediation Game
Ugwuegbulam, Charles N.; Ibrahim, Haj. Naheed
2015-01-01
Primary and secondary school in Nigeria encourage punctuality to school yet a good number of the learners came late to school. This is especially true in the case of day students. Learners who come late to school are usually punished in one way or the other yet the lateness to school phenomenon still persist. Lateness to school behaviour affects…
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Progressive multifocal leukoencephalopathy: new concepts
Directory of Open Access Journals (Sweden)
Marco A. Lima
2013-09-01
Full Text Available Progressive multifocal leukoencephalopathy (PML is a demyelinating disease of the CNS caused by reactivation of JC virus (JCV in a setting of cellular immunosuppression. Originally, PML was observed in patients with advanced HIV infection, lymphoproliferative disorders and transplant recipients. However, the widespread use of HIV antiretroviral drugs and the new selective immunomodulatory and immunosuppressive medications, such as Rituximab and Natalizumab, has recently modified the epidemiology, clinical presentation and prognosis of PML. Herein, we discuss the new concepts on PML, emphasizing the recent modification in the epidemiology; the impact of new immunomodulatory treatments in the disease, PML-IRIS (Immune reconstitution inflammatory síndrome, new treatment strategies and other JCV related CNS diseases.
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7 CFR 920.112 - Late payments.
2010-01-01
... Miscellaneous Provisions § 920.112 Late payments. Pursuant to § 920.41(a), interest will be charged at a 1.5 percent monthly simple interest rate. Assessments for kiwifruit shall be deemed late if not received... late charge will be assessed when payment becomes 30 days late. Interest and late payment charges shall...
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Hashida, Yumiko; Nakajima, Kimiko; Nakajima, Hideki; Shiga, Takeo; Tanaka, Moe; Murakami, Masanao; Matsuzaki, Shigenobu; Naganuma, Seiji; Kuroda, Naoki; Seki, Yasutaka; Katano, Harutaka; Sano, Shigetoshi; Daibata, Masanori
2016-09-01
Although Merkel cell polyomavirus (MCPyV) has the potential to cause Merkel cell carcinoma (MCC), it is also found in the normal skin of healthy individuals. However, the mechanism for transformation of MCPyV to an oncogenic form is unknown. To investigate the levels of MCPyV infection in the normal skin patients with MCC compared with those in a control cohort. We studied a total of six Japanese patients with cutaneous MCC. Sun-exposed and sun-unexposed skin swabs were obtained and analyzed for MCPyV loads using quantitative real-time polymerase chain reaction. At first, we found a patient with MCC carrying an extremely high load of MCPyV DNA in normal skin. This unique case prompted us to further explore the levels of MCPyV as skin microbiota in patients with MCC. We showed that MCPyV DNA levels were significantly higher in swabs obtained from normal skin samples of six patients with MCC compared with those from 30 age-matched healthy individuals and 19 patients with other cutaneous cancers. Whereas MCPyV strains obtained from the normal skin of patients with MCC had gene sequences without structural alterations, sequences of the tumor-derived strains showed truncating mutations or deletions. Although the number of patients with MCC studied was small, our findings suggest that MCC may occur with a background of high MCPyV load in the skin, and are expected to stimulate further studies on whether such skin virome levels could be one of predictive markers for the development of MCC. Copyright © 2016 Elsevier B.V. All rights reserved.
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Directory of Open Access Journals (Sweden)
Imajoh Masayuki
2012-08-01
Full Text Available Abstract Background Merkel cell polyomavirus (MCPyV was identified originally in Merkel cell carcinoma (MCC, a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i the major histological type of cervical cancer is the SCC; (ii the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV. In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19% and 4/16 cervical ACs (25% were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset
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Zeng, G; Huang, Y; Huang, Y; Lyu, Z; Lesniak, D; Randhawa, P
2016-11-01
This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus-reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V-family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J-gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.
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DEFF Research Database (Denmark)
Carlson, N; Hansen, Jesper Melchior
2014-01-01
in circumstances of extreme immunodeficiency. Development of fulminant PML is rare and treatment options are limited. CASE REPORT: We have presented a case of JCV reactivation resulting in PML 19 years after renal allograft transplantation and after recent conversion of immunosuppressive treatment. One year after...... reaction analysis of the cerebrospinal fluid. Owing to severe renal insufficiency, treatment options were limited to tapering of immunosuppressive treatment in hopes of achieving host clearance of the viral infection. Despite prompt termination of immunosuppressive treatment, the patient suffered rapid...... progressive neurologic decline and death rapidly ensued. CONCLUSION: Development of PML in transplant recipients remains rare. Despite advances in our understanding of JCV infection and PML, treatment options remain limited and prognosis is often poor....
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Late effects from hadron therapy
Energy Technology Data Exchange (ETDEWEB)
Blakely, Eleanor A.; Chang, Polly Y.
2004-06-01
Successful cancer patient survival and local tumor control from hadron radiotherapy warrant a discussion of potential secondary late effects from the radiation. The study of late-appearing clinical effects from particle beams of protons, carbon, or heavier ions is a relatively new field with few data. However, new clinical information is available from pioneer hadron radiotherapy programs in the USA, Japan, Germany and Switzerland. This paper will review available data on late tissue effects from particle radiation exposures, and discuss its importance to the future of hadron therapy. Potential late radiation effects are associated with irradiated normal tissue volumes at risk that in many cases can be reduced with hadron therapy. However, normal tissues present within hadron treatment volumes can demonstrate enhanced responses compared to conventional modes of therapy. Late endpoints of concern include induction of secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor margins need further study, and there is need for more acute molecular studies underlying late effects of hadron therapy.
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Álvarez-Argüelles, Marta E; Melón, Santiago; Rojo, Susana; Fernandez-Blázquez, Ana; Boga, Jose A; Palacio, Ana; Vivanco, Blanca; de Oña, María
2017-12-01
This study investigates the presence of Merkel cell polyomavirus (MCPyV) in skin lesions of patients with Merkel cell carcinoma (MCC). MCPyV was quantified using quantitative Real-Time-PCR (qRT-PCR) in 34 paraffinized MCC samples (resected/biopsied) originally taken between 1977 and 2015, and six non-MCC samples. In 31 (91.2%) MCC-individuals, MCPyV was detected. No virus was observed in any non-MCC tumor. Average age at diagnosis was 78.2 ± 9.35 (55-97) years for women (n = 19) and 69.5 ± 14.7 (45-91) for men (n = 15) (P = 0.04). MCC tumor location, known in 25 cases, was: 11 (44%) in the head region, 6 (24%) in upper limbs, 4 (16%) in lower limbs, and 4 (16%) in the trunk. All but one patient had received some sort of treatment: 15 (45.45%) underwent both radio and chemotherapy, 13 (39.39%) only surgery, 2 (6.06%) surgery, plus radio and chemotherapy, 2 (6.06%) surgery and chemotherapy, and 1 (3.03%) only radiotherapy. Follow up data were available for 21/34 patients: recurrence was recorded for 4 (19.04%), and metastasis for 13 (61.9%). Recorded data showed that 10 men and 5 women (total 44.1%) died during follow up, 7 (46.7%) of them within 2 years of diagnosis. Viral load was 5.8 ± 1.4 log copies/10 5 cells (3.1-8.6), independent of any variable. MCPyV was very frequent in MCC. It was principally associated with head and limb tumors, it more commonly affected men, who in this study were, on average, younger than women, and had high rates of recurrence and mortality. The amplification techniques described here are easily applied and suitable for detecting the presence of MCPyV virus in MCC. © 2017 Wiley Periodicals, Inc.
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International Nuclear Information System (INIS)
Colombara, Danny V.; Manhart, Lisa E.; Carter, Joseph J.; Hawes, Stephen E.; Weiss, Noel S.; Hughes, James P.; Qiao, You-Lin; Taylor, Philip R.; Smith, Jennifer S.; Galloway, Denise A.
2016-01-01
Studies of human polyomavirus (HPyV) infection and lung cancer are limited and those regarding the association of human papillomavirus (HPV) infection and lung cancer have produced inconsistent results. We conducted a nested case–control study to assess the association between incident lung cancer of various histologies and evidence of prior infection with HPyVs and HPVs. We selected serum from 183 cases and 217 frequency matched controls from the Yunnan Tin Miner’s Cohort study, which was designed to identify biomarkers for early detection of lung cancer. Using multiplex liquid bead microarray (LBMA) antibody assays, we tested for antibodies to the VP1 structural protein and small T antigen (ST-Ag) of Merkel cell, KI, and WU HPyVs. We also tested for antibodies against HPV L1 structural proteins (high-risk types 16, 18, 31, 33, 52, and 58 and low-risk types 6 and 11) and E6 and E7 oncoproteins (high risk types 16 and 18). Measures of antibody reactivity were log transformed and analyzed using logistic regression. We found no association between KIV, WUV, and MCV antibody levels and incident lung cancer (P-corrected for multiple comparisons >0.10 for all trend tests). We also found no association with HPV-16, 18, 31, 33, 52, and 58 seropositivity (P-corrected for multiple comparisons >0.05 for all). Future studies of infectious etiologies of lung cancer should look beyond HPyVs and HPVs as candidate infectious agents. The online version of this article (doi:10.1186/s12885-016-2381-3) contains supplementary material, which is available to authorized users
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Haugg, Anke M; Rennspiess, Dorit; zur Hausen, Axel; Speel, Ernst-Jan M; Cathomas, Gieri; Becker, Jürgen C; Schrama, David
2014-12-15
The Merkel cell polyomavirus (MCPyV) is detected in 80% of Merkel cell carcinomas (MCC). Clonal integration and tumor-specific mutations in the large T antigen are strong arguments that MCPyV is a human tumor virus. However, the relationship between viral presence and cancer induction remains discussed controversially. Since almost all studies on virus prevalence are based on PCR techniques, we performed MCPyV fluorescence in situ hybridization (FISH) on MCC to gain information about the quality of the viral presence on the single cell level. MCPyV-FISH was performed on tissue microarrays containing 62 formalin-fixed and paraffin-embedded tissue samples including all tumor grades of 42 patients. The hybridization patterns were correlated to the qPCR data determined on corresponding whole tissue sections. Indeed, MCPyV-FISH and qPCR data were highly correlated, i.e. 83% for FISH-positive and 93% for FISH-negative cores. Accordingly, the mean of the qPCR values of all MCPyV-positive cores differed significantly from the mean of the negative cores (p = 0.0076). Importantly, two hybridization patterns were definable in the MCPyV-FISH: a punctate pattern (85%) indicating viral integration, which correlated with a moderate viral abundance and a combination of the punctate with a diffuse pattern (15%), suggesting a possible coexistence of integrated and episomal virus which was associated with very high viral load and VP1 expression. Thus, MCPyV-FISH adds important information on the single cell level within the histomorphological context and could therefore be an important tool to further elucidate MCPyV related carcinogenesis. © 2014 UICC.
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DEFF Research Database (Denmark)
Mortensen, Erik Lykke; Flensborg-Madsen, Trine; Molbo, Drude
2014-01-01
To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits and cognitive ability in late midlife; and to evaluate how these associations are influenced by demographic factors....
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Harms, Paul W; Collie, Angela M B; Hovelson, Daniel H; Cani, Andi K; Verhaegen, Monique E; Patel, Rajiv M; Fullen, Douglas R; Omata, Kei; Dlugosz, Andrzej A; Tomlins, Scott A; Billings, Steven D
2016-03-01
Merkel cell carcinoma is a rare but highly aggressive cutaneous neuroendocrine carcinoma. Cytokeratin 20 (CK20) is expressed in ~95% of Merkel cell carcinomas and is useful for distinction from morphologically similar entities including metastatic small-cell lung carcinoma. Lack of CK20 expression may make diagnosis of Merkel cell carcinoma more challenging, and has unknown biological significance. Approximately 80% of CK20-positive Merkel cell carcinomas are associated with the oncogenic Merkel cell polyomavirus. Merkel cell carcinomas lacking Merkel cell polyomavirus display distinct genetic changes from Merkel cell polyomavirus-positive Merkel cell carcinoma, including RB1 inactivating mutations. Unlike CK20-positive Merkel cell carcinoma, the majority of CK20-negative Merkel cell carcinomas are Merkel cell polyomavirus-negative, suggesting CK20-negative Merkel cell carcinomas predominantly arise through virus-independent pathway(s) and may harbor additional genetic differences from conventional Merkel cell carcinoma. Hence, we analyzed 15 CK20-negative Merkel cell carcinoma tumors (10 Merkel cell polyomavirus-negative, four Merkel cell polyomavirus-positive, and one undetermined) using the Ion Ampliseq Comprehensive Cancer Panel, which assesses copy number alterations and mutations in 409 cancer-relevant genes. Twelve tumors displayed prioritized high-level chromosomal gains or losses (average 1.9 per tumor). Non-synonymous high-confidence somatic mutations were detected in 14 tumors (average 11.9 per tumor). Assessing all somatic coding mutations, an ultraviolet-signature mutational profile was present, and more prevalent in Merkel cell polyomavirus-negative tumors. Recurrent deleterious tumor suppressor mutations affected TP53 (9/15, 60%), RB1 (3/15, 20%), and BAP1 (2/15, 13%). Oncogenic activating mutations included PIK3CA (3/15, 20%), AKT1 (1/15, 7%) and EZH2 (1/15, 7%). In conclusion, CK20-negative Merkel cell carcinoma display overlapping genetic changes
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Harms, Paul W.; Collie, Angela M. B.; Hovelson, Daniel H.; Cani, Andi K.; Verhaegen, Monique E.; Patel, Rajiv M.; Fullen, Douglas R.; Omata, Kei; Dlugosz, Andrzej A.; Tomlins, Scott A.; Billings, Steven D.
2016-01-01
Merkel cell carcinoma is a rare but highly aggressive cutaneous neuroendocrine carcinoma. Cytokeratin-20 (CK20) is expressed in approximately 95% of Merkel cell carcinomas and is useful for distinction from morphologically similar entities including metastatic small cell lung carcinoma. Lack of CK20 expression may make diagnosis of Merkel cell carcinoma more challenging, and has unknown biological significance. Approximately 80% of CK20-positive Merkel cell carcinomas are associated with the oncogenic Merkel cell polyomavirus. Merkel cell carcinomas lacking Merkel cell polyomavirus display distinct genetic changes from Merkel cell polyomavirus-positive Merkel cell carcinoma, including RB1 inactivating mutations. Unlike CK20-positive Merkel cell carcinoma, the majority of CK20-negative Merkel cell carcinomas are Merkel cell polyomavirus-negative, suggesting CK20-negative Merkel cell carcinomas predominantly arise through virus-independent pathway(s) and may harbor additional genetic differences from conventional Merkel cell carcinoma. Hence, we analyzed 15 CK20-negative Merkel cell carcinoma tumors (ten Merkel cell polyomavirus-negative, four Merkel cell polyomavirus-positive, and one undetermined) using the Ion Ampliseq Comprehensive Cancer Panel, which assesses copy number alterations and mutations in 409 cancer-relevant genes. Twelve tumors displayed prioritized high-level chromosomal gains or losses (average 1.9 per tumor). Non-synonymous high confidence somatic mutations were detected in 14 tumors (average 11.9 per tumor). Assessing all somatic coding mutations, an ultraviolet-signature mutational profile was present, and more prevalent in Merkel cell polyomavirus-negative tumors. Recurrent deleterious tumor suppressor mutations affected TP53 (9/15, 60%), RB1 (3/15, 20%), and BAP1 (2/15, 13%). Oncogenic activating mutations included PIK3CA (3/15, 20%), AKT1 (1/15, 7%)) and EZH2 (1/15, 7%). In conclusion, CK20-negative Merkel cell carcinoma display overlapping
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Late effects of childhood leukemia therapy.
Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J
2011-09-01
As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.
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LATE VISION: PROCESSES AND EPISTEMIC STATUS
Directory of Open Access Journals (Sweden)
Athanassios eRaftopoulos
2011-12-01
Full Text Available In this paper, I examine the processes that occur in late vision and address the problem of whether late vision should be construed as a properly speaking perceptual stage, or as a thought-like discursive stage. Specifically, I argue that late vision, its (partly conceptual nature notwithstanding, neither is constituted by nor does it implicate what I call pure thoughts, that is, propositional structures that are formed in the cognitive areas of the brain through, and participate in, discursive reasoning and inferences. At the same time, the output of late vision, namely an explicit belief concerning the identity and category membership of an object (that is, a recognitional belief or its features, eventually enters into discursive reasoning. Using Jackendoff’s distinction between visual awareness, which characterizes perception, and visual understanding, which characterizes pure thought, I claim that the contents of late vision belong to visual awareness and not to visual understanding and that although late vision implicates beliefs, either implicit or explicit, these beliefs are hybrid visual/conceptual constructs and not pure thoughts. Distinguishing between these hybrid representations and pure thoughts and delineating the nature of the representations of late vision lays the ground for examining, among other things, the process of conceptualization that occurs in visual processing and the way concepts modulate perceptual content affecting either its representational or phenomenal character. I also do not discuss the epistemological relations between the representations of late vision and the perceptual judgments they ‘support’, or ‘guide’ or ‘render possible’ or ‘evidence’ or ‘entitle’. However, the specification of the epistemology of late vision lays the ground for attacking that problem as well.
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Late prematurity: a systematic review
Directory of Open Access Journals (Sweden)
Luís Carlos Machado Júnior
2014-06-01
Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed.
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Carr, Michael; Gonzalez, Gabriel; Sasaki, Michihito; Dool, Serena E; Ito, Kimihito; Ishii, Akihiro; Hang'ombe, Bernard M; Mweene, Aaron S; Teeling, Emma C; Hall, William W; Orba, Yasuko; Sawa, Hirofumi
2017-10-06
Polyomaviruses (PyVs) are considered to be highly host-specific in different mammalian species, with no well-supported evidence for host-switching events. We examined the species diversity and host specificity of PyVs in horseshoe bats (Rhinolophus spp.), a broadly distributed and highly speciose mammalian genus. We annotated six PyV genomes, comprising four new PyV species, based on pairwise identity within the large T antigen (LTAg) coding region. Phylogenetic comparisons revealed two instances of highly related PyV species, one in each of the Alphapolyomavirus and Betapolyomavirus genera, present in different horseshoe bat host species (Rhinolophus blasii and R. simulator), suggestive of short-range host-switching events. The two pairs of Rhinolophus PyVs in different horseshoe bat host species were 99.9 and 88.8 % identical with each other over their respective LTAg coding sequences and thus constitute the same virus species. To corroborate the species identification of the bat hosts, we analysed mitochondrial cytb and a large nuclear intron dataset derived from six independent and neutrally evolving loci for bat taxa of interest. Bayesian estimates of the ages of the most recent common ancestors suggested that the near-identical and more distantly related PyV species diverged approximately 9.1E4 (5E3-2.8E5) and 9.9E6 (4E6-18E6) years before the present, respectively, in contrast to the divergence times of the bat host species: 12.4E6 (10.4E6-15.4E6). Our findings provide evidence that short-range host-switching of PyVs is possible in horseshoe bats, suggesting that PyV transmission between closely related mammalian species can occur.
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Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems
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Cohort Profile: The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE
Directory of Open Access Journals (Sweden)
Michael Kreiberg
2018-02-01
Full Text Available The cohort was set up in order to analyze late effects in long-term testicular cancer survivors (TCS and to contribute to the design of future follow-up programs addressing and potentially preventing late effects. Data for this cross-sectional study were collected between January 1, 2014, and December 31, 2016, among living Danish TCS and 60% agreed to participate in the cohort (N = 2,572. Mean time since testicular cancer (TC diagnosis was 18 years (range 7–33 and mean age of participants was 53 years (range 25–95. Data consist of results of a questionnaire with patient reported outcomes which covers a broad range of items on late-effects. The study also included data obtained through linkages to Danish registries, a biobank, and clinical data from hospital files and pathology reports originating from the Danish Testicular Cancer Database (DaTeCa. The treatment during the observation period has been nearly the same for all stages of TC and is in agreement with today’s standard treatment, this allows for interesting analysis with a wide timespan. We have extensive data on non-responders and are able to validate our study findings. Data from a Danish reference population (N = 162,283 allow us to compare our findings with a Danish background population. The cohort can easily be extended to access more outcomes, or include new TCS. A limitation of the present study is the cross-sectional design and despite the large sample size, The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE lacks statistical power to study very rare late effects. Since it was voluntary to participate in the study we have some selection bias, for instance, we lack responders who were not in a paired relationship, but we would still argue that this cohort of TCSs is representative for TCSs in Denmark.Collaboration and data accessResearches interested in collaboration with the DaTeCa-LATE study group please contact Professor Gedske Daugaard
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Fuentes, Lara; Gómez-Lara, Josep; Salvatella, Neus; Gonzalo, Nieves; Hernández-Hernández, Felipe; Fernández-Nofrerias, Eduard; Sánchez-Recalde, Ángel; Alfonso, Fernando; Romaguera, Rafael; Ferreiro, José Luis; Roura, Gerard; Teruel, Luis; Gracida, Montserrat; Marcano, Ana Lucrecia; Gómez-Hospital, Joan-Antoni; Cequier, Ángel
2018-05-01
Stent thrombosis (ST) is a life-threatening complication after stent implantation. Intravascular ultrasound is able to discern most causes of ST. The aim of this study was to compare intravascular ultrasound findings between bare-metal stents (BMS) and drug-eluting stents (DES) in patients with late (31 days to 1 year) or very late ST (> 1 year). Of 250 consecutive patients with late or very late ST in 7 Spanish institutions, 114 patients (45.5% BMS and 54.5% DES) were imaged with intravascular ultrasound. Off-line intravascular ultrasound analysis was performed to assess malapposition, underexpansion, and neoatherosclerosis. The median time from stent implantation to ST was 4.0 years with BMS and 3.4 years with DES (P = .04). Isolated malapposition was similarly observed in both groups (36.5% vs 46.8%; P = .18) but was numerically lower with BMS (26.6% vs 48.0%; P = .07) in patients with very late ST. Isolated underexpansion was similarly observed in both groups (13.5% vs 11.3%; P = .47). Isolated neoatherosclerosis occurred only in patients with very late ST and was more prevalent with BMS (22.9%) than with DES (6.0%); P = .02. At 2.9 years' follow-up, there were 0% and 6.9% cardiac deaths, respectively (P = .06) and recurrent ST occurred in 4.0% and 5.2% of patients, respectively (P = .60). Malapposition was the most common finding in patients with late and very late ST and is more prevalent with DES in very late ST. In contrast, neoatherosclerosis was exclusively observed in patients with very late ST and mainly with BMS. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
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Directory of Open Access Journals (Sweden)
Marilys Corbex
Full Text Available The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups.One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology.Viral DNA was found in 22 (17.9% of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type than non-IBC tumors (30% vs. 13%, p<0.04. Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009.Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative. While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.
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DEFF Research Database (Denmark)
Sørensen, Per Soelberg; Bertolotto, Antonio; Edan, Gilles
2012-01-01
using or considering natalizumab therapy. Recommendations for clinical management of patients with MS and use of natalizumab are provided based on the presence of these three risk factors. The identification of risk factors that increase the likelihood of PML in natalizumab-treated patients can......Natalizumab is a highly effective immunomodulator in the treatment of multiple sclerosis (MS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), an infection of the central nervous system (CNS) caused by a pathogenic form of the normally benign JC......-treated patients. With the development of a reliable and validated assay for detection of antibodies in patients with MS directed against JCV, it is now possible to identify persons who are carriers of JCV. The availability of this assay provides an additional option for risk stratification of PML in patients...
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Late-onset Huntington's disease: diagnostic and prognostic considerations.
Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios
2014-07-01
To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). We analyzed a cohort of 41 late-onset (≥60 years) HD patients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HD patients. Disease severity was assessed by the Total Functional Capacity Scale. Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HD patients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HD patients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a severe stage of illness on average 2.8 years earlier than usual-onset HD patients (p = 0.046). A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Late effects on normal tissues: oesophagus
International Nuclear Information System (INIS)
Pavy, J.J.; Bosset, J.F.
1997-01-01
Radiation-induced late effects of oesophagus are observed after treatment of various cancers. Acute reactions, mainly oesophagitis, are well known and accurately described; late effects share, for most of these, a common consequence: alteration of the main oesophageal function, namely to conduct the food bolus; clinically they are impaired in terms of mobility and stenosis. More rarely, ulcerations and pseudodiverticulae can be observed. Chemotherapy further increases the risk of late effects, especially in case of concomitant chemo-radiotherapy. All numbers and statistical data on oesophagus late effects should be regarded with caution due to recent changes in the therapeutic attitudes (more and more combined chemotherapy-radiotherapy) and some progress in given cancer locations. A common scale like the LENT-SOMA should enable the clinician to better know these late effects on oesophagus which is required to initiate effective prevention measures and adapted treatments. (authors)
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Directory of Open Access Journals (Sweden)
Abdulaziz AlHadlaq
2016-04-01
Full Text Available We report an extremely rare presentation of late-onset endophthalmitis in a young adult patient with an unexposed Ahmed tube implant. The implant was inserted 11 years prior to presentation. There was no history of trauma or any obvious exposure on clinical examination and the tube plate was filled with purulent material. After aqueous and vitreous tap, the patient underwent intracameral, intravitreal subconjunctival antibiotic injections and was started on systemic antibiotics with good response. Endophthalmitis associated with tube drainage device can present as late as 11 years and even without an unexposed tube.
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Gratkorn - A new late Middle Miocene vertebrate fauna from Styria (Late Sarmatian, Austria)
Gross, M.; Böhme, M.; Prieto, J.
2009-04-01
Integrated stratigraphic approaches provide precise correlations of global standard stages with regional Paratethys stages. Nevertheless, higher resolution stratigraphic matching of terrestrial deposits remains challenging due to the lack of a practical continental biostratigraphy. The mostly used tool for biostratigraphic correlation of non-marine deposits in the Old World is still the concept of Neogene Mammal-zones (MN-zones). However, at higher biostratigraphic resolution (reptiles (scincids, lacertids, gekkonids, anguids, varanids, colubrids, testudinids, emydids), birds (coliiformes), rodents and lagomorphs (cricetids, glirids, eomyids, sciurids, castorids), insectivores and chiropterans (erinaceids, soricids, talpids), and large mammals (suids, tragulids, moschids, cervids, ?palaeomerycids, equids, chalicotheriids, rhinos, proboscidians, carnivors). Litho- and biostratigraphy (terrestrial gastropods) as well as magnetostratigraphic data and the sequence stratigraphic and geodynamic frame indicate an age of 12-12.2 Ma (early Late Sarmatian s.str., chron 5An.1n) for the locality. Therefore, Gratkorn is one of richest and most complete fauna of the late Middle Miocene of Central Europe and will be confidentially one of the key faunas for a high-resolution continental biostratigraphy and the comprehension of the faunal succession and interchanges near the Middle/Late Miocene transition. Acknowledgements This is a preliminary overview of the Gratkorn vertebrate fauna. Several taxa are still under investigation. We are especially grateful to Gudrun Daxner-Höck, Ursula Göhlich (both Natural History Museum Vienna) and Getrud Rössner (University of Munich) for their comments to the rodents, ruminants, proboscidians and bird remains. References Böhme, M., Ilg, A., Winklhofer, M. 2008. Late Miocene "washhouse" climate in Europe.- Earth and Planetary Science Letters, 275: 393-401. Gross, M., 2008. A limnic ostracod fauna from the surroundings of the Central
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Energy Technology Data Exchange (ETDEWEB)
Yu, Rucong [Chinese Academy of Sciences, LASG, Institute of Atmospheric Physics, Beijing (China); China Meteorological Administration, LaSW, Chinese Academy of Meteorological Sciences, Beijing (China); Yuan, Weihua [Chinese Academy of Sciences, LASG, Institute of Atmospheric Physics, Beijing (China); Graduate School of the Chinese Academy of Sciences, Beijing (China); Li, Jian [China Meteorological Administration, LaSW, Chinese Academy of Meteorological Sciences, Beijing (China); Fu, Yunfei [Chinese Academy of Sciences, LASG, Institute of Atmospheric Physics, Beijing (China); University of Science and Technology of China, Laboratory of Satellite Remote Sensing and Climate Environment, Hefei, Anhui (China)
2010-09-15
Using the tropical rainfall measuring mission (TRMM) Precipitation Radar (PR) observations combined with the surface rain gauge data during 1998-2006, the robust diurnal features of summer stratiform and convective precipitation over the southern contiguous China are revealed by exploring the diurnal variations of rain rate and precipitation profile. The precipitation over the southern contiguous China exhibits two distinguishing diurnal phases: late-night (2200-0600 LST) and late-afternoon (1400-2200 LST), dependent on the location, precipitation type and duration time. Generally, the maximum rain rate and the highest profile of stratiform precipitation occur in the late-afternoon (late-night) over the southeastern (southwestern) China, while most of the stratiform short-duration rain rate tends to present late-afternoon peaks over the southern China. For convective precipitation, the maximum rain rate and the highest profile occur in the late-afternoon over most of the southern contiguous China, while the convective long-duration rain rate exhibits late-night peaks over the southwestern China. Without regional dependence, the convective precipitation exhibits much larger amplitude of diurnal variations in both near surface rain rate and vertical extension compared with stratiform precipitation and the convective rain top rises most rapidly between noon and afternoon. However, there are two distinctive sub-regions. The diurnal phases of precipitation there are very weakly dependent on precipitation type and duration time. Over the eastern periphery of the Tibetan Plateau, the maximum rain rate and the highest profile of either convective or stratiform precipitation occur in the late-night. Over the southeastern coastal regions, both the near surface rain rate and rain top of convective and stratiform precipitation peak in the late-afternoon. (orig.)
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Batinica, M; Akgül, B; Silling, S; Mauch, C; Zigrino, P
2015-07-01
Merkel cell carcinoma (MCC) is a neuroendocrine cancer of the skin postulated to originate through Merkel cell polyomavirus (MCPyV) oncogenesis and/or by mutations in molecules implicated in the regulation of cell growth and survival. Despite the fact that MCPvV is detected more broadly within the population, only a part of the infected people also develop MCC. It is thus conceivable that together, virus and for example mutations, are necessary for disease development. However, apart from a correlation between MCPyV positivity or mutations and MCC development, less is known about the association of these factors with progressive disease. To analyze MCPyV positivity, load and integration in MCC as well as presence of mutations in PDGFRα and TP53 genes and correlate these with clinical features and disease progression to identify features with prognostic value for clinical progression. This is a study on a MCC population group of 64 patients. MCPyV positivity, load and integration in parallel to mutations in the PDGFRα and TP53 were analyzed on genomic DNA from MCC specimens. In addition, expression of PDGFRα, survivin and p53 proteins was analyzed by immunodetection in tissues specimens. All these parameters were analyzed as function of patient's disease progression status. 83% of MCCs were positive for the MCPyV and among these 36% also displayed virus-T integration. Viral load ranged from 0.006 to 943 viral DNA copies/β-globin gene and was highest in patients with progressive disease. We detected more than one mutation within the PDGFRα gene and identified two new SNPs in 36% of MCC patients, whereas no mutations were found in TP53 gene. Survivin was expressed in 78% of specimens. We could not correlate either mutations in PDGFR or expression of PDGFR, p53 and surviving either to the disease progression or to the MCPyV positivity. In conclusion, our data indicate that the viral positivity when associated with high viral load, correlates with poor disease
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Sais, Giovanni; Wyler, Stephen; Hudolin, Tvrtko; Banzola, Irina; Mengus, Chantal; Bubendorf, Lukas; Wild, Peter J.; Hirsch, Hans H.; Sulser, Tullio; Spagnoli, Giulio C.
2012-01-01
The role of the polyomavirus BK (BKV) large tumor antigen (L-Tag) as a target of immune response in patients with prostate cancer (PCa) has not been investigated thus far. In this study, we comparatively analyzed humoral and cellular L-Tag-specific responsiveness in age-matched patients bearing PCa or benign prostatic hyperplasia, expressing or not expressing BKV L-Tag-specific sequences in their tissue specimens, and in non-age-matched healthy individuals. Furthermore, results from patients with PCa were correlated to 5-year follow-up clinical data focusing on evidence of biochemical recurrence (BR) after surgery (prostate specific antigen level of ≥0.2 ng/ml). In peripheral blood mononuclear cells (PBMC) from patients with PCa with evidence of BR and BKV L-Tag-positive tumors, stimulation with peptides derived from the BKV L-Tag but not those derived from Epstein-Barr virus, influenza virus, or cytomegalovirus induced a peculiar cytokine gene expression profile, characterized by high expression of interleukin-10 (IL-10) and transforming growth factor β1 and low expression of gamma interferon genes. This pattern was confirmed by protein secretion data and correlated with high levels of anti-BKV L-Tag IgG. Furthermore, in PBMC from these PCa-bearing patients, L-Tag-derived peptides significantly expanded an IL-10-secreting CD4+ CD25+(high) CD127− FoxP3+ T cell population with an effector memory phenotype (CD103+) capable of inhibiting proliferation of autologous anti-CD3/CD28-triggered CD4+ CD25− T cells. Collectively, our findings indicate that potentially tolerogenic features of L-Tag-specific immune response are significantly associated with tumor progression in patients with BKV+ PCa. PMID:22647697
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The late administration of surfactant
African Journals Online (AJOL)
HMD and 4 as having congenital pneumonia. Overall there was a significant and sustained improvement ... 3 infants weighing> 2 400 g with congenital pneumonia responded to a single delayed dose of SRT. Late SRT is ..... pneumonia and meconium aspiration syndrome.' It does not appear that late SRT compromised the ...
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Late Onset Bipolar Disorder: Case Report
Filipa Araújo; Adriana Horta
2016-01-01
Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1%) in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life (76years old) with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad different...
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Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Nagata, Keiko; Kato, Masako; Kuwamoto, Satoshi; Murakami, Ichiro; Hayashi, Kazuhiko
2016-02-01
Merkel cell carcinoma (MCC) is a clinically aggressive neuroendocrine skin cancer; 80% of the cases are associated with the Merkel cell polyomavirus (MCPyV). We previously reported that MCPyV-negative MCCs have more irregular nuclei with abundant cytoplasm and significantly unfavorable outcomes than do MCPyV-positive MCCs. These results suggest that some cell adhesion or structural stabilization molecules are differently expressed depending on MCPyV infection status. Thus, we investigated the association of prognosis or MCPyV infection status in MCCs with cell adhesion molecule 1 (CADM1)/differentially expressed in adenocarcinoma of the lung protein 1 (DAL-1)/membrane protein, palmitoylated 3 (MPP3) tripartite complex and mal T-cell differentiation protein (MAL) expression, which play important roles in cell adhesion and oncogenesis and are related to cancer outcomes in various malignancies, to elucidate the role of these molecules. We analyzed the pathological and molecular characteristics of 26 MCPyV-positive and 15 MCPyV-negative MCCs. Univariate Cox regression analysis showed that advanced age (hazard ratio [HR], 8.249; P = .007) and high CADM1 expression (HR, 5.214; P = .012) were significantly unfavorable overall survival parameters, whereas MCPyV infection (HR, 0.043, P Merkel cells expressed DAL-1 and MAL but not CADM1. This study revealed that MCPyV-negative MCCs significantly expressed higher CADM1 and lower MAL than MCPyV-positive MCCs; these expression levels were markedly related to unfavorable outcomes. These data will give us important insights to develop novel molecular target therapies for MCCs. Copyright © 2015 Elsevier Inc. All rights reserved.
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48 CFR 852.273-70 - Late offers.
2010-10-01
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Late offers. 852.273-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 852.273-70 Late offers. As prescribed in 873.110(a), insert the following provision: Late Offers (JAN 2003) This provision replaces...
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Late Effects of Polio: An Overview
... Polio Wellness Retreats For Health Professionals The Late Effects of Polio: An Overview FRENCH | GERMAN | PORTUGUESE POLIOMYELITIS ( ... largest and most inclusive category is called Late Effects of Polio or Polio Sequelae and is defined ...
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Nephrogenic systemic fibrosis: late skin manifestations
DEFF Research Database (Denmark)
Bangsgaard, Nannie; Marckmann, Peter; Rossen, Kristian
2009-01-01
BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadolinium-containing contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists...... and nephrologists recognize the disease. OBSERVATIONS: We studied 17 patients with NSF late in the disease. All patients showed epidermal atrophy and hairlessness of the affected regions, primarily the lower legs. Affected areas were symmetrically distributed and hyperpigmented in most cases. Eleven patients showed......: This descriptive case series of patients with NSF gives a detailed clinical picture of the skin manifestations late in the disease. It demonstrates that the clinical picture in the late stage has a varied presentation and that NSF has a significant effect on the quality of life....
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International Nuclear Information System (INIS)
Gilbert, E.S.
1989-01-01
Late effects are by definition effects that occur at least one year, and in most cases decades, after the time of exposure. The late effects considered in this chapter are limited to latent cancer incidence and mortality, and benign thyroid disease. A model is provided for estimating risks of late effects resulting from the radiation exposure likely to be received in the event of a nuclear power plant accident. It is assumed that exposure to high-LET radiation would be negligible in such an accident, and thus only risks from low-LET exposure are evaluated. Separate estimates are provided for risks of leukemia, bone cancer, lung cancer, gastrointestinal cancers, thyroid cancer, skin cancer, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. Because the time of death is also important in assessing the impact of an accident, and because the quality of life after the occurrence of cancer will often be reduced, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated
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Radiobiological considerations of late effects arising from radiotherapy
International Nuclear Information System (INIS)
Kogelnik, H.D.; Kaercher, K.H.
1977-01-01
A variety of clinical and experimental data are reviewed to investigate the different factors leading to appearance of late complications. Higher individual doses per fraction are related to an increase in the incidence and severity of late effects and massive dose techniques result in catastrophic late complications. There is no apparent relation between the severity of initial skin reactions and late effects, indicating that matching of acute radiation reactions on skin or mucous membranes cannot be extrapolated to late damage in connective tissues and organs. The probability of late tissue injury increases with the volume of tissue irradiated. Several phenomena, e.g. parenchymal cell depletion, vascular injury and fibrocyte dysfunction, are likely to operate together as well as separately in the pathogenesis of late effects. The late complications of radiotherapy develop in cells with a slow proliferation, and this is consistent with the hypothesis that parenchymal cell killing may be the basis for the injury. The response of cells with a slow proliferation to a course of fractionated irradiation differs from that of rapidly proliferative cells in three biological processes: repair of potentially lethal damage, redistribution and regeneration. (author)
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Risk acceptance in multiple sclerosis patients on natalizumab treatment.
Directory of Open Access Journals (Sweden)
Carmen Tur
Full Text Available OBJECTIVE: We aimed to investigate the ability of natalizumab (NTZ-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance. METHODS: From a total of 185 patients, 114 patients on NTZ as of July 2011 carried out a comprehensive survey. We obtained disease severity perception scores, personality traits' scores, and risk-acceptance scores (RAS so that higher RAS indicated higher risk acceptance. We recorded JC virus status (JCV+/-, prior immunosuppression, NTZ treatment duration, and clinical characteristics. NTZ patients were split into subgroups (A-E, depending on their individual PML risk. Some 22 MS patients on first-line drugs (DMD acted as controls. RESULTS: No differences between treatment groups were observed in disease severity perception and personality traits. RAS were higher in NTZ than in DMD patients (p<0.01. Perception of the own disease as a more severe condition tended to predict higher RAS (p=0.07. Higher neuroticism scores predicted higher RAS in the NTZ group as a whole (p=0.04, and in high PML-risk subgroups (A-B (p=0.02. In low PML-risk subgroups (C-E, higher RAS were associated with a JCV+ status (p=0.01. Neither disability scores nor pre-treatment relapse rate predicted RAS in either group. CONCLUSIONS: Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.
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2014-01-23
The Food and Drug Administration (FDA) is classifying John Cunningham Virus (JCV) serological reagents into class II (special controls). The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.
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Late style as exile: De/colonising the life course.
Hartung, Heike
2016-12-01
In the collection of essays On Late Style, Edward Said reflects on the new idiom achieved by great artists in their work near the end of their lives as "late style." Drawing on Adorno's essay on Beethoven's late style, Said also focuses on the aesthetic aspects of lateness. Defining the late works of artists as "a form of exile," however, Said moves beyond Adorno's aesthetic conception of late style. Highlighting the artist's abandonment of communication with the established social order, who achieves a contradictory, alienated relationship with it instead, Said compares artistic lateness with the experience of the subject in exile. Drawing on the analogy provided by Said, this article argues that the relationship between "self" and "other" in the different theoretical contexts of Postcolonial Studies and Age Studies can be usefully combined in the composite concept of "late style as exile." In order to explore how the concept of lateness correlates with that of exile, this contribution turns to theoretical and autobiographical texts by Edward Said. Copyright © 2016 Elsevier Inc. All rights reserved.
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Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas.
González-Vela, María Del Carmen; Curiel-Olmo, Soraya; Derdak, Sophia; Beltran, Sergi; Santibañez, Miguel; Martínez, Nerea; Castillo-Trujillo, Alfredo; Gut, Martha; Sánchez-Pacheco, Roxana; Almaraz, Carmen; Cereceda, Laura; Llombart, Beatriz; Agraz-Doblas, Antonio; Revert-Arce, José; López Guerrero, José Antonio; Mollejo, Manuela; Marrón, Pablo Isidro; Ortiz-Romero, Pablo; Fernandez-Cuesta, Lynnette; Varela, Ignacio; Gut, Ivo; Cerroni, Lorenzo; Piris, Miguel Ángel; Vaqué, José Pedro
2017-01-01
Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55-90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Diabetes mellitus: a predictor for late radiation morbidity
International Nuclear Information System (INIS)
Herold, David M.; Hanlon, Alexandra L.; Hanks, Gerald E.
1999-01-01
Purpose: Given the high frequency of diabetes, as well as prostate cancer in the elderly population, we sought to determine whether diabetic patients treated with three-dimensional conformal external-beam radiotherapy (3DCRT) had an increased risk of late gastrointestinal (GI) or genitourinary (GU) complications. Methods and Materials: Nine-hundred forty-four prostate cancer patients were treated between April 1989 and October 1996 using 3DCRT. Median patient age was 69 years (range 48-89), median center of prostate dose was 7211 cGy (range 6211-8074) and median follow-up was 36 months (range 2-99). Patients were evaluated every 6 months with digital rectal examinations, serum PSAs and symptom questionnaires. Radiation morbidity was quantified using Radiation Therapy Oncology Group (RTOG) and modified Late Effects Normal Tissue Task Force (LENT) scales. Patients with a preexisting history of either Type I or Type II diabetes mellitus were coded as diabetics. Results: One hundred twenty-one patients had diabetes (13% of total). Rates of acute morbidity did not differ between diabetics and nondiabetics; however, diabetics experienced significantly more late grade 2 GI toxicity (28% vs. 17%, p = 0.011) and late grade 2 GU toxicity (14% vs. 6%, p 0.001). There was a trend toward increased late grade 3 and 4 GI complications in diabetics, but not for late grade 3 and 4 GU complications; however, the total number of recorded events for these categories was small. Examining the onset of late toxicity, diabetics developed GU complications earlier than nondiabetics (median: 10 months vs. 24 months, p = 0.02). Considering age, dose, rectal blocking, field size, and history of diabetes in a stepwise multivariate regression model for late grade 2 GI toxicity, dose (p 0.0001), diabetes (p = 0.0110), and rectal blocking (p = 0.0163) emerged independently predictive for complications. For late grade 2 GU toxicity, only the presence of diabetes remained independently significant
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DEFF Research Database (Denmark)
Andersen, Asger Lau; Lassen, David Dreyer; Nielsen, Lasse Holbøll Westh
are negative rather than positive; and when there is divided government. We test the hypotheses of the model using a unique data set of late budgets for US state governments, based on dates of budget approval collected from news reports and a survey of state budget o¢ cers for the period 1988...
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Early- versus Late-Onset Dysthymia
Sansone, Lori A.
2009-01-01
In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145
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Comparing Measures of Late HIV Diagnosis in Washington State
Directory of Open Access Journals (Sweden)
Laura Saganic
2012-01-01
Full Text Available As more US HIV surveillance programs routinely use late HIV diagnosis to monitor and characterize HIV testing patterns, there is an increasing need to standardize how late HIV diagnosis is measured. In this study, we compared two measures of late HIV diagnosis, one based on time between HIV and AIDS, the other based on initial CD4+ results. Using data from Washington's HIV/AIDS Reporting System, we used multivariate logistic regression to identify predictors of late HIV diagnosis. We also conducted tests for trend to determine whether the proportion of cases diagnosed late has changed over time. Both measures lead us to similar conclusions about late HIV diagnosis, suggesting that being male, older, foreign-born, or heterosexual increase the likelihood of late HIV diagnosis. Our findings reaffirm the validity of a time-based definition of late HIV diagnosis, while at the same time demonstrating the potential value of a lab-based measure.
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... Caregiving Middle-Stage Caregiving Late-Stage Caregiving Behaviors Aggression & Anger Anxiety & Agitation Depression Hallucinations Memory Loss & Confusion Repetition Sleep Issues & Sundowning Suspicion & Delusions Wandering Abuse Start Here What You Need to Know Online ...
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Late Onset Bipolar Disorder: Case Report
Directory of Open Access Journals (Sweden)
Filipa Araújo
2016-07-01
Full Text Available Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1% in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life (76years old with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad differential diagnosis and pharmacologic management when approaching new-onset manic/depressive symptoms among geriatric patients.
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The polyimage poetics in Ibsen's late plays
Directory of Open Access Journals (Sweden)
Wang Yuli
2015-02-01
Full Text Available The unique poetics of polyimage implied in Ibsen’s late plays can be excavated with aesthetic reading. The term polyimage is coined to describe Ibsen’s original design in aesthetic form and ingenious realm in aesthetic reaction in his late plays; that is, beyond an imagery realm, another imagery realm exists, which construct a deep vision of significance. In each of the excellent late plays, what Ibsen creates is one or more veiled holistic imagery realms in addition to an ordinary entire imagery realm perceived by most audiences. The “layers of imagery realm” result from Ibsen’s “double self-examinations”, including self-examination of soul and of art. It is these “double self-examinations” that make polyimage possible in his late plays and generates the attribute of “meta-art” in these works. Compared with polyphony in Dostoevsky’s novels, the polyimage in Ibsen’s late plays contains a unique modernity, which is of great significance to modern artistic creation.
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An in-house assay for BK polyomavirus quantification using the Abbott m2000 RealTime system.
Muldrew, Kenneth L; Lovett, Jennie L
2013-11-01
BK polyomavirus (BKPyV) quantification is useful for monitoring renal transplant patient response to therapy. The Abbott m2000 RealTime System employed by some clinical laboratories to perform US Food and Drug Administration-approved assays can also be used to develop in-house assays such as the one presented here. This study aimed to validate an in-house quantitative real-time PCR assay targeting the BKPyV major capsid VP1 gene for assessment of viral load using the Abbott m2000 RealTime System. BKPyV load was measured in 95 urine and plasma samples previously tested for BKPyV by one of three laboratories (46 BKPyV-positive samples consisting of 35 plasma and 11 urine samples; 49 samples negative for BKPyV consisting of 47 plasma and two urine samples). Two additional plasma specimens from the College of American Pathologists proficiency testing survey were also analysed. Precision studies were performed by diluting a high-viral-titre patient sample into BKPyV-negative pooled plasma to create high-positive (6.16 log10 copies ml(-1)) and low-positive (3.16 log10 copies ml(-1)) samples. For precision studies of inter-assay variability, a high-positive (7.0 log10 copies ml(-1)) and a low-positive (3.0 log10 copies ml(-1)) sample were measured in 20 separate runs. The assay's limit of quantification and limit of detection were 2.70 and 2.25 log10 copies ml(-1), respectively. The assay was linear from 2.70 to 9.26 log10 copies ml(-1). Of the 48 known positives, 43 were detected as positive, with three reported by the reference laboratory as values lower than the limit of detection. Two known positives at 3.27 and 3.80 log10 copies ml(-1) tested negative by the m2000 BKPyV assay. Of the 49 known negative samples, 48 were negative by the m2000 BKPyV load assay, with one sample confirmed positive by a reference laboratory. Qualitative analysis prior to discrepancy testing demonstrated a sensitivity of 89.58 % and a specificity of 97.96 %. Precision studies
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Evaluating late detection capability against diverse insider adversaries
International Nuclear Information System (INIS)
Sicherman, A.
1987-01-01
The threat of theft or diversion of special nuclear material (SNM) by insiders is a key concern for safeguards planners. Different types of employees having varying degrees of access to both SNM and safeguards systems pose a difficult challenge for theft detection. Safeguards planners rely on physical security, material control, and accountability to provide detection of a theft attempt. When detection occurs too late to prevent a theft, it is called a late detection or late alarm. Activities or events that many provide late detection usually belong to material control and accountability (MC ampersand A) activities. A model has been developed for evaluating the probability of late detection as a function of time elapsed since the theft. Late detection capability is beneficial if it is timely enough to improve the ability to determine the cause of an alarm, speed recovery of SNM, prevent an incorrect response to a threat demand, or promote assurance that no theft has occurred in the absence of an alarm. The model provides insight into the effectiveness of late detection safeguards components in place and helps to identify areas where the MC ampersand A can be most effectively improved
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DEFF Research Database (Denmark)
Ulrik, Charlotte Suppli
2017-01-01
Late-onset asthma is common, associated with poor outcome, underdiagnosed and undertreated, possibly due to the modifying effect of ageing on disease expression. Although the diagnostic work-up in elderly individuals suspected of having asthma follows the same steps as in younger individuals (case......, to objectively confirm asthma. If necessary, a trial of oral or inhaled corticosteroid might be necessary. Asthma can be diagnosed when increased airflow variability is identified in a symptomatic patient, and if the patient does not have a history of exposure, primarily smoking, known to cause chronic...... obstructive pulmonary disease, the diagnosis is asthma even if the patient does not have fully reversible airflow obstruction. Pharmacological therapy in patients with late-onset asthma follows international guidelines, including treatment with the lowest effective dose of inhaled corticosteroid to minimize...
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Late onset depression: A recent update
Directory of Open Access Journals (Sweden)
Ananya Mahapatra
2015-01-01
Full Text Available Late onset depression has recently emerged as a serious mental health issue in the geriatric population with significant public health implications. It is often challenging to diagnose and treat this entity. Various theories have been postulated to elucidate the etiology of late onset depression, but a unifying hypothesis is lacking. Although the vascular hypothesis is most researched; a complex interaction of multiple vulnerability factors is the current focus of attention. Numerous psychosocial variables have been implicated to play a significant role in predicting the onset and severity of late-life depression. Phenomenological differences have been delineated from depression occurring at a younger age, but the findings are equivocal. A better understanding of the natural trajectory of depression in the elderly is required for early diagnosis and effective treatment. This review attempts to summarize the current status of evidence regarding epidemiology, etiology, clinical features, and treatment options available for late-onset depression.
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Childhood abuse in late-life depression
Comijs, Hannie C; van Exel, Eric; van der Mast, Roos C; Paauw, Anna; Oude Voshaar, Richard; Stek, Max L
Background: Little is known about the role of childhood abuse in late-life depression. The aim of the study is therefore to study whether childhood abuse is associated with late-life depression according to its onset, and which clinical characteristics play a role in this association. Methods: Data
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Advances in the management of PML: focus on natalizumab.
Fox, Robert
2011-11-01
Progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system, occurs mainly in the setting of broad-based and selective immunosuppression. The immunomodulatory agent most often implicated in the development of PML is the monoclonal antibody natalizumab. Management of PML begins with risk stratification. Factors that predict the risk of PML are JC virus (JCV) antibody status, history of chemotherapy use, and cumulative exposure to natalizumab. The risk of natalizumab-related PML increases up to a duration of 36 months of therapy, after which the risk appears to level off. If suspicious for PML, the use of a sensitive JCV polymerase chain reaction assay permits early diagnosis. Immune reconstitution represents the mainstay of treatment for PML. With rapid reversal of immunosuppression followed by immunologic recovery, almost all patients suffer clinical deterioration termed immune reconstitution inflammatory syndrome (IRIS). High-dose corticosteroids are often recommended if a clinical and imaging syndrome resembling IRIS develops after immune restoration.
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Late presentation of HIV infection: a consensus definition
DEFF Research Database (Denmark)
Antinori, A; Coenen, T; Costagiola, D
2010-01-01
clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection. Methods Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition...... of what is meant by a 'late-presenting' patient. Results Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/muL or presenting with an AIDS-defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease...... able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infection....
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Late washing filter cleaning cycle demonstration
International Nuclear Information System (INIS)
Meyer, M.L.; McCabe, D.J.
1992-01-01
The DWPF Late Washing Facility will filter cesium and potassium tetraphenyl borate (TPB) solids using a Mott sintered metal filter, identical to the filter now used in the In-tank Precipitation Facility. The purpose of the late wash step is primarily to remove the nitrite salts from the slurry prior to delivery to DWPF. Periodic chemical cleaning of the filter will be required, presumably after each batch although the actual required frequency could not be determined on the lab-scale. Minimization of chemical cleaning solution volumes is key to maximizing the attainment of the Late Wash facility. This report summarizes work completed in experiments designed to identify minimum cleaning solution requirements
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Comparative Earth history and Late Permian mass extinction
Knoll, A. H.; Bambach, R. K.; Canfield, D. E.; Grotzinger, J. P.
1996-01-01
The repeated association during the late Neoproterozoic Era of large carbon-isotopic excursions, continental glaciation, and stratigraphically anomalous carbonate precipitation provides a framework for interpreting the reprise of these conditions on the Late Permian Earth. A paleoceanographic model that was developed to explain these stratigraphically linked phenomena suggests that the overturn of anoxic deep oceans during the Late Permian introduced high concentrations of carbon dioxide into surficial environments. The predicted physiological and climatic consequences for marine and terrestrial organisms are in good accord with the observed timing and selectivity of Late Permian mass extinction.
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Leroux-Kozal, Valérie; Lévêque, Nicolas; Brodard, Véronique; Lesage, Candice; Dudez, Oriane; Makeieff, Marc; Kanagaratnam, Lukshe; Diebold, Marie-Danièle
2015-03-01
Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.
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International Nuclear Information System (INIS)
Bessell, M.S.
1991-01-01
Far-red spectra and VRIJHK photometry have been obtained for a sample of late-M dwarfs selected on the basis of large reduced red magnitudes from the LHS Catalog. Half of the stars in the three faintest 1 mag bins are late-M stars, the other red stars are metallic-hydride subdwarfs. Relations between various colors for the late-M dwarfs are investigated. Of all the colors I - K most reliably correlates with spectral type. FeH bands near 9900 A are clearly seen in the spectra of all dwarf stars later than M5. Two stars cooler than VB10, and similar in temperature to LHS2924 have been identified; both have H-alpha in emission and appear variable in magnitude and R - I color; one is a flare star. The other stars are of earlier spectral type and resemble W359 and VB8. The observed MI, I - K main sequence is in good agreement with the IG theoretical main sequence of Stringfellow, and the faintest stars could be about 0.09 solar mass red dwarfs or lower mass brown dwarfs. 65 refs
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Merkel cell carcinoma in an immunosuppressed patient.
Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da
2017-01-01
Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.
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Quantification of late complications after radiation therapy
International Nuclear Information System (INIS)
Jung, Horst; Beck-Bornholdt, Hans-Peter; Svoboda, Vladimir; Alberti, Winfried; Herrmann, Thomas
2001-01-01
Background: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15x2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p a =10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time
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Late post-operative hypoxaemia and organ dysfunction
DEFF Research Database (Denmark)
Kehlet, H; Rosenberg, J
1995-01-01
an adverse effect of tissue hypoxia on wound healing and on resistance to bacterial wound infections. Finally, mental confusion and surgical delirium may be related to inadequate arterial oxygenation during the late post-operative period. Late post-operative constant and episodic hypoxaemia may therefore......Constant and episodic hypoxaemia are common after major operations in the late post-operative period in the surgical ward. Recent studies have shown that hypoxaemia may be related to the development of myocardial ischaemia and cardiac arrhythmias. Experimental and clinical studies have demonstrated...
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Recent casualties of late globalization
DEFF Research Database (Denmark)
Turcan, Romeo V.
2016-01-01
In this essay I will expand my thoughts on universities as ‘late globalizers’ and the impact ‘being late’ has on university internationalization or globalization activities. In my earlier essay I viewed universities as ‘late globalizers’ and briefly introduced the impact of being ‘late’, e.g., wi.......g., withdrawal or de-internationalization of universities due to incompatibility between university autonomy and the context in the target country or universities unwillingness to compromise on their freedom and autonomy....
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Pathological review of late cerebral radionecrosis
International Nuclear Information System (INIS)
Yoshii, Yoshihiko
2008-01-01
Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and glial fibrillary acidic protein (GFAP)-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions. (author)
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Energy Technology Data Exchange (ETDEWEB)
Gupta, Tushar; Robles, Maria Teresa Sáenz [Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Schowalter, Rachel M.; Buck, Christopher B. [Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4263 (United States); Pipas, James M., E-mail: pipas@pitt.edu [Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States)
2016-01-15
Polyomaviruses induce cell proliferation and transformation through different oncoproteins encoded within the early region (ER): large T antigen (LT), small T antigen (sT) and, in some cases, additional components. Each virus utilizes different mechanisms to achieve transformation. For instance, the LTs of Simian virus 40 (SV40), BK and/or JC virus can induce transformation; but Merkel Cell Polyomavirus (MCPyV) requires expression of sT. Lymphotropic Papovavirus (LPV) is closely related to Human Polyomavirus 9 (HuPyV9) and, under similar conditions, mice expressing LPV.ER exhibit higher rates of tumor formation than mice expressing SV40.ER. We have investigated the contributions of individual LPV.ER components to cell transformation. In contrast to SV40, LPV.ER transforms mouse embryonic fibroblasts (MEFs), but expression of LPV LT is insufficient to transform MEFs. Furthermore, LPV sT induces immortalization and transformation of MEFs. Thus, in the case of LPV, sT is the main mediator of oncogenesis. - Highlights: • Characterization of early region products from the Lymphotropic Polyomavirus (LPV). • On its own, sT immortalizes and transforms mouse primary cells, and is able to block p53 activation. • Combined LT and sT expression induces a greater rate of proliferation than either LT or sT alone.
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Savage, W
1990-09-01
In the UK in 1988, 13.3% of abortions were performed at 13 weeks' gestation or later. Reasons for this delay, in addition to the diagnosis through amniocentesis of a fetal abnormality, include late recognition of pregnancy, a change of mind about completing the pregnancy, a failure of primary care physicians to entertain the diagnosis of pregnancy, travel or financial problems, and referral difficulties and scheduling delays. Women with little education and very young women are most likely to present for late abortions. From 13-16 weeks, dilatation and evacuation is the safest method of pregnancy termination. The procedure can be made easier through preparation of the cervix with a prostaglandin pessary or Foley catheter. After 16 weeks, an instillation method is recommended; prostaglandin administration can be intro- or extra-amniotic. Complication rates at 13-19 weeks are 14.5/1000 for vaginal methods of abortion and 7.2/1000 for prostaglandin methods. The risk of complications is 3 times higher for women who have 2nd-trimester abortions through the National Health Service. Although it is not realistic to expect that late abortions ever can be eliminated, improved sex education and contraceptive reliability as well as reforms in the National Health Service could reduce the number substantially. To reduce delay, it is suggested that the National Health Service set up satellite day care units and 1-2 central units in each region to deal quickly with midtrimester abortions. Delays would be further reduced by legislation to allow abortion on request in at least the 1st trimester of pregnancy.
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Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria
2016-01-01
Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients.
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[Cause of late death in liver transplant recipients].
Coelho, Júlio Cézar Uili; Parolin, Mônica B; Matias, Jorge Eduardo Fouto; Jorge, Fernando Marcus Felipe; Canan Júnior, Lady Wilson
2003-01-01
The objective is to present the causes of late death in patients subjected to liver transplantation. A total of 209 patients were subjected to 223 liver transplantations (14 retransplantations). The computerized study protocol sheets were evaluated to determine the causes of late death (> 6 months after transplantation). Of the 209 patients, 30 had late death. Ductopenic rejection (chronic rejection) was the most common cause and it was observed in 10 patients. Time after transplantation at the moment of death of this group of patients varied from 11 to 57 months, with an average of 29 months. Seven patients died at the hospital admission of hepatic retransplantation. Other causes of late death were sepsis, lymphoproliferative disease, chronic renal insufficiency, and hepatic insufficiency. The most common cause of late death after liver transplantation is ductopenic rejection, followed by complications of retransplantation and sepsis. Death owing to ductopenic rejection may occur even many years after transplantation.
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Requests for late termination of pregnancy: Tower Hamlets, 1983.
Savage, W
1985-01-01
The case histories of all women seeking late (more than 20 weeks' gestation) abortion in the NHS district of Tower Hamlets in 1983 were assessed. Of 12 women requesting late abortion, seven underwent termination of pregnancy. All the women had severe social or psychological problems, or both. The main reasons for late presentation were denial of pregnancy, youth, and mental disorder. In a small group of atypical women late abortion seems to be justified for reasons other than fetal abnormality.
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Are we ready to predict late effects?
DEFF Research Database (Denmark)
Salz, Talya; Baxi, Shrujal S; Raghunathan, Nirupa
2015-01-01
BACKGROUND: After completing treatment for cancer, survivors may experience late effects: consequences of treatment that persist or arise after a latent period. PURPOSE: To identify and describe all models that predict the risk of late effects and could be used in clinical practice. DATA SOURCES:...
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Radiation therapy and late reactions in normal tissues
International Nuclear Information System (INIS)
Aoyama, Takashi; Kuroda, Yasumasa
1998-01-01
Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)
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Neurocognitive outcome in young adults born late-preterm.
Heinonen, Kati; Lahti, Jari; Sammallahti, Sara; Wolke, Dieter; Lano, Aulikki; Andersson, Sture; Pesonen, Anu-Katriina; Eriksson, Johan G; Kajantie, Eero; Raikkonen, Katri
2018-03-01
This study examined whether late-preterm birth (34+0 to 36+6wks+d gestational age) was associated with neurocognitive deficit in young adulthood, and whether small for gestational age (SGA) birth amplified any adversity. Participants derived from the prospective regional cohort study, the Arvo Ylppö Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD 8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, intelligence, executive functioning, attention, and memory, and reported their education. Those born late-preterm scored -3.71 (95% confidence interval [CI] -6.71 to -0.72) and -3.11 (95% CI -6.01 to -0.22) points lower on Full-scale and Verbal IQ than peers born at term. Compared with those born at term and appropriate for gestational age (≥-2 to increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and SGA seems to increase this risk. Late-preterm birth did not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and being small for gestational age did increase this risk. © 2017 Mac Keith Press.
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DEFF Research Database (Denmark)
Andersen, Bjørn Schiermer
2014-01-01
The article deals with the cultural significance of a new figure in late-modern Western culture: the hipster. The current hipster culture, so I argue, can be used as a magnifying glass that makes impending changes to our conception of culture and of cultural development visible. It ushers...
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Paradoxical physiological transitions from aging to late life in Drosophila.
Shahrestani, Parvin; Quach, Julie; Mueller, Laurence D; Rose, Michael R
2012-02-01
In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used ∼57,600 Drosophila melanogaster from six replicate populations to examine the physiological transitions from aging to late life in four functional characters that decline during aging: desiccation resistance, starvation resistance, time spent in motion, and negative geotaxis. Time spent in motion and desiccation resistance declined less quickly in late life compared to their patterns of decline during aging. Negative geotaxis declined at a faster rate in late life compared to its rate of decline during aging. These results yield two key findings: (1) Late-life physiology is distinct from the physiology of aging, in that there is not simply a continuation of the physiological trends which characterize aging; and (2) late life physiology is complex, in that physiological characters vary with respect to their stabilization, deceleration, or acceleration in the transition from aging to late life. These findings imply that a correct understanding of adulthood requires identifying and appropriately characterizing physiology during properly delimited late-life periods as well as aging periods.
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Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C
2018-03-01
Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.
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Late-onset CMV disease following CMV prophylaxis.
LENUS (Irish Health Repository)
Donnelly, C
2012-02-01
BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection after solid-organ transplantation, increasing morbidity and mortality. Three months of oral valganciclovir have been shown to provide effective prophylaxis. Late-onset CMV disease, occurring after the discontinuation of prophylaxis, is now increasingly recognised. AIMS: To investigate the incidence and the time of detection of CMV infections in liver transplant recipients who received CMV prophylaxis. METHODS: Retrospective review of 64 high- and moderate-risk patients with 1 year of follow-up. RESULTS: The incidence of CMV infection was 12.5%, with 4.7% disease. All cases of symptomatic CMV disease were of late-onset. CONCLUSIONS: The incidence of CMV infections in this study was low compared with literature reports; however, the late-onset disease is an emerging problem. Detection of late-onset disease may be delayed because of less frequent clinic follow-up visits. Increased regular laboratory monitoring may allow earlier detection at the asymptomatic infection stage.
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Progression of Late-Onset Stargardt Disease
Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M.; Mauschitz, Matthias M.; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I.; Weber, Bernhard H. F.; Holz, Frank G.; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B.
2016-01-01
Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. Methods: We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype...
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Observations of the late superhump in VW Hydri
International Nuclear Information System (INIS)
Van Der Woerd, H.; Van Der Klis, M.; Van Paradijs, J.; Beuermann, K.; Motch, C.
1988-01-01
This paper presents the results of simultaneous optical and near-IR photometry, optical fast spectroscopy, and Exosat X-ray observations of the dwarf nova VW Hyi, obtained simultaneously during three consecutive orbital cycles, approximately two days after the 1983 November superoutburst terminated. The optical data show clear evidence for a late superhump, which is shifted + 0.7 in phase relative to the orbital modulation. An attempt is made to derive from the observed spectral distribution the contribution of the late superhump. The orbital hump and the late superhump apparently are not related to each other. This important effect excludes all models, in which the late superhump phenomenon is interpreted in terms of variations in the bright-spot brightness. 43 references
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Late effects of thoracic irradiation in children
Energy Technology Data Exchange (ETDEWEB)
Boelling, T.; Koenemann, S.; Ernst, I.; Willich, N. [Dept. of Radiotherapy, Univ. Hospital of Muenster (Germany)
2008-06-15
Purpose: to summarize the literature regarding the late effects of radiotherapy to the thorax in childhood and adolescence with special emphasis on cardiac and pulmonary impairment. Material und methods: the literature was critically reviewed using the PubMed {sup registered} database with the key words 'late effects', 'late sequelae', 'child', 'childhood', 'adolescence', 'radiation', 'radiotherapy', 'thorax', 'lung', 'heart', and 'pulmonary'. Results: 17 publications dealing with radiation-induced pulmonary and cardiac late sequelae in children could be identified and were analyzed in detail. 29 further publications with additional information were also included in the analysis. Pulmonary function impairment after mediastinal irradiation arose in one third of all pediatric patients, even when treatment was performed with normofractionated lower doses (15-25 Gy). Whole lung irradiation was regularly followed by pulmonary function impairment with differing rates in several reports. However, clinically symptomatic function impairment like dyspnea was less frequent. Irradiation of up to 25 Gy (single doses {<=} 2 Gy) to the heart showed little or no cardiac toxicity in analyses of irradiated children (median follow-up 1.3-14.3 years). Doses of > 25 Gy (single doses {<=} 2-3.3 Gy) led to several cardiac dysfunctions. However, new data from adults with longer follow-up may indicate threshold doses as low as 1 Gy. Impairment of skeletal growth, breast hypoplasia, and secondary malignancy were further potential late sequelae. Conclusion: several retrospective reports described radiation-associated late sequelae in children. However, there is still a lack of sufficient data regarding the characterization of dose-volume effects. (orig.)
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International Nuclear Information System (INIS)
Worthy, T.H.; Roscoe, D.
2003-01-01
A rich terrestrial vertebrate fauna from the pitfall trap deposit of Takaka Fossil Cave on Takaka Hill, South Island, New Zealand, is described. Radiocarbon ages on moa bones bracket the onset of sedimentation in the site to between 12361 and 11354 14 C yrs BP. Euryapteryx geranoides was in the Late Glacial moa fauna that predates the onset of sedi-mentation in the site, but was absent in younger faunas. The moa Anomalopteryx didiformis was present in the Late Glacial fauna as well throughout the Holocene. A total of 1633 bones from 25 species of birds and a further 895 bones of 154 individuals of vertebrates other than birds (two species of frog, one tuatara, three lizards, two bats, and a rat) were identified in the total recovered fauna. A well-preserved partial skeleton of Haast's eagle (Harpagornis moorei) of Late Glacial age had severe arthritis. Unusually small specimens of Euryapteryx were morphologically diagnosed as E. geranoides, and confirmed as such by mitochondrial DNA analysis. The molluscan fauna contained two aquatic, troglobitic hydrobiids and 29 taxa of land snails. While there is little change in species diversity between lower and upper layers, there are marked changes in relative abundance of some taxa that suggest the environment was drier in the Early and Middle Holocene than it was in the Late Holocene. (author). 26 refs., 3 figs., 4 tabs
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Climate predictors of late quaternary extinctions
DEFF Research Database (Denmark)
Nogués-Bravo, David; Ohlemüller, Ralf; Batra, Persaram
2010-01-01
Between 50,000 and 3,000 years before present (BP) 65% of mammal genera weighing over 44 kg went extinct, together with a lower proportion of small mammals. Why species went extinct in such large numbers is hotly debated. One of the arguments proposes that climate changes underlie Late Quaternary...... extinctions, but global quantitative evidence for this hypothesis is still lacking. We test the potential role of global climate change on the extinction of mammals during the Late Quaternary. Our results suggest that continents with the highest climate footprint values, in other words, with climate changes...... of greater magnitudes during the Late Quaternary, witnessed more extinctions than continents with lower climate footprint values, with the exception of South America. Our results are consistent across species with different body masses, reinforcing the view that past climate changes contributed to global...
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Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.
Safari, Fereshteh; Shekarforoosh, Shahnaz; Hashemi, Tahmineh; Namvar Aghdash, Simin; Fekri, Asefeh; Safari, Fatemeh
2017-07-01
The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.
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2D CFT partition functions at late times
Dyer, Ethan; Gur-Ari, Guy
2017-08-01
We consider the late time behavior of the analytically continued partition function Z( β + it) Z( β - it) in holographic 2 d CFTs. This is a probe of information loss in such theories and in their holographic duals. We show that each Virasoro character decays in time, and so information is not restored at the level of individual characters. We identify a universal decaying contribution at late times, and conjecture that it describes the behavior of generic chaotic 2 d CFTs out to times that are exponentially large in the central charge. It was recently suggested that at sufficiently late times one expects a crossover to random matrix behavior. We estimate an upper bound on the crossover time, which suggests that the decay is followed by a parametrically long period of late time growth. Finally, we discuss gravitationally-motivated integrable theories and show how information is restored at late times by a series of characters. This hints at a possible bulk mechanism, where information is restored by an infinite sum over non-perturbative saddles.
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Late effects of radiation therapy on the gastrointestinal tract
International Nuclear Information System (INIS)
Coia, Lawrence R.; Myerson, Robert J.; Tepper, Joel E.
1995-01-01
Late gastrointestinal complications of radiation therapy have been recognized but not extensively studied. In this paper, the late effects of radiation on three gastrointestinal sites, the esophagus, the stomach, and the bowel, are described. Esophageal dysmotility and benign stricture following esophageal irradiation are predominantly a result of damage to the esophageal wall, although mucosal ulcerations also may persist following high-dose radiation. The major late morbidity following gastric irradiation is gastric ulceration caused by mucosal destruction. Late radiation injury to the bowel, which may result in bleeding, frequency, fistula formation, and, particularly in small bowel, obstruction, is caused by damage to the entire thickness of the bowel wall, and predisposing factors have been identified. For each site a description of the pathogenesis, clinical findings, and present management is offered. Simple and reproducible endpoint scales for late toxicity measurement were developed and are presented for each of the three gastrointestinal organs. Factors important in analyzing late complications and future considerations in evaluation and management of radiation-related gastrointestinal injury are discussed
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Late Pleistocene dune activity in the central Great Plains, USA
Mason, J.A.; Swinehart, J.B.; Hanson, P.R.; Loope, D.B.; Goble, R.J.; Miao, X.; Schmeisser, R.L.
2011-01-01
Stabilized dunes of the central Great Plains, especially the megabarchans and large barchanoid ridges of the Nebraska Sand Hills, provide dramatic evidence of late Quaternary environmental change. Episodic Holocene dune activity in this region is now well-documented, but Late Pleistocene dune mobility has remained poorly documented, despite early interpretations of the Sand Hills dunes as Pleistocene relicts. New optically stimulated luminescence (OSL) ages from drill cores and outcrops provide evidence of Late Pleistocene dune activity at sites distributed across the central Great Plains. In addition, Late Pleistocene eolian sands deposited at 20-25 ka are interbedded with loess south of the Sand Hills. Several of the large dunes sampled in the Sand Hills clearly contain a substantial core of Late Pleistocene sand; thus, they had developed by the Late Pleistocene and were fully mobile at that time, although substantial sand deposition and extensive longitudinal dune construction occurred during the Holocene. Many of the Late Pleistocene OSL ages fall between 17 and 14 ka, but it is likely that these ages represent only the later part of a longer period of dune construction and migration. At several sites, significant Late Pleistocene or Holocene large-dune migration also probably occurred after the time represented by the Pleistocene OSL ages. Sedimentary structures in Late Pleistocene eolian sand and the forms of large dunes potentially constructed in the Late Pleistocene both indicate sand transport dominated by northerly to westerly winds, consistent with Late Pleistocene loess transport directions. Numerical modeling of the climate of the Last Glacial Maximum has often yielded mean monthly surface winds southwest of the Laurentide Ice Sheet that are consistent with this geologic evidence, despite strengthened anticyclonic circulation over the ice sheet. Mobility of large dunes during the Late Pleistocene on the central Great Plains may have been the result of
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Late injury of cancer therapy on the female reproductive tract
International Nuclear Information System (INIS)
Grigsby, Perry W.; Russell, Anthony; Bruner, Deborah; Eifel, Patricia; Koh, Wui-Jin; Spanos, William; Stetz, Joann; Stitt, Judith Anne; Sullivan, Jessie
1995-01-01
The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptoms, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapy should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed
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The late Cainozoic East Antarctic ice sheet
International Nuclear Information System (INIS)
Colhoun, E.A.
1999-01-01
A review, mainly of East Antarctic late Cainozoic (post 40 Ma) geological and geomorphological evidence, supports the hypothesis of the continuous presence of an ice sheet, of about the present size, since the late Miocene. Evidence is presented and the view advanced that, during the late Wisconsin maximum of isotope stage 2, ice was not nearly as thick or extensive over the continental shelf as required by the model of 'maximum' Antarctic glaciation. Some of the factors influencing the contribution of Antarctica to post-glacial sea-level rise are discussed. It is considered that Antarctica's contribution was probably considerably less than previously estimated. The dating of marine and freshwater sequences in the Vestfold and Bunger Hills is consistent with deglaciation around the Pleistocene Holocene boundary, after the Late Wisconsin maximum. A date of ∼25 ka BP from permafrost in the Larsemann Hills means that either the Larsemann Hills were not glaciated during the Late Wisconsin or the ice failed to erode much of the permafrost surface. The degree of weathering of rock and glacial drifts in the Vestfold, Larsemann and Bunger Hills suggests a long time for formation, perhaps considerably longer than indicated by the dated marine and freshwater sediment sequences. Cosmogenic isotope dating in the Vestfold Hills has provided equivocal ages for deglaciation. While the results could indicate deglaciation before 80 ka BP, they do not confirm such early deglaciation. If the ice cover was thin and failed to remove the previous rock exposure profile, then the assays could predate the last ice advance. Weathered iron crust fragments in the till suggest little erosion. The raised beaches of the oases are Holocene. Assuming they have been produced by post Late Wisconsin isostatic uplift and by the Holocene transgression, calculations show that the Antarctic continental ice sheet could not have been more than ∼500 m thicker in the inner shelf-coastal zone. The
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Late radiation effects in animals surviving lethal irradiation
International Nuclear Information System (INIS)
Dimitrov, L.A.
1974-01-01
Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival
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Assche, Van, Lies; Morrens, Manuel; Luyten, Patrick; Ven, Van de, Luc; Vandenbulcke, Mathieu
2017-01-01
Abstract: OBJECTIVE: The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. METHOD: A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. RESULTS: Although mildly progressive co...
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Response in the late phase to a radiological emergency
International Nuclear Information System (INIS)
Morrey, M.; Nisbet, A.; Thome, D.; Savkin, M.; Hoe, S.; Brynildsen, L.
2004-01-01
This paper looks at the key issues that need to be addressed during the transition from the emergency phase to the late phase of a radioactive release, and the development of the initial late phase strategy. It discusses the extent to which current national plans and international advice address the needs of decision makers following contamination of inhabited areas and food production systems. Based on this the following recommendations are made: (1) the issues that will arise at the start of the late phase response to a radioactive release require preparation work in advance of any release; (2) this preparation should consider the adequacy of legislation, technical data and modelling, options for waste storage and disposal, resources for monitoring and implementing clean up; (3) late phase preparedness requires regular exercising and (4) the possibility of terrorist releases adds further emphasis to the need for preparedness for the late phase. (authors)
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Paradox of Prescribing Late Chemotherapy: Oncologists Explain.
Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J
2016-12-01
The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.
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Horstmann, Cay S
2012-01-01
Big Java: Late Objects is a comprehensive introduction to Java and computer programming, which focuses on the principles of programming, software engineering, and effective learning. It is designed for a two-semester first course in programming for computer science students.
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Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease
Directory of Open Access Journals (Sweden)
Raquel Burger-Calderon
2015-07-01
Full Text Available Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV has conclusively been linked to human cancer, all members of the polyomavirus (PyV family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD. HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.
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Late Embryogenesis Abundant Proteins
Shih, M.D.; Hoekstra, F.A.; Hsing, Y.I.C.
2008-01-01
During the late maturation stage of seed development, water content decreases greatly. One of the most striking characteristics of mature orthodox seeds is their ability to withstand severe desiccation. Mechanisms of plant drought/desiccation tolerance have been studied by numerous groups, and a
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Late Globalization and Evolution and Metamorphoses of Industries
DEFF Research Database (Denmark)
Boujarzadeh, Behnam; Turcan, Romeo V.; Dholakia, Nikhilesh
2016-01-01
In this paper we explore the effect of late globalization on evolution of industries. Specifically we investigate the impact of late globalization on the evolution and metamorphoses of Danish Textile and Fashion Industry (DTFI). Using historical data, we survey the development of DTFI between 1945...
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Late baryogenesis faces primordial nucleosynthesis
International Nuclear Information System (INIS)
Delbourgo-Salvador, P.; Audouze, J.; Salati, P.
1991-11-01
Since the sphalleron mechanism present in the standard theory of electro-weak interactions violates B+L, models have been suggested where baryogenesis takes place at late epochs and is concomitant with primordial nucleosynthesis. The possibility for the baryon asymmetry to be generated was numerically investigated at the same time as the light elements are cooked. The primordial yields of D, 3 He, 4 He and 7 Li were shown to exceed the upper limits inferred from observation, unless baryogenesis is anterior to the freeze-out of the weak interactions. This implies strong constraints on scenarios where the baryon asymmetry originates from the late decay of massive gravitinos. (author) 18 refs., 6 figs
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Late somatic sequelae after treatment of childhood cancer in Slovenia
Directory of Open Access Journals (Sweden)
Erman Nuša
2012-05-01
Full Text Available Abstract Background This is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic. Methods The data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model. Results The incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis. Conclusions The change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment
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Jones, Rosemary E.; Kirstein, Linda A.; Kasemann, Simone A.; Litvak, Vanesa D.; Poma, Stella; Alonso, Ricardo N.; Hinton, Richard; EIMF
2016-10-01
The tectonic and geodynamic setting of the southern Central Andean convergent margin changed significantly between the Late Cretaceous and the Late Miocene, influencing magmatic activity and its geochemical composition. Here we investigate how these changes, which include changing slab-dip angle and convergence angles and rates, have influenced the contamination of the arc magmas with crustal material. Whole rock geochemical data for a suite of Late Cretaceous to Late Miocene arc rocks from the Pampean flat-slab segment (29-31 °S) of the southern Central Andes is presented alongside petrographic observations and high resolution age dating. In-situ U-Pb dating of magmatic zircon, combined with Ar-Ar dating of plagioclase, has led to an improved regional stratigraphy and provides an accurate temporal constraint for the geochemical data. A generally higher content of incompatible trace elements (e.g. Nb/Zr ratios from 0.019 to 0.083 and Nb/Yb from 1.5 to 16.4) is observed between the Late Cretaceous ( 72 Ma), when the southern Central Andean margin is suggested to have been in extension, and the Miocene when the thickness of the continental crust increased and the angle of the subducting Nazca plate shallowed. Trace and rare earth element compositions obtained for the Late Cretaceous to Late Eocene arc magmatic rocks from the Principal Cordillera of Chile, combined with a lack of zircon inheritance, suggest limited assimilation of the overlying continental crust by arc magmas derived from the mantle wedge. A general increase in incompatible, fluid-mobile/immobile (e.g., Ba/Nb) and fluid-immobile/immobile (e.g., Nb/Zr) trace element ratios is attributed to the influence of the subducting slab on the melt source region and/or the influx of asthenospheric mantle. The Late Oligocene ( 26 Ma) to Early Miocene ( 17 Ma), and Late Miocene ( 6 Ma) arc magmatic rocks present in the Frontal Cordillera show evidence for the bulk assimilation of the Permian-Triassic (P
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Late complications after radiotherapy for prostate cancer
Energy Technology Data Exchange (ETDEWEB)
Jung, H. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; University Hospital Hamburg-Eppendorf (Germany). Lab. of Radiobiology and Experimental Radiooncology; Beck-Bornholdt, H.P. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; Svoboda, V. [University Hospital Hamburg-Eppendorf (Germany). Inst. of Biophysics and Radiobiology; Portsmouth Oncology Centre, Saint Mary' s Hospital (United Kingdom). Dept. of Radiotherapy; Alberti, W. [University Hospital Hamburg-Eppendorf (Germany). Dept. of Radiotherapy and Radiooncology; Herrmann, T. [Technical Univ. Dresden (Germany). Dept. of Radiotherapy and Radiooncology
2012-11-15
Background: The aim of the present study was to analyze in detail the time course of the incidence of radiation-induced late effects. For this purpose, unpublished data of patients treated by radiation therapy in Hamburg in the late 1980s were analyzed. Relatively large volumes were exposed to comparatively high doses, thus leading to a high rate of treatment-related side effects. Patients and methods: A total of 180 consecutive patients received radiotherapy for prostate cancer. The median age was 66 years (range 41-88 years). The median of the maximum dose was 77.5 Gy (range 56.3-95 Gy) and overall treatment time was 51 days (range 28-128 days). Endpoints analyzed were late complications of grade 3 or higher, overall and disease-free survival, local tumor control, and distant metastases. Data analysis was actuarial and the log-rank test was used to compare the various subgroups. Results After 2 years, 80.5 {+-} 3.2% of the patients were without any complications of grade 3 or higher, and after 5 years a constant level of 70.3 {+-} 4.0% was approached. When multiple lesions occurred per patient, the later events were disregarded. A total of 66 complications occurred in 42 patients. The percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by an exponential function and a constant fraction. Complications approached a constant level of 70.3% at a rate of 5.3% per month. This means that patients who will develop a complication do so at exponential kinetics and at a relatively high rate, whereas about 70% of the patients will never experience a late effect even over long observation periods. After subdividing the maximum dose into three equal dose groups of 55 patients each (< 73.3 Gy, 73.3-80 Gy, > 80 Gy), the constant fraction decreased from 85.7 to 72.8% and 52.2%, whereas the incidence rate was 4.3%, 7.7%, and 5.6% per month and, thus, almost independent of radiation dose
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Late Career Decision-Making: A Qualitative Panel Study
Wilmar Schaufeli; Annet de Lange; Juhani Ilmarinen; Per Erik Solem; Trude Furunes; Reidar Mykletun; Astri Syse
2015-01-01
The aim of this longitudinal qualitative interview study (3 waves of interviews) was to examine the nature of older workers’ late career decision-making processes, including the main drivers and obstacles for prolonging working life or retiring. Late career decision-making is regarded as a process
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Mobile ICT Acceptance in Late Adopter Countries
DEFF Research Database (Denmark)
Gimpel, Gregory; Sudzina, Frantisek; Petrovcikova, Katarina
2014-01-01
Despite the rapid global diffusion of the smartphone, some countries have experienced much slower uptake of the technology. The low smartphone penetration within Slovakia provides the opportunity to explore what drives smartphone use in late majority countries. Slovakia is a central European nation...... and part of the Eurozone. It has advanced telecommunications infrastructure and is subject to the same telecommunications regulations as other EU members. While neighbours have high smartphone penetration, Slovakia is a late majority adopter. This study uses Triandis’ theory of interpersonal behavior...... to investigate the question: What drives the use of smartphones in late majority countries? By studying the differences between current and potential smartphone users, the study revisits Karahanna et al.’s research question: Do potential adopters and users of IT hold the same behavioral and normative beliefs...
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Late presentation of developmental dysplasia of the hip.
LENUS (Irish Health Repository)
Gul, R
2012-02-03
BACKGROUND: A neonatal screening programme for developmental dysplasia of the hip (DDH) is ongoing in Cork. Despite early screening, infants continue to present at later ages with DDH. The impact of late diagnosis is significant. Established DDH causes significant morbidity and may have major medicolegal implications. AIM: To identify the reasons for the late presentation of DDH in the presence of a screening programme. METHODS: In a retrospective study all cases of late DDH presenting from 1988 to 2000 were identified using inpatient database. RESULTS: Forty-nine cases of DDH were diagnosed. The mean age of diagnosis was 14.8 months (range 6-47). Multiple risk factors were identified in four patients only. More than one risk factor was identified in 10 patients. CONCLUSION: Despite screening, children continue to present with late DDH. In this study, only 14 patients had multiple risk factors and only four patients had more than two risk factors, highlighting the low incidence of suspicion in this patient group.
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Directory of Open Access Journals (Sweden)
DIETER UHL
2012-07-01
Full Text Available For the first time fossil macroscopic remains of charcoal as direct evidence of palaeo-wildfires from the Late Permian Gröden Formation of the Bletterbach-Butterloch area in Northern Italy is described. The charcoal consists of pycnoxylic wood and originates from gymnosperms, but a more specific affiliation is not possible due to the fragmentary nature of the material. On a global scale our knowledge about Late Permian fire-ecology is still rather scarce and this finding helps to fill one of the numerous geographical gaps in our current knowledge about Late Permian wildfires.
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Late effecten van kankerbehandeling
Langeveld, Nelia E.
2004-01-01
In dit artikel wordt ingegaan op de lange termijn effecten van kanker op de kinderleeftijd. Vervolgens wordt een kort overzicht gegeven van de belangrijkste late gevolgen die kunnen optreden na een oncologische behandeling met radio- en/of chemotherapie toegepast in de kinderleeftijd. Er wordt kort
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Henry, Tom F. K.; Joannides, Paul; González Mozo, Ana; Martín, Bruno
2012-01-01
Exhibition catalogue (co-authored with P. Joannides) in English, Spanish and French by the Museo del Prado and the Musée du Louvre, 2012. English edition, publisher: Museo Nacional del Prado (ISBN 978-84-8480-237-2). 382 pages, of which 300 were co-authored with P. Joannides. This publication was the catalogue of the major exhibtion of Raphael's late work which was at the Prado and the Louvre in 2012-13. The exhibition was seen by more than 650,000 visitors, and was widely reviewed in the int...
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Steele, John M.
The last five centuries BC saw the development of several new forms of astrology in Babylonia. Key to these new astrological techniques was the invention of the zodiac in about 400 BC. These new forms of astrology include personal horoscopes, astral medicine, and the exploitation of geometrical relationships between the position of heavenly bodies. Several Late Babylonian astrological doctrines were later adopted within Greek astrology.
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Late-modern transformation of Islam or Islamic transformation of Late-modern Religiosity?
DEFF Research Database (Denmark)
Riexinger, Martin Thomas
2017-01-01
The Turkish author Muhammed Bozdağ, who has no formal religious education, has been popular since the late 1990s because of his self-help seminars and self-help books. Though they are based on the adaptation of Western New Age-inspired models, Bozdağ uses many of the models’ parascientific concepts...
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Anatomy of the late radiation encephalopathy
Energy Technology Data Exchange (ETDEWEB)
De Reuck, J; vander Eecken, H
1975-01-01
The clinico-pathological data and the topography of the lesions were determined in 13 cases of late radiation encephalopathy. In one case the arterial vascularisation was studied by the translucidation technique after filling of the blood vessels with a colloidal barium sulphate solution. The radiation lesions consisted of areas of focal necrosis and of diffuse demyelination and necrosis of the deep cerebral structures and the brain stem. Demyelination was predominantly present in cases of late appearance of the neurological symptoms while necrosis was found in cases with a short latency period. The cerebral cortex and the arcuate fibres were always the most preserved structures. The topography of the focal lesions in the cerebral hemispheres and in the brain stem corresponded well to the vascular supply areas of the deep perforating arteries, while the diffuse lesions always had a predominant distribution in the periventricular arterial end- and border-zones. These observations were also confirmed by a post mortem angiographic study. The present report argues once more for a vascular aetiology as cause of the late radiation encephalopathy.
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PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)
Energy Technology Data Exchange (ETDEWEB)
Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Zhu, Jiang [Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Ozaki, Toshinori [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuohku, Chiba 260-8717 (Japan); Bu, Youquan, E-mail: buyqcn@aliyun.com [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China)
2015-03-13
Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited
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PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)
International Nuclear Information System (INIS)
Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei; Zhu, Jiang; Ozaki, Toshinori; Bu, Youquan
2015-01-01
Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited
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LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS
Directory of Open Access Journals (Sweden)
E.S. Stolyarevich
2014-01-01
Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection.
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Inflammatory markers of radiation-induced late effects
International Nuclear Information System (INIS)
Dubner, D.; Gallegos, C.; Michelin, S.; Portas, M.
2011-01-01
Up to now there is no established parameters for the follow-up of delayed radiation injuries. Late toxicity is generally irreversible and can have devastating effects on quality of life of people exposed either accidentally or during therapeutic radiation treatments. Histologically, late manifestations of radiation damage include fibrosis, necrosis, atrophy and vascular lesions. Although many etiologies have been suggested regarding these late toxicities, persistent inflammation has been described as playing a key role. The recruitment of leukocytes from circulating blood is decisive in the inflammatory reaction. All the steps in the recruitment cascade are orchestrated by cell-adhesion molecules (CAMs) on both leukocytes and endothelial cells, and different subsets of CAMs are responsible for different steps in extravasation. A link between radiation –induced inflammatory processes and alterations in T-cell immunity are still demonstrable in the blood of A-bomb survivors. The following study was conducted to examine the response of the immune system in the inflammatory reactions in patients with late skin injuries after radiotherapy or interventional fluoroscopy procedures. The expression of adhesion molecules ICAM1 and β1-integrin on granulocytes and lymphocytes, as well as changes in subpopulations of T lymphocytes and the level of C-reactive protein, a well- studied inflammatory marker were evaluated. (authors)
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Late Jute seed production in cropland agroforestry system
Directory of Open Access Journals (Sweden)
Kazi Noor-E-Alam Jewel
2015-12-01
Full Text Available Farmers were not self-sufficient in jute seed production and cultivation to avoid use exotic jute seed from different resources. Though the conventional method of jute seed production was not enough to meet the demand of farmers because of shrinkage of jute seed production land. So, late jute seed production technique was applied in agroforestry systems at both established and newly developed orchards. The study was conducted in the selected three sites of Rangpur, Dinajpur and Faridpur. Both White (Corchorus capsularis L.cv. CVL-1 and Tossa (two popular cultivars, eg., Corchorus olitorius L. cv. O-9897, and cv. O-72 varieties were used for to evaluate the late jute seed production in cropland agroforestry in 2011- 2013. It was observed that 600 kg ha-1 to 725 kg ha-1 of jute seed was produced in different types of orchard plantation. Seeds from Litchi orchard showed the higher fiber yield (1051.11, 2511.11 and 3555.56 kg ha-1 at Rangpur, Dinajpur and Faridpur, respectively than the mango orchard. Nutrient contents of soil in three sits were improved significantly due to the cultivation of late jute seed production. Moreover, late jute seed production in early stages of orchard plantation was more profitable and late jute can be produced economically for five to seven years depending on the plantations type and age.
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Feng, Zhuo
2017-09-11
Land plants are one of the major constituents of terrestrial ecosystems on Earth, and play an irreplaceable role in human activities today. If we are to understand the extant plants, it is imperative that we have some understanding of the fossil plants from the deep geological past, particularly those that occurred during their early evolutionary history, in the late Palaeozoic. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Zajac Paul
2006-11-01
Full Text Available Abstract Human polyomavirus BK (BKV has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag to products of tumor-suppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. Peptides selected from either p53-binding region (LTag351–450 and LTag533–626 by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture. We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag579–587; LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations. These data indicate that widespread cellular immune responses against epitopes within BKV LTag-p53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection.
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A case of late-onset oligomeganephronia
Directory of Open Access Journals (Sweden)
Rafael José Vargas Alves
2012-12-01
Full Text Available A 33-year old caucasian man was investigated for pain in the right flank, proteinuria, hemathuria and an elevated serum creatinine level. He also presented an abnormal ultrasonography, which revealed asymmetric kidneys. Through renal biopsy, the diagnosis of oligomeganephronia (OMN was confirmed. OMN is a very rare form of renal hypoplasia, and late-onset in adulthood is even rarer. In the pediatric population, OMN leads to end-stage-renal-failure(ESRF in a few years. This is the sixth case related in the literature of a late-onset OMN who have not yet developed ESRF.
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Update on Merkel Cell Carcinoma.
Harms, Paul W
2017-09-01
Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.
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Late-time cosmological phase transitions
International Nuclear Information System (INIS)
Schramm, D.N.
1990-11-01
It is shown that the potential galaxy formation and large-scale structure problems of objects existing at high redshifts (Z approx-gt 5), structures existing on scales of 100M pc as well as velocity flows on such scales, and minimal microwave anisotropies (ΔT/T) approx-lt 10 -5 can be solved if the seeds needed to generate structure form in a vacuum phase transition after decoupling. It is argued that the basic physics of such a phase transition is no more exotic than that utilized in the more traditional GUT scale phase transitions, and that, just as in the GUT case, significant random gaussian fluctuations and/or topological defects can form. Scale lengths of ∼100M pc for large-scale structure as well as ∼1 M pc for galaxy formation occur naturally. Possible support for new physics that might be associated with such a late-time transition comes from the preliminary results of the SAGE solar neutrino experiment, implying neutrino flavor mixing with values similar to those required for a late-time transition. It is also noted that a see-saw model for the neutrino masses might also imply a tau neutrino mass that is an ideal hot dark matter candidate. However, in general either hot or cold dark matter can be consistent with a late-time transition. 47 refs., 2 figs
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Psychiatry: life events and social support in late life depression
Directory of Open Access Journals (Sweden)
Clóvis Alexandrino-Silva
2011-01-01
Full Text Available OBJECTIVES: To examine the association of life events and social support in the broadly defined category of depression in late life. INTRODUCTION: Negative life events and lack of social support are associated with depression in the elderly. Currently, there are limited studies examining the association between life events, social support and late-life depression in Brazil. METHODS: We estimated the frequency of late-life depression within a household community sample of 367 subjects aged 60 years or greater with associated factors. ''Old age symptomatic depression'' was defined using the Composite International Diagnostic Interview 1.1 tool. This diagnostic category included only late-life symptoms and consisted of the diagnoses of depression and dysthymia as well as a subsyndromal definition of depression, termed ''late subthreshold depression''. Social support and life events were assessed using the Comprehensive Assessment and Referral Evaluation (SHORT-CARE inventory. RESULTS: ''Old age symptomatic depression'' occurred in 18.8% of the patients in the tested sample. In univariate analyses, this condition was associated with female gender, lifetime anxiety disorder and living alone. In multivariate models, ''old age symptomatic depression'' was associated with a perceived lack of social support in men and life events in women. DISCUSSION: Social support and life events were determined to be associated with late-life depression, but it is important to keep in mind the differences between genders. Also, further exploration of the role of lifetime anxiety disorder in late-life depression may be of future importance. CONCLUSIONS: We believe that this study helps to provide insight into the role of psychosocial factors in late-life depression.
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Multiple determinants controlling activation of yeast replication origins late in S phase.
Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L
1996-07-01
Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.
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International Nuclear Information System (INIS)
Hardoff, R.; Shefer, A.; Gips, S.; Merdler, A.; Flugelman, M.Y.; Halon, D.A.; Lewis, B.S.
1990-01-01
To examine whether late coronary restenosis may be predicted by abnormalities of myocardial perfusion in the early hours after successful percutaneous transluminal coronary angioplasty and to study in greater detail the mechanisms involved in the development of late coronary restenosis after angioplasty, a prospective study was undertaken in 90 consecutive patients. Thallium-201 scintigrams were recorded at rest and during the stress of atrial pacing, 12 to 24 h after angioplasty, and the results were related to the findings at angiography in 70 patients undergoing late cardiac catheterization. A reversible thallium-201 perfusion defect was found in 39 (38%) of 104 myocardial regions supplied by the dilated coronary vessel and identified a subset of patients at high risk of late (6 to 12 months) angiographic restenosis (sensitivity 77%, specificity 67%). In contrast, late coronary restenosis developed in only 7 (11%) of 65 vessels and in 5 (14%) of 37 patients with a nonischemic thallium-201 scintigram on day 1 (p less than 0.005). Multivariate logistic regression analysis of 14 possible preangioplasty and periangioplasty clinical and angiographic variables selected reversible perfusion defect on the thallium-201 scintigram on day 1 (p = 0.016) and immediate postangioplasty residual coronary narrowing (p = 0.004) as significant independent predictors of late restenosis, with younger patient age as an additional less powerful predictor (p less than 0.05). The findings have important implications regarding the pathogenesis of late coronary restenosis in patients undergoing successful angioplasty and they imply that in the majority of these patients pathophysiologic events in the early minutes and hours after angioplasty may determine the development of late restenosis
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Reproductive rights: Current issues of late abortion
Directory of Open Access Journals (Sweden)
Mujović-Zornić Hajrija
2009-01-01
Full Text Available This article considers the legal issues surrounding induced late abortion in cases when severe medical, therapeutic or ethical reasons have not been in dispute. Generally discussing the essential question about abortion today, it means not anymore legality of abortion but, in the first place, safety of abortion. From the aspect of woman health the most important aim is to detect and avoid possible risks of medical intervention, such as late abortion present. This is the matter of medical law context and also the matter of the woman's reproductive rights, here observed through legislation and court practice. The gynecologist has an obligation to obtain the informed consent of each patient. Information's should be presented in reasonably understandable terms and include alternative modes of treatment, objectives, risks, benefits, possible complications, and anticipated results of such treatment. Pregnant woman should receive supportive counseling before and particularly after the procedure. The method chosen for all terminations should ensure that the fetus is born dead. This should be undertaken by an appropriately trained practitioner. Reform in abortion law, making it legally accessible to woman, is not necessarily the product of a belief in woman's rights, but can be a means of bringing the practice of abortion back under better control. Counseling and good medical practice in performing late abortion are the instruments to drive this point even further home. It does not undermine the woman who wants to make a positive decision about her life and its purpose is not to produce feelings of insecurity and guilt. It concludes that existing law should not be changed but that clear rules should be devised and board created to review late term abortion. In Serbia, this leads to creation and set up guidelines for reconciling medical justification for late abortion with existing law, especially with solutions which brings comparative law. .
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Heterogeneity of late-life depression : relationship with cognitive functioning
Korten, Nicole C M; Penninx, Brenda W J H; Kok, Rob M; Stek, Max L; Oude Voshaar, Richard C; Deeg, Dorly J H; Comijs, Hannie C
BACKGROUND: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. METHODS: Cross-sectional data of
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Heterogeneity of late-life depression : relationship with cognitive functioning
Korten, Nicole C. M.; Penninx, Brenda W. J. H.; Kok, Rob M.; Stek, Max L.; Oude Voshaar, Richard; Deeg, Dorly J. H.; Comijs, Hannie C.
Background: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. Methods: Cross-sectional data of
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Diabetes mellitus is associated with late-onset post-stroke depression.
Zhang, Yu; He, Ji-Rong; Liang, Huai-Bin; Lu, Wen-Jing; Yang, Guo-Yuan; Liu, Jian-Rong; Zeng, Li-Li
2017-10-15
To explore the associated factors of late-onset post-stroke depression (PSD). A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD. Copyright © 2017 Elsevier B.V. All rights reserved.
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Late prematurity: a systematic review
Directory of Open Access Journals (Sweden)
Luís Carlos Machado, Júnior
2014-05-01
Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed. Resumo: Objetivo: revisar a literatura sobre prematuridade tardia (nascimentos de 34 semanas a 36 semanas e seis dias em seus vários aspectos. Fonte dos dados: buscas nas bases MEDLINE, LILACS e Biblioteca Cochrane, sem limite de tempo, e nas referências bibliográficas dos artigos encontrados. Síntese dos dados: muitos estudos mostram aumento na taxa de prematuridade tardia nos últimos anos. Em todas as séries, os prematuros tardios correspondem à maioria dos nascimentos prematuros. Estudos envolvendo análises de milhões de
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Late adverse reactions to intravascular iodinated contrast media
International Nuclear Information System (INIS)
Webb, Judith A.W.; Stacul, Fulvio; Thomsen, Henrik S.; Morcos, Sameh K.
2003-01-01
Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after non-ionic dimers. The majority of late skin reactions after contrast medium exposure are probably T-cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interleukin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions. (orig.)
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LATE DEVONIAN-CARBONIFEROUS CONODONTS FROM EASTERN IRAN
Directory of Open Access Journals (Sweden)
MEHDI YAZDI
1999-07-01
Full Text Available Conodont data from acid-leaching 110 samples from two Late Devonian-Carboniferous areas in the Shotori Range (Tabas region of eastern Iran are presented. At Howz-e-Dorah, a section (88 samples commencing high in the Bahram Formation (Givetian-early Frasnian extended through the Shishtu Formation (Frasnian, Early hassi Zone or older, to latest Tournaisian, anchoralis-latus Zone and the Sardar Formation (earliest Visean, texanus Zone, to late Namurian, sinuatus-corrugatus-sulcatus Zone and into the Jamal Formation (Permian. Four less exhaustively sampled sections (22 samples show the Kale Sardar area to be tectonically more complicated than the Howz-e-Dorah area. Useful marker horizons in the Howz-e-Dorah section, well constrained by conodont data, are: the early Frasnian (no older than Early hassi Zone biostromal beds of the Shishtu Formation, an early Famennian (Late triangularis to Early crepida interval of oolitic limestone, a cyclothem sequence straddling the Early Carboniferous-Late Carboniferous boundary, and an Early Permian interval of siliceous sand ("the white quartzite" of previous authors. Additionally, several iron-rich horizons, readily traceable from locality to locality, are well constrained by conodont ages. Eighty-five conodont species/subspecies are documented representing 24 genera.. Two new species, Polygnathus capollocki and Polygnathus ratebi and one new subspecies, Icriodus alternatus mawsonae are described.
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Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.
Directory of Open Access Journals (Sweden)
Komla Sobo
Full Text Available BACKGROUND: Pathological accumulation of cholesterol in late endosomes is observed in lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects of cholesterol accumulation in NPC cells, or as phenocopied by the drug U18666A, on late endosomes membrane organization and dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cholesterol accumulation did not lead to an increase in the raft to non-raft membrane ratio as anticipated. Strikingly, we observed a 2-3 fold increase in the size of the compartment. Most importantly, properties and dynamics of late endosomal intralumenal vesicles were altered as revealed by reduced late endosomal vacuolation induced by the mutant pore-forming toxin ASSP, reduced intoxication by the anthrax lethal toxin and inhibition of infection by the Vesicular Stomatitis Virus. CONCLUSIONS/SIGNIFICANCE: These results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.
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Vaginal bleeding in late pregnancy
... this page: //medlineplus.gov/ency/patientinstructions/000627.htm Vaginal bleeding in late pregnancy To use the sharing ... JavaScript. One out of 10 women will have vaginal bleeding during their 3rd trimester. At times, it ...
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Late Cretaceous vicariance in Gondwanan amphibians.
Directory of Open Access Journals (Sweden)
Ines Van Bocxlaer
Full Text Available Overseas dispersals are often invoked when Southern Hemisphere terrestrial and freshwater organism phylogenies do not fit the sequence or timing of Gondwana fragmentation. We used dispersal-vicariance analyses and molecular timetrees to show that two species-rich frog groups, Microhylidae and Natatanura, display congruent patterns of spatial and temporal diversification among Gondwanan plates in the Late Cretaceous, long after the presumed major tectonic break-up events. Because amphibians are notoriously salt-intolerant, these analogies are best explained by simultaneous vicariance, rather than by oceanic dispersal. Hence our results imply Late Cretaceous connections between most adjacent Gondwanan landmasses, an essential concept for biogeographic and palaeomap reconstructions.
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Late-onset ADHD in adults: milder, but still dysfunctional.
Karam, Rafael G; Bau, Claiton H D; Salgado, Carlos A I; Kalil, Katiane L S; Victor, Marcelo M; Sousa, Nyvia O; Vitola, Eduardo S; Picon, Felipe A; Zeni, Gregory D; Rohde, Luis A; Belmonte-de-Abreu, Paulo; Grevet, Eugenio H
2009-04-01
The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients. The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models. Late-onset subjects were diagnosed later (P=0.04), had a lower frequency of problems with authority and discipline (P=0.004), and lower scores in SNAP-IV (Pactivities (P=0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P=0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics. This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.
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Increased number of applications for late termination of pregnancy in Denmark
DEFF Research Database (Denmark)
Theibel, Sara Sofie; Petersson, Birgit H; Christensen, Anne Vinggaard
2014-01-01
INTRODUCTION: Last year, it was 40 years since the introduction of legal abortion until the 12th week of gestation and the possibility of late termination of pregnancy in Denmark. The aim of this study was to describe the development in applications for late termination of pregnancy in the 1986......%. CONCLUSION: Significant changes in the women's age and the reasons they provide when applying for late termination of pregnancy have been observed from 1986 to 2011. Further investigation of this subject will contribute to securing the best possible conditions for women going through late termination...
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Ermolov, P. V.; Degtyarev, K. E.; Salnikova, E. B.; Tretyakov, A. A.; Kotov, A. B.; Anisimova, I. V.; Plotkina, Yu. V.
2018-02-01
U-Pb dating of the Torangalyk Complex (Northern Balkhash) yielded a Late Carboniferous age of 305 ± 2 Ma. Taking into account the previous data, a new scheme for Late Paleozoic granitic magmatism in this region has been proposed. It includes the Early Carboniferous granite-granodiorite Balkhash Complex, Late Carboniferous monzonite-granosyenite Kokdombak and Torangalyk complexes, and the Late Carboniferous-Early Permian granite-leucogranite Akchatau Complex.
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Late Cretaceous neosuchian crocodiles from the Sultanate of Oman
Buscalioni, Angela D.; Schulp, Anne S.; Jagt, John W M; Hanna, Samir S.; Hartman, Axel Frans
Two apparently new crocodilian taxa from the Late Cretaceous (Late Campanian-Maastrichtian) Al-Khod Conglomerate of the Sultanate of Oman are described. The fragmentary state of preservation precludes formal naming, yet enables comparisons to be made with other taxa. One is a short-snouted
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Directory of Open Access Journals (Sweden)
Sílvia Bofill-Mas
2013-01-01
Full Text Available Many different viruses are excreted by humans and animals and are frequently detected in fecal contaminated waters causing public health concerns. Classical bacterial indicator such as E. coli and enterococci could fail to predict the risk for waterborne pathogens such as viruses. Moreover, the presence and levels of bacterial indicators do not always correlate with the presence and concentration of viruses, especially when these indicators are present in low concentrations. Our research group has proposed new viral indicators and methodologies for determining the presence of fecal pollution in environmental samples as well as for tracing the origin of this fecal contamination (microbial source tracking. In this paper, we examine to what extent have these indicators been applied by the scientific community. Recently, quantitative assays for quantification of poultry and ovine viruses have also been described. Overall, quantification by qPCR of human adenoviruses and human polyomavirus JC, porcine adenoviruses, bovine polyomaviruses, chicken/turkey parvoviruses, and ovine polyomaviruses is suggested as a toolbox for the identification of human, porcine, bovine, poultry, and ovine fecal pollution in environmental samples.
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LATE NEUROSYPHILIS: TRENDS AND CHALLENGES.
Directory of Open Access Journals (Sweden)
Ivan Dimitrov
2015-09-01
Full Text Available Background: Syphilis is not only a disease of historical importance. It has been recognized that nowadays, in the era of AIDS, it still remains a serious challenge. For the last two decades there has been a resumption of neurosyphilis cases. This has revived the interest in the diagnostic and therapeutic challenges that the disease presents to clinical practice and to healthcare systems. Material/Methods: We present the overall picture of newly registered cases of syphilis in Varna municipality between 2009 and 2013, and report a case of neurosyphilis diagnosed at the first clinic of neurological diseases of St. Marina University Hospital during this period. Results: For the 5-year period, newly registered cases of syphilis in Varna have shown a tendency towards a decrease. Patients were typically in the early stages of the disease, primary and secondary. Late manifestations dropped from 29 in 2009 to 0 in 2010, but increased again to 15 in 2013. Only 1 case of neurosyphilis was registered during the 5-year period, in 2013. Conclusions: Neurological syndromes observed in cases of late neurosyphilis, presenting in different clinical forms, require a broad spectrum of differential diagnoses. Attention in everyday clinical practice should be focused on these cases which, though rare, are of high medical and social importance. Clinical cases of late neurosyphilis are often atypical and the early consideration of serologic tests or even biopsy may be of critical importance.
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Late radiation injury to muscle and peripheral nerves
International Nuclear Information System (INIS)
Gillette, E. L.; Mahler, P. A.; Powers, B. E.; Gillette, S. M.; Vujaskovic, Z.
1995-01-01
Late radiation injury to muscles and peripheral nerves is infrequently observed. However, the success of radiation oncology has led to longer patient survival, providing a greater opportunity for late effects to develop, increase in severity and, possibly, impact the quality of life of the patient. In addition, when radiation therapy is combined with surgery and/or chemotherapy, the risk of late complications is likely to increase. It is clear that the incidence of complications involving muscles and nerves increases with time following radiation. The influence of volume has yet to be determined; however, an increased volume is likely to increase the risk of injury to muscles and nerves. Experimental and clinical studies have indicated that the (α(β)) ratio for muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating the great influence of fractionation on response of these tissues. This is of concern for intraoperative radiation therapy, and for high dose rate brachytherapy. This review of clinical and experimental data discusses the response of muscle and nerves late after radiation therapy. A grading system has been proposed and endpoints suggested
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Late radiation effects in animals surviving lethal irradiation
Energy Technology Data Exchange (ETDEWEB)
Dimitrov, L A
1974-01-01
Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.
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Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kato, Masako; Nagata, Keiko; Murakami, Ichiro; Hayashi, Kazuhiko
2015-08-01
Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
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Toward late career transitioning: a proposal for academic surgeons.
Richards, Robin; McLeod, Robin; Latter, David; Keshavjee, Shaf; Rotstein, Ori; Fehlings, Michael G; Ahmed, Najma; Nathens, Avery; Rutka, James
2017-09-01
In the absence of a defined retirement age, academic surgeons need to develop plans for transition as they approach the end of their academic surgical careers. The development of a plan for late career transition represents an opportunity for departments of surgery across Canada to initiate a constructive process in cooperation with the key stakeholders in the hospital or institution. The goal of the process is to develop an individual plan for each faculty member that is agreeable to the academic surgeon; informs the surgical leadership; and allows the late career surgeon, the hospital, the division and the department to make plans for the future. In this commentary, the literature on the science of aging is reviewed as it pertains to surgeons, and guidelines for late career transition planning are shared. It is hoped that these guidelines will be of some value to academic programs and surgeons across the country as late career transition models are developed and adopted.
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Late nonstochastic changes in pig skin after β irradiation
International Nuclear Information System (INIS)
Peel, D.M.; Hopewell, J.W.; Wells, J.; Charles, M.W.
1985-01-01
Late radiation-induced changes in pig skin have been assessed following irradiation with β-rays from a 22.5- or 15-mm-diameter 90 Sr/ 90 Y source and a 19- or 9-mm-diameter 170 Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness of 40-50% of the control value, occurred at a dose of approx. 40 Gy from the 22.5-mm source and approx. 75 Gy from the 15-mm source. In the case of 170 Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approx. 70 Gy, when the dermis was approx. 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin
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Lee, Jung Yeon; Brook, Judith S; Pahl, Kerstin; Brook, David W
2017-11-01
A quarter of people living with human immunodeficiency virus (HIV) infection in the United States are women. Furthermore, African American and Hispanic/Latina women continue to be disproportionately affected by HIV, compared with women of other races/ethnicities. Cannabis use prior to intercourse may be associated with increased risky sexual behaviors which are highly related to HIV. The ultimate goal of this research is to better understand the relationships between unconventional personal attributes (e.g., risk-taking behaviors) in the late 20s, substance use (e.g., alcohol) in the mid 30s, and cannabis use prior to intercourse in the late 30s using a community sample; such an understanding may inform interventions. This study employing data from the Harlem Longitudinal Development Study includes 343 female participants (50% African Americans, 50% Puerto Ricans). Structural equation modeling indicated that unconventional personal attributes in the late 20s were associated with substance use in the mid 30s (β=0.32, pcannabis use prior to sexual intercourse in the late 30s (β=0.64, pcannabis use prior to sexual intercourse in the late 30s (β=0.39, pprevention are that these precursors may be useful as patient screening tools. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Quantified Effects of Late Pregnancy and Lactation on the Osmotic ...
African Journals Online (AJOL)
Quantified Effects of Late Pregnancy and Lactation on the Osmotic Stability of ... in the composition of erythrocyte membranes associated with the physiologic states. Keywords: Erythrocyteosmotic stability, osmotic fragility, late pregnancy, ...
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Hypothyroidism in late-onset Pompe disease.
Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle; Whitley, Chester B; Jarnes Utz, Jeanine
2016-09-01
In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.
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Early- versus Late-Onset Systemic Sclerosis
Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard
2014-01-01
Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463
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Association between simian virus 40 and non-Hodgkin lymphoma
Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.
2002-01-01
BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.
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Working with Students Who Are Late-Deafened. PEPNet Tipsheet
Clark, Mary
2010-01-01
Late-deafness means deafness that happened postlingually, any time after the development of speech and language in a person who has identified with hearing society through schooling, social connections, etc. Students who are late-deafened cannot understand speech without visual aids such as speechreading, sign language, and captioning (although…
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Kant, Rik Henricus Nicolaas van der
2013-01-01
Late endosomal transport is disrupted in several diseases such as Niemann-Pick type C, ARC syndrome and Alzheimer’s disease. This thesis describes the regulation of late endosomal dynamics by cholesterol and multi-protein complexes. We find that cholesterol acts as a cellular tomtom that steers the
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Consequential late radiation damage in the skin in nasopharyngeal carcinoma
International Nuclear Information System (INIS)
Li Wei; Kong Ling; Zhang Youwang; Hu Chaosu; Wu Yongru
2008-01-01
Objective: To evaluate the relationship between early and late radiation damage in skin. Methods: 335 patients with nasopharyngeal carcinoma treated with radical radiotherapy were evaluated. 240 patients had lymph nodes in the neck at initial diagnosis. The median doses were 70 Gy (55-86 Gy) to the nasopharyngeal region by external beam radiotherapy. The median doses were 64 Gy (46-72 Gy) to the neck with lymph node metastases, 55 Gy (21-67 Gy) to the node-negative neck. 71 patients were treated with facial-neck fields, while 264 patients were treated with pre-auricular fields. Chemotherapy was given in 48 patients. According to the 1995 SOMA scales late radiation damage in the skin was evaluated. Results: The median time from the radiotherapy to follow up was 14 years (range, 5-38 years). 63 patients have grade 0 late radiation reactions in the neck skin, the grade 1,2, 3,4 late radiation reactions in the neck skin were 43.9% (147 patients), 20.9% (70 patients), 13.7% (46 patients) and 2.7% (9 patients), respectively. 44 patients had moist desquamation in the medical records. The grade 1,2,3,4 late radiation reactions in the neck skin were 41%, 23%, 30% and 5%, respectively in patients with moist desquamation, while in patients without moist desquamation, the corresponding rates were 44.3%, 20.6%, 11.3% and 2.4%, respectively. The difference were significant between these two groups by chi-square analysis(χ 2 =17.42, P=0.002). Furthermore, whether patients had positive lymph node in the neck or not, the size of facial-neck fields and higher doses to the neck had more severe late radiation reaction in the neck skin, while age, gender and chemotherapy failed to show any effects on the development of late radiation reactions in the neck skin. Conclusion: The severe early radiation damage in the skin possibly increases the late radiation damage in the neck skin. (authors)
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Late Emerging Reading Difficulties in English Language Learners
Garcia, Nicole Marie
2015-01-01
Research has identified a group of students who do not begin to exhibit reading difficulties until fourth or fifth grade, suggesting late-emerging reading difficulties. Considering that these students do not show signs of reading difficulties in early grades, attempting to identify these students early becomes problematic. Additionally, little is known regarding the characteristics of late-emerging reading deficits within English language learner (ELL) populations. The purpose of this study w...
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Development of Probabilistic Rigid Pavement Design Methodologies for Military Airfields.
1983-12-01
equations. This was accomplished by the use of the Statistical Package for the Social Sciences (SPSS). A multiple regression analysis was performed on...a 3 )CALL t’ 06... spo1i li $use outu NE S( NCw C 1jC.V) 03prml O’ a ftC, ------- 00 IS THE OPTiON SEI 00o DETERMINAN EVALUS ION is I ,Kt OPION K. to
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Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E.; Wehbe, Firas; Cesar, Carina; Cortés, Claudia; Padgett, Denis; Koenig, Serena; Gotuzzo, Eduardo; Cahn, Pedro; McGowan, Catherine; Masys, Daniel; Sierra-Madero, Juan
2011-01-01
Background Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. Methodology Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4+ count ≤200cells/mm3 prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. Principal Findings Among subjects starting HAART (n = 9817) who had baseline CD4+ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. Conclusion LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation
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Radiation dose and late failures in prostate cancer
International Nuclear Information System (INIS)
Morgan, Peter B.; Hanlon, Alexandra L.; Horwitz, Eric M.; Buyyounouski, Mark K.; Uzzo, Robert G.; Pollack, Alan
2007-01-01
Purpose: To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone. Methods: The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months. Results: Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at ≤4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in ≤4 years. Radiation dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74-Gy group. In patients receiving ≥74 Gy, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree. Conclusion: The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both
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Otitis Media and Speech/Language Development in Late-Talkers.
Paul, Rhea; And Others
This study examines otitis media as a possible factor associated with increased risk for communicative handicap in a group of children with a possible vulnerability for language delay: "late-talkers." Speech and language outcomes at ages 3 and 4 were examined in 28 late talkers and 24 children with normal language development. Late…
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Nitric acid flowsheet with late wash PHA testing
International Nuclear Information System (INIS)
Zamecnik, J.R.
1993-01-01
This Task Technical Plan outlines the activities to be conducted in the Integrated DWPF Melter System (IDMS) in ongoing support of the Defense Waste Processing Facility (DWPF) Chemical Process Cell (CPC) utilizing the Nitric Acid Flowsheet in the Sludge Receipt and Adjustment Tank (SRAT) and Precipitate Hydrolysis Aqueous (PHA) produced by the Late Wash Flowsheet. The IDMS facility is to be operated over a series of runs (2 to 4) using the Nitric Acid Flowsheet. The PHA will be produced with the Late Wash Flowsheet in the Precipitate Hydrolysis Experimental Facility (PHEF). All operating conditions shall simulate the expected DWPF operating conditions as closely as possible. The task objectives are to perform at least two IDMS runs with as many operating conditions as possible at nominal DWPF conditions. The major purposes of these runs are twofold: verify that the combined Late Wash and Nitric Acid flowsheets produce glass of acceptable quality without additional changes to process equipment, and determine the reproducibility of data from run to run. These runs at nominal conditions will be compared to previous runs made with PHA produced from the Late Wash flowsheet and with the Nitric Acid flowsheet in the SRAT (Purex 4 and Purex 5)
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Parental and Late Adolescent Psychopathology: Mothers May Provide Support When Needed Most
McKinney, Cliff; Milone, Mary Catherine
2012-01-01
Research links negative parenting and parental psychopathology to poorer outcomes among youth. Less research examines these effects simultaneously during late adolescence. The current study examines parenting, parental psychopathology, and late adolescent psychopathology as reported by late adolescents (N = 328) with the use of structural equation…
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Comparison between late-presenting and isolated neonatal congenital diaphragmatic hernias
Directory of Open Access Journals (Sweden)
Christos Plataras
2011-01-01
Full Text Available Purpose: Late-presenting posterolateral congenital diaphragmatic hernias (CDH are anatomically similar to isolated neonatal CDH but are diagnosed and treated after the first month of life. We aim to characterise the clinical manifestations and short-term postoperative course of this entity and compare it with isolated CDH of the neonatal period. Materials and Methods: In the 30-year period from 1980 to 2010, 116 children with CDH were treated at the Aghia Sophia Children′s Hospital, Athens, Greece. Twenty-three (19% of these children were late-presenting cases, being diagnosed between the ages of 1 month and 4 years. Ninety-three were neonatal cases, of whom 22 (24% were excluded due to severe associated anomalies, leaving 71 cases of isolated neonatal CDH. We compared these two groups of patients with regard to preoperative symptoms, postoperative hospital stay, time to complete feeding, overall complication rate, and reoperation rate. Results: Isolated neonatal cases presented more often with acute respiratory symptoms (n=25; P= 0.016 and failure to thrive (n= 38; P= 0.03. Late-presenting cases presented more often with chronic respiratory symptoms (n=14;P= 0.0044 or gastrointestinal symptoms (n=12; P= 0.006. Thirty-five cases with minor or serious complications were reported in the neonatal group, whereas only five complications were observed in the late-presenting group (P= 0.028. We did not record any recurrences or reoperations in the late-presenting group, but we had two recurrences and three reoperations in the neonatal group. Time to full feeds and postoperative hospital stay was shorter in the late-presenting group. Conclusions: Our data demonstrate differences between the two groups in preoperative symptoms and short-term postoperative complications and short-term outcome. Late-presenting cases of CDH had a greater number of chronic symptoms preoperatively, more favorable postoperative outcomes, and less recurrences and reoperations.
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Hadronic decay of late-decaying particles and big-bang nucleosynthesis
Energy Technology Data Exchange (ETDEWEB)
Kawasaki, Masahiro [Research Center for the Early Universe, Graduate School of Science, University of Tokyo, Tokyo 113-0033 (Japan)]. E-mail: masahiro_kawasaki@mac.com; Kohri, Kazunori [Department of Earth and Space Science, Osaka University, Osaka 560-0043 (Japan); Moroi, Takeo [Department of Physics, Tohoku University, Sendai 980-8578 (Japan)
2005-10-06
We study the big-bang nucleosynthesis (BBN) scenario with late-decaying exotic particles with lifetime longer than {approx}1 s. With a late-decaying particle in the early universe, predictions of the standard BBN scenario can be significantly altered. Therefore, we derive constraints on its primordial abundance. We pay particular attention to hadronic decay modes of such particles. We see that the non-thermal production process of D, {sup 3}He and {sup 6}Li provides a stringent upper bound on the primordial abundance of late-decaying particles with hadronic branching ratio.
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Early and Late Retirement Exits
Brougham, Ruby R.; Walsh, David A.
2009-01-01
The current study proposes that personal need fulfillment (relatedness, generativity, identity, growth, and finances) predicts early and late retirement intentions. The personal needs of 160 full-time older employees were measured by personal goals, job satisfactions, job characteristics, and intrinsic motivation. Results suggest that the personal…
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Does Late-onset Anorexia Nervosa Exist? Findings From a Comparative Study in Singapore.
Tan, Shian Ming; Kwok, Kah Foo Victor; Zainal, Kelly A; Lee, Huei Yen
2018-03-01
The incidence of cases of older onset anorexia nervosa (AN) has increased in recent years. However, the literature on late-onset AN has been inconclusive. The goal of this study was to compare late-onset with early-onset cases of AN. Cases of AN presenting to an eating disorders treatment service were identified and the associated medical records were studied retrospectively. Of the 577 cases of AN that were studied, 7.1% were late-onset. Unlike the early-onset cases of AN, the late-onset cases reported less teasing and more relationship problems as a trigger for the illness. They were also less likely to join the eating disorders treatment program. Otherwise, the late-onset AN cases were largely similar to the early-onset cases. Although differences exist between early-onset and late-onset cases of AN, these are few. Until stronger evidence emerges over time, there currently seems to be minimal justification to accord late-onset AN a unique position in psychiatric nosology.
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Late-Treated Phenylketonuria and Partial Reversibility of Intellectual Impairment
Grosse, Scott D.
2010-01-01
Individuals with late-treated phenylketonuria (PKU) not detected by newborn screening but who followed dietary treatment for at least 12 months before 7 years of age have intelligence quotient (IQ) scores that range from severe impairment to the low-normal range. Among adults with late-treated PKU in California, 85% of those who were born from…
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Harrison, Robert W; Radhakrishnan, Vaishnavi; Lam, Peter S; Allocco, Dominic J; Brar, Sandeep; Fahy, Martin; Fisher, Rebecca; Ikeno, Fumiaki; Généreux, Philippe; Kimura, Takeshi; Liu, Minglei; Lye, Weng Kit; Mintz, Gary S; Nagai, Hirofumi; Suzuki, Yuka; White, Roseann; Allen, John C; Krucoff, Mitchell W
2016-12-01
The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs. Copyright © 2016 Elsevier Inc. All rights reserved.
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Late haemorrhagic disease of the newborn.
Zengin, Emine; Sarper, Nazan; Türker, Gülcan; Corapçioğlu, Funda; Etuş, Volkan
2006-09-01
Late haemorrhagic disease of the newborn (HDN) can occur owing to a lack of vitamin K prophylaxis, as a manifestation of an underlying disorder or idiopatically from the 8th day to 12 weeks after birth. Eight infants admitted to Kocaeli University Hospital with nine episodes of late HDN between January 2002 and April 2005 were evaluated retrospectively from hospital records. The median age at presentation was 46 (26-111) days. All the infants were born at full-term to healthy mothers and were exclusively breast-fed. All had an uneventful perinatal history, except one who had meconium aspiration. Four patients had received no vitamin K prophylaxis and another three had uncertain histories. At presentation, six had intracranial bleeding and the remainder had bleeding either from the venepuncture site or the gastro-intestinal tract. The presenting signs and symptoms were irritability, vomiting, bulging or full fontanelle, convulsions and diminished or absent neonatal reflexes. Galactosaemia was detected in a 2-month-old infant with prolonged jaundice. There was no surgery-related mortality or complications but one survived for only 2 days on ventilatory support following surgery. Only one of the six survivors had severe neurological sequelae. Late HDN frequently presents with intracranial haemorrhage, leading to high morbidity and mortality. HDN can be the manifestation of an underlying metabolic disorder. Vitamin K prophylaxis of the newborn should be routine in developing countries.
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Late onset startle induced tics
Tijssen, MAJ; Brown, P; Morris, HR; Lees, A
1999-01-01
Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor ties were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The ties developed after physical trauma or a period of undue emotional stress. Reflex ties may occur in
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Late onset startle induced tics
Tijssen, M. A.; Brown, P.; Morris, H. R.; Lees, A.
1999-01-01
Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor tics were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The tics developed after physical trauma or a period of undue emotional stress. Reflex tics may occur in
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Research and clinical aspects of the late effects of poliomyelitis
Energy Technology Data Exchange (ETDEWEB)
Halstead, L.S.; Wiechers, D.O.
1986-01-01
This book contains 32 selections. Some of the titles are: Late effects of Polio: Historical Perspectives; Sleep-Disordered Breathing as a Late Effect of Poliomyelitis; Clinical Subtypes, DNA Repair Efficiency, and Therapeutic Trials in the Post-Polio Syndromes; and Post-Polio Muscle Function.
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The Early vs. Late Infantile Strabismus Surgery Study: Monitoring Report
H.J. Simonsz (Huib)
1995-01-01
textabstractAbstract: The Early vs. Late Infantile Strabismus Surgery Study Group is a group of strabismologists and orthoptists who investigate whether early or late surgery is preferable in infantile strabismus, in a non-randomized, prospective, multi-center trial. Infants between six and 18
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Gene Profiling in Late Blight Resistance in Potato Genotype SD20
Directory of Open Access Journals (Sweden)
Xiaohui Yang
2018-06-01
Full Text Available Late blight caused by the oomycete fungus Phytophthora infestans (Pi is the most serious obstacle to potato (Solanum tuberosum production in the world. A super race isolate, CN152, which was identified from Sichuan Province, China, could overcome nearly all known late blight resistance genes and caused serious damage in China. The potato genotype SD20 was verified to be highly resistant to CN152; however, the molecular regulation network underlying late blight resistance pathway remains unclear in SD20. Here, we performed a time-course experiment to systematically profile the late blight resistance response genes using RNA-sequencing in SD20. We identified 3354 differentially expressed genes (DEGs, which mainly encoded transcription factors and protein kinases, and also included four NBS-LRR genes. The late blight responsive genes showed time-point-specific induction/repression. Multi-signaling pathways of salicylic acid, jasmonic acid, and ethylene signaling pathways involved in resistance and defense against Pi in SD20. Gene Ontology and KEGG analyses indicated that the DEGs were significantly enriched in metabolic process, protein serine/threonine kinase activity, and biosynthesis of secondary metabolites. Forty-three DEGs were involved in immune response, of which 19 were enriched in hypersensitive response reaction, which could play an important role in broad-spectrum resistance to Pi infection. Experimental verification confirmed the induced expression of the responsive genes in the late blight resistance signaling pathway, such as WRKY, ERF, MAPK, and NBS-LRR family genes. Our results provided valuable information for understanding late blight resistance mechanism of potato.
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Role of Solanum dulcamara L. in Potato Late Blight Epidemiology
Golas, T.M.; Weerden, van der G.M.; Berg, van den R.G.; Mariani, C.; Allefs, J.J.H.M.
2010-01-01
Four sites with naturally growing Solanum dulcamara were surveyed during 2006 and 2007 for the presence of late blight. Despite 2 years of observations, no late blight was detected among natural populations of bittersweet. Nevertheless, repeated infections occurred on few S. dulcamara plants from a
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The clinical features of late onset anorexia nervosa.
Joughin, N. A.; Crisp, A. H.; Gowers, S. G.; Bhat, A. V.
1991-01-01
This study examines clinical features of late onset anorexia nervosa. This involved the scrutiny of a large database of patients with anorexia nervosa comprising data gathered at standardized initial assessments over the period 1960-1990. Patients with a late onset were compared to other selected patient samples. The population comprised 12 patients with a first onset of anorexia nervosa at or after the age of 30, 415 patients with an onset after 15 but before 20 and 9 patients with an onset ...
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International Nuclear Information System (INIS)
Taylor, Andrew M.; Dymarkowski, Steven; Bogaert, Jan; Verbeken, Eric K.
2006-01-01
To examine the value of late-enhancement cardiac magnetic resonance imaging (MRI) for detection of pericardial inflammation. Late-enhancement cardiac MRI was performed in 16 patients with clinical suspicion of pericardial disease. Pericardial effusion, pericardial thickening and pericardial enhancement were assessed. MRI findings were compared with those of definitive pericardial histology (n=14) or microbiology (n=2). A control group of 12 patients with no clinical evidence of pericardial disease were also imaged with the same MRI protocol. Sensitivity and specificity for late-enhancement MRI detection of pericardial inflammation was of 100%. There was MRI late enhancement of the pericardial layers in all five patients with histological/microbiological evidence of inflammatory pericarditis. MRI demonstrated no pericardial thickening and no MRI late enhancement with or without a pericardial effusion in any of the five patients with histological evidence of a normal pericardium. MRI detected pericardial thickening in the absence of both pericardial effusion and late enhancement in all six patients with histological evidence of chronic fibrosing pericarditis. The 12 control subjects showed no evidence of pericardial MRI late enhancement. These findings demonstrate that MRI late enhancement can be used to visualize pericardial inflammation in patients with clinical suspicion of pericardial disease. (orig.)
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VERY LATE PHOTOMETRY OF SN 2011fe
International Nuclear Information System (INIS)
Kerzendorf, W. E.; Taubenberger, S.; Seitenzahl, I. R.; Ruiter, A. J.
2014-01-01
The Type Ia supernova SN 2011fe is one of the closest supernovae of the past decades. Due to its proximity and low dust extinction, this object provides a very rare opportunity to study the extremely late time evolution (>900 days) of thermonuclear supernovae. In this Letter, we present our photometric data of SN 2011fe taken at an unprecedented late epoch of ≈930 days with GMOS-N mounted on the Gemini North telescope (g = 23.43 ± 0.28, r = 24.14 ± 0.14, i = 23.91 ± 0.18, and z = 23.90 ± 0.17) to study the energy production and retention in the ejecta of SN 2011fe. Together with previous measurements by other groups, our result suggests that the optical supernova light curve can still be explained by the full thermalization of the decay positrons of 56 Co. This is in spite of theoretical predicted effects (e.g., infrared catastrophe, positron escape, and dust) that advocate a substantial energy redistribution and/or loss via various processes that result in a more rapid dimming at these very late epochs
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KECK NIRSPEC RADIAL VELOCITY OBSERVATIONS OF LATE-M DWARFS
Energy Technology Data Exchange (ETDEWEB)
Tanner, Angelle; White, Russel [Department of Astronomy, Georgia State University, One Park Place, Atlanta, GA 30303 (United States); Bailey, John [Department of Astronomy, University of Michigan, 830 Dennison Building, 500 Church Street, Ann Arbor, MI 48109-1042 (United States); Blake, Cullen [Department of Astrophysical Sciences, Princeton University, Peyton Hall, Ivy Lane, Princeton, NJ 08544 (United States); Blake, Geoffrey [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Cruz, Kelle [Department of Physics and Astronomy, Hunter College, 695 Park Avenue, New York, NY 10065 (United States); Burgasser, Adam J. [Center for Astrophysics and Space Science, University of California San Diego, La Jolla, CA 92093 (United States); Kraus, Adam [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)
2012-11-15
We present the results of an infrared spectroscopic survey of 23 late-M dwarfs with the NIRSPEC echelle spectrometer on the Keck II telescope. Using telluric lines for wavelength calibration, we are able to achieve measurement precisions of down to 45 m s{sup -1} for our late-M dwarfs over a one- to four-year long baseline. Our sample contains two stars with radial velocity (RV) variations of >1000 m s{sup -1}. While we require more measurements to determine whether these RV variations are due to unseen planetary or stellar companions or are the result of starspots known to plague the surface of M dwarfs, we can place upper limits of <40 M{sub J} sin i on the masses of any companions around those two M dwarfs with RV variations of <160 m s{sup -1} at orbital periods of 10-100 days. We have also measured the rotational velocities for all the stars in our late-M dwarf sample and offer our multi-order, high-resolution spectra over 2.0-2.4 {mu}m to the atmospheric modeling community to better understand the atmospheres of late-M dwarfs.
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KECK NIRSPEC RADIAL VELOCITY OBSERVATIONS OF LATE-M DWARFS
International Nuclear Information System (INIS)
Tanner, Angelle; White, Russel; Bailey, John; Blake, Cullen; Blake, Geoffrey; Cruz, Kelle; Burgasser, Adam J.; Kraus, Adam
2012-01-01
We present the results of an infrared spectroscopic survey of 23 late-M dwarfs with the NIRSPEC echelle spectrometer on the Keck II telescope. Using telluric lines for wavelength calibration, we are able to achieve measurement precisions of down to 45 m s –1 for our late-M dwarfs over a one- to four-year long baseline. Our sample contains two stars with radial velocity (RV) variations of >1000 m s –1 . While we require more measurements to determine whether these RV variations are due to unseen planetary or stellar companions or are the result of starspots known to plague the surface of M dwarfs, we can place upper limits of J sin i on the masses of any companions around those two M dwarfs with RV variations of –1 at orbital periods of 10-100 days. We have also measured the rotational velocities for all the stars in our late-M dwarf sample and offer our multi-order, high-resolution spectra over 2.0-2.4 μm to the atmospheric modeling community to better understand the atmospheres of late-M dwarfs.
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Clinical presentation of late haemorrhagic disease of newborn
International Nuclear Information System (INIS)
Majeed, R.; Memon, Y.; Majeed, F.
2008-01-01
To observe the clinical presentation of late haemorrhagic disease of the newborn (LHDNB), and clinical improvement after the administration of vitamin K/sub 1/. This is a prospective descriptive study. All the children older than seven days who presented with bleeding were admitted in pediatrics ward of Isra University Hyderabad from April 2006 to April 2007 were included. Data collection was done by means of detailed proforma. Analysis was done on SPSS version 11. Thirty five cases were included. Commonest site of bleeding was subcutaneous followed by oral and injection site. Mean age of late haemorrhagic disease of newborn was 109 days and minimum age of presentation was 28 days. Common clinical presentations were irritability, convulsions, poor reflexes and poor feeding. Mostly recovery was within 24 hours after vit K. Late HDN results in severe hemorrhage especially hemorrhage in the central nervous system. Administration of Vitamin K (1mg, 1M) at birth can present these severe complications. (author)
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Energy Technology Data Exchange (ETDEWEB)
Goncalves, Fabricio Guimaraes; Lamb, Leslie; Del Carpio-O' Donovan, Raquel, E-mail: goncalves.neuroradio@gmail.com [McGill University Health Center Montreal General Hospital (Canada)
2011-11-15
Progressive multifocal leukoencephalopathy is a neurological infectious disease caused by the John Cunningham polyoma virus (JCV), an opportunistic agent with worldwide distribution. This disease is frequently seen in immunosuppressed patients and rarely associated with systemic lupus erythematosus. In the central nervous system PML demyelinating lesions occur in the supratentorial compartment. The authors describe a rare case of PML secondary to SLE treatment with atypical presentation restricted to the posterior fossa (author)
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International Nuclear Information System (INIS)
Goncalves, Fabricio Guimaraes; Lamb, Leslie; Del Carpio-O'Donovan, Raquel
2011-01-01
Progressive multifocal leukoencephalopathy is a neurological infectious disease caused by the John Cunningham polyoma virus (JCV), an opportunistic agent with worldwide distribution. This disease is frequently seen in immunosuppressed patients and rarely associated with systemic lupus erythematosus. In the central nervous system PML demyelinating lesions occur in the supratentorial compartment. The authors describe a rare case of PML secondary to SLE treatment with atypical presentation restricted to the posterior fossa (author)
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Late complication after radiotherapy for testicular tumor
Energy Technology Data Exchange (ETDEWEB)
Mineyama, Hirotada; Komatsubara, Shuichi; Sakata, Yasunosuke; Abe, Norio (Niigata Prefectural Cancer Center (Japan). Niigata Hospital)
1983-12-01
During the past 21 years, 105 patients with germinal testicular tumor were treated in our hospital; 86 out of 105 patients were irradiated postoperatively. Late radiation injury was observed in 14 patients: Cutaneosigmoidal fistula in 1 patient, ileus (jejunum necrosis) in 1 patient, gastric ulcer in 1 patient, duodenal ulcer and stenosis in 1 patient, lung fibrosis in 1 patient, radiation cystitis in 1 patient, severe lymph edema of lower extremity in 1 patient, muscle atrophy of lower extremity in 1 patient, lower extremity growth disturbances in 3 children and severe abdominal cutancosubcutaneal fibrosis in 3 patient. Two cases of late radiation injury are presented and discussed.
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Late replication domains are evolutionary conserved in the Drosophila genome.
Andreyenkova, Natalya G; Kolesnikova, Tatyana D; Makunin, Igor V; Pokholkova, Galina V; Boldyreva, Lidiya V; Zykova, Tatyana Yu; Zhimulev, Igor F; Belyaeva, Elena S
2013-01-01
Drosophila chromosomes are organized into distinct domains differing in their predominant chromatin composition, replication timing and evolutionary conservation. We show on a genome-wide level that genes whose order has remained unaltered across 9 Drosophila species display late replication timing and frequently map to the regions of repressive chromatin. This observation is consistent with the existence of extensive domains of repressive chromatin that replicate extremely late and have conserved gene order in the Drosophila genome. We suggest that such repressive chromatin domains correspond to a handful of regions that complete replication at the very end of S phase. We further demonstrate that the order of genes in these regions is rarely altered in evolution. Substantial proportion of such regions significantly coincide with large synteny blocks. This indicates that there are evolutionary mechanisms maintaining the integrity of these late-replicating chromatin domains. The synteny blocks corresponding to the extremely late-replicating regions in the D. melanogaster genome consistently display two-fold lower gene density across different Drosophila species.
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Jilesen, Anneke P. J.; Tol, Johanna A. M. G.; Busch, Olivier R. C.; van Delden, Otto M.; van Gulik, Thomas M.; Nieveen van Dijkum, Els J. M.; Gouma, Dirk J.
2014-01-01
The mortality rate due to late hemorrhage after surgery for periampullary tumors is high, especially in patients with anastomotic leakage. Patients usually require emergency intervention for late hemorrhage. In this study patients with late hemorrhage and their outcomes were analyzed. Furthermore,
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The vulnerability of silver fir populations to damage from late frosts
Directory of Open Access Journals (Sweden)
Klisz Marcin
2016-03-01
Full Text Available The aim of the study was to determine the vulnerability of selected silver fir populations to damage from late frost in the climatic conditions of south-eastern Poland. To determine the vulnerability of apical and lateral shoots to damage caused by late frosts, we observed four test plots in 2009 and 2014, each containing progenies of selected seed stands. Our statistical analyses were based on a model incorporating the following variables: site, year, type of frost damage, population as well as the possible interaction between these variables. Significant differences between the populations were found in terms of their sensitivity to damage from low temperature occurring during the growth period. Furthermore, we indirectly demonstrated differences in the severity of late frost on the experimental plots, as well as the intensity and variability of late frost shoot damage. Based on these results, we divided the studied populations into two groups of low (EF, KRA1 and NAR and high (LES2 and BAL2 sensitivity to late frost damage.
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Impact of late radiation effects on cancer survivor children: an integrative review
International Nuclear Information System (INIS)
Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia; Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia
2016-01-01
We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses
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Impact of late radiation effects on cancer survivor children: an integrative review
Energy Technology Data Exchange (ETDEWEB)
Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)
2016-07-01
We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses.
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Short-Term Neonatal Outcome in Late Preterm vs. Term Infants
International Nuclear Information System (INIS)
Haroon, A.; Ali, S. R.; Ahmed, S.; Maheen, H.
2014-01-01
Objective: To determine the short-term neonatal outcomes in late preterm infants (LPIs) as compared to term infants and their association with maternal risk factors. Study Design: A case control, descriptive study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, Pakistan, from January to December 2009. Methodology: The study included 326 late preterm babies (defined as those born between 34 to 37 weeks of gestation) and equal number of term control babies at the Aga Khan University Hospital, Karachi, Pakistan. Data, including obstetric history, maternal complications, neonatal morbidities, etc., was retrieved from patients medical records. The data was compared with the control group for complications, fetal morbidity and maternal morbidity. Results: Late preterm infants constituted 10.6% of all deliveries and 77% of all live preterm births during the study period. Respiratory distress syndrome (RDS) (16.5% vs. 0.3%, p < 0.001), growth retardation (24.8% vs. 4%, p < 0.001), hyperbilirubinemia requiring phototherapy (37.9% vs. 11%, p < 0.001), and sepsis (4.9% vs. 0.3%, p < 0.001) were found to be the major morbidities in the study group. The need for resuscitation was 12.7 times higher in the study group as compared to the term babies (21.4% vs. 1.2%, p < 0.001). NICU admissions in the study group were also higher (18.8% vs. 2.4%, p < 0.001). Hypertension (12.5% vs. 1.5%, p < 0.001), diabetes (12.5% vs. 9.2%, p < 0.001), antenatal history of UTI (1.5% vs. 0.3%, p < 0.001), and prolong rupture of membrane (8.9% vs. 4%, p < 0.001) were significant maternal morbidities in the late preterm group. Conclusion: The late preterm group had greater morbidity, compared to term neonates. Prior awareness of the morbidities associated with late preterm babies is helpful for the health care providers to anticipate and manage potential complications in late preterm infants. (author)
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Neuropsychiatric manifestations in late-onset urea cycle disorder patients
Serrano Mercedes L.; Martins Cecilia E.; Pérez-Dueñas Belén; Gómez-López Lilian; Murgui Empar; Fons Carmen; García-Cazorla Ángels; Artuch Rafael M D; Jara Fernando; Arranz José Antonio; Häberle Johannes; Briones Paz; Campistol Jaume M D; Pineda Mercè; Vilaseca María Antònia Antonia
2010-01-01
Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation attention deficit hyper...
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Origin and mixing timescale of Earth's late veneer
Prescher, C.; Allu Peddinti, D.; Bell, E. A.; Bello, L.; Cernok, A.; Ghosh, N.; Tucker, J.; Wielicki, M. M.; Zahnle, K. J.
2012-12-01
Experimental studies on the partitioning behavior of highly siderophile elements (HSE) between silicate and metallic melts imply that the Earth's mantle should have been highly depleted in these elements by core formation in an early magma ocean. However, present HSE contents of the Earth's mantle are ~3 orders of magnitude higher than that expected by experiments. The apparent over-abundance of HSE has commonly been explained by the addition of meteoritic material in the "late veneer" which describes the exogenous mass addition following the moon forming impact and concluding with the late heavy bombardment at ~3.8-3.9 Ga. The strongest evidence for this theory is that the platinum group element (PGE) contents in today's mantle are present in chondritic relative abundances, as opposed to a fractionated pattern expected with metal-silicate partitioning. Archean komatiites indicate that the PGE content of the Earth's mantle increased from about half their present abundances at 3.5 Ga to their present abundances at 2.9 Ga. This secular increase in PGE content suggests a progressive mixing of the late veneer material into the Earth's mantle. However, this time scale also implies that the whole mantle was relatively well mixed by 2.9 Ga. We use a compilation of existing isotopic and trace element data in order to constrain the origin and composition of the late veneer. We use PGE abundances, W abundances and W isotopic compositions in chondritic meteorites and the primitive upper mantle to compute the amount of mass delivered during the late veneer and find the late veneer mass to be ~0.6 % the mass of the bulk silicate Earth (consistent with earlier estimates). We also use the 187Re-187Os and 190Pt-186Os systems to constrain the composition and timing of delivery of the impacting population. We model the efficiency of mantle mixing in this time frame by using 3-dimensional numerical geodynamical simulations and geochemical constraints. Initial parameters include the
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Differential Parenting between Mothers and Fathers: Implications for Late Adolescents
McKinney, Cliff; Renk, Kimberly
2008-01-01
Although the relationship between parenting and outcomes for children and adolescents has been examined, differences between maternal and paternal parenting styles have received less attention, particularly in the case of late adolescents. As a result, this article examines the relationship between late adolescents' perceptions of their mothers'…
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Influence of social factors on patient-reported late symptoms
DEFF Research Database (Denmark)
Kjaer, Trille Kristina; Johansen, Christoffer; Andersen, Elo
2016-01-01
BACKGROUND: The incidence of head and neck cancer and morbidity and mortality after treatment are associated with social factors. Whether social factors also play a role in the prevalence of late-onset symptoms after treatment for head and neck cancer is not clear. METHODS: Three hundred sixty...... ratio [OR] = 3.20; 95% confidence interval [CI] = 1.18-8.63). For survivors who lived alone, the adjusted ORs were significantly increased for physical functioning (2.17; 95% CI = 1.01-4.68) and trouble with social eating (OR = 2.26; 95% CI = 1.14-4.47). CONCLUSION: Self-reported severe late symptoms...... were more prevalent in survivors with short education and in those living alone, suggesting differences in perception of late symptoms between social groups. © 2015 Wiley Periodicals, Inc. Head Neck, 2015....
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Marden, Jessica R; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria
2017-10-01
Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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International Nuclear Information System (INIS)
Morrissey, M.F.
1992-01-01
Interim Waste Technology has demonstrated the Late Washing concept on the Experimental Laboratory Filter (ELF) at TNX. In two tests, washing reduced the [NO 2 - ] from 0.08 M to approximately 0.01 M on slurries with 2 year equivalent radiation exposures and 9.5 wt. % solids. For both washes, the [NO 2 - ] decreased at rates near theoretical for a constant volume stirred vessel, indicating approximately l00% washing efficiency. Permeate flux was greater than 0.05 gpm/ft 2 for both washes at a transmembrane pressure of 50 psi and flow velocity of 9 ft/sec
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Abiotic landscape and vegetation patterns in the Netherlands during the Weichselian Late Glacial
Hoek, W.Z.
2000-01-01
The Late Glacial landscape of the Netherlands was a landscape with changing geomorphology and vegetation. Glacial, eolian and fluvial processes in the time before the Late Glacial initially had formed the main landscape types that still existed during the Late Glacial. In these landscape types,
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Late GI and GU complications in the treatment of prostate cancer
International Nuclear Information System (INIS)
Schultheiss, Timothy E.; Lee, W. Robert; Hunt, Margie A.; Hanlon, Alexandra L.; Peter, Ruth S.; Hanks, Gerald E.
1997-01-01
Purpose: To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate. Methods and Materials: Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedure) or proctitis. Late Grade 3 GU morbidity was cystitis or structure. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects ≥ Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP). Results: Acute GI and GU side effects (Grade 2 or higher ) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI morbidities were highly correlated. History of diabetes, treatment of
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Early- and Late-Onset Inherited Erythromelalgia
Directory of Open Access Journals (Sweden)
J Gordon Millichap
2009-08-01
Full Text Available A genotype-phenotype relationship at the clinical, cellular and molecular levels is shown in a case of erythromelalgia of relatively late onset, in a study at Yale University School of Medicine, and centers in China.
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Late-presenting congenital diaphragmatic hernia
Directory of Open Access Journals (Sweden)
Raashid Hamid
2014-01-01
Full Text Available Background: This study was undertaken to highlight the clinical profile, misdiagnosis, surgical treatment,and prognosis of late-presenting congenital diaphragmatic hernia (CDH cases in a tertiary level hospital. Patients and Methods: This retrospective study included all the babies and children >1 month of age with CDH who were admitted in our Hospital (Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India during the period between January 2008 and December 2013. Babies with age <1 month were excluded from the study. Data regarding clinical profile, operative records, and follow-up was reviewed and analysed statistically. Results: A total of 20 patients were included in this study. The clinical picture ranged from respiratory distress (13 patients to non-specific gastrointestinal complaints (5 patients. In two patients, CDH was misdiagnosed as pneumothorax and had got chest tube inserted in other hospitals before referral to this tertiary care centre. In 14 patients chest, X-ray revealed the diagnosis of CDH and in remaining five patients (including the two patients with misdiagnosis further investigations were undertaken to establish the diagnosis. Age ranged from 45 days to 17 years with an average age of 58.9 months. There were 12 male and 8 female patients. In all the 20 patients, surgical procedures were undertaken with the retrieval of herniated contents from the thoracic cavity and repair of the diaphragmatic defect. There was no mortality in our series. All the 20 patients were followed-up for a period ranging from 6 months to 5 years (median 3.1 years. Conclusions: Late-presenting CDH can have diverse clinical presentation. Late diagnosis and misdiagnosis can result in significant morbidity and potential mortality if these cases are not managed properly at an appropriate stage. Outcome is favourable if these patients are expeditiously identified and surgically repaired.
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The epidemiology of acne vulgaris in late adolescence.
Lynn, Darren D; Umari, Tamara; Dunnick, Cory A; Dellavalle, Robert P
2016-01-01
Acne vulgaris is the most common skin condition affecting late adolescents across the globe. Although prior studies have evaluated epidemiologic patterns of acne vulgaris in various ethnicities and regions, adequate understanding of the worldwide burden of the disease associated with patients in their late adolescence (15-19-year olds) remains lacking. To assess the global burden of the disease associated with acne vulgaris for late adolescents (15-19-year olds) and provide an overview of the epidemiology, pathophysiology, and treatment options for acne in this population. Database summary study. Global Burden of Disease Study 2010 database. Global Burden of Disease regions comprised countries with prevalence of acne vulgaris between the ages of 15 and 19 years. Geographic region-level disability-adjusted life year rates (per 100,000 persons) associated with acne vulgaris in years 1990 through 2010. Median percentage change in disability-adjusted life year rates was estimated for each region across the specified study period. Acne vulgaris-associated disease burden exhibits global distribution and has continued to grow in prevalence over time within this population. This continued growth suggests an unmet dermatologic need worldwide for this disorder and potential opportunities for improved access and delivery of dermatologic care. Our analysis of the literature reveals numerous opportunities for enhanced patient care. To that end, we highlight some of the effective and promising treatments currently available and address important factors, such as sex, nationality, genetics, pathophysiology, and diet, as they relate to acne vulgaris in late adolescence.
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Vandenberg, Laura N; Levin, Michael
2010-04-01
How embryos consistently orient asymmetries of the left-right (LR) axis is an intriguing question, as no macroscopic environmental cues reliably distinguish left from right. Especially unclear are the events coordinating LR patterning with the establishment of the dorsoventral (DV) axes and midline determination in early embryos. In frog embryos, consistent physiological and molecular asymmetries manifest by the second cell cleavage; however, models based on extracellular fluid flow at the node predict correct de novo asymmetry orientation during neurulation. We addressed these issues in Xenopus embryos by manipulating the timing and location of dorsal organizer induction: the primary dorsal organizer was ablated by UV irradiation, and a new organizer was induced at various locations, either early, by mechanical rotation, or late, by injection of lithium chloride (at 32 cells) or of the transcription factor XSiamois (which functions after mid-blastula transition). These embryos were then analyzed for the position of three asymmetric organs. Whereas organizers rescued before cleavage properly oriented the LR axis 90% of the time, organizers induced in any position at any time after the 32-cell stage exhibited randomized laterality. Late organizers were unable to correctly orient the LR axis even when placed back in their endogenous location. Strikingly, conjoined twins produced by late induction of ectopic organizers did have normal asymmetry. These data reveal that although correct LR orientation must occur no later than early cleavage stages in singleton embryos, a novel instructive influence from an early organizer can impose normal asymmetry upon late organizers in the same cell field.
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Educating Citizens in Late Modern Societies
DEFF Research Database (Denmark)
Christensen, Torben Spanget
2011-01-01
One way or the other democratic states need to take on the task of educating its rising generation in governmental affairs, societal matters and citizenship in order to sustain the democracy itself. This article presents a model for analysing civic education in late modern, globalised world....... The model is based on the fundamental belief that the overall aim of civic education in democratic, late modern and global societies is empowerment of the citizen in order to establish a self governing citizen who simultaneous is capable of managing and keeping together partly contradictory citizens tasks...... studies and evaluations of the Danish upper secondary school completed at my department at University of Southern Denmark in recent years, especially connected to a quite far reaching curriculum reform from 2005. It is assumed that this Danish development is an expression of a more general phenomenon...
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Provenance studies of Sgraffiato and Late Green Glazed wares from Siraf, Iran
International Nuclear Information System (INIS)
Michel, H.V.; Asaro, F.; Frierman, J.D.
1975-03-01
Results of neutron activation analyses of 23 elements in ceramic archaeological specimens are given. Various wares are divided into the following categories: early Sgraffiato, late Sgraffiato, late Green A, late Green B, and Samarra ware. Results are given on the following elements: Al, Ca, Dy, Mn, Na, K, U, Sm, La, Ti, Lu, Co, Sc, Fe, Cs, Cr, Ni, Eu, Ce, Hf, Ta, Th, and Yb. (JGB)
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Women’s demand for late-term abortion: A social or psychiatric issue?
Directory of Open Access Journals (Sweden)
Nikolić Gordana
2014-01-01
Full Text Available Introduction/Aim. Induced termination of unwanted pregnancy after 12th gestational week (late-term abortion is legally restricted in Serbia as well as in many other countries. On the other hand, unwanted pregnancy very often brings women into the state of personal crisis. Psychiatric indications for legally approved late-term abortion on women’s demand include only severe psychiatric disorders. The aim of this paper was to compare sociodemographic, psychological characteristics and claimed reasons for abortion in the two groups of women with late-term demand for abortion - the group of women satisfying legally prescribed mental health indications, and the group of women not satisfying these indications. The aim of the study was also to determine predictive validity of the abovementioned parameters for late-term abortion as the outcome of unwanted pregnancy. Methods. A total of 62 pregnant women with demand for late-term abortion were divided into two groups according to the criteria of satisfying or not satisfying legally proposed psychiatric indications for late-term abortion after psychiatric evaluation. For the assessment of sociodemographic and psychological parameters sociodemographic questionnaire and symptom checklist - 90 revised (SCL-90® scale were used, respectively. The outcome of unwanted pregnancy was followed 6 months after the initial assessment. Results. The obtained results showed a statistically significant difference between the groups in educational level, satisfaction with financial situation, elevated anxiety and distress reactions. Unfavorable social circumstances were the main reason for an abortion in both groups and were predictive for an abortion. A 6-month follow-up showed that women had abortion despite legal restrictions. Conclusion. Pregnant women with psychiatric indication for late-term abortion belong to lower socioeconomic and educational level group compared to women without this indication who have more
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Prevalence and associated factors of late HIV diagnosis in north ...
African Journals Online (AJOL)
Information regarding age, sex, WHO stage, type of opportunistic condition, HIV testing service and on diagnosis CD4 counts were all collected. On diagnosis CD4 counts <200cells/µl was coded as Late HIV diagnosis. The proportion of with Late HIV diagnosis was calculated and logistic regression modal was used to ...
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Effect of Tetracycline on Late-stage African trypanosomiasis in Rats ...
African Journals Online (AJOL)
Effect of Tetracycline on Late-stage African trypanosomiasis in Rats. T.O. Johnson, J.T. Ekanem. Abstract. The effect of tetracycline on late stage African trypanosomiasis was examined in an in vivo experiment using rats infected with Trypanosoma brucei brucei. Infected rats were treated on the 5th day of infection with ...
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Reactions of some potato genotypes to late blight in Cameroon ...
African Journals Online (AJOL)
Reactions of some potato genotypes to late blight in Cameroon. D. K. Njualem, P. Demo, H. A. Mendoza, J. T. Koi, S. F. Nana. Abstract. Field experiments were conducted in Cameroon in 1995 and 1996 to evaluate reactions of different potato genotypes to late blight. There were significant differences among genotypes for ...
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Circumscribing late dark matter decays model-independently
International Nuclear Information System (INIS)
Yueksel, Hasan; Kistler, Matthew D.
2008-01-01
A number of theories, spanning a wide range of mass scales, predict dark matter candidates that have lifetimes much longer than the age of the Universe, yet may produce a significant flux of gamma rays in their decays today. We constrain such late-decaying dark matter scenarios model-independently by utilizing gamma-ray line emission limits from the Galactic Center region obtained with the SPI spectrometer on INTEGRAL, and the determination of the isotropic diffuse photon background by SPI, COMPTEL, and EGRET observations. We show that no more than ∼5% of the unexplained MeV background can be produced by late dark matter decays either in the Galactic halo or cosmological sources.
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Progression of Late-Onset Stargardt Disease
Lambertus, S.; Lindner, M.; Bax, N.M.; Mauschitz, M.M.; Nadal, J.; Schmid, M.; Schmitz-Valckenberg, S.; Hollander, A.I. den; Weber, B.H.; Holz, F.G.; Wilt, G.J. van der; Fleckenstein, M.; Hoyng, C.B.
2016-01-01
Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy
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Late onset globoid cell leukodystrophy.
Grewal, R P; Petronas, N; Barton, N W
1991-01-01
A 29 year old male with onset of globoid cell leukodystrophy at age 14 is described. This is the first case of enzymatically confirmed globoid cell leukodystrophy with onset of symptoms after the age of ten. This patient is unique because of the late onset and slow progression and extends the clinical spectrum of globoid cell leukodystrophy.
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Late onset globoid cell leukodystrophy.
Grewal, R P; Petronas, N; Barton, N W
1991-11-01
A 29 year old male with onset of globoid cell leukodystrophy at age 14 is described. This is the first case of enzymatically confirmed globoid cell leukodystrophy with onset of symptoms after the age of ten. This patient is unique because of the late onset and slow progression and extends the clinical spectrum of globoid cell leukodystrophy.
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A Cost-effectiveness Analysis of Early vs Late Tracheostomy.
Liu, C Carrie; Rudmik, Luke
2016-10-01
The timing of tracheostomy in critically ill patients requiring mechanical ventilation is controversial. An important consideration that is currently missing in the literature is an evaluation of the economic impact of an early tracheostomy strategy vs a late tracheostomy strategy. To evaluate the cost-effectiveness of the early tracheostomy strategy vs the late tracheostomy strategy. This economic analysis was performed using a decision tree model with a 90-day time horizon. The economic perspective was that of the US health care third-party payer. The primary outcome was the incremental cost per tracheostomy avoided. Probabilities were obtained from meta-analyses of randomized clinical trials. Costs were obtained from the published literature and the Healthcare Cost and Utilization Project database. A multivariate probabilistic sensitivity analysis was performed to account for uncertainty surrounding mean values used in the reference case. The reference case demonstrated that the cost of the late tracheostomy strategy was $45 943.81 for 0.36 of effectiveness. The cost of the early tracheostomy strategy was $31 979.12 for 0.19 of effectiveness. The incremental cost-effectiveness ratio for the late tracheostomy strategy compared with the early tracheostomy strategy was $82 145.24 per tracheostomy avoided. With a willingness-to-pay threshold of $50 000, the early tracheostomy strategy is cost-effective with 56% certainty. The adaptation of an early vs a late tracheostomy strategy depends on the priorities of the decision-maker. Up to a willingness-to-pay threshold of $80 000 per tracheostomy avoided, the early tracheostomy strategy has a higher probability of being the more cost-effective intervention.
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PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy.
Liu, Laura X; Rowe, Glenn C; Yang, Steven; Li, Jian; Damilano, Federico; Chan, Mun Chun; Lu, Wenyun; Jang, Cholsoon; Wada, Shogo; Morley, Michael; Hesse, Michael; Fleischmann, Bernd K; Rabinowitz, Joshua D; Das, Saumya; Rosenzweig, Anthony; Arany, Zoltan
2017-12-08
Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood. To determine the mechanisms underlying cardiac substrate use during pregnancy. We use here 13 C glucose, 13 C lactate, and 13 C fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid cycle, while reducing glucose and lactate oxidation. Mitochondrial quantity, morphology, and function do not seem altered. Insulin signaling seems intact, and the abundance and localization of the major fatty acid and glucose transporters, CD36 (cluster of differentiation 36) and GLUT4 (glucose transporter type 4), are also unchanged. Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy. Taken together, these data indicate that the hormonal environment of late pregnancy promotes metabolic remodeling in the heart at the level of PDH, rather than at the level of insulin signaling. © 2017 American Heart Association, Inc.
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Late-type components of slow novae and symbiotic stars
Energy Technology Data Exchange (ETDEWEB)
Allen, D A [Anglo-Australian Observatory, Epping (Australia); Royal Observatory, Edinburgh (UK))
1980-08-01
It is argued that the various types of symbiotic stars and the slow novae are the same phenomena exhibiting a range of associated time-scales, the slow novae being of intermediate speed. Evidence is summarized showing that both types of object contain normal M giants or mira variables. This fact is at odds with currently fashionable single-star models for slow novae, according to which the M star is totally disrupted before the outburst. Spectral types of the late-type components are presented for nearly 80 symbiotic stars and slow novae, derived from 2 ..mu..m spectroscopy. It is found that both the intensity of the emission spectrum and the electron density of the gas are functions of the spectral type of the late-type star. Explanations for these correlations are given. On the assumption that the late-type components are normal giants, spectroscopic parallaxes are determined; credible distances are derived which indicate that the known symbiotic stars have been sampled as far afield as the Galactic Centre. Hydrogen shell flashes on a white dwarf accreting gas from the late-type components offer an attractive explanation of the phenomena of slow novae and symbiotic stars, and such models are discussed in the concluding section.
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Late effects of various dose-fractionation regimens
International Nuclear Information System (INIS)
Turesson, I.; Notter, G.
1983-01-01
These clinical investigations of various dose-fractionation regimens on human skin show that: The late reactions cannot be predicted from the early reactions; The dose-response curves for late reactions are much steeper than for early reactions; Equivalent doses for various fractionation schedules concerning late effects can be calculated by means of a corrected CRE (NSD) formula; the correction must be considered preliminary because further follow-up is needed. A clinical fractionation study of this type requires: Extremely careful dosimetry; Study of the same anatomical region; Very long follow-up; Studies at different effect levels; Skin reaction is the only end point we have studied systematically for different fractionation regimens. Experience with the CRE formula as a model for calculating isoeffect doses for different fractionation schedules in routine clinical use can be summarized as follows: The CRE formula has been used prospectively since 1972 in all patients; CRE-equivalent weekly doses to 5 x 2.0 Gy per week has been used. (Although the fractionation schedule is changed, the overall treatment time is still the same); The CRE range was 18 to 21 for curative radiotherapy on carcinomas; No irradiation was applied during pronounced acute reactions. No unexpected complications have been observed under these conditions
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Late Globalization and Evolution, Episodes and Epochs of Industries
DEFF Research Database (Denmark)
Turcan, Romeo V.; Boujarzadeh, Behnam; Dholakia, Nikhilesh
While the empirical focus of this paper is the Danish Textile and Fashion Industry (DTFI) – specifically the episodes and epochs in the emergence and evolution of DTFI, in essence the micro and macro time-slices – the theoretical intent is wider. We aim to explore the conceptual terrain of what we...... for further exploration of the late globalization phenomenon. To get to the empirical case study, we follow a macro-conceptual to a micro-empirical path. We discuss the multidisciplinary and multifaceted field of late globalization and employing the historic-analytic approach to study DTFI we draw out very...... specific, empirically derived, conceptual themes about the patterns of global interactions that characterized the evolutionary trajectory of DTFI. We return to a final macro-conceptual section on late globalization where the particular DTFI case study advances the knowledge register only slightly; and we...
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Determinants and prevalence of late HIV testing in Tijuana, Mexico.
Carrizosa, Claudia M; Blumberg, Elaine J; Hovell, Melbourne F; Martinez-Donate, Ana P; Garcia-Gonzalez, Gregorio; Lozada, Remedios; Kelley, Norma J; Hofstetter, C Richard; Sipan, Carol L
2010-05-01
Timely diagnosis of HIV is essential to improve survival rates and reduce transmission of the virus. Insufficient progress has been made in effecting earlier HIV diagnoses. The Mexican border city of Tijuana has one of the highest AIDS incidence and mortality rates in all of Mexico. This study examined the prevalence and potential correlates of late HIV testing in Tijuana, Mexico. Late testers were defined as participants who had at least one of: (1) an AIDS-defining illness within 1 year of first positive HIV test; (2) a date of AIDS diagnosis within 1 year of first positive HIV test; or (3) an initial CD4 cell count below 200 cells per microliter within 1 year of first positive HIV test. Medical charts of 670 HIV-positive patients from two HIV/AIDS public clinics in Tijuana were reviewed and abstracted; 362 of these patients were interviewed using a cross-sectional survey. Using multivariate logistic regression, we explored potential correlates of late HIV testing based on the Behavioral Ecological Model. From 342 participants for whom late testing could be determined, the prevalence of late testing was 43.2%. Multivariate logistic regression results (n = 275) revealed five significant correlates of late testing: "I preferred not to know I had HIV" (adjusted odds ratio [AOR] = 2.78, 1.46-5.31); clinic (AOR = 1.90, 1.06-3.41); exposure to peers engaging in high-risk sexual behavior (AOR = 1.14, 1.02-1.27); stigma regarding HIV-infected individuals (AOR = 0.65, 0.47-0.92); and stigma regarding HIV testing (AOR = 0.66, 0.45-0.97). These findings may inform the design of interventions to increase timely HIV testing and help reduce HIV transmission in the community at large.
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Attention and Word Learning in Toddlers Who Are Late Talkers
MacRoy-Higgins, Michelle; Montemarano, Elizabeth A.
2016-01-01
The purpose of this study was to examine attention allocation in toddlers who were late talkers and toddlers with typical language development while they were engaged in a word-learning task in order to determine if differences exist. Two-year-olds who were late talkers (11) and typically developing toddlers (11) were taught twelve novel…
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Acute and late effects of multimodal therapy on normal tissues
International Nuclear Information System (INIS)
Phillips, T.L.; Fu, K.K.
1977-01-01
The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined
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Early- versus Late-Onset Dysthymia: A Meaningful Clinical Distinction?
Sansone, Randy A.; Sansone, Lori A.
2009-01-01
In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared ...
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Job shop scheduling problem with late work criterion
Piroozfard, Hamed; Wong, Kuan Yew
2015-05-01
Scheduling is considered as a key task in many industries, such as project based scheduling, crew scheduling, flight scheduling, machine scheduling, etc. In the machine scheduling area, the job shop scheduling problems are considered to be important and highly complex, in which they are characterized as NP-hard. The job shop scheduling problems with late work criterion and non-preemptive jobs are addressed in this paper. Late work criterion is a fairly new objective function. It is a qualitative measure and concerns with late parts of the jobs, unlike classical objective functions that are quantitative measures. In this work, simulated annealing was presented to solve the scheduling problem. In addition, operation based representation was used to encode the solution, and a neighbourhood search structure was employed to search for the new solutions. The case studies are Lawrence instances that were taken from the Operations Research Library. Computational results of this probabilistic meta-heuristic algorithm were compared with a conventional genetic algorithm, and a conclusion was made based on the algorithm and problem.
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Late malignant transformation of vestibular schwannoma in the absence of irradiation
DEFF Research Database (Denmark)
Bashir, Asma; Poulsgaard, Lars; Broholm, Helle
2016-01-01
Late malignant transformation of vestibular schwannoma (VS) following irradiation has previously been reported 29 times in the literature. Here, the authors report the first late malignant transformation of VS unrelated to neurofibromatosis or radiation exposure. After undergoing a near-total exc...
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Late Miocene magnetostratigraphy in the Mediterranean
Langereis, C.G.
1984-01-01
Reversals of the geomagnetic field In the geological past are recorded globally in the natural remanent magnetization (NRM) of igneous and sedimentary rock sequences. The accurate and rei iable reconstruction of this record is the basis of magnetostratigraphy. The magnetostratigraphy of Late
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Late Miocene magnetostratigraphy in the Mediterranean
Langereis, C.G.
1984-01-01
Reversals of the geomagnetic field In the geological past are recorded globally in the natural remanent magnetization (NRM) of igneous and sedimentary rock sequences. The accurate and rei iable reconstruction of this record is the basis of magnetostratigraphy. The magnetostratigraphy of Late Miocene
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Arvia, Rosaria; Sollai, Mauro; Pierucci, Federica; Urso, Carmelo; Massi, Daniela; Zakrzewska, Krystyna
2017-08-01
Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma and high viral load in the skin was proposed as a risk factor for the occurrence of this tumour. MCPyV DNA was detected, with lower frequency, in different skin cancers but since the viral load was usually low, the real prevalence of viral DNA could be underestimated. To evaluate the performance of two assays (qPCR and ddPCR) for MCPyV detection and quantification in formalin fixed paraffin embedded (FFPE) tissue samples. Both assays were designed to simultaneous detection and quantification of both MCPyV as well as house-keeping DNA in clinical samples. The performance of MCPyV quantification was investigated using serial dilutions of cloned target DNA. We also evaluated the applicability of both tests for the analysis of 76 FFPE cutaneous biopsies. The two approaches resulted equivalent with regard to the reproducibility and repeatability and showed a high degree of linearity in the dynamic range tested in the present study. Moreover, qPCR was able to quantify ≥10 5 copies per reaction, while the upper limit of ddPCR was 10 4 copies. There was not significant difference between viral load measured by the two methods The detection limit of both tests was 0,15 copies per reaction, however, the number of positive samples obtained by ddPCR was higher than that obtained by qPCR (45% and 37% respectively). The ddPCR represents a better method for detection of MCPyV in FFPE biopsies, mostly these containing low copies number of viral genome. Copyright © 2017 Elsevier B.V. All rights reserved.
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Etiology and electroclinical pattern of late onset epilepsy in Ibadan ...
African Journals Online (AJOL)
Late onset epilepsy (LOE) is a common neurological problem throughout the world. It is an area that has not been fully explored in the developing countries like Nigeria. The aim of the present study is to determine the pattern of presentation of late onset epilepsy with the view to identifying the etiologic as well as describe ...
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Late presentation of posterior urethral valves.
Jalbani, Imran Khan; Biyabani, Syed Raziuddin
2014-05-01
Presence of posterior urethral valves (PUV) is the most common cause of urinary tract obstruction in the male neonate. Late presentation occurs in 10% of cases. We present a case of PUVs in an adult male who presented with history of obstructive lower urinary tract symptoms and hematuria. On evaluation, he was found to have raised serum creatinine level. A voiding cystourethrogram (VCUG) could not be completely performed because of narrowing in the posterior urethra. A rigid urethrocystoscopy was performed at which he was found to have type-I posterior urethral valve which were fulgurated. A repeat uroflowmetry revealed maximum flow rate of 12 ml/second. This case highlights that PUVs is not solely a disease of infancy but may also present late. VCUG is the radiological investigation of choice but the diagnosis may be missed. A urethrocystoscopy is advised if there is a high index of suspicion.
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Factor analysis of symptom profile in early onset and late onset OCD.
Grover, Sandeep; Sarkar, Siddharth; Gupta, Gourav; Kate, Natasha; Ghosh, Abhishek; Chakrabarti, Subho; Avasthi, Ajit
2018-04-01
This study aimed to assess the factor structure of early and late onset OCD. Additionally, cluster analysis was conducted in the same sample to assess the applicability of the factors. 345 participants were assessed with Yale Brown Obsessive Compulsive Scale symptom checklist. Patients were classified as early onset (onset of symptoms at age ≤ 18 years) and late onset (onset at age > 18 years) OCD depending upon the age of onset of the symptoms. Factor analysis and cluster analysis of early-onset and late-onset OCD was conducted. The study sample comprised of 91 early onset and 245 late onset OCD subjects. Males were more common in the early onset group. Differences in the frequency of phenomenology related to contamination related, checking, repeating, counting and ordering/arranging compulsions were present across the early and late onset groups. Factor analysis of YBOCS revealed a 3 factor solution for both the groups, which largely concurred with each other. These factors were named as hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual and religious factor (factor-3). To conclude this study shows that factor structure of symptoms of OCD seems to be similar between early-onset and late-onset OCD. Copyright © 2017 Elsevier B.V. All rights reserved.
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LATE CREATACEOUS-CENOZOIC SEDIMENTS OF THE BAIKAL RIFT BASIN AND CHANGING NATURAL CONDITIONS
Directory of Open Access Journals (Sweden)
Viktor D. Mats
2010-01-01
Full Text Available The late Cretaceous-Cenozoic sediments of fossil soils and weathering crusts of the Baikal rift have been subject to long-term studies. Based on our research results, it is possible to distinguish the following litho-stratigraphic complexes which are related to particular stages of the rift development: the late Cretaceous–early Oligocene (crypto-rift Arheo-baikalian, the late Oligocene–early Pliocene (ecto-rift early orogenic Pra-baikalian, and the late Pliocene-Quaternary (ecto-rift late orogenic Pra-baikalian – Baikalian complexes. Changes of weathering modes (Cretaceous-quarter, soil formation (Miocene-quarter and differences of precipitation by vertical and lateral stratigraphy are analysed with regard to specific features of climate, tectonics and facial conditions of sedimentation. Tectonic phases are defined in the Cenozoic period of the Pribaikalie.
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Early versus Late Parenteral Nutrition in Critically Ill Children.
Fivez, Tom; Kerklaan, Dorian; Mesotten, Dieter; Verbruggen, Sascha; Wouters, Pieter J; Vanhorebeek, Ilse; Debaveye, Yves; Vlasselaers, Dirk; Desmet, Lars; Casaer, Michael P; Garcia Guerra, Gonzalo; Hanot, Jan; Joffe, Ari; Tibboel, Dick; Joosten, Koen; Van den Berghe, Greet
2016-03-24
Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients
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Hot Dust! Late-Time Infrared Emission From Supernovae
Fox, Ori; Skrutskie, M. F.; Chevalier, R. A.
2010-01-01
Supernovae light curves typically peak and fade in the course of several months. Some supernovae , however, exhibit late-time infrared emission that in some cases can last for several years. These supernovae tend to be of the Type IIn subclass, which is defined by narrow hydrogen and helium emission lines arising from a dense, pre-existing circumstellar medium excited by the supernova radiation. Such a late-time ``IR excess'' with respect to the optical blackbody counterpart typically indicates the presence of warm dust. The origin and heating mechanism of the dust is not, however, always well constrained. In this talk, I will explore several scenarios that explain the observed late-time emission. In particular, I will discuss the case of the Type IIn SN 2005ip, which has displayed an ``IR excess'' for over 3 years. The results allow us to interpret the progenitor system and better understand the late stages of stellar evolution. Much of the data used for this analysis were obtained with TripleSpec, a medium-resolution near-infrared spectrograph located at Apache Point Observatory, NM, and FanCam, a JHK imager located at Fan Mountain Observatory, just outside of Charlottesville, VA. These two instruments were designed, fabricated, built, and commissioned by our instrumentation group at the University of Virginia. I will also spend some time discussing these instruments. I would like to thank the following for financial support of this work throughout my graduate career: NASA GSRP, NSF AAG-0607737, Spitzer PID 50256, Achievement Reward for College Scientists (ARCS), and the Virginia Space Grant Consortium.
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The epidemiology of acne vulgaris in late adolescence
Lynn, Darren D; Umari, Tamara; Dunnick, Cory A; Dellavalle, Robert P
2016-01-01
Importance Acne vulgaris is the most common skin condition affecting late adolescents across the globe. Although prior studies have evaluated epidemiologic patterns of acne vulgaris in various ethnicities and regions, adequate understanding of the worldwide burden of the disease associated with patients in their late adolescence (15–19-year olds) remains lacking. Objective To assess the global burden of the disease associated with acne vulgaris for late adolescents (15–19-year olds) and provide an overview of the epidemiology, pathophysiology, and treatment options for acne in this population. Design Database summary study. Setting Global Burden of Disease Study 2010 database. Participants Global Burden of Disease regions comprised countries with prevalence of acne vulgaris between the ages of 15 and 19 years. Main outcomes and measures Geographic region-level disability-adjusted life year rates (per 100,000 persons) associated with acne vulgaris in years 1990 through 2010. Median percentage change in disability-adjusted life year rates was estimated for each region across the specified study period. Conclusion and relevance Acne vulgaris-associated disease burden exhibits global distribution and has continued to grow in prevalence over time within this population. This continued growth suggests an unmet dermatologic need worldwide for this disorder and potential opportunities for improved access and delivery of dermatologic care. Our analysis of the literature reveals numerous opportunities for enhanced patient care. To that end, we highlight some of the effective and promising treatments currently available and address important factors, such as sex, nationality, genetics, pathophysiology, and diet, as they relate to acne vulgaris in late adolescence. PMID:26955297
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Late Pliocene Depositional History and Paleoclimate Reconstructions of the Southwest Pacific
Royce, B.; Patterson, M. O.; Pietras, J.
2017-12-01
Drift deposits off the eastern margin of New Zealand are important archives for the paleoclimate and paleoceanographic history of the southwest Pacific. Ocean Drilling Program (ODP) Site 1123 is located on the North Chatham rise drift just North of the westerly wind driven Subtropical Front (STF) and provides a record of near continuous sediment deposition since the Miocene along the southwest Pacific deep western boundary current (DWBC). While the Miocene and Late Pleistocene portion of this record have been well studied, the Late Pliocene record is less well developed. Southern Ocean geological records demonstrate that Late Pliocene cooling is the transient time bracketing the warmer than present Early Pliocene and bipolar glaciation at 2.7 Ma. A newly developed, robust, and astronomically tuned long-term record of benthic δ13C from ODP Site 1123 spanning the Early to Late Pliocene implies a reduction in Southern Ocean ventilation and lowering of preformed values from waters sourced along the Antarctic margin during the Late Pliocene. Thus, Late Pliocene Southern Hemisphere cooling and sea ice expansion may have drastically reduced outgassing and increased the burial of heat into the deep ocean. South Atlantic records off the west coast of Africa demonstrate an increase in the flux of iron to the open ocean during this time potentially enhancing surface ocean productivity and providing an additional cooling mechanism. Currently, atmospheric transport of dust to the Southern Ocean is dominated by persistent mid-latitude circumpolar westerly winds; this is particularly relevant for dust sourced from New Zealand. The Late Pliocene to Early Pleistocene uplift of the North Island axial ranges and South Island southern alps potentially provided a greater amount of not only sediment to the deep ocean, but also wind blow dust to the Pacific sector of the Southern Ocean. We will present a detailed high-resolution sedimentological study on the development of the Chatham
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Berto, Claudio; Luzi, Elisa; Canini, Guido Montanari; Guerreschi, Antonio; Fontana, Federica
2018-03-01
The site of Riparo Tagliente (north-eastern Italy) contains one of the main Upper Pleistocene archaeological sequences of south-western Europe. It also represents a key site for the study of human adaptation to Late Glacial environmental changes in the southern Alpine area. These climatic and environmental conditions are here reconstructed based on small mammal assemblages, using the Bioclimatic model and Habitat Weighting methods. Climate proxies indicate a rise in temperature during the transition between HE1 and the Bølling-Allerød interstadial, while the landscape surrounding the shelter was still dominated by open grasslands. By comparing the data obtained from Riparo Tagliente with other coeval small mammal faunas from the Italian Peninsula and Europe we contribute to the reconstruction of the processes of faunal renewal registered during the Late Glacial across the continent and of the climatic and environmental context in which the Late Epigravettian hunter-gatherer groups lived.
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Late toxicity in breast cancer radiotherapy
International Nuclear Information System (INIS)
Gonzalez Coletti, F.; Rafailovici, L.; Filomia, M.L.; Chiozza, J.; Dosoretz, B.
2008-01-01
Full text: The aim of this study is to describe and classify chronic complications due to radiotherapy in breast cancer. Also the impact of radiotherapy on the quality of life of patients is evaluated. Materials and methods: 50 patients with breast cancer at early stages (78% in situ, 22% I and II) treated with radiotherapy in breast volume plus boost (45/50 Gy + 18/20 Gy) with a follow up over 5 years. Acute toxicities were found retrospectively and chronic toxicities were assessed though physical examination and review of complementary studies. To facilitate data collection, pre printed forms were used. Bibliographic searches were made. Results: 10% received chemotherapy and 64% tamoxifen. The predominant chronic toxicity were found in skin (66%), although grade I and II (hyperpigmentation 26%, dryness 22%, telangiectasia 10% fibrosis, 4%, other 4%). A 50% of the patients showed hypoesthesia in ipsilateral upper limb. The other toxicities were presented in low rate and magnitude: mastodynia 16%; actinic pneumonitis 4%, pyrosis 4%, Tachycardia 2%, among others. Of the patients with acute toxicity, only 30% were grade III. The 70% of the patients had a positive impact of radiotherapy on quality of life. Conclusions: We found low rates and degrees of late toxicity. It was noticed a relationship between acute and chronic toxicity, because those who presented adverse effects during treatment developed late effects. It reflects the importance of integrating monitoring as part of radiation treatment. It should be adopted a single score of late toxicity measurement to unify data from different series. (authors) [es
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Computed tomography of late-onset epilepsy
International Nuclear Information System (INIS)
Kim, Young Sik; Im, Jae Yung; Joo, Yang Goo; Park, Sam Kyoon
1982-01-01
Epilepsy can be divided into idiopathic epilepsy and symptomatic epilepsy according to the existence of underlying organic brain disease. It has been said that the incidence of the symptomatic epilepsy caused by underlying organic brain disease is higher in late-onset epilepsy after the age of 20 than in childhood-onset epilepsy. CT is very sensitive and non-invasive method for detection of organic brain disease. 168 cases of late-onset epilepsy after the age of of 20 were studied by CT in recent 2 years were analyzed. The results were as follows: 1. The 3rd decade was the most frequent age group, and the ratio of male to female was 2.5 : 1. 2. Structural abnormality on brain CT was demonstrated in 51.8% of the patient. 3. The older onset of age was, the higher the ratio of abnormal CT findings, except 5th decade which showed less CT abnormality than 4th decade. 4. The most frequent history related to epilepsy was trauma. 63.1% of patients had no relevant history: and they showed CT findings of brain tumor, atrophy and infraction in decreasing order of frequency. 5. Abnormal CT findings was demonstrated in 49.2% of normal neurologic examination and in 46.4% of normal EEG study. 6. The most frequent lesion of abnormal CT scan in late-onset epilepsy was 30 cases (18.4%) of brain atrophy. The next frequent lesion was 18 cases (10.7%) of brain tumor. Infarction, parasites and calcification were other frequent lesions
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Directory of Open Access Journals (Sweden)
Piotr Dudek
2017-06-01
Full Text Available In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH. In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.
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Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J
2007-12-01
Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.
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Cognitive advantages and disadvantages in early and late bilinguals.
Pelham, Sabra D; Abrams, Lise
2014-03-01
Previous research has documented advantages and disadvantages of early bilinguals, defined as learning a 2nd language by school age and using both languages since that time. Relative to monolinguals, early bilinguals manifest deficits in lexical access but benefits in executive function. We investigated whether becoming bilingual after childhood (late bilinguals) can produce the cognitive advantages and disadvantages typical of early bilinguals. Participants were 30 monolingual English speakers, 30 late English-Spanish bilinguals, and 30 early Spanish-English bilinguals who completed a picture naming task (lexical access) and an attentional network task (executive function). Late and early bilinguals manifested equivalent cognitive effects in both tasks, demonstrating lexical access deficits and executive function benefits. These findings provide support for the hypothesis that cognitive effects associated with bilingualism arise as the result of proficient, habitual use of 2 languages and not of developmental changes associated with becoming bilingual during childhood.
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Separation-individuation and assertiveness in late adolescents
Directory of Open Access Journals (Sweden)
Aslan, Sevda
2013-07-01
Full Text Available An adolescent can experience some problems regarding assertiveness during the course of separation-individuation from their caregivers. The purpose of this study is to describe the relationship between separation-individuation and assertiveness, which was examined in terms of how assertiveness predicts the separation-individuation of Turkish late adolescents. The sampling group consisted of 283 university students. The data gathered were analyzed by involving several simple regression analysis method. The findings revealed that aassertiveness predicts separation anxiety in a meaningful way. Furthermore, the assertiveness predicts engulfment anxiety, peer enmeshment, need denial, practicing-mirroring, rejection expectancy, and healthy separation. These findings suggest that psycho-educational studies improving assertiveness can be carried out for the late adolescents who experience separation-individuation problems.
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Late Bronze Age hoard studied by PIXE
Energy Technology Data Exchange (ETDEWEB)
Gutierrez Neira, P.C., E-mail: carolina.gutierrez@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Zucchiatti, A., E-mail: alessandro.zucchiatti@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Montero-Ruiz, I., E-mail: ignacio.montero@cchs.csic.es [CCHS-CSIC, Albasanz 26-28, E 28037 Madrid (Spain); Vilaca, R., E-mail: rvilaca@fl.uc.pt [University of Coimbra, Largo da Porta Ferrea, 3000-447 Coimbra (Portugal); Bottaini, C., E-mail: keret18@yahoo.it [University of Coimbra, Largo da Porta Ferrea, 3000-447 Coimbra (Portugal); Gener, M., E-mail: marc.gener@cchs.csic.es [CCHS-CSIC, Albasanz 26-28, E 28037 Madrid (Spain); Climent-Font, A., E-mail: acf@uam.es [CMAM, Universidad Autonoma de Madrid, c/Farady 3, E-28049 Madrid (Spain); Department of Applied Physics, Universidad Autonoma de Madrid, Campus Cantobalanco, E-28049 Madrid (Spain)
2011-12-15
The hoards of metallic objects belonging to the Late European Bronze Age can be interpreted differently depending on the type, number and composition of the artefacts. PIXE analysis has been performed in nine items from the Hoard of Freixanda in Portugal comprising four socket axes, a palstave axe, a ring, a chisel, a dagger, and a casting debris. Besides the composition of the main matrix elements, that is Cu and Sn, the amount of trace elements of interest like, As, Pb, Ni, and Ag has been determined using this ion beam technique. The high tin content alloy and the high purity of the metals from the Freixanda hoard are characteristic of the Portuguese and Spanish Late Bronze Age metallurgy, supporting the idea of a regional production.
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The location of late night bars and alcohol-related crashes in Houston, Texas.
Levine, Ned
2017-10-01
A study in the City of Houston, Texas, related the location of establishments primarily serving alcohol ("bars") after midnight to late night alcohol-related motor vehicle crashes. There were three data sets for 2007-09: 1) 764bars that were open after midnight; 2) 1660 alcohol-related crashes that occurred within the City of Houston between midnight and 6 am; and 3) 4689 modeling network road segments to which bars and alcohol-related crashes were assigned. Forty-five percent of the late night alcohol-related crashes were within a quarter mile of a late night bar. The bars were highly concentrated in 17 small bar clusters. Using the modeling network, Poisson-Gamma-CAR and Poisson-Lognormal-CAR spatial regression models showed a positive exponential relationship between late night alcohol-related crashes and the number of late nights bars and bar clusters, and a negative exponential relationship to distance to the nearest late night bar controlling for the type of road segment (freeway, principal arterial, minor arterial). A more general model dropped the bar cluster variable. Further, the Poisson-Gamma-CAR model appeared to produce a better representation than the Poisson-Lognormal-CAR model though the errors were different. The general Poisson-Gamma-CAR model showed that each late night bar increased the frequency of alcohol-related crashes on a segment by approximately 190%. For each mile closer a segment was to a late night bar, the likelihood increased by 42%. Copyright © 2017 Elsevier Ltd. All rights reserved.
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The Protocol for the Early vs. Late Infantile Strabismus Surgery Study
H.J. Simonsz (Huib)
1993-01-01
textabstractAbstract. The Early vs. Late Infantile Strabismus SurgerY Study Group is a group of strabismologists and orthoptists who investigate whether early or late surgery is preferable in infantile strabismus, in a non-randomized, prospective, multi-centre trial. Infants between 6 and 18 months
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Streel, Maurice; Caputo, Mário V.; Loboziak, Stanislas; Melo, José Henrique G.
2000-11-01
Palynomorph distribution in Euramerica and western Gondwana, from the Latest Givetian to the Latest Famennian, may be explained, to some extent, by climatic changes. Detailed miospore stratigraphy dates accurately the successive steps of these changes. Interpretation is built on three postulates which are discussed: Euramerica at slightly lower latitudes than generally accepted by most paleomagnetic reconstructions; a conodont time-scale accepted as the most used available subdivision of time; and Late Devonian sea-level fluctuations mainly governed by glacio-eustasy. The Frasnian-Famennian timescale is also evaluated. The comparison, based on conodont correlations, between Givetian and most of the Frasnian miospore assemblages from, respectively, northern and southern Euramerica demonstrates a high taxonomic diversity in the equatorial belt and much difference between supposed equatorial and (sub) tropical vegetations. On the contrary, a similar vegetation pattern and therefore probably compatible climatic conditions were present from tropical to subpolar areas. A rather hot climate culminated during the Latest Frasnian when equatorial miospore assemblages reached their maximum width. The miospore diversity shows also a rather clear global Late Frasnian minimum which is also recorded during the Early and Middle Famennian but only in low latitude regions while, in high latitude, very cold climates without perennial snow may explain the scarcity of miospores and so, of vegetation. The Early and Middle Famennian conspicuous latitudinal gradient of the vegetation seems to attenuate towards the Late and Latest Famennian but this might be above all the result of the development, of cosmopolitan coastal lowland vegetations (downstream swamps) depending more on the moisture and equable local microclimates than on the probably adverse climates of distant hinterland areas. During that time, periods of cold climate without perennial snow cover and with rare vegetation may
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Increased number of applications for late termination of pregnancy in Denmark
DEFF Research Database (Denmark)
Theibel, Sara Sofie; Petersson, Birgit; Christensen, Anne Vinggaard
2014-01-01
INTRODUCTION: Last year, it was 40 years since the introduction of legal abortion until the 12th week of gestation and the possibility of late termination of pregnancy in Denmark. The aim of this study was to describe the development in applications for late termination of pregnancy in the 1986......-2011-period focusing on indications related to the women's conditions. MATERIAL AND METHODS: All applications for late termination of pregnancy in 1986 were reviewed by Nordentoft et al, and access to all applications from 2011 was granted by the abortion committees and the Appeals Board. All applications...
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Social Capital is Associated With Late HIV Diagnosis: An Ecological Analysis.
Ransome, Yusuf; Galea, Sandro; Pabayo, Roman; Kawachi, Ichiro; Braunstein, Sarah; Nash, Denis
2016-10-01
Late HIV diagnosis is associated with higher medical costs, early mortality among individuals, and HIV transmission in the population. Even under optimal configurations of stable or declining HIV incidence and increase in HIV case findings, no change in proportion of late HIV diagnosis is projected after year 2019. We investigated the association among social capital, gender, and late HIV diagnosis. We conduct ecological analyses (ZIP code, N = 166) using negative binomial regression of gender-specific rates of late HIV diagnoses (an AIDS defining illness or a CD4 count ≤200 cell/μL within 12 months of a new HIV diagnosis) in 2005 and 2006 obtained from the New York City HIV Surveillance Registry, and social capital indicators (civic engagement, political participation, social cohesion, and informal social control) from the New York Social Indicators Survey, 2004. Overall, low to high political participation and social cohesion corresponded with significant (P social control [RR = 0.67, 95% CI: (0.48 to 0.93)] among men only and moderate social cohesion [RR = 0.71, 95% CI: (0.55 to 0.92)] among women only were associated with the outcome adjusting for social fragmentation, income inequality, and racial composition. The magnitude of association between social capital and late HIV diagnosis varies by gender and by social capital indicator.
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A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.
Pelletier, Daniel J; Czeczok, Thomas W; Bellizzi, Andrew M
2018-07-01
Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective. Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches. The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma. © 2018 John Wiley & Sons Ltd.
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Peeters, J.; Busschers, F. S.; Stouthamer, E.; Bosch, J. H. A.; Van den Berg, M. W.; Wallinga, J.; Versendaal, A. J.; Bunnik, F. P. M.; Middelkoop, H.
2016-01-01
This paper describes the sedimentary architecture, chronostratigraphy and palaeogeography of the late Middle and Late Pleistocene (Marine Isotope Stage/MIS 6-2) incised Rhine-valley fill in the central Netherlands based on six geological transects, luminescence dating, biostratigraphical data and a 3D geological model. The incised-valley fill consists of a ca. 50 m thick and 10-20 km wide sand-dominated succession and includes a well-developed sequence dating from the Last Interglacial: known as the Eemian in northwest Europe. The lower part of the valley fill contains coarse-grained fluvio-glacial and fluvial Rhine sediments that were deposited under Late Saalian (MIS 6) cold-climatic periglacial conditions and during the transition into the warm Eemian interglacial (MIS 5e-d). This unit is overlain by fine-grained fresh-water flood-basin deposits, which are transgressed by a fine-grained estuarine unit that formed during marine high-stand. This ca. 10 m thick sequence reflects gradual drowning of the Eemian interglacial fluvial Rhine system and transformation into an estuary due to relative sea-level rise. The chronological data suggests a delay in timing of regional Eemian interglacial transgression and sea-level high-stand of several thousand years, when compared to eustatic sea-level. As a result of this glacio-isostatic controlled delay, formation of the interglacial lower deltaic system took only place for a relative short period of time: progradation was therefore limited. During the cooler Weichselian Early Glacial period (MIS 5d-a) deposition of deltaic sediments continued and extensive westward progradation of the Rhine system occurred. Major parts of the Eemian and Weichselian Early Glacial deposits were eroded and buried as a result of sea-level lowering and climate cooling during the early Middle Weichselian (MIS 4-3). Near complete sedimentary preservation occurred along the margins of the incised valley allowing the detailed reconstruction presented
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Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects
Energy Technology Data Exchange (ETDEWEB)
Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)
2016-01-01
Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late
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Early and late endocrine effects in pediatric central nervous system diseases.
Aslan, Ivy R; Cheung, Clement C
2014-01-01
Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.
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Clinical impact of predictive assays for acute and late radiation morbidity
International Nuclear Information System (INIS)
Budach, W.; Classen, J.; Belka, C.; Bamberg, M.
1998-01-01
Background: Clinically reliable predictive assays for normal tissue radiation sensitivity would help to avoid severe radiation induced morbidity and result in individualized dose prescriptions. Profound differences of individual fibroblast and lymphocyte radiation sensitivity in vitro have been documented in patients with certain genetic syndromes but also in patients without known genetic disorders. The following review evaluates whether fibroblast or lymphocyte radiation sensitivity measured in vitro correlates with the degree of acute and late radiation induced morbidity. Results: Acute radiation side effects and lymphocyte sensitivity has been investigated in 2 studies. One of them reported an insecure correlation, the other no correlation at all. Fibroblast radiation sensitivity and the extent of acute radiation induced side effects on skin and mucosal sites has been compared in a total of 5 studies. None of these studies found a consistent significant correlation. Lymphocyte radiation sensitivity and late effects have been studied by 2 institutions. Late radiation induced skin and mucosal changes did not correlate with lymphocyte sensitivity in head and neck cancer patients, whereas in breast cancer patients a weak (R 2 =0.06) correlation between the degree of late skin reactions and lymphocyte sensitivity was observed. Late skin or mucosal radiation reactions and fibroblast sensitivity were examined by 5 research groups. Data analysis revealed significant correlations or at least a trend towards a significant correlation in all studies. The quality of the reported correlations expressed as R 2 ranged from 0.13 to 0.60, indicating a low predictive value. Conclusions: Lymphocyte radiation sensitivity as measured by currently available assays does not or only poorly correlate with acute and late effects of radiation in patients, precluding predictive tests based on lymphocyte sensitivity. Fibroblast radiation sensitivity does not correlate with acute but
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Late time solution for interacting scalar in accelerating spaces
Energy Technology Data Exchange (ETDEWEB)
Prokopec, Tomislav, E-mail: t.prokopec@uu.nl [Institute for Theoretical Physics, Spinoza Institute and EMME$\\Phi$, Utrecht University, Postbus 80.195, Utrecht, 3508 TD The Netherlands (Netherlands)
2015-11-01
We consider stochastic inflation in an interacting scalar field in spatially homogeneous accelerating space-times with a constant principal slow roll parameter ε. We show that, if the scalar potential is scale invariant (which is the case when scalar contains quartic self-interaction and couples non-minimally to gravity), the late-time solution on accelerating FLRW spaces can be described by a probability distribution function (PDF) ρ which is a function of φ/H only, where φ=φ( x-vector ) is the scalar field and H=H(t) denotes the Hubble parameter. We give explicit late-time solutions for ρarrow ρ{sub ∞}(φ/H), and thereby find the order ε corrections to the Starobinsky-Yokoyama result. This PDF can then be used to calculate e.g. various n-point functions of the (self-interacting) scalar field, which are valid at late times in arbitrary accelerating space-times with ε= constant.
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Neuropsychiatric manifestations in late-onset urea cycle disorder patients.
Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A
2010-03-01
Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.
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Efficacy of brain scanning in epilepsy of late onset
International Nuclear Information System (INIS)
Jain, A.N.; Ramanathan, P.; Ganatra, R.D.
1978-01-01
Brain scans of 513 patients with epilepsy of late onset were analysed with reference to the patient's age and sex and to the nature of convulsion. Only 17 of them showed an abnormal concentration of radionuclide indicating a space-occupying lesion in the brain. The findings of those patients who had positive brain scans were correlated with EEG findings. It was found that the incidence of epilepsy of late onset is almost 3 times higher in males than in females and that the age cannot be considered as a criterion for screening the patients for brain scan investigation as far as epilepsy of late onset is concerned. In the authors' opinion, the incidence of 3.3% is not too low. A positive brain scan finding calls for further investigation and helps in deciding the management and further line of treatment of the patients. Moreover, a normal scan rules out the presence of a space-occupying lesion and helps as a screening procedure. (orig.) 891 MG [de
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Report of the laboratory building for late occurring injury
International Nuclear Information System (INIS)
1978-01-01
In order to estimate the danger of low level radiation to human beings, the studies of the late-occurring injuries and internal exposure due to radionuclide deposition are necessary. In the National Institute of Radiological Sciences, research on the estimation of the danger of late-occurring injuries due to radiation is proceeding. In this connection, a late-occurring injury laboratory building has been completed recently. Basic ideas behind it are as follows. To carry out the above mentioned studies effectively and efficiently, many experimental animals of high quality must be kept under best possible environment. For the observation in a series of experiments, irradiation room and laboratory rooms are essential. The building comprises the following: the first floor for animal receiving, the second floor for laboratory rooms, the third floor for RI facility and X-ray irradiated animal keeping, the fourth floor for SPF animal keeping, and attic floor for water supply, etc. (J.P.N.)
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Late-life factors associated with healthy aging in older men.
Bell, Christina L; Chen, Randi; Masaki, Kamal; Yee, Priscilla; He, Qimei; Grove, John; Donlon, Timothy; Curb, J David; Willcox, D Craig; Poon, Leonard W; Willcox, Bradley J
2014-05-01
To identify potentially modifiable late-life biological, lifestyle, and sociodemographic factors associated with overall and healthy survival to age 85. Prospective longitudinal cohort study with 21 years of follow-up (1991-2012). Hawaii Lifespan Study. American men of Japanese ancestry (mean age 75.7, range 71-82) without baseline major clinical morbidity and functional impairments (N = 1,292). Overall survival and healthy survival (free from six major chronic diseases and without physical or cognitive impairment) to age 85. Factors were measured at late-life baseline examinations (1991-1993). Of 1,292 participants, 1,000 (77%) survived to 85 (34% healthy) and 309 (24%) to 95 (healthy). Late-life factors associated with survival and healthy survival included biological (body mass index, ankle-brachial index, cognitive score, blood pressure, inflammatory markers), lifestyle (smoking, alcohol use, physical activity), and sociodemographic factors (education, marital status). Cumulative late-life baseline risk factor models demonstrated that age-standardized (at 70) probability of survival to 95 ranged from 27% (no factors) to 7% (≥ 5 factors); probability of survival to 100 ranged from 4% (no factors) to 0.1% (≥ 5 factors). Age-standardized (at 70) probability of healthy survival to 90 ranged from 4% (no factors) to 0.01% (≥ 5 factors). There were nine healthy survivors at 95 and one healthy survivor at 100. Several potentially modifiable risk factors in men in late life (mean age 75.7) were associated with markedly greater probability of subsequent healthy survival and longevity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
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Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.
Farace, Paolo; Tambalo, Stefano; Fiorini, Silvia; Merigo, Flavia; Daducci, Alessandro; Nicolato, Elena; Conti, Giamaica; Degrassi, Anna; Sbarbati, Andrea; Marzola, Pasquina
2011-03-01
To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns. Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251. In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG. In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema. Copyright © 2011 Wiley-Liss, Inc.
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Impact of Urban Neighborhood Disadvantage on Late Stage Breast Cancer Diagnosis in Virginia.
DeGuzman, Pam Baker; Cohn, Wendy F; Camacho, Fabian; Edwards, Brandy L; Sturz, Vanessa N; Schroen, Anneke T
2017-04-01
Research suggests that residents of inner-city urban neighborhoods have higher rates of late stage cancer diagnosis. Identifying urban neighborhoods with high rates of both concentrated disadvantage and late stage cancer diagnosis may assist health care providers to target screening interventions to reduce disparities. The purposes of this study were to (1) create an index to evaluate concentrated disadvantage (CD) using non-racial measures of poverty, (2) determine the impact of neighborhood CD on late stage breast cancer diagnosis in US cities, and (3) to understand the role of obesity on this relationship. We used census block group- (CBG) level poverty indicators from five Virginia cities to develop the index. Breast cancer cases of women aged 18-65 who lived in the five cities were identified from the 2000-2012 Virginia Cancer Registry. A logistic regression model with random intercept was used to evaluate the impact of disadvantage on late stage breast cancer diagnosis. CBG-level maps were developed to geographically identify neighborhoods with both high rates of CD and late breast cancer staging. Over 900 CBGs and 6000 breast cases were included. Global fit of the concentrated disadvantage model was acceptable. The effect of disadvantage on late stage was significant (OR = 1.0083, p = 0.032). Inner-city poverty impacts risk of late stage breast cancer diagnosis. Area-level obesity is highly correlated with neighborhood poverty (ρ = 0.74, p diagnosis for urban poor and for minorities living in these underserved neighborhoods, but more study is needed to understanding the complex relationship between concentrated neighborhood poverty, obesity, and late stage diagnosis.
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49 CFR 89.23 - Interest, late payment penalties, and collection charges.
2010-10-01
... received. Interest shall be calculated only on the principal of the debt (simple interest). The rate of... 49 Transportation 1 2010-10-01 2010-10-01 false Interest, late payment penalties, and collection... THE FEDERAL CLAIMS COLLECTION ACT Collection of Claims § 89.23 Interest, late payment penalties, and...
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The Late Ordovician deglaciation sequence of the SW Murzuq Basin (Libya)
DEFF Research Database (Denmark)
Moreau, Julien
2011-01-01
Rocks of Late Ordovician to Silurian age are well exposed on the western rim of theMurzuq Basin (Ghat-Tikiumit area,Libya)where seismic-scale exposures allow spectacular insights into the growth and decay of the LateOrdovician (Hirnantian) ice sheet.The ¢nal deglaciation left a complex topography...
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Partial resistance of tomatoes against Phytophthora infestans, the late blight fungus
Turkensteen, L.J.
1973-01-01
In the Netherlands, the source of inoculum of the late blight fungus on tomatoes is the late blight fungus on potato crops. In regions of Europe mentioned, where tomatoes are grown in the open, P. infestans on tomatoes is the main source of inoculum. Especially in -
Early and late synovectomy of the knee in rheumatoid arthritis
DEFF Research Database (Denmark)
Jensen, C M; Poulsen, S; Ostergren, M
1991-01-01
was reduced and range of motion was unchanged. Total knee alloplasty (TKA) was performed in one knee among the patients who underwent early synovectomy, while reoperation with TKA had been performed in 12 out of 28 knees after late synovectomy. It is concluded that early synovectomy is indicated when medical...... treatment has failed. Late synovectomy must be regarded as a palliative procedure in order to postpone TKA....
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Language Control Abilities of Late Bilinguals
Festman, Julia
2012-01-01
Although all bilinguals encounter cross-language interference (CLI), some bilinguals are more susceptible to interference than others. Here, we report on language performance of late bilinguals (Russian/German) on two bilingual tasks (interview, verbal fluency), their language use and switching habits. The only between-group difference was CLI:…
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Environmental roots of the late bronze age crisis.
Directory of Open Access Journals (Sweden)
David Kaniewski
Full Text Available The Late Bronze Age world of the Eastern Mediterranean, a rich linkage of Aegean, Egyptian, Syro-Palestinian, and Hittite civilizations, collapsed famously 3200 years ago and has remained one of the mysteries of the ancient world since the event's retrieval began in the late 19(th century AD/CE. Iconic Egyptian bas-reliefs and graphic hieroglyphic and cuneiform texts portray the proximate cause of the collapse as the invasions of the "Peoples-of-the-Sea" at the Nile Delta, the Turkish coast, and down into the heartlands of Syria and Palestine where armies clashed, famine-ravaged cities abandoned, and countrysides depopulated. Here we report palaeoclimate data from Cyprus for the Late Bronze Age crisis, alongside a radiocarbon-based chronology integrating both archaeological and palaeoclimate proxies, which reveal the effects of abrupt climate change-driven famine and causal linkage with the Sea People invasions in Cyprus and Syria. The statistical analysis of proximate and ultimate features of the sequential collapse reveals the relationships of climate-driven famine, sea-borne-invasion, region-wide warfare, and politico-economic collapse, in whose wake new societies and new ideologies were created.
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Central-peripheral Temperature Monitoring as a Marker for Diagnosing Late-onset Neonatal Sepsis.
Leante-Castellanos, José Luis; Martínez-Gimeno, Antonio; Cidrás-Pidré, Manuel; Martínez-Munar, Gerardo; García-González, Ana; Fuentes-Gutiérrez, Carmen
2017-12-01
The prognosis for late-onset sepsis depends largely on a timely diagnosis. We assess central-peripheral temperature difference monitoring as a marker for late-onset neonatal sepsis diagnosis. We performed a prospective, observational study focusing on a cohort of 129 very low-birth-weight infants. Thermal gradient alteration was defined as a difference of > 2°C maintained during 4 hours. We then determined its association with the late-onset sepsis variable through logistic regression. We enrolled 129 preterm babies in 52 months. Thermal gradient alterations showed an adjusted odds ratio for late-onset sepsis of 23.60 (95% confidence interval [CI], 6.80-81.88), with a sensitivity of 83% and negative predictive value of 94%. In 71% of cases, thermal gradient alteration was the first clinical sign of sepsis, while C-reactive protein was peripheral temperature differences are an early sign of evolving late-onset sepsis.
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Is Late or Non-Payment a Significant Problem to Malaysian Contractors?
Directory of Open Access Journals (Sweden)
M.E. Che Munaaim
2007-12-01
Full Text Available Some developed countries have drawn lip construction-specific statutory security of payment acts/legislations typically known as Construction Contracts Act to eliminate poor payment practices and to assist continuous uninterrupted construction works. Malaysia too cannot pretend not to have these problems. This paper presents findings of a study conducted amongst Malaysian contractors with the aims to determine the seriousness of late and non- payment problems; to identify the main causes and effects of late and non-payment; and to identify ways to sustain the payment flows in the Malaysian construction industry. The study focused on contractual payments from the paymaster (government or private to the contractors. The main factors for late and nonpayment in the construction industry identified from the study include: delay in certification, paymaster's poor financial management, local culture/attitude, pay master's failure to implement good governance in business, underpayment of certified amounts by the pay master and the use of 'pay when paid' clauses in contracts. The research findings show that late and non-payment can create cash flow problems, stress and financial hardship on the contractors. Amongst the most appropriate solutions to overcome the problem of late and non-payment faced by local contractors include: a right to regular periodic payment, a right to a defined time frame (or payment and a right to a speedy dispute resolution mechanism. Promptness of submitting, processing, issuing interim payment certificates and honouring the certificates are extremely important issues in relation to progress payment claims. Perhaps, an increased sense of professionalism in construction industry could overcome some of the problems related to late and non- payment issues.
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Preventability of early vs. late readmissions in an academic medical center.
Directory of Open Access Journals (Sweden)
Kelly L Graham
Full Text Available It is unclear if the 30-day unplanned hospital readmission rate is a plausible accountability metric.Compare preventability of hospital readmissions, between an early period [0-7 days post-discharge] and a late period [8-30 days post-discharge]. Compare causes of readmission, and frequency of markers of clinical instability 24h prior to discharge between early and late readmissions.120 patient readmissions in an academic medical center between 1/1/2009-12/31/2010.Sum-score based on a standard algorithm that assesses preventability of each readmission based on blinded hospitalist review; average causation score for seven types of adverse events; rates of markers of clinical instability within 24h prior to discharge.Readmissions were significantly more preventable in the early compared to the late period [median preventability sum score 8.5 vs. 8.0, p = 0.03]. There were significantly more management errors as causative events for the readmission in the early compared to the late period [mean causation score [scale 1-6, 6 most causal] 2.0 vs. 1.5, p = 0.04], and these errors were significantly more preventable in the early compared to the late period [mean preventability score 1.9 vs 1.5, p = 0.03]. Patients readmitted in the early period were significantly more likely to have mental status changes documented 24h prior to hospital discharge than patients readmitted in the late period [12% vs. 0%, p = 0.01].Readmissions occurring in the early period were significantly more preventable. Early readmissions were associated with more management errors, and mental status changes 24h prior to discharge. Seven-day readmissions may be a better accountability measure.
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van Rijssen, A. L.; Wilmink, Han; van Wingerden, Jan J.; van der Lei, Berend
Late hematoma formation is a rare complication of augmentation mammaplasty. Late hematoma formation related to excessive or vigorous squeezing of the breast during sexual activity has not been described. We present 2 such cases and review the English-language literature on all causes of late
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van Rijssen, A. L.; Wilmink, Han; van Wingerden, Jan J.; van der Lei, Berend
2008-01-01
Late hematoma formation is a rare complication of augmentation mammaplasty. Late hematoma formation related to excessive or vigorous squeezing of the breast during sexual activity has not been described. We present 2 such cases and review the English-language literature on all causes of late
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Features of Social Cognition in Late Adulthood
Directory of Open Access Journals (Sweden)
Melehin A.I.
2015-12-01
Full Text Available The paper presents outcomes of researches on the central component of social cognition — theory of mind in late adulthood. The outcomes show that, in normal aging, in advanced adulthood (55—74 years as well as in old age (75—90 years there are several qualitative changes in the affective (understanding and differentiation of emotions and cognitive (understanding irony and deceit components of theory of mind. Also, at these ages individuals may develop various forms of theory of mind deficits. They may encounter difficulties with reading facial expressions and recognizing other people’s emotions. It becomes harder for them to recognize negative emotions (such as sorrow, fear, anger than positive ones (joy. The paper describes features of pragmatic interpretation of events and understanding of deceit and irony in late adulthood.
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Cornulitids (tubeworms) from the Late Ordovician Hirnantia fauna of Morocco
Gutiérrez-Marco, Juan Carlos; Vinn, Olev
2018-01-01
Two species of cornulitids, Cornulites gondwanensis sp. nov. and C. aff. shallochensis Reed are described from the Hirnantian of Morocco, within an assemblage representative of the Hirnantia brachiopod fauna occurring near the Ordovician South Pole. The dominance of aggregated and solitary free forms could be explained by particular sedimentary environments preceding the Hirnantian glaciation and the latest Ordovician Extinction Event. The diversity of cornulitids in the Late Ordovician of Gondwana and related terranes was relatively low, and less diverse than the cornulitids of Laurentia and Baltica. Hirnantian cornulitids from Morocco do not resemble Late Ordovician cornulitids of Baltica and Laurentia. Moroccan cornulitids seem to be closely allied to some older Gondwanan cornulitids, especially Sardinian ones. They resemble species described from the Late Ordovician and Llandovery of Scotland suggesting a palaeobiogeographic link.
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An Empirical Typology of Narcissism and Mental Health in Late Adolescence
Lapsley, Daniel K.; Aalsma, Matthew C.
2006-01-01
A two-step cluster analytic strategy was used in two studies to identify an empirically derived typology of narcissism in late adolescence. In Study 1, late adolescents (N=204) responded to the profile of narcissistic dispositions and measures of grandiosity (''superiority'') and idealization (''goal instability'') inspired by Kohut's theory,…
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Late presentation to HIV care despite good access to health services
DEFF Research Database (Denmark)
Darling, Katharine Ea; Hachfeld, Anna; Cavassini, Matthias
2016-01-01
infection rates are rising, and diagnosing HIV early in the course of infection remains a challenge. Late presentation to care in HIV refers to individuals newly presenting for HIV care with a CD4 count below 350 cells/µl or with an acquired immune deficiency syndrome (AIDS)-defining event. Late...
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Christensen, Anne Vinggaard; Christiansen, Anne Hjøllund; Petersson, Birgit
2013-12-01
The introduction of prenatal screening for all pregnant women in Denmark in 2004 has lead to an increase in the number of late terminations of pregnancy after the 12th week of pregnancy. Midwives' experiences with late termination of pregnancy (TOP) are still poorly described in the scientific literature. To explore Danish midwives' experiences with and attitudes towards late TOP. Focus was on how midwives perceive their own role in late TOP, and how their professional identity is influenced by working with late TOP in a time where prenatal screening is rapidly developing. A qualitative study consisting of ten individual interviews with Danish midwives, all of whom had taken part in late TOP. Current practice of late TOP resembles the practice of normal deliveries and is influenced by a growing personalisation of the aborted foetus. The midwives strongly supported women's legal right to choose TOP and considerations about the foetus' right to live were suppressed. Midwives experienced a dilemma when faced with aborted foetuses that looked like newborns and when aborted foetuses showed signs of life after a termination. Furthermore, they were critical of how physicians counsel women/couples after prenatal diagnosis. The midwives' practice in relation to late TOP was characterised by an acknowledgement of the growing ethical status of the foetus and the emotional reactions of the women/couples going through late TOP. Other professions as well as structural factors at the hospital highly influenced the midwives' ability to organize their work with late terminations. There is a need for more thorough investigation of how to secure the best possible working conditions for midwives, and how to optimise the care for women/couples going through late TOP. © 2012 The Authors Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.
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International Nuclear Information System (INIS)
Jereczek-Fossa, Barbara A.; Jassem, Jacek; Badzio, Andrzej
2002-01-01
Purpose: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. Results: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p=0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p<0.001 and p=0.47, respectively). The severity of acute
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Reporting Late Rectal Toxicity in Prostate Cancer Patients Treated With Curative Radiation Treatment
International Nuclear Information System (INIS)
Faria, Sergio L.; Souhami, Luis; Joshua, Bosede; Vuong, Te; Freeman, Carolyn R.
2008-01-01
Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients
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Late effects of normal tissues (lent) scoring system: the soma scale
International Nuclear Information System (INIS)
Mornex, F.; Pavy, J.J.; Denekamp, J.
1997-01-01
Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)
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DEFF Research Database (Denmark)
Christoffersen, Mogens; Lausten, Mette
2009-01-01
The study investigates parental child rearing methods, structural factors relating to the family during adolescence geographic segregation, individual resource deficits and social background of first time late live births among 32 to 37 years old women and compare to teenagers before becoming...... economic and social gradient for first-time teenage mothers. Teenagers who had experienced family separation or who were formerly in out-of-home care in particular had an increased risk of early childbearing. Results showed that teenage mothers were in every respect in a more disadvantaged position than...
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International Nuclear Information System (INIS)
Kiat, H.; Berman, D.S.; Maddahi, J.; De Yang, L.; Van Train, K.; Rozanski, A.; Friedman, J.
1988-01-01
Twenty-one patients were studied who underwent thallium-201 stress-redistribution single photon emission computed tomography (SPECT) both before and after coronary artery bypass grafting (n = 15) or transluminal coronary angioplasty (n = 6). All patients underwent thallium imaging 15 min, 4 h and late (18 to 72 h) after stress as part of the preintervention thallium-201 scintigram. In a total of 201 tomographic myocardial segments with definite post-stress thallium-201 perfusion defects in which the relevant coronary arteries were subsequently successfully reperfused, the 4 h redistribution images did not predict the postintervention scintigraphic improvement: 67 (85%) of the 79 4 h reversible as well as 88 (72%) of the 122 4 h nonreversible segments improved (p = NS). The 18 to 72 h late redistribution images effectively subcategorized the 4 h nonreversible segments with respect to postintervention scintigraphic improvement: 70 (95%) of the 74 late reversible segments improved after intervention, whereas only 18 (37%) of the 48 late nonreversible segments improved (p less than 0.0001). The frequency of late reversible defects and the frequency of postrevascularization improvement of late nonreversible defects are probably overestimated by this study because of referral biases. The cardiac counts and target to background ratios from late redistribution studies resulted in satisfactory cardiac images for visual interpretation. For optimal assessment of the extent of viable myocardium by thallium-201 scintigraphic studies, late redistribution imaging should be performed when nonreversible defects are observed on 4 h redistribution images
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The association of sleep and late-night cell phone use among adolescents
Directory of Open Access Journals (Sweden)
Babak Amra
Full Text Available Abstract Objective: This study aims to assess the relationship of late-night cell phone use with sleep duration and quality in a sample of Iranian adolescents. Methods: The study population consisted of 2400 adolescents, aged 12-18 years, living in Isfahan, Iran. Age, body mass index, sleep duration, cell phone use after 9 p.m., and physical activity were documented. For sleep assessment, the Pittsburgh Sleep Quality Index questionnaire was used. Results: The participation rate was 90.4% (n = 2257 adolescents. The mean (SD age of participants was 15.44 (1.55 years; 1270 participants reported to use cell phone after 9 p.m. Overall, 56.1% of girls and 38.9% of boys reported poor quality sleep, respectively. Wake-up time was 8:17 a.m. (2.33, among late-night cell phone users and 8:03 a.m. (2.11 among non-users. Most (52% late-night cell phone users had poor sleep quality. Sedentary participants had higher sleep latency than their peers. Adjusted binary and multinomial logistic regression models showed that late-night cell users were 1.39 times more likely to have a poor sleep quality than non-users (p-value < 0.001. Conclusion: Late-night cell phone use by adolescents was associated with poorer sleep quality. Participants who were physically active had better sleep quality and quantity. As part of healthy lifestyle recommendations, avoidance of late-night cell phone use should be encouraged in adolescents.
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The association of sleep and late-night cell phone use among adolescents.
Amra, Babak; Shahsavari, Ali; Shayan-Moghadam, Ramin; Mirheli, Omid; Moradi-Khaniabadi, Bita; Bazukar, Mehdi; Yadollahi-Farsani, Ashkan; Kelishadi, Roya
This study aims to assess the relationship of late-night cell phone use with sleep duration and quality in a sample of Iranian adolescents. The study population consisted of 2400 adolescents, aged 12-18 years, living in Isfahan, Iran. Age, body mass index, sleep duration, cell phone use after 9p.m., and physical activity were documented. For sleep assessment, the Pittsburgh Sleep Quality Index questionnaire was used. The participation rate was 90.4% (n=2257 adolescents). The mean (SD) age of participants was 15.44 (1.55) years; 1270 participants reported to use cell phone after 9p.m. Overall, 56.1% of girls and 38.9% of boys reported poor quality sleep, respectively. Wake-up time was 8:17 a.m. (2.33), among late-night cell phone users and 8:03a.m. (2.11) among non-users. Most (52%) late-night cell phone users had poor sleep quality. Sedentary participants had higher sleep latency than their peers. Adjusted binary and multinomial logistic regression models showed that late-night cell users were 1.39 times more likely to have a poor sleep quality than non-users (p-value<0.001). Late-night cell phone use by adolescents was associated with poorer sleep quality. Participants who were physically active had better sleep quality and quantity. As part of healthy lifestyle recommendations, avoidance of late-night cell phone use should be encouraged in adolescents. Copyright © 2017. Published by Elsevier Editora Ltda.
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Late kinetic decoupling of light magnetic dipole dark matter
International Nuclear Information System (INIS)
Gondolo, Paolo; Kadota, Kenji
2016-01-01
We study the kinetic decoupling of light (≲10 GeV) magnetic dipole dark matter (DM). We find that present bounds from collider, direct DM searches, and structure formation allow magnetic dipole DM to remain in thermal equilibrium with the early universe plasma until as late as the electron-positron annihilation epoch. This late kinetic decoupling leads to a minimal mass for the earliest dark protohalos of thousands of solar masses, in contrast to the conventional weak scale DM scenario where they are of order 10 −6 solar masses.
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30 CFR 870.21 - Late payments.
2010-07-01
... Government. The Treasury current value of funds rate is published annually in the Federal Register and on... fees and interest. (c) When a reclamation fee debt is more than 91 days overdue, a 6 percent annual... fee was owed are subject to interest. Late reclamation fee payments are subject to interest at the...
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Early and late humoral rejection: a clinicopathologic entity in two times.
Péfaur, J; Díaz, P; Panace, R; Salinas, P; Fiabane, A; Quinteros, N; Chea, R; Naranjo, E; Wurgaft, A; Beltran, E; Elgueta, S; Wegmann, M E; Gajardo, J G; Contreras, L
2008-11-01
Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.
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Fires in the Cenozoic: a late flowering of flammable ecosystems
Directory of Open Access Journals (Sweden)
William John Bond
2015-01-01
Full Text Available Modern flammable ecosystems include tropical and subtropical savannas, steppe grasslands, boreal forests and temperate sclerophyll shrublands. Despite the apparent fiery nature of much contemporary vegetation, terrestrial fossil evidence would suggest we live in a time of low fire activity relative to the deep past. The inertinite content of coal, fossil charcoal, is strikingly low from the Eocene to the Pleistocene and no charcoalified mesofossils have been reported for the Cenozoic. Marine cores have been analysed for charcoal in the North Pacific, the north and south Atlantic off Africa, and the south China sea. These tell a different story with the oldest records indicating low levels of fire activity from the Eocene but a surge of fire from the late Miocene (~7 Ma. Phylogenetic studies of woody plants adapted to frequent savanna fires show them beginning to appear from the Late Miocene with peak origins in the late Pliocene in both South American and African lineages. Phylogenetic studies indicate ancient origins (60 Ma+ for clades characteristic of flammable sclerophyll vegetation from Australia and the Cape region of South Africa. However, as for savannas, there was a surge of speciation from the Late Miocene associated with the retreat of closed fire-intolerant forests. The wide geographic spread of increased fire activity in the last few million years suggests a global cause. However none of the potential global factors (oxygen, rainfall seasonality, CO2 , novel flammable growth forms provides an adequate explanation as yet. The global patterns and processes of fire and flammable vegetation in the Cenozoic, especially since the Late Miocene, deserve much more attention to better understand fire in the earth system.
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Fires in the Cenozoic: a late flowering of flammable ecosystems.
Bond, William J
2014-01-01
Modern flammable ecosystems include tropical and subtropical savannas, steppe grasslands, boreal forests, and temperate sclerophyll shrublands. Despite the apparent fiery nature of much contemporary vegetation, terrestrial fossil evidence would suggest we live in a time of low fire activity relative to the deep past. The inertinite content of coal, fossil charcoal, is strikingly low from the Eocene to the Pleistocene and no charcoalified mesofossils have been reported for the Cenozoic. Marine cores have been analyzed for charcoal in the North Pacific, the north and south Atlantic off Africa, and the south China sea. These tell a different story with the oldest records indicating low levels of fire activity from the Eocene but a surge of fire from the late Miocene (~7 Ma). Phylogenetic studies of woody plants adapted to frequent savanna fires show them beginning to appear from the Late Miocene with peak origins in the late Pliocene in both South American and African lineages. Phylogenetic studies indicate ancient origins (60 Ma+) for clades characteristic of flammable sclerophyll vegetation from Australia and the Cape region of South Africa. However, as for savannas, there was a surge of speciation from the Late Miocene associated with the retreat of closed fire-intolerant forests. The wide geographic spread of increased fire activity in the last few million years suggests a global cause. However, none of the potential global factors (oxygen, rainfall seasonality, CO2, novel flammable growth forms) provides an adequate explanation as yet. The global patterns and processes of fire and flammable vegetation in the Cenozoic, especially since the Late Miocene, deserve much more attention to better understand fire in the earth system.
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Pain perception is increased in congenital but not late onset blindness
DEFF Research Database (Denmark)
Slimani, Hocine; Danti, Sabrina; Ptito, Maurice
2014-01-01
There is now ample evidence that blind individuals outperform sighted individuals in various tasks involving the non-visual senses. In line with these results, we recently showed that visual deprivation from birth leads to an increased sensitivity to pain. As many studies have shown that congenit......There is now ample evidence that blind individuals outperform sighted individuals in various tasks involving the non-visual senses. In line with these results, we recently showed that visual deprivation from birth leads to an increased sensitivity to pain. As many studies have shown...... that congenitally and late blind individuals show differences in their degree of compensatory plasticity, we here address the question whether late blind individuals also show hypersensitivity to nociceptive stimulation. We therefore compared pain thresholds and responses to supra-threshold nociceptive stimuli...... in congenitally blind, late blind and normally sighted volunteers. Participants also filled in questionnaires measuring attention and anxiety towards pain in everyday life. Results show that late blind participants have pain thresholds and ratings of supra-threshold heat nociceptive stimuli similar...
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Potato agriculture, late blight science, and the molecularization of plant pathology.
Turner, R Steven
2008-01-01
By the mid-1980s nucleic-acid based methods were penetrating the farthest reaches of biological science, triggering rivalries among practitioners, altering relationships among subfields, and transforming the research front. This article delivers a "bottom up" analysis of that transformation at work in one important area of biological science, plant pathology, by tracing the "molecularization" of efforts to understand and control one notorious plant disease -- the late blight of potatoes. It mobilizes the research literature of late blight science as a tool through which to trace the changing typography of the research front from 1983 to 2003. During these years molecularization intensified the traditional fragmentation of the late blight research community, even as it dramatically integrated study of the causal organism into broader areas of biology. In these decades the pathogen responsible for late blight, the oomycete "Phytophthora infestans," was discovered to be undergoing massive, frightening, and still largely unexplained genetic diversification -- a circumstance that lends the episode examined here an urgency that reinforces its historiographical significance as a case-study in the molecularization of the biological sciences.
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Daidzein enhances immune function in late lactation cows under heat stress.
Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting
2014-01-01
Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.
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Biogeography of late Silurian and devonian rugose corals
Oliver, W.A.
1977-01-01
Three marine benthic faunal realms can be recognized in the Early and Middle Devonian. The Eastern Americas Realm consisted of most of the eastern half of North America and South America north of the Amazon. This realm extended in a southwest direction from the Devonian equator to approximately 35??S and was an isolated epicontinental sea during much of its history. The Eastern Americas Realm was bounded on the west by the Transcontinental Arch, on the north by the Canadian Shield and on the east and southeast by a peninsular extension of the Old Red Continent. These barriers were emergent during much, but not all, of Devonian time. Seaways beyond these barriers belonged to the Old World Realm. The Malvinokaffric Realm that was farther south was apparently temperate to arctic in climate and latitudinal position and contained few corals. Rugose corals in the Eastern Americas Realm show increasing generic-level endemism from the Late Silurian through the Early Devonian; during the late Early Devonian, 92% of the rugosan genera are not known anywhere else in the world. Endemism decreased through the Middle Devonian to zero in the early Late Devonian. The Early Devonian increase in endemism paralleled, and was probably related to, the development of the Old Red Continent as a barrier between America and Africa-Europe. The waning of endemism in the Middle Devonian reflects the breaching of the land barriers. This permitted some migration in and out of the realm in early Middle Devonian time but greatest movements were in late Middle Devonian time. Principal migration directions were from western or Arctic North America into the Michigan-Hudson Bay area and from the southern Appalachian area into Africa. ?? 1977.
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Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang
2010-10-06
Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.
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Early and late arrhythmogenic effects of doxorubicin.
Kilickap, Saadettin; Barista, Ibrahim; Akgul, Ebru; Aytemir, Kudret; Aksoy, Sercan; Tekuzman, Gulten
2007-03-01
To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.
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Late changes in barium sulfate aspiration: HRCT features
International Nuclear Information System (INIS)
Voloudaki, A.; Ergazakis, N.; Gourtsoyiannis, N.
2003-01-01
Aspiration of barium sulfate occurs accidentally. Lung reaction is usually mild in the early phase due to inert character of the substance and long-term reactions or late toxicities are not expected. Little if any fibrotic response is speculated. We present a case with barium aspiration, studied by high-resolution computed tomography (HRCT) 1 year after the event, as late pulmonary sequelae studied by CT have not been described yet, to the best of our knowledge. The HRCT revealed thickened interlobular septa, subpleural lines, subpleural cysts, and centrilobular micronodules along with barium particles in a subpleural distribution. Those findings indicated that barium is capable of producing mild though silent clinically fibrosis. (orig.)
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[Relationship between fatigue recovery after late-night shifts and stress relief awareness].
Kakamu, Takeyasu; Tsuji, Masayoshi; Hidaka, Tomoo; Kumagai, Tomohiro; Hayakawa, Takehito; Fukushima, Tetsuhito
2014-01-01
To examine the factors related to fatigue accumulation by irregular shift workers after the late-night shift. We studied employees of a company in the transportation industry in Fukushima prefecture. The company transports passengers, and many employees, including the crew, engage in irregular shift work. We performed the investigation by using a self-administered questionnaire which was sent to 89 employees in October, 2011. Of the 89 who were given the survey, 84 replied, and 52 of those employees had worked the late-night shift (straddling midnight) at least once during September. In answer to the question "How long does it take you to recover after working the late-night-shift?" choices were "I don't feel tired ", "I recover the next day", "I recover in two or three days", and "It takes more than three days". We classified the choices into two groups of: 1) "I don't feel tired" and "I recover the next day", and 2) "I recover in two or three days" and "It takes more than three days". Other questions were asked about age, BMI, weekday average duration of sleep, whether or not a nap was taken before the late-night shift, risk of lifestyle-related diseases (hypertension, dyslipidemia, and diabetes), awareness of life stress accumulation, and exercise habits. Thirty-two employees answered that they recovered from the late-night shift by the next day, whereas 20 employees answered that it took more than 2 days to recover after the late-night-shift. The group who answered that recovery time after the late-night shift took more than 2 days significantly (p=0.035) felt that their stress management was insufficient. Age, BMI, weekday average duration of sleep, whether or not a nap was taken before the late-night shifts, risk of lifestyle-related diseases, and exercise habits showed no significant association with fatigue accumulation. The group who answered that their stress management was insufficient significantly chose liquor (p=0.045) and cigarettes (p=0.030) for
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Comorbid anxiety disorders in late-life depression : results of a cohort study
van der Veen, D.C.; van Zelst, W. H.; Schoevers, R. A.; Comijs, H. C.; Oude Voshaar, Richard
Background: Comorbid anxiety disorders are common in late-life depression and negatively impact treatment outcome. This study aimed to examine personality characteristics as well as early and recent life-events as possible determinants of comorbid anxiety disorders in late-life depression, taking
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Comorbid anxiety disorders in late-life depression: results of a cohort study
van Veen, D.; van Zelst, W.; Schoevers, R.; Comijs, H.; Oude Voshaar, R.
2015-01-01
Background: Comorbid anxiety disorders are common in late-life depression and negatively impact treatment outcome. This study aimed to examine personality characteristics as well as early and recent life-events as possible determinants of comorbid anxiety disorders in late-life depression, taking
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Energy Technology Data Exchange (ETDEWEB)
Mann, Andrew W.; Hilton, Eric J. [Institute for Astronomy, University of Hawai' i, 2680 Woodlawn Dr, Honolulu, HI 96822 (United States); Brewer, John M. [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Gaidos, Eric [Department of Geology and Geophysics, University of Hawai' i, 1680 East-West Road, Honolulu, HI 96822 (United States); Lepine, Sebastien [Department of Astrophysics, American Museum of Natural History, New York, NY 10024 (United States)
2013-02-01
Knowledge of late K and M dwarf metallicities can be used to guide planet searches and constrain planet formation models. However, the determination of metallicities of late-type stars is difficult because visible wavelength spectra of their cool atmospheres contain many overlapping absorption lines, preventing the measurement of equivalent widths. We present new methods, and improved calibrations of existing methods, to determine metallicities of late K and M dwarfs from moderate resolution (1300 < R < 2000) visible and infrared spectra. We select a sample of 112 wide binary systems that contain a late-type companion to a solar-type primary star. Our sample includes 62 primary stars with previously published metallicities, as well as 50 stars with metallicities determined from our own observations. We use our sample to empirically determine which features in the spectrum of the companion are best correlated with the metallicity of the primary. We find {approx_equal}120 features in K and M dwarf spectra that are useful for predicting metallicity. We derive metallicity calibrations for different wavelength ranges, and show that it is possible to get metallicities reliable to <0.10 dex using either visible, J-, H-, or K-band spectra. We find that the most accurate metallicities derived from visible spectra requires the use of different calibrations for early-type (K5.5-M2) and late-type (M2-M6) dwarfs. Our calibrations are applicable to dwarfs with metallicities of -1.04 < [Fe/H] <+0.56 and spectral types from K7 to M5. Lastly, we use our sample of wide binaries to test and refine existing calibrations to determine M dwarf metallicities. We find that the {zeta} parameter, which measures the ratio of TiO can CaH bands, is correlated with [Fe/H] for super-solar metallicities, and {zeta} does not always correctly identify metal-poor M dwarfs. We also find that existing calibrations in the K and H bands are quite reliable for stars with [Fe/H] >-0.5, but are less useful
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Ecological impacts of the late Quaternary megaherbivore extinctions.
Gill, Jacquelyn L
2014-03-01
As a result of the late Quaternary megafaunal extinctions (50,000-10,000 before present (BP)), most continents today are depauperate of megaherbivores. These extinctions were time-transgressive, size- and taxonomically selective, and were caused by climate change, human hunting, or both. The surviving megaherbivores often act as ecological keystones, which was likely true in the past. In spite of this and extensive research on the causes of the Late Quaternary Extinctions, the long-term ecological consequences of the loss of the Pleistocene megafauna remained unknown until recently, due to difficulties in linking changes in flora and fauna in paleorecords. The quantification of Sporormiella and other dung fungi have recently allowed for explicit tests of the ecological consequences of megafaunal extirpations in the fossil pollen record. In this paper, I review the impacts of the loss of keystone megaherbivores on vegetation in several paleorecords. A growing number of studies support the hypothesis that the loss of the Pleistocene megafauna resulted in cascading effects on plant community composition, vegetation structure and ecosystem function, including increased fire activity, novel communities and shifts in biomes. Holocene biota thus exist outside the broader evolutionary context of the Cenozoic, and the Late Quaternary Extinctions represent a regime shift for surviving plant and animal species.
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The late biological effects of ionizing radiation
Energy Technology Data Exchange (ETDEWEB)
NONE
1978-06-15
Full text: The principal objective of the symposium was to review the current status of understanding of the late biological effects of ionizing radiation from external and internal sources. A second objective was to critically evaluate information obtained from epidemiological studies of human population groups as well as from animal experimentation in order to provide a solid scientific basis upon which problems of current concern, such as radiation protection standards and risk-benefit analysis, could be deliberated. Eighty-one papers were presented in 10 sessions which covered epidemiological studies of late effects in human populations exposed to internal and/or external ionizing radiation; quantitative and qualitative data from animal experimentation of late effects; methodological problems and modern approaches; factors influencing susceptibility or expression of late radiation injury; comparative evaluation of late effects induced by radiation and other environmental pollutants, and problems of risk assessment. In addition, there were two evening sessions for free discussion of problems of interpreting animal data, and of the epidemiological studies of occupationally exposed populations. Reports on atomic bomb survivors showed that these epidemiological studies are providing dependable data, such as dose-related excess infant mortality. The reports also revealed the need for consensus in the method employed in the interpretation of data. That was also the case with studies on occupationally exposed populations at Hanford plant, where disparate results were presented on radiation-induced neoplasia among radiation workers. These data are, however, considered not so significant in relative terms when compared to risks involved in other industries. It was recommended that national registry systems for the dosimetry and medical records of radiation workers be established and co-ordinated internationally in order to facilitate reliable epidemiological
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Soil-landscape development and late Quaternary environmental change in coastal Estremadura, Portugal
Daniels, Michael; Haws, Jonathan; Benedetti, Michael; Bicho, Nuno
2015-04-01
This poster integrates soil-landscape analysis with archaeological survey and paleoenvironmental reconstruction. Soils in surface and buried contexts in Estremadura, Portugal, provide evidence of landscape stability and instability, relative age relationships between landforms, and general paleoenvironmental conditions during the late Quaternary. These factors provide insight into the distribution and condition of Paleolithic archaeological sites and help understand the record of human settlement in the region. Late Pleistocene and Holocene dunes extend inland approximately 10 km from coastal source regions. Surface soils in Holocene dunes under maritime pine (Pinus pinaster) forest exhibit A, E, C/Bh and A, C horizon sequences and classify as Quartzipsamments. Surface soils in late Pleistocene dunes exhibit A, E, Bh, Bhs, Bs horizon sequences and classify as Haplorthods. Both Pleistocene and Holocene dunes commonly bury a heavily weathered soil formed in calcareous sandstone. The boundary between underlying buried soils and overlying surface soils is characterized by a lag deposit of medium to coarse, moderately-rounded gravels, underlain immediately by subsurface Bt and Bss horizons. The lag deposit and absence of buried A horizons both indicate intense and/or prolonged surface erosion prior to burial by late Quaternary dunes. Soil-geomorphic relationships therefore suggest at least two distinct episodes of dune emplacement and subsequent landscape stability following an extensive episode late Pleistocene landscape instability and soil erosion. A conceptual model of soil-landscape evolution through the late Quaternary and Holocene results from the integration of soil profile data, proxy paleoenvironmental data, and the partial record of human settled as revealed in the archaeological record.
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Hominin teeth from the early Late Pleistocene site of Xujiayao, Northern China.
Xing, Song; Martinón-Torres, María; Bermúdez de Castro, Jose María; Wu, Xiujie; Liu, Wu
2015-02-01
It is generally accepted that from the late Middle to the early Late Pleistocene (∼340-90 ka BP), Neanderthals were occupying Europe and Western Asia, whereas anatomically modern humans were present in the African continent. In contrast, the paucity of hominin fossil evidence from East Asia from this period impedes a complete evolutionary picture of the genus Homo, as well as assessment of the possible contribution of or interaction with Asian hominins in the evolution of Homo sapiens and Homo neanderthalensis. Here we present a comparative study of a hominin dental sample recovered from the Xujiayao site, in Northern China, attributed to the early Late Pleistocene (MIS 5 to 4). Our dental study reveals a mosaic of primitive and derived dental features for the Xujiayao hominins that can be summarized as follows: i) they are different from archaic and recent modern humans, ii) they present some features that are common but not exclusive to the Neanderthal lineage, and iii) they retain some primitive conformations classically found in East Asian Early and Middle Pleistocene hominins despite their young geological age. Thus, our study evinces the existence in China of a population of unclear taxonomic status with regard to other contemporary populations such as H. sapiens and H. neanderthalensis. The morphological and metric studies of the Xujiayao teeth expand the variability known for early Late Pleistocene hominin fossils and suggest the possibility that a primitive hominin lineage may have survived late into the Late Pleistocene in China. Copyright © 2014 Wiley Periodicals, Inc.
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Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection.
Fernández-Sampedro, M; Fariñas-Alvarez, C; Garces-Zarzalejo, C; Alonso-Aguirre, M A; Salas-Venero, C; Martínez-Martínez, L; Fariñas, M C
2017-08-25
A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI. A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas. One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001. For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of
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On the Importance of the Flare's Late Phase for the Solar Extreme Ultraviolet Irradiance
Woods, Thomas N.; Eparvier, Frank; Jones, Andrew R.; Hock, Rachel; Chamberlin, Phillip C.; Klimchuk, James A.; Didkovsky, Leonid; Judge, Darrell; Mariska, John; Bailey, Scott;
2011-01-01
The new solar extreme ultraviolet (EUV) irradiance observations from NASA Solar Dynamics Observatory (SDO) have revealed a new class of solar flares that are referred to as late phase flares. These flares are characterized by the hot 2-5 MK coronal emissions (e.g., Fe XVI 33.5 nm) showing large secondary peaks that appear many minutes to hours after an eruptive flare event. In contrast, the cool 0.7-1.5 MK coronal emissions (e.g., Fe IX 17.1 nm) usually dim immediately after the flare onset and do not recover until after the delayed second peak of the hot coronal emissions. We refer to this period of 1-5 hours after the fl amrea sin phase as the late phase, and this late phase is uniquely different than long duration flares associated with 2-ribbon flares or large filament eruptions. Our analysis of the late phase flare events indicates that the late phase involves hot coronal loops near the flaring region, not directly related to the original flaring loop system but rather with the higher post-eruption fields. Another finding is that space weather applications concerning Earth s ionosphere and thermosphere need to consider these late phase flares because they can enhance the total EUV irradiance flare variation by a factor of 2 when the late phase contribution is included.
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Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.
Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan
2017-09-01
Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.
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Late-onset pathological gambling: clinical correlates and gender differences.
Grant, Jon E; Kim, Suck Won; Odlaug, Brian L; Buchanan, Stephanie N; Potenza, Marc N
2009-01-01
Age at illness onset has significant clinical implications for psychiatric disorders. Prior research has not systematically examined age at illness onset and its relationship to the clinical characteristics of pathological gambling (PG). Among a sample of 322 consecutive subjects with current DSM-IV PG, those with late-onset (at or after age 55 years) PG were compared to those with earlier onsets (at or prior to age 25, 26-54 years old) on measures of PG severity, co-occurring disorders, social and legal problems, and family history. Forty-two (13.4%) subjects reported onset of PG at or after age 55 years, 63 (19.6%) reported onset prior to age 25 years, and the majority (n=217; 67.4%) reported onset between the ages of 26 and 54 years. The late-onset group were less likely to declare bankruptcy (p=.029) or have credit card debt attributable to gambling (p=.006). Late-onset PG subjects were significantly more likely to have an anxiety disorder (pgambling problem. Exploratory analyses identified an age-by-gender interaction with respect to treatment-seeking, with more pronounced age-related shortening in the duration between problem onset and treatment seeking observed in men. Age at onset of PG is associated with multiple important clinical features. Long durations of PG prior to treatment-seeking indicate the need for improved prevention efforts among individuals with early PG onset. Late-onset PG is relatively common and has distinct clinical characteristics suggesting that this population might benefit from unique prevention and treatment strategies.
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Daytime activity and risk factors for late-life insomnia.
Morgan, Kevin
2003-09-01
Laboratory evidence linking exercise with improved sleep quality raises the possibility that the lower levels of physical activity characteristic of older age groups may contribute to late-life insomnia. While support for this hypothesis appears to come from epidemiological surveys, few such studies have distinguished satisfactorily between social and physical activities which differ widely in terms of energy cost and theoretical significance. The present analyses were, therefore, designed to assess the independent influence of physical and social activity levels on the prevalence and natural history of late-life insomnia. Survivors from a nationally representative UK sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). Detailed assessments of physical and social activities, mental and physical health status, and sleep quality were made at each survey wave. Logistic regression models, adjusted for age, sex and health status, were used to assess relationships between activity levels and the prevalence, remission/persistence, and incidence of late-life insomnia. Lower physical health, depressed mood and lower physical (but not social) activity levels consistently emerged as significant risk factors for prevalent, persistent and incident insomnia. Age was unrelated to insomnia variables in all the cross-sectional models, but did emerge as a significant risk for cumulative 4-8-year insomnia incidence. These findings suggest that, independent of those activities more closely associated with social engagement, higher levels of customary physical activity per se appear to be protective against incident and chronic late-life insomnia.
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Late effects of radiation: host factors
International Nuclear Information System (INIS)
Fry, R.J.M.; Storer, J.B.
1983-01-01
The paper discusses the influence of host factors on radiation late effects and in particular cancer. Radiation induces cellular changes that result in initiated cells with a potential to become cancers. The expression of the initiated cells as tumors is influenced, if not determined, by both tissue and systemic factors that are sex-, age-, and species-dependent
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Hypothyroidism in late-onset Pompe disease
Directory of Open Access Journals (Sweden)
Joseph Schneider
2016-09-01
Conclusions: Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.
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Late Posthemorrhagic Structural and Functional Changes in Pulmonary Circulation Arteries
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S. A. Andreyeva
2008-01-01
Full Text Available Objective: to reveal the major regularities and mechanisms of morphological changes in the rat pulmonary circulation arteries in the late posthemorrhagic period and to compare them with age-related features of the vessels. Materials and methods: experiments to generate graduated hemorrhagic hypotension with the blood pressure being maintained at 40 mm Hg were carried out on young (5—6-month albino male Wistar rats. Throughout hypotension and 60 days after blood loss, the blood was tested to determine low and average molecular-weight substances by spectrophotometry and the pro- and antioxidative systems by chemiluminescence. Pulmonary circulation arteries were morphologically studied in young animals, rats in the late posthemorrhagic period and old (24—25-month rats. Results. Sixty-minute hemorrhagic hypotension leads to the development of endotoxemia and imbalance of the pro- and antioxidative systems, the signs of which are observed in the late periods (2 months after hypotension. At the same time, the posthemorrhagic period is marked by the significant pulmonary circulation arterial morphological changes comparable with their age-related alterations in old rat. This shows up mainly in the reorganization of a connective tissue component in the vascular wall: the elevated levels of individual collagen fibers, their structural changes, elastic medial membrane destruction and deformity. At the same time, there is a change in the morphometric parameters of vessels at all study stages while their lowered flow capacity is only characteristic for intraorgan arteries. Conclusion: The increased activity of free radical oxidation and endotoxemia may be believed to be one of the causes of morphological changes in pulmonary circulation arteries in the late posthemorrhagic period, which is similar to age-related vascular alterations. Key words: hemorrhagic hypotension, pulmonary circulation arteries, free radical oxidation, endotoxemia, remodeling, late
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Late-Glacial radiocarbon- and palynostratigraphy in the Swiss Plateau
International Nuclear Information System (INIS)
Ammann, B.; Lotter, A.F.
1989-01-01
A detailed Late-Glacial radiocarbon stratigraphy for the Swiss Plateau has been established on the basis of over 90 accelerator 14 C dates on terrestrial plant macrofossils. A comparison of the radiocarbon ages derived from terrestrial, telmatic and limnic material at different sites on the Swiss Plateau yields a proposal for modifying the zonation system of Welten for the Late-Glacial. By retaining the limits of chronozones and by refining the palynostratigraphic criteria for the limits of biozones, a separation between chrono- and biozonation at the beginning of the Boelling and the Younger Dryas becomes obvious. 54 refs
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Boundy-Sanders, S. Q.; Sandberg, C.A.; Murchey, B.L.; Harris, A.G.
1999-01-01
Co-occuring conodonts, radiolarians, and sponge spicules from the type locality of the Slaven Chert, northern Shoshone Range, Nevada, indicate that the radiolarian and sponge spicule assemblage described herein correlates with the Late rhenana conodont Zone (late Frasnian). The moderately well preserved radiolarians are the first Frasnian-age fauna described from the Western Hemisphere. They include spumellarians, Ceratoikiscum, and Paleoscenidium, and a radiolarian which we have assigned to a new genus, Durahelenifore Boundy-Sanders and Murchey, with its type species, Durahelenifore robustum Boundy-Sanders and Murchey. Sponge spicules include umbellate microscleres of the Subclass Amphidiscophora, Order Hemidiscosa, previously documented only in Pennsylvanian and younger rocks.
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A stable-isotope tree-ring timescale of the Late Glacial/Holocene boundary
International Nuclear Information System (INIS)
Becker, Bernd; Kromer, Bernd; Trimborn, Peter
1991-01-01
Late Glacial and Holocene tree-ring chronologies, like deep-sea sediments or polar ice cores, contain information about past environments. Changes in tree-ring growth rates can be related to past climate anomalies and changes in the isotope composition of tree-ring cellulose reflect changes in the composition of the atmosphere and the hydrosphere. We have established a 9,928-year absolutely dated dendrochronological record of Holocene oak (Quercus robur, Quercus petraea)-and a 1,604-year floating Late Glacial and Early Holocene chronology of pine (Pinus sylvestris) from subfossil tree remnants deposited in alluvial terraces of south central European rivers. The pine sequence provides records of dendro-dated 14 C, 13 C and 2 H patterns for the late Younger Dryas and the entire Preboreal (10,100-9,000 yr BP). Through the use of dendrochronology, radiocarbon age calibration and stable isotope analysis, we suggest that the Late Glacial/Holocene transition may be identified and dated by 13 C and 2 H tree-ring chronologies. (author)
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Division of volcanic activity cycles in the late mesozoic in South Jiangxi and North Guangdong
International Nuclear Information System (INIS)
Li Qinglong; Wu Jianhua
1999-01-01
Based on stratigraphical unconformity, rock association, fossil assemblage, isotope age and tectonic features, the volcanic activity in late Mesozoic in south Jiangxi and north Guandong can be divided into four cycles: Yutian volcanic activity cycle, Lianhuazhai volcanic activity cycle. Banshi volcanic activity cycle and Nanxiong volcanic activity cycle. Yutian volcanic cycle which occurs in middle Jurassic epoch is the bimodal rock association composed of rhyolite and basalt. Lianhuazhai volcanic cycle which occurs in late Jurassic epoch is unimodal rock association composed of rhyolite. Banshi volcanic cycle occurs from the late stage of early Cretaceous to the early stage of late Cretaceous epoch. There are two types of rock associations related to this cycle: unimodal rock association composed of rhyolite or basalt and bimodal rock association composed of rhyolite and basalt. Nanxiong volcanic activity cycle which occurred in late stage of late Cretaceous epoch is the unimodal rock association composed of basalt which is the interlayer of the red sedimentary series
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Bąk, Krzysztof; Bąk, Marta
2013-06-01
Bąk, K. and Bąk M. 2013. Foraminiferal and radiolarian biostratigraphy of the youngest (Late Albian through Late Cenomanian) sediments of the Tatra massif, Central Western Carpathians. Acta Geologica Polonica, 63 (2), 223-237. Warszawa. The foraminiferal and radiolarian biostratigraphy of selected sections of the Zabijak Formation, the youngest sediments of the Tatra massif (Central Western Carpathians), have been studied. Benthic foraminifers, mainly agglutinated species, occur abundantly and continuously throughout the studied succession, while planktic foraminifers are generally sparse. Five planktic and two benthic foraminiferal zones have been recognized. The marly part of the Zabijak Formation comprises the Pseudothalmanninella ticinensis (Upper Albian) through the Rotalipora cushmani (Upper Cenomanian) planktic foraminiferal zones, and the Haplophragmoides nonioninoides and Bulbobaculites problematicus benthic foraminiferal zones. The radiolarians were recognized exclusively in the Lower Cenomanian part of the formation.
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Late Mesozoic basin and range tectonics and related magmatism in Southeast China
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Dezi Wang
2012-03-01
Full Text Available During the Late Mesozoic Middle Jurassic–Late Cretaceous, basin and range tectonics and associated magmatism representative of an extensional tectonic setting was widespread in southeastern China as a result of Pacific Plate subduction. Basin tectonics consists of post-orogenic (Type I and intra-continental extensional basins (Type II. Type I basins developed in the piedmont and intraland during the Late Triassic to Early Jurassic, in which coarse-grained terrestrial clastic sediments were deposited. Type II basins formed during intra-continental crustal thinning and were characterized by the development of grabens and half-grabens. Graben basins were mainly generated during the Middle Jurassic and were associated with bimodal volcanism. Sediments in half-grabens are intercalated with rhyolitic tuffs and lavas and are Early Cretaceous in age with a dominance of Late Cretaceous–Paleogene red beds. Ranges are composed of granitoids and bimodal volcanic rocks, A-type granites and dome-type metamorphic core complexes. The authors analyzed lithological, geochemical and geochronological features of the Late Mesozoic igneous rock assemblages and proposed some geodynamical constraints on forming the basin and range tectonics of South China. A comparison of the similarities and differences of basin and range tectonics between the eastern and western shores of the Pacific is made, and the geodynamical evolution model of the Southeast China Block during Late Mesozoic is discussed. Studied results suggest that the basin and range terrane within South China developed on a pre-Mesozoic folded belt was derived from a polyphase tectonic evolution mainly constrained by subduction of the western Pacific Plate since the Late Mesozoic, leading to formation of various magmatism in a back-arc extensional setting. Its geodynamic mechanism can compare with that of basin and range tectonics in the eastern shore of the Pacific. Differences of basin and range
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Control of Late Blight of Tomato and Potato by Oilgochitosan
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Yong Ho Choi
2011-08-01
Full Text Available Chitosan is a linear polysaccharide composed of randomly distributed β-(1-4-linked D-glucosamine and Nacetyl- D-glucosamine. There have been many reports on the induced systemic resistance and in vivo antifungal activities of higher molecular weight chitosans with molecular weights over 3,000 amu (atomatic mass unit, but there are few papers on in vivo antifungal activities of low molecular weight chitosans (oligochitosans with molecular weights less than 3,000 amu. In our study, an oligochitosan sample (320?3,000 amu showed a potent 1-day protective activity with control values more than 94% at concentrations of 500 and 1,000 ?g/ml especially against tomato late blight caused by Phytophthora infestans under growth chamber conditions. It also displayed a moderate 1-day protective activity with control values of 67?89% at concentrations of 500 and 1,000 ?g/ml against wheat leaf rust and red pepper anthracnose. On the other hand, it showed a 16-hr curative activity against red pepper anthracnose, but not against tomato late blight and wheat leaf rust. In field experiments, oligochitosan effectively suppressed the development of late blight on potato and tomato plants with control values of 72% and 48%, respectively. The results strongly indicate that oligochitosan can be used as an eco-friendly organic material for the control of late blight on tomato and potato plants.
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Late-time tails of wave propagation in higher dimensional spacetimes
International Nuclear Information System (INIS)
Cardoso, Vitor; Yoshida, Shijun; Dias, Oscar J.C.; Lemos, Jose P.S.
2003-01-01
We study the late-time tails appearing in the propagation of massless fields (scalar, electromagnetic, and gravitational) in the vicinities of a D-dimensional Schwarzschild black hole. We find that at late times the fields always exhibit a power-law falloff, but the power law is highly sensitive to the dimensionality of the spacetime. Accordingly, for odd D>3 we find that the field behaves as t -(2l+D-2) at late times, where l is the angular index determining the angular dependence of the field. This behavior is entirely due to D being odd; it does not depend on the presence of a black hole in the spacetime. Indeed this tail is already present in the flat space Green's function. On the other hand, for even D>4 the field decays as t -(2l+3D-8) , and this time there is no contribution from the flat background. This power law is entirely due to the presence of the black hole. The D=4 case is special and exhibits, as is well known, t -(2l+3) behavior. In the extra dimensional scenario for our Universe, our results are strictly correct if the extra dimensions are infinite, but also give a good description of the late-time behavior of any field if the large extra dimensions are large enough
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Late radiation pathology of mammals
Energy Technology Data Exchange (ETDEWEB)
Alexandrov, S N
1982-01-01
The comprehensive monograph on delayed radiation effects in mammals including man comprises 3 main chapters dealing with non-neoplastic as well as neoplastic manifestations of late radiation pathology, with the prophylaxis of delayed radiation effects, and with the therapy of radiation injuries. Alterations induced by whole-body irradiation and delayed radiation effects caused by partial body irradiation are described in detail. The developmental mechanisms and pathogenesis of non-neoplastic pathological changes and of radiation-induced neoplasms are elaborated.
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Late time CMB anisotropies constrain mini-charged particles
Energy Technology Data Exchange (ETDEWEB)
Burrage, C.; Redondo, J.; Ringwald, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Jaeckel, J. [Univ. of Durham, Inst. for Particle Physics Phenomenology (United Kingdom)
2009-09-15
Observations of the temperature anisotropies induced as light from the CMB passes through large scale structures in the late universe are a sensitive probe of the interactions of photons in such environments. In extensions of the Standard Model which give rise to mini-charged particles, photons propagating through transverse magnetic fields can be lost to pair production of such particles. Such a decrement in the photon flux would occur as photons from the CMB traverse the magnetic fields of galaxy clusters. Therefore late time CMB anisotropies can be used to constrain the properties of mini- charged particles. We outline how this test is constructed, and present new constraints on mini-charged particles from observations of the Sunyaev-Zel'dovich effect in the Coma cluster. (orig.)
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The virtues of balm in late medieval literature.
Truitt, Elly R
2009-01-01
This article argues that balm, or balsam, was, by the late medieval period, believed to be a panacea, capable of healing wounds and illnesses, and also preventing putrefaction. Natural history and pharmacological texts on balm from the ancient and late antique periods emphasized specific qualities of balm, especially its heat; these were condensed and repeated in medieval encyclopedias. The rarity and cost of balsam, from antiquity through the medieval period, and the high rate of counterfeiting also demonstrate its high demand and significance in medicine and religious ritual. Travel writing and itineraria from the early and central medieval periods added a new layer to ideas about the capabilities of balsam: that it originated from a Christian miracle and was a particularly Christian plant.
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Precarity in late life: Understanding new forms of risk and insecurity.
Grenier, Amanda; Phillipson, Chris; Laliberte Rudman, Debbie; Hatzifilalithis, Stephanie; Kobayashi, Karen; Marier, Patrik
2017-12-01
Population aging and longevity in the context of declining social commitments, raises concerns about disadvantage and widening inequality in late life. This paper explores the concept of precarity as a means to understand new and sustained forms of risk and insecurity that affect late life. The article begins with a review of the definition and uses of precarity in a range of scholarly fields including social gerontology. It then draws on illustrations from three locations of experience including older women, aging with a disability, and the foreign-born, to outline how precarity renders visible the disadvantages carried into late life, and new insecurities that emerge at the moment of needing care in the context of austerity. The argument being put forward is that precarity can be used to illustrate how risks and insecurities, experienced over time, in longevity, and the context of austerity, can deepen disadvantage. This lens thus holds the potential to challenge individual interpretations of risk, and situate experiences of disadvantage in the economic and political context. We conclude that contemporary conditions of austerity and longevity intersect to produce and sustain risk and disadvantage into late life. Copyright © 2017 Elsevier Inc. All rights reserved.
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Study on the early and late mutants of radiation induced rice
International Nuclear Information System (INIS)
Yang Hefeng; Chen Xiulan; He Zhentian; Gu Shiliang; Xu Chenwu
1990-12-01
After three years of consecutive experiments for the irradiated M 2 generations of 53 different varieties of rice, the following results have been obtained: (1) The average of early mutant plant rate is 1.4%. The rate in the early-maturing varieties is lower than that in the late-maturing varieties. It is in proportion to the length of growing period of these varieties tested. The shortened days of growing period of early mutants are 3 to 32 days (the average was 9.5 days), and it is increasing as the growing period increases. (2) In the irradiated M 2 generation of same variety, the early mutants and late mutants could be simultaneously happened, but the rate of the late mutants is 2.67%, which is higher than the rate of early mutants (1.39%). The shortened and prolonged days of growing period are 11.5 and 10.5 days respectively. These early and late mutants have some changes, both good and bad, in agronomical traits such as plant height, weight per kilo-grains and grains number per tassel. In some extent these changes are significant
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Late Sleeping Affects Sleep Duration and Body Mass Index in Adolescents
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Rajesh G.Kathrotia1,
2010-03-01
Full Text Available During adolescence, there is a tendency to sleep late andsleep less because of altered psychosocial and life-stylechanges. Recent studies have demonstrated the link betweensleeping less and gaining weight in children, adolescents, andadults. We studied the effect of late sleeping and sleepingless on body mass index (BMI in medical college freshmen.All participants were adolescents (104 male and 38 femaleadolescents, mean age 17.77±0.79 years. After obtaininginformed consent, they filled out a questionnaire about theirsleeping habits. Height and weight were measured after abrief history taking and clinical examination. BMI increasedsignificantly with decrease in total sleep duration and withdelayed bedtime. Late sleeping individuals (after midnighthad significantly less sleep duration (6.78 hours v 7.74 hours,P<0.001, more day time sleepiness (85.2% v 69.3%,P=0.033 and more gap between dinner time and going tosleep (234.16 min v 155.45 min, P<0.001. Increased BMI inlate sleepers may be explained by low physical activity duringthe day caused by excess sleepiness and increased calorieintake with a gap of 5-6 hours between dinner and sleep.Sleep habits of late sleeping and sleeping less contribute toincrease BMI in adolescents.