scholarly journals Plasma EBV DNA: A Promising Diagnostic Marker for Endemic Burkitt Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Rena R. Xian ◽  
Tobias Kinyera ◽  
Isaac Otim ◽  
Joshua N. Sampson ◽  
Hadijah Nabalende ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Copy Number ◽  
Diagnostic Marker ◽  
High Plasma ◽  
Interquartile Range ◽  
High Copy Number ◽  
Future Research ◽  
High Risk Population ◽  
Median Plasma ◽  
Ebv Dna

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in regions of equatorial Africa where P. falciparum malaria is holoendemic. The tumor is consistently associated with Epstein-Barr virus (EBV). Screening for EBV DNA in plasma in a high-risk population in Hong Kong has been shown to be useful in facilitating the early diagnosis of nasopharyngeal carcinoma, another EBV-associated tumor. Here, we investigate plasma EBV as a diagnostic marker for eBL in children in Uganda. We studied plasma specimens from 25 children with eBL and 25 controls matched for age (<3-16 years), gender and geography, including many with asymptomatic P. falciparum infection. These specimens were previously collected under the auspices of the EMBLEM (Epidemiology of Burkitt lymphoma in East African children and minors) study. After cell-free DNA isolation, plasma EBV DNA was measured using a quantitative PCR assay that amplifies the large internal repeats of the EBV genome. All children with eBL had measurable plasma EBV, as compared to 84% of control children. The median plasma EBV DNA level was 5.23 log10 copies/mL (interquartile range 3.54-6.08 log10 copies/mL) in children with eBL. In contrast, the median plasma EBV DNA level was 0.37 log10 copies/mL (interquartile range 0.18-1.05 log10 copies/mL) in children without lymphoma. An EBV threshold of 2.52 log10 copies/mL yielded a sensitivity of.88 and a specificity of 1. The estimated AUC was 0.936 (95% CI: 0.8496 – 1.00) for the corresponding ROC curve. Plasma EBV copy number did not depend on age, gender, or malaria screening status. However, two control children with asymptomatic P. falciparum infection and parasitemia also had high plasma EBV copy number. Our analysis suggests that measurements of EBV copy number in plasma may be useful in identifying children with eBL versus control children. A promising area for future research is the differentiation of high copy number associated with tumor versus high copy number associated with asymptomatic parasitemia.

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

scholarly journals Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities

2020 ◽  
Vol 22 (1) ◽  
pp. 165
Author(s):  
Lucía Pérez-Roque ◽  
Elena Núñez-Gómez ◽  
Alicia Rodríguez-Barbero ◽  
Carmelo Bernabéu ◽  
José M. López-Novoa ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Ex Vivo ◽  
Clinical Manifestations ◽  
High Plasma ◽  
Trophoblast Invasion ◽  
Future Research ◽  
Soluble Factors ◽  
Human Trophoblast ◽  
Soluble Endoglin ◽  
Pregnant Mice

Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.

Genetic interactions between CDC31 and KAR1, two genes required for duplication of the microtubule organizing center in Saccharomyces cerevisiae.

Genetics ◽  
1994 ◽  
Vol 137 (2) ◽  
pp. 407-422 ◽  
Author(s):  
E A Vallen ◽  
W Ho ◽  
M Winey ◽  
M D Rose
Keyword(s):  
Copy Number ◽  
Gene Dosage ◽  
Spindle Pole Body ◽  
Direct Interaction ◽  
Spindle Pole ◽  
High Copy Number ◽  
Temperature Sensitive ◽  
Microtubule Organizing Center ◽  
Recessive Mutations ◽  
Organizing Center

Abstract KAR1 encodes an essential component of the yeast spindle pole body (SPB) that is required for karyogamy and SPB duplication. A temperature-sensitive mutation, kar1-delta 17, mapped to a region required for SPB duplication and for localization to the SPB. To identify interacting SPB proteins, we isolated 13 dominant mutations and 3 high copy number plasmids that suppressed the temperature sensitivity of kar1-delta 17. Eleven extragenic suppressor mutations mapped to two linkage groups, DSK1 and DSK2. The extragenic suppressors were specific for SPB duplication and did not suppress karyogamy-defective alleles. The major class, DSK1, consisted of mutations in CDC31. CDC31 is required for SPB duplication and encodes a calmodulin-like protein that is most closely related to caltractin/centrin, a protein associated with the Chlamydomonas basal body. The high copy number suppressor plasmids contained the wild-type CDC31 gene. One CDC31 suppressor allele conferred a temperature-sensitive defect in SPB duplication, which was counter-suppressed by recessive mutations in KAR1. In spite of the evidence for a direct interaction, the strongest CDC31 alleles, as well as both DSK2 alleles, suppressed a complete deletion of KAR1. However, the CDC31 alleles also made the cell supersensitive to KAR1 gene dosage, arguing against a simple bypass mechanism of suppression. We propose a model in which Kar1p helps localize Cdc31p to the SPB and that Cdc31p then initiates SPB duplication via interaction with a downstream effector.

Characterization of High-Copy-Number Retrotransposons From the Large Genomes of the Louisiana Iris Species and Their Use as Molecular Markers

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 685-697 ◽  
Author(s):  
Edward K Kentner ◽  
Michael L Arnold ◽  
Susan R Wessler
Keyword(s):  
Molecular Markers ◽  
Copy Number ◽  
High Copy Number ◽  
Marker System ◽  
Transposon Display ◽  
Plant Genomes ◽  
Large Plant ◽  
Backcross Hybrids ◽  
Abundance And Distribution

Abstract The Louisiana iris species Iris brevicaulis and I. fulva are morphologically and karyotypically distinct yet frequently hybridize in nature. A group of high-copy-number TY3/gypsy-like retrotransposons was characterized from these species and used to develop molecular markers that take advantage of the abundance and distribution of these elements in the large iris genome. The copy number of these IRRE elements (for iris retroelement), is ∼1 × 105, accounting for ∼6–10% of the ∼10,000-Mb haploid Louisiana iris genome. IRRE elements are transcriptionally active in I. brevicaulis and I. fulva and their F1 and backcross hybrids. The LTRs of the elements are more variable than the coding domains and can be used to define several distinct IRRE subfamilies. Transposon display or S-SAP markers specific to two of these subfamilies have been developed and are highly polymorphic among wild-collected individuals of each species. As IRRE elements are present in each of 11 iris species tested, the marker system has the potential to provide valuable comparative data on the dynamics of retrotransposition in large plant genomes.

Plasmid pMTL153: a high copy number version of pAT153 and its use to obtain high expression of the Pseudomonas carboxypeptidase G2 gene

1988 ◽  
Vol 29 (6) ◽  
pp. 572-578 ◽  
Author(s):  
Steve P. Chambers ◽  
Sue E. Prior ◽  
Rachell A. Evans ◽  
Roger F. Sherwood ◽  
Nigel P. Minton
Keyword(s):  
Copy Number ◽  
High Expression ◽  
High Copy Number ◽  
Carboxypeptidase G2

scholarly journals Intracellular and Extracellular Expression of Bacillus thuringiensis Crystal Protein Cry5B in Lactococcus lactis for Use as an Anthelminthic

2015 ◽  
Vol 82 (4) ◽  
pp. 1286-1294 ◽  
Author(s):  
Evelyn Durmaz ◽  
Yan Hu ◽  
Raffi V. Aroian ◽  
Todd R. Klaenhammer
Keyword(s):  
Bacillus Thuringiensis ◽  
Lactococcus Lactis ◽  
Copy Number ◽  
Oral Delivery ◽  
Membrane Integrity ◽  
Biologically Active ◽  
High Copy Number ◽  
Cry Protein ◽  
Western Blots ◽  
Content Type

ABSTRACTTheBacillus thuringiensiscrystal (Cry) protein Cry5B (140 kDa) and a truncated version of the protein, tCry5B (79 kDa), are lethal to nematodes. Genes encoding the two proteins were separately cloned into a high-copy-number vector with a strong constitutive promoter (pTRK593) inLactococcus lactisfor potential oral delivery against parasitic nematode infections. Western blots using a Cry5B-specific antibody revealed that constitutively expressed Cry5B and tCry5B were present in both cells and supernatants. To increase production,cry5Bwas cloned into the high-copy-number plasmid pMSP3535H3, carrying a nisin-inducible promoter. Immunoblotting revealed that 3 h after nisin induction, intracellular Cry5B was strongly induced at 200 ng/ml nisin, without adversely affecting cell viability or cell membrane integrity. Both Cry5B genes were also cloned into plasmid pTRK1061, carrying a promoter and encoding a transcriptional activator that invoke low-level expression of prophage holin and lysin genes inLactococcuslysogens, resulting in a leaky phenotype. Cry5B and tCry5B were actively expressed in the lysogenic strainL. lactisKP1 and released into cell supernatants without affecting culture growth. Lactate dehydrogenase (LDH) assays indicated that Cry5B, but not LDH, leaked from the bacteria. Lastly, using intracellular lysates fromL. lactiscultures expressing both Cry5B and tCry5B,in vivochallenges ofCaenorhabditis elegansworms demonstrated that the Cry proteins were biologically active. Taken together, these results indicate that active Cry5B proteins can be expressed intracellularly in and released extracellularly fromL. lactis, showing potential for future use as an anthelminthic that could be delivered orally in a food-grade microbe.

Isolation of STD1, a high-copy-number suppressor of a dominant negative mutation in the yeast TATA-binding protein

1993 ◽  
Vol 13 (6) ◽  
pp. 3650-3659
Author(s):  
R W Ganster ◽  
W Shen ◽  
M C Schmidt
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Copy Number ◽  
Slow Growth ◽  
Tata Binding Protein ◽  
Dominant Negative ◽  
High Copy Number ◽  
N Terminus ◽  
Growth Phenotype

The TATA-binding protein (TBP) is an essential component of the transcriptional machinery of all three nuclear RNA polymerase enzymes. Comparison of the amino acid sequence of TBPs from a number of species reveals a highly conserved 180-residue C-terminal domain. In contrast, the N terminus is variable in both size and amino acid sequence. Overexpression of a TBP protein with a deletion of the nonconserved N terminus (TBP delta 57) in Saccharomyces cerevisiae results in a dominant negative phenotype of extremely slow growth. Associated with the slow-growth phenotype are defects in RNA polymerase II transcription in vivo. We have screened a high-copy-number yeast genomic library for suppression of the slow-growth phenotype and have isolated plasmids which encode suppressors of TBP delta 57 overexpression. Here we report the sequence and initial characterization of one suppressor, designated STD1 for suppressor of TBP deletion. The STD1 gene contains a single continuous open reading frame with the potential to encode a 50.2-kDa protein. Disruption of the STD1 gene indicates that it is not essential for vegetative growth, mating, or sporulation. High-copy-number suppression by the STD1 gene is not the result of a decrease in TBP delta 57 protein accumulation or DNA-binding activity; instead, STD1 suppression is coincident with the elimination of TBP delta 57-induced RNA polymerase II defects in both uninduced and induced transcription in vivo.

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