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Results for “Copy Number Variations”

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PubMed1993

Episomal and integrated copies of Epstein-Barr virus coexist in Burkitt lymphoma cell lines.

The Epstein-Barr virus genome is present in more than 95% of the African cases of Burkitt lymphoma. In this tumor, the viral genome is usually maintained in multiple episomal copies. Viral integration has been described only for Namalwa, a cell line lacking episomes. In this study, we have addressed the question of whether integrated and episomal copies can coexist in Burkitt lymphoma cells. Gel electrophoresis was used to demonstrate the presence of episomal as well as free linear DNA in three Burkitt lymphoma cell lines. The numbers of episomal copies per cell were estimated to be 5 to 10 in BL36 and BL137 cells and below 1 in BL60 cells, indicating that BL60 does not represent a homogeneous cell population. Fluorescence in situ hybridization was combined with chromosomal banding to study the association of the viral DNA with metaphase chromosomes. A symmetrical pattern of signals at both chromatids located at the same chromosomal sites in many if not all metaphases was taken as evidence for viral integration. In each of the three cell lines, one site of integration was identified: at chromosome 11p15 in BL36 cells, at chromosome 1p34 in BL137 cells, and at the site of a reciprocal t(11;19) translocation in BL60 cells. Integrated, episomal and linear copies of Epstein-Barr virus DNA thus coexist in Burkitt lymphoma cells. The biological significance of viral integration in Burkitt lymphoma cells remains to be elucidated.

Africa↗

PubMed1994

The 8993 mtDNA mutation: heteroplasmy and clinical presentation in three families.

The point mutation at bp 8993 of human mtDNA in the ATPase 6 gene is associated with neurogenic weakness, ataxia and retinitis pigmentosa, and with subacute necrotizing encephalomyelopathy (Leigh disease) when present at high copy number. In this study we describe three new multiplex families with the ATPase 8993 mtDNA mutation and demonstrate a correlation between the percentage heteroplasmy of this mutation and the clinical phenotype. By combining this study with previous data we produce a graph of age of onset of symptoms versus percentage heteroplasmy of the mutation. Finally, we determine that ATP synthesis with NAD-linked substrates in cultured lymphoblast mitochondria from three patients with Leigh disease who had a high percentage heteroplasmy was on average 66% of the rate seen in control lymphoblast mitochondria. Similar rates are observed in lymphoblast mitochondria isolated from patients with Leigh disease due to complex I deficiency. This percentage appears to be independent of the rate of electron transport in mitochondria from patient cell lines with the mtDNA 8993 mutation.

Adenosine Triphosphatases↗

PubMed1995

[Comparative analysis of patterns of localization of mobile genetic elements in genetic selection experiments on Drosophila melanogaster].

A comparative selection-genetic analysis of three heterogeneous lines of Drosophila melanogaster with an interrupted longitudinal wing vein was performed. In the control line, riC, and two selection lines, riSP and riSN, overall patterns of localization of six families mobile genetic elements (MGE) (MGE) (MDG1, MDG2, MDG3, MDG4, copia, and 297) were compared. In all, the lines contained 220 sites (copies) in 153 segments of the Bridges' map. According to response to selection, six classes of sites were identified: strong positive (P), weak positive (p), neutral (n), weak negative (n), strong negative (N), and abnormal (A). More than 50% of the sites (P+N+p+n) were shown to respond to selection; the contrasting classes (P and N and p and n) counterbalanced each other. These sites are assumed to mark actual parts of the genome, where polygenes are located. In other words, more than 50% of the total number of the genome sites act as polygenes controlling this quantitative character and respond to selection. Pleiotropy of polygenes in such a system must be very high. 22.2% of sites are neutral (class 0); apparently, they do not mark polygenes. The remaining 21.8% of sites (class A) show an anomalous response to selection. They are assumed to mark the polygenes of another genetic system, which participated in the maintenance of homeostasis in the original line riC. On the basis of this evidence, the concept of oligogenes and polygenes is developed. Oligogenes and polygenes are genes that occupy respectively limiting and nonlimiting positions in systems of expression. Adaptive properties of oligogenes are evaluated first and evolve rapidly. Adaptive properties of polygenes are evaluated only with regard to their total set and are limited by oligogenes. Variation of polygenic systems is generated by polygenic combination and spontaneous transpositions and excisions of MGE.

Animals↗

PubMed2005

Differentiation of highly prevalent IS6110 single-copy strains of Mycobacterium tuberculosis from a rural community in South India with an ongoing DOTS programme.

We have prospectively analysed the DNA fingerprinting of Mycobacterium tuberculosis strains in a rural community from high prevalence area in South India with an ongoing DOTS programme. Strains from 451 culture-positive cases, diagnosed during July 1999-December 2000, were fingerprinted initially by both IS6110 and DR probes followed by polymorphic GC-rich repeat sequences (PGRS) typing only on low-copy strains. The results were correlated with selected epidemiological and clinical data. Forty one percent of strains showed single copy of IS6110, which further got differentiated into 62 DR and 27 PGRS patterns. One predominant DR pattern (5B/2) was found in 20% of the low-copy strains and was also involved in clusters. In all, 183 patients out of 451 (40%) were clustered in total 44 clusters when analysed by IS6110 and DR probes. With additional PGRS typing, the number of patients clustered was further reduced to 106 (23%). More number of patients (131) were clustered in IS6110 single-copy group. The maximum number of clusters was found with two or three patients. Only a small percentage (16%) of the patients reported direct epidemiological links while remaining patients might have had indirect links or casual contacts. Thus, a combination of two to three genetic markers is able to differentiate the most endemic strains of M. tuberculosis in areas with a high incidence of tuberculosis. The epidemiological data do not suggest any major outbreaks or a hot-spot hypothesis of transmission in this region. Phylogenetic analysis using IS6110, DR and PGRS RFLP (restriction fragment length polymorphism, RFLP) fingerprints showed that isolates exhibited clonal evolutionary pattern. The predominance of certain genotypes and agreement between the phylogenetic trees indicated that these strains were closely related and might have evolved or propagated from the common ancestor.

Antitubercular Agents↗

PubMed1995

[Errors in bibliographic references: a retrospective study in Medicina Clinica (1962-1992)].

BACKGROUND: Misspellings of transcription or the copy of references of articles published in the literature without verifying the information with the original document may be the cause of incorrect citations. The purpose of this study was to determine the accuracy of citations to journal articles in 1962 to 1992 volumes of Medicina Clínica. METHODS: A method of systematic sampling was used to choose five references for each of the 12 original articles per year selected at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992). In the final sample of 420 references, errors in the six standard bibliographic elements--authors' names, article title, journal title, year, volume number, and page numbers--were analyzed. Major errors were defined when inaccuracies prevented identification of the cited article. RESULTS: Of the total 368 references verified, 132 (35.86%) were error free and the remaining 236 (64, 13%) were inaccurate. Multiple errors were found in 45% of cases. The mean number of errors per references was 1.13. Twelve references were incorrect, 221 errors were found in the authors' name, 131 in the title of the article, 14 in the name of the journal, 5 in the year of publication, 12 in the number of the volume, and 22 in the initial or final pages of the article. Major errors were detected in 94 (22.54%) cases and minor errors in 323 (77.45%). There were no statistically significant differences in the variation of the overall percentage of errors throughout the study period. CONCLUSIONS: A high rate of citation errors has been also documented in a Spanish medical journal. The importance of reference verification should be emphasized and authors should exercise more care in preparing bibliographies of their articles.

Bibliographies as Topic↗

PubMed2004

The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping in nonmutated CFTR alleles.

Classic cystic fibrosis (CF) is caused by two loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, whereas patients with nonclassic CF have at least one copy of a mutant gene that retains partial function of the CFTR protein. In addition, there are several other phenotypes associated with CFTR gene mutations, such as idiopathic chronic pancreatitis. In CFTR-associated disorders and in nonclassic CF, often only one CFTR mutation or no CFTR mutations can be detected. In this study, we screened 23 patients with CFTR-associated disorders for CFTR mutations by complete gene testing and quantitative transcript analysis. Mutations were found in 10 patients. In cells from respiratory epithelium, we detected aberrant splicing of CFTR mRNA in all investigated individuals. We observed a highly significant association between the presence of coding single-nucleotide polymorphisms (coding SNPs, or cSNPs) and increased skipping of exon 9 and 12. This association was found both in patients and in normal individuals carrying the same cSNPs. The cSNPs c.1540A>G, c.2694T>G, and c.4521G>A may have affected pre-mRNA splicing by changing regulatory sequence motifs of exonic splice enhancers, leading to lower amounts of normal transcripts. The analysis of CFTR exons indicated that less frequent and weak exonic splicing enhancer (ESE) motifs make exon 12 vulnerable to skipping. The number of splice variants in individuals with cSNPs was similar to previously reported values for the T5 allele, suggesting that cSNPs may enhance susceptibility to CFTR related diseases. In addition, cSNPs may be responsible for variation in the phenotypic expression of CFTR mutations. Quantitative approaches rather than conventional genomic analysis are required to interpret the role of cSNPs.

Adolescent↗

PubMed2006

Structure of the expression site reveals global diversity in MSP2 (P44) variants in Anaplasma phagocytophilum.

Anaplasma phagocytophilum, a recently reclassified bacteria in the order Rickettsiales, infects many different animal species and causes an emerging tick-borne disease of humans. The genome contains a large number of related genes and gene fragments encoding partial or apparently full-length outer membrane protein MSP2 (P44). Previous data using strains isolated from humans in the United States suggest that antigenic diversity results from RecF-mediated conversion of a single MSP2 (P44) expression site by partially homologous donor sequences. However, whether similar mechanisms operate in naturally infected animal species and the extent of global diversity in MSP2 (P44) are unknown. We analyzed the structure and diversity of the MSP2 (P44) expression site in strains derived from the United States and Europe and from infections of different animal species, including wildlife reservoirs. The results show that a syntenic expression site is present in all strains of A. phagocytophilum investigated. This genomic locus contained diverse MSP2 (P44) variants in all infected animals sampled, and variants also differed at different time points during infection. Although similar variants were found among different populations of U.S. origin, there was little sequence identity between U.S. strain variants (including genomic copies from a completely sequenced U.S. strain) and expression site variants infecting sheep and dogs in Norway and Sweden. Finally, the possibility that combinatorial mechanisms can generate additional diversity beyond the basic donor sequence repertoire is supported by the observation of shared sequence blocks throughout the MSP2 (P44) hypervariable region in reservoir hosts. These data suggest similar genetic mechanisms for A. phagocytophilum variation in all hosts but worldwide diversity of the MSP2 (P44) outer membrane protein.

Amino Acid Sequence↗

PubMed2001

Urinary calculi on computed radiography: comparison of observer performance with hard-copy versus soft-copy images on different viewer systems.

OBJECTIVE: The purpose of this study was to compare observer performance for detecting urinary calculi using abdominal computed radiography with hard-copy versus soft-copy images and with a high-resolution video monitor versus a liquid-crystal-display (LCD) monitor. MATERIALS AND METHODS: We compared observer performance for detecting urinary calculi using three sets of radiographs-hard-copy images, soft-copy images displayed on a LCD monitor (1280 x 1024 bits), and soft-copy images displayed on a high-resolution video monitor using receiver operating characteristic curve analysis with a continuous rating scale. Computed radiography was archived with a 2140 x 1760 pixel resolution and a 10-bit depth. The selected data set included 62 images: 27 images showing proven urinary calculi smaller than 6 mm and three in number, and 35 images containing no proven abnormalities. Eleven radiologists (three genitourinary radiologists and eight general radiologists) participated in the study. Interpretations of three sets of randomly distributed radiographs were performed individually in three separate sessions at 1-week intervals. RESULTS: No statistically significant differences were found in the area under the receiver operating characteristic curve for detecting urinary calculi or in the interpreting times between soft-copy and hard-copy images; the mean areas under the receiver operating characteristic curve of hard-copy images, soft-copy images displayed on an LCD monitor, and soft-copy images displayed on a high-resolution video monitor were 0.579, 0.610, and 0.732, respectively. However, soft-copy images showed relatively improved diagnostic accuracy among less experienced radiologists (p < 0.05). CONCLUSION: For detecting urinary calculi, soft-copy images offered a diagnostic accuracy similar to or slightly more accurate than that of hard-copy images obtained in a laser-printed film-based environment. The diagnostic performance with soft-copy images viewed on an LCD monitor was comparable to that of soft-copy images viewed on a high-resolution video monitor.

Data Display↗

PubMed2005

A statistical method to detect chromosomal regions with DNA copy number alterations using SNP-array-based CGH data.

Single nucleotide polymorphism (SNP) arrays were used to detect chromosomal regions with DNA copy number alterations. Current statistical methods for microarray-based comparative genomic hybridization (array-CGH) analysis generally assume certain relationships among adjacent markers on the same chromosome, and these assumptions may be questionable. For an SNP-array-based CGH study, multiple normal reference SNP arrays were collected. In order to utilize these normal reference SNP arrays, we derived an empirical distribution of signal ratios for each SNP marker. With an assumed threshold value for the overall error rate control and the defined signal ratio ranges for chromosomal amplification and deletion, we proposed a procedure to identify chromosomal alteration regions based on several bootstrapped one-sample t-tests and the false discovery rate control. When we have multiple arrays for different individuals with the same disease, our method can also be used to detect SNP markers for chromosomal alteration regions that are common among these individuals. We applied our method to a published SNP array data set for breast carcinoma cell lines. For an individual with breast cancer, numerous chromosomal alteration regions were identified. Compared to results of previous studies, our method identified more chromosomal alteration regions, with some being implicated in the literature to harbor genes associated with breast cancer. For multiple cancer arrays, our results suggested the existence of common chromosomal alteration regions. However, a high proportion of false positives also indicated that genetic variations among different individuals with breast cancer can be present.

Breast Neoplasms↗

PubMed2001

The mutant phenotype associated with P-element alleles of the vestigial locus in Drosophila melanogaster may be caused by a readthrough transcript initiated at the P-element promoter.

We report here the isolation of a new P-element-induced allele of the vestigial locus vg(2a33), the molecular characterization of which allows us to propose a unifying explanation of the phenotypes of the large number of vestigial P-element alleles that now exists. The first P-element allele of vestigial to be isolated was vg(21), which results in a very weak mutant wing phenotype that is suppressed in the P cytotype. By destabilizing vg(2a33) in a dysgenic cross, we isolated the vg(2a33) allele, which exhibits a moderate mutant wing phenotype and is not suppressed by the P cytotype. The new allele is characterized by a 46-bp deletion that removes the 3'-proximal copy of the 11-bp internal repeat from the P element of vg(21). To understand how this subtle difference between the two alleles leads to a rather pronounced difference in their phenotypes, we mapped both the vg and P-element transcription units present in wild type and mutants. Using both 5'-RACE and S1 protection, we found that P-element transcription is initiated 19 bp farther upstream than previously thought. Using primer extension, the start of vg transcription was determined to lie 435 bp upstream of the longest cDNA recovered to date and upstream of the P-element insertion site. Our discovery that the P element is situated within the first vg exon has prompted a reassessment of the large body of genetic data on a series of alleles derived from vg(21). Our current hypothesis to explain the degree of variation in the mutant phenotypes and their response to the P repressor invokes a critical RNA secondary structure in the vg transcript, the formation of which is hindered by a readthrough transcript initiated at the P-element promoter.

Alleles↗

PubMed1991

Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome.

A fatal immunodeficiency syndrome with clinical and pathologic features similar to human AIDS is inducible in cats by experimental inoculation with a specific strain of feline leukemia virus (FeLV) called FeLV-FAIDS. The course of the feline disease is characterized by an age-dependent prodromal period during which a non-disease-specific, common form of proviral DNA is detected in bone marrow. Preceding clinical onset of immunodeficiency is production of high levels of specific, pathogenic variant genomes, primarily as unintegrated viral DNA, in bone marrow. Acute immunodeficiency syndrome (survival period approximately 3 months) is associated with a short prodromal period and appearance of a characteristic variant genome (variant A) that persists at high copy number as integrated and full-length unintegrated viral DNA in bone marrow. Chronic immunodeficiency syndrome (survival greater than 1 year) is marked by a longer prodromal period, a more gradual onset of severe clinical immunosuppression, and a predominance of other variant genomes that often contain substantial internal deletions. In both forms of the disease, tissue-specific replication of certain variant viruses is noted in the bone marrow, intestine, and lymph nodes. Evidence from in vitro and in vivo virus transmission studies indicates that the appearance of FeLV-FAIDS variant viruses reflects differential replication of viral genomes pre-existing in the inoculum rather than rapid de novo evolution of new variants within each animal. These results demonstrate that retrovirus-induced immunodeficiency disease in cats can be associated with and prefigured by the amplified replication of specific viral variants in target tissues.

Animals↗

PubMed1992

Predictions of a 2-locus model for disease heterogeneity: application to adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder that exhibits a wide range of phenotypic variability within individuals in a single family carrying the mutant allele. A 2-locus epistatic model has been proposed to explain the inheritance of the severe childhood form of ALD and the milder adult-onset adrenomyloneuropathy (AMN). Under a dominant epistatic model, a single M allele at an autosomal modifier locus ameliorates the most severe effects of the disease allele leading to the milder AMN phenotype; only males with genotype mm would have ALD. Under a recessive epistatic model, 2 copies of the M allele would be necessary to have the milder AMN phenotype. Here, we show that recurrence risks for a second affected male depend on the frequency of the protective allele at this modifier locus. Whereas it is most likely that 2 affected brothers will be concordant for their disease phenotypes, discordant pairs of affected brothers are possible at all frequencies of M. Within a narrow range of modifier allele frequencies, the predicted distribution of affected sib pairs (over all families) is consistent with empiric data from a large clinic population. Here we suggest sampling discordant affected sib pairs as a strategy for detecting linkage between a polymorphic DNA marker and a possible modifier gene. Since both epistatic models predict that discordant affected pairs should not share 2 alleles at the modifier locus, we expect that departures from the null distribution could be detected with relatively small numbers of sib pairs.

Adrenoleukodystrophy↗

PubMed1997

Sequence diversity and molecular evolution of the merozoite surface antigen 2 of Plasmodium falciparum.

Eleven new alleles of the Plasmodium falciparum merozoite surface antigen 2 (MSA2) from Papua New Guinea were analyzed by direct sequencing of polymerase chain reaction (PCR) products. We have used the sequence information to trace the molecular evolution of MSA2. The repeats of ten alleles belonging to the 3D7 allelic family differed considerably in size, nucleotide sequence, and repeat copy number. In the repeat region of these new alleles, codon usage was extremely biased with an exclusive use of NNT codons. Another new allele sequenced belonged to the FC27 family and confirmed the family-specific conserved structure of 96 and 36 bp repeats. In order to assess sequence microheterogeneity within samples defined as the same genotype by restriction fragment length polymorphism (RFLP), we have analyzed single-strand conformation polymorphism (SSCP) of different samples of the most frequent allele (D10 of the FC27 family) in the study population. No sequence heterogeneity could be detected within the repeat region. Based on analysis of the repeat regions in both allelic families, we discuss the hypothesis of a different evolutionary strategy being represented by each of the allelic families. Kew words: Merozoite surface antigen 2 - Nucleotide sequence comparisons - Molecular evolution

Amino Acid Sequence↗

PubMed1986

The silkmoth late chorion locus. II. Gradients of gene conversion in two paired multigene families.

The late chorion locus of Bombyx mori is composed of two multigene families arranged as divergently oriented pairs irregularly spaced over 140 X 10(3) bases of DNA. The average sequence homology is 91% for the 15 members of each family. DNA sequence analysis reveals: that most of the sequence variants found in individual members of a family are shared by two or more members of that family; that family members sharing a particular variant are scattered throughout the locus; and adjacent variants in individual genes are often shared by different subsets of family members. The large number of shared variants scored and their distribution is most simply explained by numerous sequence transfers similar to gene conversions. These sequence transfers are not uniformly distributed along each gene pair. Sequence transfer is highest near the 3' end of each gene and lowest in the common 5' region between the divergent genes. A model is presented that explains these gradients by assuming that the events leading to gene conversion preferentially initiate in a simple-sequence DNA repeat. The resulting heteroduplexes extend to distances influenced by features of the sequence affecting their stability. The simple-sequence DNA is part of the major exon in both gene families and encodes tandem copies of the sequence Cys-Gly-Gly and Cys-Gly. Striking identity in the precise pattern of codon biases of these repeated sequences in the two families suggests that repeated sequence transfers occur also between families in this simple-sequence region.

Animals↗

PubMed1998

No influence of age on infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.

We have shown previously that in Dielmo, a Senegalese village with intense perennial Plasmodium falciparum transmission, the infection complexity and the distribution of some allelic types harbored by asymptomatic carriers was age-dependent. We report here an investigation of these parameters in Ndiop, a village located 5 km from Dielmo, where malaria is mesoendemic and seasonal, and where immunity is acquired at a very low rate, as indicated by the lifelong distribution of P. falciparum clinical attacks. Blood was collected from 143 and 125 inhabitants, including 122 individuals sampled in both surveys, during two cross-sectional surveys at one-month intervals during the 1994 transmission season. Plasmodium falciparum parasites were genotyped for three polymorphic single copy genes. Genetic diversity was very large, with 17, 43, and nine distinct alleles detected for the merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein loci, respectively. These figures, similar to those previously observed in Dielmo, indicate that the parasite genetic diversity is not directly related to the inoculation rate, at least in the range of transmission intensity studied here. The complexity of the asymptomatic infections (average number of distinct genotypes per isolate) was more than two-fold lower in Ndiop than in Dielmo and importantly, did not decrease with age. Likewise, the allele distribution was not influenced by age, contrasting with the observations made in Dielmo. This indicates that the number of parasite types per isolate and the influence of age on complexity and allele distribution depend on the level of endemicity, consistent with the interpretation that they reflect acquired anti-parasite immunity.

Adolescent↗

PubMed1998

Population genetic structure, phylogeography and spawning philopatry in walleye (Stizostedion vitreum) from mitochondrial DNA control region sequences.

Mitochondrial (mt) DNA control region sequences were used to test the genetic and phylogeographic structure of walleye Stizostedion vitreum populations at different geographical scales: among spawning sites, lake basins, lakes, and putative glacial refugia in the Great Lakes region. Sequencing 199 walleye revealed nucleotide substitutions and tandemly repeated sequences that varied in copy number, as well as in sequence composition, in approximately 1200 bp of the mtDNA control region. Variable numbers of copies of an 11-bp tandem repeat showed no geographical patterning and were not used in further analyses. Substitutions in the other areas of the control region yielded 19 haplotypes, revealing phylogeographic structure and significant differences among glacial refugia, lakes, basins and some spawning sites. Differences among spawning populations were consistent with reduced gene flow, philopatry and possible natal homing. Analysis of spawning populations showed consistency of genotypic frequencies among years and between males and females, supporting philopatry in both sexes. The unglaciated plateau in southern Ohio, USA housed a very different haplotype that diverged prior to the Missouri, Mississippi and Atlantic glacial refugia types. Haplotypes from the three refugia colonized the Great Lakes after retreat of the Wisconsin glaciers, and their present distribution reflects the geography of their prior isolation and differential colonization. Populations that became associated with spawning localities appear to have diverged further due to philopatry, resulting in fine-scale phylogeographic structuring.

Animals↗

PubMed2004

Marek's disease virus-encoded vIL-8 gene is involved in early cytolytic infection but dispensable for establishment of latency.

Marek's disease, a lymphoproliferative disease of chickens, is caused by an alphaherpesvirus, Marek's disease virus (MDV). This virus encodes a virokine, vIL-8, with general homology to cellular CXC chemokines such as interleukin-8 (IL-8) and Gro-alpha. To study the function of vIL-8 gene, we deleted both copies of vIL-8 residing in the terminal repeat long and internal repeat long region of the viral genome and generated a mutant virus with vIL-8 deleted, rMd5/DeltavIL-8. Growth kinetics study showed that vIL-8 gene is dispensable for virus replication in cell culture. In vivo, the vIL-8 gene is involved in early cytolytic infections in lymphoid organs, as evidenced by limited viral antigen expression of rMd5/DeltavIL-8. However, the rMd5/DeltavIL-8 virus is unimpaired in virus replication in the feather follicle epithelium. vIL-8 does not appear to be important for establishment of latency, since rMd5/DeltavIL-8 and the wild-type virus have similar viremia titers at 14 days postinfection, a period when the virus titer comes primarily from reactivated latent genomes. Nevertheless, because of the impaired cytolytic infections, the overall transformation efficiency of the virus with vIL-8 deleted is much lower, as reflected by the reduced number of transformed cells at 5 weeks postinoculation and the presence of fewer gross tumors. Importantly, the revertant virus that restored the expression of vIL-8 gene also restored the wild-type phenotype, indicating the deficient phenotypes are results of vIL-8 deletion. One of the interesting differences between the MDV vIL-8 gene and its cellular counterpart is the presence of a DKR (Asp-Lys-Arg) motif instead of ELR (Glu-Leu-Arg) preceding the invariable CXC motif. To study the significance of this variation, we generated recombinant MDV, rMd5/vIL-8-ELR, carrying the ELR motif. Both in vitro and in vivo studies revealed that the DKR motif is as competent as ELR in pathogenesis of MDV.

Animals↗

PubMed2000

A multicenter trial on interobserver reproducibility in reporting on 99mTc-DMSA planar scintigraphy: a Belgian survey.

UNLABELLED: Conflicting opinions have been expressed regarding reproducibility in 99mTc-dimercaptosuccinic acid (DMSA) planar renal image interpretation. The purpose of this investigation was to determine the level of interobserver variability among a large group of Belgian nuclear medicine physicians who evaluated a randomly selected series of DMSA planar scintigraphic examinations performed on children and adults. METHODS: All Belgian nuclear medicine centers (n = 82) were invited to participate in a reproducibility study on 99mTc-DMSA scintigraphy. 99mTc-DMSA scans obtained on 10 adults and 40 children were randomly selected from the databases of 2 hospitals. Those participating in this investigation (65 centers = 79%) received a series of computer disks containing 50 99mTc-DMSA studies. To avoid potential problems related to unfamiliar display, the disks were formatted to be interpretable using the participants' own computer systems. Each participant was then free to use his or her usual display (hard copies, contrast enhancement, color scale, gray scale, and so forth). For each kidney, the observers had to choose between the following answers: normal, abnormal, equivocal, and lack of quality. RESULTS: Forty-two responses were obtained from a wide variety of institutions and from observers with different levels of experience in interpreting 99mTc-DMSA scintigraphy. Altogether, the following data were obtained: 60.8% normal, 25.2% abnormal, 7.0% equivocal, and 3.2% lack of quality. The median percentage of agreement (overall reproducibility) for the 42 observers was 92%. When the results of all 42 observers were compared, the median agreements on normality and abnormality were 93.5% and 90.5%, respectively. In a small number (n = 4) of kidneys, reproducibility was poor and ranged from 51% to 70%. Except for 2 outliers, all observers had almost the same level of performance. CONCLUSION: A large number of Belgian nuclear medicine physicians participated in evaluating a large randomly selected sample of 99mTc-DMSA studies, and excellent interobserver agreement was found.

Adolescent↗