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PubMed1985

Interaction of monoclonal antibodies with MHC class I antigens on mouse spleen cells. II. Levels of expression of H-2K, H-2D, and H-2L in different mouse strains.

The numbers of MHC class I molecules expressed by spleen cells from various mouse strains were determined by using MHC-specific monoclonal antibodies and a radioactive binding assay. Although small differences were found to exist in some cases, our general conclusion is that different mice of the same strain, congenic mice of different haplotypes, and syngeneic mice of varying background all express similar numbers of class I antigens. B10.A mice (8 to 10 wk old), for example, express 5.3 X 10(4) Kk molecules/cell, 5.4 X 10(4) Dd molecules/cell, and 2.2 X 10(4) Ld molecules/cell. Some of the differences observed in class I antigen expression included: 1) the level of Kk expression increased to a small but significant extent with age in B10.A mice; 2) female B10.A mice expressed slightly higher amounts of Kk than male mice; and 3) B10.A(2R) and B10.A(4R) recombinant strains expressed elevated levels of K-end antigens and slightly decreased levels of D-end antigens when compared with the unrecombinant B10.A strain. In several strains, F1 mice express approximately 50% as many copies of each parental antigen as do the homozygous parents. B10 mice, which are negative for the L antigen, nevertheless express the same total number of D-end molecules as do B10.A mice. The data suggest that the levels of expression of MHC class I molecules are controlled by at least two factors: gene dosage and another factor(s) that gives rise to the small variations in class I antigen expression seen with age, sex, and strain, and to the low expression of Ld relative to Dd and Kk.

Animals↗

PubMed2003

Retroelements, transposons and methylation status in the genome of oil palm (Elaeis guineensis) and the relationship to somaclonal variation.

We isolated and characterized different classes of transposable DNA elements in oil palm (Elaeis guineensis) plants grown from seed, and plants regenerated from tissue culture that show mantling, an abnormality leading to flower abortion. Using PCR assays, reverse transcriptase fragments belonging to LINE-like and gypsy-like retroelements and transposase fragments of En/Spm transposons were cloned. Sequence analysis revealed the presence of a major family of LINEs in oil palm, with other diverged copies. Gypsy-like retrotransposons form a single homologous group, whereas En/Spm transposons are present in several diverged families. Southern analysis revealed their presence in low (LINEs) to medium (gypsy and En/Spm) copy numbers in oil palm, and in situ hybridization showed a limited number of distinct loci for each class of transposable element. No differences in the genomic organization of the different classes of transposable DNA elements between ortet palm (parent) and regenerated palm trees with mantled phenotype were detected, but different levels of sequence methylation were observed. During tissue culture, McrBC digestion revealed the genome-wide reduction in DNA methylation, which was restored to near-normal levels in regenerated trees. HPLC analysis showed that methylation levels were slightly lower in the regenerated trees compared to the ortet parent. The genomic organization of the transposable DNA elements in different oil palm species, accessions and individual regenerated trees was investigated revealing only minor differences. The results suggest that the mantled phenotype is not caused by major rearrangements of transposable elements but may relate to changes in the methylation pattern of other genomic components.

Amino Acid Sequence↗

PubMed2002

Quantitation of HTLV-I proviral load by a TaqMan real-time PCR assay.

A quantitative real-time PCR assay was developed to measure the proviral load of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells (PBMCs). The HTLV-I copy number was referred to the actual amount of cellular DNA by means of the quantitation of the albumin gene. Ten copies of HTLV-I DNA could be detected with 100% sensitivity, and the assay had a wide range of at least 5 log(10). Intra- and inter-assay reproducibility was evaluated using independent extractions of PBMCs from an HTLV-I-infected patient (coefficients of variation, 24 and 7% respectively). The performance of this TaqMan PCR assay, coupled with its high throughput, thus allows reliable routine follow-up of HTLV-I proviral load in infected patients. Preliminary results using clinical samples indicate a higher proviral load in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis than in asymptomatic carriers, and also suggest the usefulness of this quantitative measurement to assess the etiological link between HTLV-I and adult T-cell leukaemia/lymphoma-like syndromes.

Base Sequence↗

PubMed1993

Evidence for limited molecular genetic heterogeneity as defined by allelotyping and clonal analysis in nine metastatic breast carcinomas.

To investigate genetic intratumor heterogeneity, 42 samples of nine primary breast carcinomas and 29 related lymph node metastases were examined for DNA ploidy status, allelotype, and X chromosome inactivation pattern. Two primary breast carcinomas showed DNA index heterogeneity and five contained a single DNA aneuploid tumor stemline, whereas the two remaining primary tumors were solely DNA diploid. Most primary DNA tumor stemlines recurred in lymph node metastases (9 of 11). The allelotype, constructed with 31 different probes mapping to 23 different chromosome arms showed allelic imbalances on nearly all chromosome arms investigated. All tumors contained multiple allelic imbalances (range, 3-12). An allelic imbalance present in a primary tumor was consistently present in all DNA samples of that primary tumor and also in all DNA samples of related lymph node metastases, irrespective of DNA index heterogeneity. X chromosome inactivation pattern analysis with probe M27 beta (DXS255) confirmed the presence of clonal tumor cell populations in these tumors at the time of diagnosis. Densitometry of autoradiograms, which by eye showed retention of heterozygosity, revealed a narrow clustering of allelic imbalance factors between 1.0 and 1.4. In contrast, autoradiograms visually showing an allelic imbalance exhibited a marked interprobe, intertumor and intratumor variation in allelic imbalance factors. No relation between densitometry results and DNA ploidy status was found. Thus, at the time of diagnosis, an advanced primary breast carcinoma consists of a clonal tumor cell population with an established complement of allelic imbalances in all parts of the primary tumor and in the related lymph node metastases. Secondary to the establishment of allelic imbalances, intratumor heterogeneity for the copy number of involved alleles may develop, which in turn probably precedes metastasis.

Adult↗

PubMed2000

Conversion to soft-copy sonography: effects on imaging time and costs.

OBJECTIVE: To determine the effect of conversion to soft-copy interpretation on the number of images and imaging time. MATERIALS AND METHODS: Before and 1 year after conversion to soft-copy interpretation, 20 consecutive normal abdominal, renal, and cranial sonograms were performed by each of three technologists (360 sonograms total). The number of images and imaging time per sonogram were recorded. For each technologist and each examination type, the differences between number of images and the imaging times before and after conversion were compared. Multivariate repeated measures analysis of variance was used to analyze the data. RESULTS: After conversion to soft-copy, the number of images significantly increased for all imaging types (P = 0.004), and the imaging time significantly decreased (P < 0.001). After conversion, there were 213 more images. The average number of images increased 1.0 per abdominal sonogram, 0.5 per renal sonogram, and 2.0 per cranial sonogram. The additional storage requirement for the 213 images was 64 MB; total long-term storage media cost increased $1.06. On average, there was a 19% decrease in imaging time, with abdominal imaging time decreasing 2 min and 18 s, renal 1 min and 46 s, and cranial 40 s. This would potentially allow time for two additional sonograms to be performed per day and would generate up to $112,000 additional revenue per year. CONCLUSION: Following soft-copy conversion, there was a significant increase in the number of images acquired per examination, with an increased storage requirement but a negligible increase in storage cost. Technologist efficiency significantly improved.

Abdomen↗

PubMed1989

The molecular epidemiology of three biotypes of Corynebacterium diphtheriae in the Seattle outbreak, 1972-1982.

Between 1972 and 1982 Seattle experienced a diphtheria outbreak involving 1,100 cases, primarily adults with cutaneous lesions. Biotyping revealed three consecutive overlapping outbreaks including 433 toxinogenic intermedius cases. Isolates from each quarter year were examined for DNA restriction fragment patterns and hybridization patterns with three DNA probes. All intermedius outbreak isolates appeared identical in all analyses and most stock cultures had the outbreak DNA fragment pattern, but DNA probes detected six patterns within 11 intermedius stock cultures. The mitis outbreak was heterogeneous, involving at least five restriction fragment patterns. In contrast, DNA restriction fragment analyses indicated that 22 of 25 gravis outbreak isolates belonged to a single strain, whereas there were seven strains within eight gravis stock cultures. DNA probe analyses of gravis outbreak isolates detected seven different patterns, five involving copy numbers of the toxB fragment and attB sites that presumably reflected lysogenic events that occurred during the outbreak.

Bacterial Typing Techniques↗

PubMed1993

A family of IS1031 elements in the genome of Acetobacter xylinum: nucleotide sequences and strain distribution.

An insertion sequence (here called IS1031A) from Acetobacter xylinum ATCC 23769 has recently been isolated. This study describes the complete nucleotide sequence of IS1031A as well as the sequences of two novel iso-IS1031 elements, IS1031C and IS1031D, from A. xylinum ATCC 23769. The three ISs are all exactly 930 bp long, have imperfect terminal inverted repeats of 24 bp for IS1031A and 21 bp for IS1031C and IS1031D, are flanked by three base pair direct repeats, and contain an open reading frame encoding a putative basic protein of 278 amino acids. Because of nucleotide substitutions, IS1031C and IS1031D differ from IS1031A by 12.9% while IS1031C differs from IS1031D by only 0.6%. Hybridization analyses of total DNA from nine A. xylinum strains showed that all strains contained IS1031-like elements varying in copy number from three to at least 16. None of three Acetobacter aceti strains examined contained IS1031-like elements. Taken together, the results suggest that A. xylinum contains a family of IS1031 elements with considerably diversified nucleotide sequences.

Amino Acid Sequence↗

PubMedDate not supplied

[Restriction mapping and variability of 18S-25S ribosomal genes in some species of Gentiana genus].

Mapping of rRNA genes in four species of Gentiana genus has been carried out by blot-hybridization method using some restriction endonucleases. The following characteristics of Gentiana rDNA structural organization have been revealed: 1) interspecific and intragenomic variability of the length of ribosomic repeats; 2) conservativity of the transcribed region; 3) variability of the length and location of Hind-III site in non-transcribed spacer; 4) interspecific variability of the number of copies. Comparative analysis of the constructed restriction maps of Gentiana species and some other plants revealed the similarity of restriction site location in the transcribed DNA region.

DNA, Plant↗

PubMed2006

Genetic variation of porcine prostaglandin-endoperoxide synthase 2 (PTGS2) gene and its association with reproductive traits in an Erhualian x Duroc F2 population.

Identification of major genes that genetically impact female fertility is important for successful selection of high prolificacy pig lines. Because it is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins (PGs), which are important for ovulation, fertilization, implantation, decidualization and parturition, prostaglandin-endoperoxide synthase 2 gene (PTGS2) is a potential candidate gene affecting porcine reproductive traits. In this study, a PCR-RFLP was used to genotype a total of 1 031 animals, including 661 from twelve Chinese local pig breeds, 190 from three Western pig breeds and 180 F2 sows from Nanchang pig resource family. Differences in frequency distributions of PTGS2 among twelve Chinese and three Western pig breeds and populations generally agree with their prolificacy. The allele frequencies in Lower Changjiang River Basin Type pig breeds, North China Type and Central China Type breeds are significantly different from those in South China Type, Plateau Type and Western pig breeds (P<0.001). And no significant differences were observed among Lower Changjiang River Basin Type, North China Type, Central China Type pig breeds, between South China Type and Western pig breeds, in part because of similar fertility patterns. And notable associations as well as reliable additive and dominant effects were not detected in an Erhualian x Duroc F2 population (P>0.05). Whereas, there is a trend for animals with one copy of the favourable A allele to have an increased TNB (total number of piglet born) and TBA (the number of piglets born alive) and a decreased SB (stillborn pigs) trait. Considering its crucial role in reproductive pathways, the PTGS2 gene deserves further study.

Animals↗

PubMed1995

Phase-shift of polysaccharide capsule expression in group B streptococci, type III.

The type-specific polysaccharide capsule is an important virulence determinant in group B streptococci (GBS). The previously described inverse relationship between the buoyant density of a GBS-isolate and the capsular thickness was used to assess the frequencies of polysaccharide capsular phase-shift in clinical GBS, type III strains. Shift from intermediate density (ID) of parental strains, to high density (HD), i.e. shift from intermediate capsule thickness to poor encapsulation, was found to range from 1.2 x 10(-3) to 4.8 x 10(-6). Shift from ID to low density (LD), i.e. shift to abundant encapsulation, ranged from 1.9 x 10(-4) to 1.1 x 10(-7). Shifts were reversible in all cases, either directly (HD-->LD or vice versa) or through intermediate forms. Reversion frequencies were in some isolates as high as 10(-1). Phase-shift frequencies differed more than a thousand-fold between compared strains. Differences in phenotypic shift between strains were validated using flow cytometry. Possible modulation of capsule expression by changes in culture conditions was assessed. Variation of temperature, oxygen-tension, and presence of human serum did not affect capsule expression. However, growth at pH below 5.5 decreased the amount of capsule bound native type III polysaccharide, probably through phenotypic modification rather than genetic shift. IS861, an insertion sequence which has been proposed a regulatory function on the GBS capsule expression, was found in multiple copies in the isolates investigated. No differences in copy number or location of IS861 between the differently encapsulated phenotypes were found.

Animals↗

PubMed2003

HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder.

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC.

Adult↗

PubMed2004

Viral load in tissues during the early and chronic phase of non-pathogenic SIVagm infection.

African green monkeys (AGMs) persistently infected with SIVagm do not develop AIDS, although their plasma viremia levels can reach those reported for pathogenic HIV-1 and SIVmac infections. In contrast, the viral burden in lymph nodes in SIVagm-infected AGMs is generally lower in comparison with HIV/SIVmac pathogenic infections, at least during the chronic phase of SIVagm infection. We searched for the primary targets of viral replication, which might account for the high viremias in SIVagm-infected AGMs. We evaluated for the first time during primary infection SIVagm dissemination in various lymphoid and non-lymphoid tissues. Sixteen distinct organs at a time point corresponding to maximal virus production were analyzed for viral RNA and DNA load. At days 8 and 9 p.i., viral RNA could be detected in a wide range of tissues, such as jejunum, spleen, mesenteric lymph nodes, thymus and lung. Quantification of viral DNA and RNA as well as of productively infected cells revealed that viral replication during this early phase takes place mainly in secondary lymphoid organs and in the gut (5 x 10(4)-5 x 10(8) RNA copies/10(6) cells). By 4 years p.i., RNA copy numbers were below detection level in thymus and lung. Secondary lymphoid organs displayed 6 x 10(2)-2 x 10(6) RNA copies/10(6) cells, while some tissue fragments of ileum and jejunum still showed high viral loads (up to 10(9) copies/10(6) cells). Altogether, these results indicate a rapid dissemination of SIVagm into lymphoid tissues, including the small intestine. The latter, despite showing marked regional variations, most likely contributes significantly to the high levels of viremia observed during SIVagm infection.

Animals↗

PubMed1999

Analysis of the stabilizing effect of Rom on the genetic network controlling ColE1 plasmid replication.

A stochastic model of ColE1 plasmid replication is presented. It is implemented by using UltraSAN, a simulation tool based on an extension of stochastic Petri nets (SPNs). It allows an exploration of the variation in plasmid number per bacterium, which is not possible using a deterministic model. In particular, the rate at which plasmid-free bacteria arise during bacterial division is explored in some detail since spontaneous plasmid loss is a widely observed empirical phenomenon. The rate of spontaneous plasmid loss provides an evolutionary explanation for the maintainance of Rom protein. The presence of Rom acts to reduce variance in plasmid copy number, thereby reducing the rate of plasmid loss at bacterial division. The ability of stochastic models to link biochemical function with evolutionary considerations is discussed.

Cell Division↗

PubMed1986

The evolution of DNA sequences in Escherichia coli.

It is proposed that certain families of transposable elements originally evolved in plasmids and functioned in forming replicon fusions to aid in the horizontal transmission of non-conjugational plasmids. This hypothesis is supported by the finding that the transposable elements Tn3 and gamma delta are found almost exclusively in plasmids, and also by the distribution of the unrelated insertion sequences IS4 and IS5 among a reference collection of 67 natural isolates of Escherichia coli. Each insertion sequence was found to be present in only about one-third of the strains. Among the ten strains found to contain both insertion sequences, the number of copies of the elements was negatively correlated. With respect to IS5, approximately half of the strains containing a chromosomal copy of the insertion element also contained copies within the plasmid complement of the strain.

Base Sequence↗

PubMed1996

Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats.

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 x 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.

Alleles↗

PubMed1982

Insertion of a repetitive element at the same position in the 5'-flanking regions of two dissimilar yeast tRNA genes.

The regions 5' proximal to many yeast tRNA genes exhibit a high frequency of DNA sequence polymorphisms. DNA sequence analysis of polymorphic variants of SUQ5, a tRNA Ser UCA gene, and SUP2, a tRNA Tyr gene, shows that in each case one sequence variant of the tRNA gene is 346 base pairs longer than the other. The longer variants appear to have arisen from the shorter ones by the insertion of nearly identical copies of a 341-base pair sigma element into a site 16 base pairs upstream from the 5' ends of the tRNA-coding regions. The sequences of the two copies of the sigma element differ at only five positions. The element has a number of properties that are typical of many transposable elements: (i) there is a perfect eight-base-pair inverted repeat at its ends, (ii) these ends are flanked by a five-base-pair direct repeat of a sequence that occurs only once in the target DNA, (iii) there are approximately 20 copies of the element in the yeast genome, and (iv) there is considerable strain-to-strain variation in the sizes of the restriction fragments on which these copies lie. The presence of the sigma element has no gross effect on the phenotype of a SUP2 ochre suppressor. Analysis of the SUQ5 and SUP2 sequences favors the hypothesis that sigma is a transposable element with a novel type of insertion specificity, which is primarily based on the presence of a tRNA-coding region a fixed distance from the insertion site, rather than on the immediate target sequences.

Base Sequence↗

PubMed2005

Large-scale structure of genomic methylation patterns.

The mammalian genome depends on patterns of methylated cytosines for normal function, but the relationship between genomic methylation patterns and the underlying sequence is unclear. We have characterized the methylation landscape of the human genome by global analysis of patterns of CpG depletion and by direct sequencing of 3073 unmethylated domains and 2565 methylated domains from human brain DNA. The genome was found to consist of short (<4 kb) unmethylated domains embedded in a matrix of long methylated domains. Unmethylated domains were enriched in promoters, CpG islands, and first exons, while methylated domains comprised interspersed and tandem-repeated sequences, exons other than first exons, and non-annotated single-copy sequences that are depleted in the CpG dinucleotide. The enrichment of regulatory sequences in the relatively small unmethylated compartment suggests that cytosine methylation constrains the effective size of the genome through the selective exposure of regulatory sequences. This buffers regulatory networks against changes in total genome size and provides an explanation for the C value paradox, which concerns the wide variations in genome size that scale independently of gene number. This suggestion is compatible with the finding that cytosine methylation is universal among large-genome eukaryotes, while many eukaryotes with genome sizes <5 x 10(8) bp do not methylate their DNA.

Animals↗

PubMed1999

Replication of Mus dunni endogenous retrovirus depends on promoter activation followed by enhancer multimerization.

Mus dunni endogenous virus (MDEV) is an apparently intact retrovirus that normally lies transcriptionally silent in cultured M. dunni cells, but the provirus can be activated by treatment of the cells with hydrocortisone or 5-iodo-2'-deoxyuridine. Sequence analysis of a molecular clone of the replicating virus revealed a simple retrovirus with a chimeric VL30/GALV-like structure. Interestingly, in the region of the long terminal repeat (LTR) that typically contains the retroviral transcription enhancers, we found over six 80-bp repeats with only a single mismatch, indicating that acquisition of the repeats was a recent event. Here we provide evidence for the following model of MDEV activation and replication. The MDEV provirus in M. dunni cells has a chimeric structure similar to that of the molecular clone but has only 1.15 copies of the 80-bp repeat sequence found in the molecular clone. Activating chemicals directly stimulate transcription from the LTR, allowing a low level of virus replication. Copying errors made during reverse transcription allow multimerization of the 80-bp enhancer region, resulting in viruses with higher transcriptional rates and improved fitness, but increased enhancer copy number is likely balanced by the natural instability of retroviral repeats and constraints imposed by virion packaging limits. The resultant population of replicating MDEV is widely heterogeneous, having from 2.15 to 13.15 enhancer repeats in the LTR. These results reveal a novel mechanism for regulation of transcription and replication of an endogenous retrovirus, in terms of both activation of the virus by the steroid hydrocortisone and the large number and variation in enhancer repeats observed.

Animals↗