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At least 469 records · Page 26Linked to original sources
PubMed2005

Lattice dystrophy-like localized amyloidosis of the cornea secondary to trichiasis.

PURPOSE: To report a case of stellate and branching linear corneal stromal amyloid deposits secondary to trichiasis and the use of molecular genetic analysis to exclude lattice corneal dystrophy. METHODS: Case report and review of the literature. A 30-year-old man with a history of chronic ocular irritation was found to have distichiasis, epiblepharon, and unilateral corneal amyloidosis indistinguishable from lattice corneal dystrophy. Screening of the TGFBI gene was performed to rule out a previously reported mutation associated with lattice corneal dystrophy. RESULT: A corneal biopsy performed before presentation to the authors confirmed the presence of corneal amyloidosis. Screening of exons 4, 11, 12, and 14 in the TGFBI gene identified 2 previously reported polymorphisms, Leu472Leu and Phe540Phe, but no other coding region changes. CONCLUSION: Corneal stromal amyloidosis clinically resembling lattice corneal dystrophy may be associated with trichiasis. The exclusion of a TGFBI-associated corneal dystrophy in this case, leaving trichiasis as the most likely cause of the corneal amyloid deposition, demonstrates the utility of molecular genetic analysis in confirming or refuting a presumptive clinical diagnosis.

Adult↗
PubMed1995

Nucleotide sequence analysis of Jembrana disease virus: a bovine lentivirus associated with an acute disease syndrome.

The complete nucleotide sequence of the RNA genome of Jembrana disease virus (JDV), a lentivirus that causes an acute disease syndrome in Bali cattle (Bos javanicus), is reported. In addition to the gag, pol and env genes and flanking long terminal repeats (LTRs) that characterize all retroviruses, a number of accessory genes represented by small multiply spliced ORFs in the central and 3'-terminal regions of the genome, including tat and rev that are typical of lentiviruses, were identified. The genome of JDV was 7732 bp in length, 750 bp smaller than the genome of bovine immunodeficiency virus (BIV) strain BIV127. A striking feature of the genome was the many deletions relative to BIV127, the largest of which were 471 bp from the env gene and 157 bp from the U3 (promoter) region in the LTR. There were also several insertions of up to 33 bp in the JDV genome relative to BIV127 found in the env gene and small ORFs that overlap env. Other significant genomic differences between JDV and BIV127 included changes to cis-acting sequences throughout the genome such as promoter and enhancer sequences in the LTR, the trans-activation response region, splice sites and frameshift sequences; alterations to the gag precursor protein cleavage sites and thus the processed products; loss of the vpw and vpy ORFs; and amino acid changes in all coding regions. The significance of these changes is discussed in relation to the differences in pathogenicity between JDV and BIV.

Acute Disease↗
PubMed1993

Double, independent mutational events in the rpsL gene of Escherichia coli: an example of hypermutability?

A proportion (up to 20%) of newly arising streptomycin-dependent (SmD) colonies of Escherichia coli WP2 contain bacteria where, in addition to a known SmD-determining (primary) mutation in the rpsL gene, there is a further ancillary mutation in the same gene. These ancillary mutations occur at 10 sites between 11 and 201bp away from the primary mutation. Ancillary mutations have been found in mutant colonies arising both spontaneously and after treatment with ultraviolet light and some have been found repeatedly. Ancillary mutations were frequently found to occur in mixed clones with an excess of bacteria carrying only the primary SmD mutation. No ancillary mutations were found in an adjacent non-coding region and there were no coding sequence changes that did not alter the amino acid specified. Although a selective advantage for bacteria containing ancillary mutations could not be demonstrated directly in every case, some small advantage must be presumed to have occurred to explain the absence of mutations at the other sites and particularly at third (wobble) codon positions. Ancillary mutations appear to occur fairly early in the life of a newly arisen SmD mutant clone in some sort of hypermutable process. Whether they are noticed appears to depend on their conferment of some selective advantage on the bacteria carrying them. While the ancillary mutations within rpsL lie close to, and may be consequent upon the formation of a primary SmD mutation, their mechanism of formation appears to be at least to some extent independent and does not involve the recA or umuC genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1998

HLA-C high resolution typing: analysis of exons 2 and 3 by sequence based typing and detection of polymorphisms in exons 1-5 by sequence specific primers.

HLA-C high resolution sequence based typing developed in this study involves a unique DNA amplification encompassing exon 1 to intron 3 and four fluorescent sequencing reactions covering exon 2 and 3. Both dye primer and dye terminator sequencing techniques were performed and results compared. This approach allowed the identification of all of the 50 HLA-C allelic variants so far described, except for two allele pairs that are distinguished by non-coding nucleotide changes (Cw*12021 = 12022, Cw*15051 = 15052) and three allele pairs (Cw*0701 = 706, Cw*1701 = 1702 and Cw*1801 = 1802) that share the same nucleotide sequence in exon 2 and 3. For complete subtyping of these allelic variants, an amplification based on sequence specific primers (PCR-SSP) was used. No ambiguous heterozygous combinations of alleles were detected in our panel so far. HLA-C typing data obtained by this method were compared with data from serological and low resolution PCR-SSP typing, which had been performed previously on the samples sequenced.

Base Sequence↗
PubMed1983

Comparison of the DNA sequence of the Crawford small-plaque variant of polyomavirus with those of polyomaviruses A2 and strain 3.

The DNA sequence of two wild-type strains of polyomavirus (A2 and strain 3) are known. We have determined the majority of the DNA sequence of a third strain, the Crawford small-plaque virus. This virus has been noted for its capacity to induce readily detected tumor-specific transplantation antigen in hamster cells, a property that is most likely attributable to an altered middle T-antigen. A comparison of its DNA sequence with those of the A2 and strain 3 viruses reveals numerous nucleotide substitutions, insertions, and deletions throughout the genome. Most sequence changes in coding regions are silent mutations; however, variability in proteins can be predicted from these sequence data at 5 locations in middle T-antigen, 10 in large T-antigen, and 10 in VP1. The Crawford small-plaque virus noncoding regulatory region contains, in addition to nucleotide substitutions, a 44-base-pair tandem repeat of sequences on the late side of the origin of DNA replication.

Antigens, Viral, Tumor↗
PubMed1990

Mutagenesis of the conserved 51-nucleotide region of Sindbis virus.

We have constructed 25 site-specific mutations in a domain of 51 nucleotides in Sindbis virus that is highly conserved among all alphaviruses sequenced to date. These 51 nucleotides are capable of forming two hairpin structures and are found from nucleotides 155 to 205 in Sindbis virus within the region encoding nsP1. Of the mutations, 21 were silent and did not lead to a change in the amino acid sequence encoded. These silent mutations changed not only the linear sequence but also the stability of the hairpins in most cases. Two double mutants that were constructed led to the replacement of one base pair by another so that the linear sequence was altered but the nature of the hairpins was not. All of the mutants with silent mutations were viable, but 19 of the 21 mutants were severely impaired for growth in both chicken and mosquito cells. Compared with the parental virus, they grew slowly and produced virus at rates of 10(-1) to 10(-4) times the parental rate. Surprisingly, however, the plaques produced by these mutants were indistinguishable from those produced by the parental virus. Two of the silent mutations, found within the first hairpin structure, produced virus at a faster rate than the parental virus. It is clear that the exact sequence of this region is important for some aspect of virus replication. We suggest that one or more proteins, either virus encoded or cellular, bind to the hairpin structures in a sequence-specific fashion in a step that promotes replication of the viral RNA. Of the mutations that resulted in a change of coding, only one of four was viable, suggesting that the amino acid sequence encoded in this domain is essential for virus replication.

Animals↗
PubMed1991

Yeast CBP1 mRNA 3' end formation is regulated during the induction of mitochondrial function.

Alternative mRNA processing is one mechanism for generating two or more polypeptides from a single gene. While many mammalian genes contain multiple mRNA 3' cleavage and polyadenylation signals that change the coding sequence of the mature mRNA when used at different developmental stages or in different tissues, only one yeast gene has been identified with this capacity. The Saccharomyces cerevisiae nuclear gene CPB1 encodes a mitochondrial protein that is required for cytochrome b mRNA stability. This 66-kDa protein is encoded by a 2.2-kb mRNA transcribed from CPB1. Previously we showed that a second 1.2-kb transcript is initiated at the CBP1 promoter but has a 3' end near the middle of the coding sequence. Furthermore, it was shown that the ratio of the steady-state level of 2.2-kb CBP1 message to 1.2-kb message decreases 10-fold during the induction of mitochondrial function, while the combined levels of both messages remain constant. Having proposed that regulation of 3' end formation dictates the amount of each CBP1 transcript, we now show that a 146-bp fragment from the middle of CBP1 is sufficient to direct carbon source-regulated production of two transcripts when inserted into the yeast URA3 gene. This fragment contains seven polyadenylation sites for the wild-type 1.2-kb mRNA, as mapped by sequence analysis of CBP1 cDNA clones. Deletion mutations upstream of the polyadenylation sites abolished formation of the 1.2-kb transcript, whereas deletion of three of the sites only led to a reduction in abundance of the 1.2-kb mRNA. Our results indicate that regulation of the abundance of both CBP1 transcripts is controlled by elements in a short segment of the gene that directs 3' end formation of the 1.2-kb transcript, a unique case in yeast cells.

Base Sequence↗
PubMed1996

p53 tumour suppressor gene expression in pancreatic neuroendocrine tumour cells.

Neuroendocrine pancreatic tumours grow slower and metastasise later than ductal and acinar carcinomas. The expression of the p53 tumour suppressor gene in pancreatic neuroendocrine tumour cells is unknown. Pancreatic neuroendocrine cell lines (n = 5) and human tumour tissues (n = 19) were studied for changed p53 coding sequence, transcription, and translation. Proliferative activity of tumour cells was determined analysing Ki-67 expression. No mutation in the p53 nucleotide sequence of neuroendocrine tumour cell was found. However, an overexpression of p53 could be detected in neuroendocrine pancreatic tumour cell lines at a protein level. As no p53 mutations were seen, it is suggested that post-translational events can also lead to an overexpression of p53.

Autoradiography↗
PubMed2005

Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions.

BACKGROUND: Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci Blmpf1 and Blmpf2 on chromosomes 17 and 11, respectively, in a C57BL/6J (B6, susceptible) and C3Hf/KAM (C3H, resistant) mouse cross. METHODS: Herein, the genetic basis of bleomycin induced pulmonary fibrosis was investigated in an approach combining gene expression and sequencing data with previously mapped linkage intervals. RESULTS: In this study, gene expression analysis with microarrays revealed 1892 genes or ESTs (expressed sequence tags) to be differentially expressed between bleomycin treated B6 and C3H mice and 67 of these genetic elements map to Blmpf1 or Blmpf2. This group included genes involved in an oxidative stress response, in apoptosis, and in immune regulation. A comparison of the B6 and C3H sequence, for Blmpf1 and Blmpf2, made using the NCBI database and available C3H sequence, revealed approximately 35% of the genes in these regions contain non-synonymous coding sequence changes. An assessment of genotype/phenotype correlation among other inbred strains revealed 36% of these B6/C3H sequence variations predict for the known bleomycin induced fibrosis susceptibility of the DBA (susceptible) and A/J (resistant) mouse strains. CONCLUSIONS: Combining genomics approaches of differential gene expression and sequence variation potentially identifies approximately 5% the linked genes as fibrosis susceptibility candidate genes in this mouse cross.

Animals↗
PubMed1996

Smoking on hospital grounds and the impact of outdoor smoke-free zones.

OBJECTIVES: To describe the type and location of smokers on the grounds of smoke-free public hospitals and to observe the impact of introducing smoke-free signs in outdoor areas of the hospital grounds. DESIGN: Observation study of outdoor smoking behaviour before and after the introduction of outdoor smoke-free signs at one hospital (H1) and at the same two time periods at a nearby control hospital (H2), which already had some outdoor smoke-free signs at Time 1. SETTING: The John Hunter Hospital (H1) in Newcastle, Australia and a nearby control hospital, Maitland Hospital (H2) in 1991. SUBJECTS: All people in defined outdoor sites of the two hospitals on seven randomly selected days over two weeks before and after the policy change were coded as either "smoker" or "non-smoker" and as either "staff", "patient", or "visitor". The number of smokers observed in each site was measured as a proportion of all smokers observed on the grounds of that hospital. INTERVENTION: Introduction of outdoor smoke-free zones and signs at H1. RESULTS: Less than 10% of observed outdoor smokers in both hospitals were patients, 40% were visitors, and more than 50% were staff. Of outdoor smokers, 82% were observed less than 10 m from entrances to the hospital building at time 1. After the introduction of signs in H1, a 4-percentage point decrease (P < 0.05) occurred in the percentage of smokers observed in smoke-free zones at time 2 (from 32% to 28%), compared with a 2-percentage point decrease (P > 0.05 at time 2 in H2 (from 48% to 46%). DISCUSSION: This observation study of smoking behaviour in hospital grounds highlights the need to reduce smoking among staff and visitors near hospital entrances. Specific strategies are discussed, which are likely to enhance compliance and hence enable the effective introduction of smoke-free policies on hospital grounds.

Hospitals↗
PubMed2004

Polyploidization-induced genome variation in triticale.

Polyploidization-induced genome variation in triticale (x Triticosecale Wittmack) was investigated using both AFLP and RFLP analyses. The AFLP analyses were implemented with both EcoRI-MseI (E-M) and PstI-MseI (P-M) primer combinations, which, because of their relative differences in sensitivity to cytosine methylation, primarily amplify repetitive and low-copy sequences, respectively. The results showed that the genomic sequences in triticale involved a great degree of variation including both repetitive and low-copy sequences. The frequency of losing parental bands was much higher than the frequency of gaining novel bands, suggesting that sequence elimination might be a major force causing genome variation in triticale. In all cases, variation in E-M primer-amplified parental bands was more frequent in triticale than that using P-M primers, suggesting that repetitive sequences were more involved in variation than low-copy sequences. The data also showed that the wheat (Triticum spp.) genomes were relatively highly conserved in triticales, especially in octoploid triticales, whereas the rye (Secale cereale L.) genome consistently demonstrated a very high level of genomic sequence variation (68%-72%) regardless of the triticale ploidy levels or primers used. In addition, when a parental AFLP band was present in both wheat and rye, the tendency of the AFLP band to be present in triticale was much higher than when it was present in only one of the progenitors. Furthermore, the cDNA-probed RFLP analyses showed that over 97% of the wheat coding sequences were maintained in triticale, whereas only about 61.6% of the rye coding sequences were maintained, suggesting that the rye genome variation in triticale also involved a high degree of rye coding sequence changes. The data also suggested that concerted evolution might occur in the genomic sequences of triticale. In addition, the observed genome variation in wheat-rye addition lines was similar to that in triticale, suggesting that wheat-rye addition lines can be used to thoroughly study the genome evolution of polyploid triticale.

Biological Evolution↗
PubMed1993

Decline in US stroke mortality in the era before antihypertensive therapy.

BACKGROUND AND PURPOSE: This study was done to determine if reported declines in stroke mortality in the era before antihypertensive therapy are artifactual. METHODS: This study involved analyses of national and state vital statistics data using adjusted and specific rates. RESULTS: Adoption of the third revision of the International List of Causes of Death in 1921 produced an abrupt 6.6% decrease in stroke mortality rates, but otherwise, changes in disease classification systems had little effect on stroke mortality rates. Adoption of the second revision of the joint-cause manual produced a 9.2% drop in stroke death rates, but other revisions of the joint-cause selection rules had little effect. While rates for the expanding group of states in the death registration area progressively declined, rates for fixed component areas remained constant until around 1925 and then declined. Reselection of the underlying cause from aggregate multiple cause data for 1917, 1925, and 1940 using uniform selection rules confirmed a decline after 1925. Correlation analyses of rates of change for stroke and heart disease rates did not support a shift in diagnosis to explain the divergent trends. CONCLUSIONS: The apparent decline in stroke mortality rates before 1925 is an artifact of changes in disease classification systems, joint-cause selection rules, and nonrandom incorporation of states with different mortality rates into the expanding registration area. The decline after 1925 could not be explained by changes in coding systems or joint-cause selection rules or by a shift in diagnosis from stroke to heart disease.

Age Factors↗
PubMed2006

A large GLC1C Greek family with a myocilin T377M mutation: inheritance and phenotypic variability.

PURPOSE: POAG is a complex disease; therefore, families in which a glaucoma gene has been mapped may carry additional POAG genes. The goal of this study was to determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are present in two POAG families, which have previously been mapped to the GLC1C locus on chromosome 3. METHODS: The three exons of MYOC were screened by denaturing (d)HPLC. Samples with heteroduplex peaks were sequenced. Clinical findings were compared with genotype status in all available family members over the age of 20 years. RESULTS: A T377M coding sequence change in MYOC was identified in family members of the Greek GLC1C family but not in the Oregon GLC1C family. Individuals carrying both the MYOC T377M variant and the GLC1C haplotype were more severely affected at an earlier age than individuals with just one of the POAG genes, suggesting that these two genes interact or that both contribute to the POAG phenotype in a cumulative way.

Adult↗
PubMed2002

Pioglitazone, a PPAR-gamma ligand, provides protection from dextran sulfate sodium-induced colitis in mice in association with inhibition of the NF-kappaB-cytokine cascade.

Nuclear factor-kappaB-dependent up-regulation of inflammatory cytokines occurs in inflammatory bowel disease. We investigated the effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma ligand, on dextran sulfate sodium-induced colonic mucosal injury and inflammation in mice. Acute colitis was induced in female mice receiving 0, 1, 3, and 10 mg/kg i.p. of pioglitazone daily. Colonic mucosal inflammation was evaluated chemically and histologically. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in intestinal mucosa as indices of lipid peroxidation and neutrophil infiltration, respectively. Colonic mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase was measured by reverse transcription-PCR and nuclear factor-kappaB activation was evaluated by electrophoretic mobility shift assay. Dextran sulfate sodium administration resulted in decreases in body weight and colon length and increases in lipid peroxide and neutrophil accumulation of the intestine. In contrast, co-administration with pioglitazone prevented these changes. Transcripts coding for pro-inflammatory cytokines and inducible nitric oxide were expressed in high levels after the development of colitis, and pioglitazone markedly reduced mRNA expression of these genes. DNA binding activity of nuclear factor-kappaB was markedly increased, whereas in pioglitazone co-treated intestines the effect was significantly reduced. These data suggest that peroxisome proliferator-activated receptor-gamma may be a novel therapeutic target for the therapy of inflammatory bowel disease.

Animals↗