Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “coding change”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed2003

A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.

The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-coding regions of the gene, this variant occurs within the coding region and causes the change of amino acid sequence (a substitution of a cysteine for a glycine residue). The minor allele frequencies were 0.042 and 0.27 (P<0.001) for control and hypertriglyceridemic patients, respectively. The serum triglyceride level was significantly different among the genotypic groups (G/G 92.5+/-37.8 mg/dl, G/T 106.6+/-34.8 mg/dl, T/T 183.0 mg/dl, P=0.014) in control subjects. Multiple logistic regression revealed individuals carrying the minor allele had age, gender and BMI (body mass index)-adjusted odds ratio of 11.73 (95% confidence interval of 6.617-20.793; P<0.0001) for developing hypertriglyceridemia in comparison to individuals without that allele. These findings suggest the possible use of c.553G>T polymorphisms in APOA5 as prognostic indicators for hypertriglyceridemia susceptibility in Chinese.

Age Factors↗
PubMed1989

A new approach to surveillance for acute myocardial infarction: reproducibility and cost efficiency.

A new approach to surveillance of myocardial infarction, the major cardiovascular endpoint is described using an algorithm which depends primarily on enzyme data, using evidence of chest pain and positive electrocardiogram findings as supplemental information only. This approach is evaluated with respect to reproducibility by minimally trained abstractors, cost, and robustness with respect to different hospital systems as well as changes in diagnostic techniques and/or labelling over time. Two pilot studies demonstrate that, in comparison to more traditional approaches, the new surveillance system provides at least a 50% reduction in cost, is highly reproducible over different hospital systems, and potentially, is resilient to changes in diagnostic procedures or coding. The more general applicability of such an innovative surveillance approach to other disease endpoints, in which one reliable procedure contains most of the diagnostic information, is discussed with particular reference to cancer.

Algorithms↗
PubMed1989

Early abortion and breast cancer risk among women under age 40.

In New York State, incidence of cancer and fetal death are reportable health events mandated by state law. These data enabled a population-based record linkage study of the effect of early pregnancy termination on breast cancer risk to be conducted. In upstate New York 1451 cases under age 40 were reported to the Cancer Registry during 1976-1980. Cases were matched with 1451 population controls by year of birth and by residence using zip codes. All names including those changed by marriage were matched with the reports of fetal deaths occurring between 1971 and 1980. Matched pairs analyses revealed an excess of early pregnancy terminations among cases in all categories. Odds ratios (OR) were significantly elevated among those with an induced abortion (OR = 1.9) and a spontaneous abortion (OR = 1.5). Elevated risks were also noted for consecutive abortion events without intervening livebirths.

Abortion, Incomplete↗
PubMed1994

AT base pairs are the main target for mutations at the hprt locus of rat skin fibroblasts exposed in vitro to the monofunctional alkylating agent N-ethyl-N-nitrosourea.

Spectra of N-ethyl-N-nitrosourea (ENU)-induced mutations differ widely among various in vitro and in vivo mutational systems. To investigate possible reasons for these differences, a mutational system is needed in which the same target gene is used for comparison in the same type of cells in vitro and in vivo. In the present study, this was achieved by analysing at the molecular level 35 hprt mutant rat fibroblast clones obtained from cell populations exposed in vitro to ENU and comparing the mutational spectrum with the previously determined spectrum of ENU-induced hprt mutants in the same target cells exposed in vivo. Twenty-eight mutants contained a single base pair alteration in the hprt coding sequence. Most of these changes were found at AT base pairs (19/28), the AT to TA transversion being the most frequent kind of mutation (12/19), which is probably caused by O2-ethylthymine. Transversions at AT base pairs showed all mutated T's to be located in the nontranscribed strand of the hprt gene, suggesting a strand specific fixation of mutations induced by O2-ethylthymine, which appears to be a general feature of ENU- and ENNG-induced hprt mutations in mammalian cells. GC to AT transitions, probably caused by O6-ethylguanine, were detected at a lower frequency (7/28). This in vitro mutational spectrum was very similar to that of the same target cells exposed in vivo to ENU. A comparison of the mutational spectra in AGT-proficient and AGT-deficient rodent cells exposed to ethylating agents showed that in contrast to the situation in AGT-proficient rat fibroblasts, GC to AT base pair changes (and not AT to TA) are the predominant mutations in AGT-deficient hamster cells.

Alkylating Agents↗
PubMed1997

Changes in the alpha 2-adrenergic receptor subtypes gene expression in rat dorsal root ganglion in an experimental model of neuropathic pain.

We examined changes in expression of genes coding for alpha 2-AR subtypes in the dorsal root ganglion (DRG) in a rat model (spinal nerve ligation) or neuropathic pain. The present study demonstrates that the majority of DRG neurons express alpha 2C-AR mRNA and a small proportion of neurons express alpha 2A-AR mRNA, while few neurons express alpha 2B-AR mRNA in non-operated animals. In addition, alpha 2C- and alpha 2A mRNA levels in the DRG showed a significant decrease and increase, respectively in ligated animals. These findings suggest that alpha 2A- and alpha 2C-ARs in the DRG may play an important role in generating sympathetically maintained neuropathic pain.

Animals↗
PubMed1982

Declining mortality from hypertension and stroke.

Recorded mortality from hypertension and stroke has decreased dramatically in most countries during the last 50 to 75 years. The reported reduction in mortality may be due to changes in diagnostic fashions or coding procedures. However, the magnitude and consistency of the decline suggests the occurrence of a true decrease. The possibility that better treatment of hypertension is responsible for the reduction in mortality is attractive. However, based on temporal relationships, it seems more likely that much of the fall has resulted from an alteration in the determinants of blood pressure. Increasing use of antihypertensive drug therapy may account for an acceleration in the decline of stroke mortality during the last decade. If so, this represents one of the first tangible benefits of the massive public health efforts to detect and treat hypertension in the community.

Age Factors↗
PubMed1997

Associations between spinal deformity and outcomes after decompression for spinal stenosis.

STUDY DESIGN: Prospective observational study. OBJECTIVES: To examine associations between radiographic parameters (scoliosis and olisthesis) and outcomes of surgery for degenerative spinal stenosis. SUMMARY OF BACKGROUND DATA: Preoperative degenerative scoliosis generally is thought to be associated with an unfavorable outcome of surgery for spinal stenosis. Data on the relationship between an increase in olisthesis after laminectomy for spinal stenosis and outcomes of surgery are sparse and conflicting. METHODS: Radiographs were obtained before surgery and at least 6 months after surgery and coded for preoperative scoliosis and change in olisthesis after surgery. The reviewers of radiographs were blind to outcome information. Patients completed questionnaires on demographic and clinical data as well as on back pain, lower extremity pain, walking capacity, and satisfaction with surgery. Associations between radiographic data and patient reported outcomes were examined with the Spearman rank correlation and confirmed with multiple linear regression models that adjusted for potential confounders. RESULTS: Ninety patients met eligibility criteria. Preoperative scoliosis was associated with less improvement in back pain at 6 months and at 24 months after surgery. An increase in olisthesis after surgery was associated with greater improvement in lower extremity pain at 6 months and at 24 months after surgery. An increase in olisthesis also was associated with greater improvement in walking capacity at 6 months and at 24 months after surgery. In multivariable analyses that adjusted for potential confounders, a change in olisthesis was not associated significantly with greater improvement in any of the outcomes. CONCLUSION: The data support the widely held view that preoperative scoliosis is associated with an unfavorable outcome after decompression for degenerative lumbar spinal stenosis. Increase in olisthesis was not associated with unfavorable results. In fact, there was a weak trend toward better outcomes with greater slip. These data indicate that minor increases in olisthesis after surgery for spinal stenosis generally are tolerated well.

Aged↗
PubMed1994

Direct sequencing of the reserpine-sensitive vesicular monamine transporter complementary DNA in unipolar depression and manic depressive illness.

The reserpine model and the reduced monoamine hypothesis of the depressive symptom spectrum suggest that the reserpine-sensitive brain vesicular monoamine transporter (VMT) is a candidate for susceptibility to affective disorder. VMT nonselectively accumulates cytoplasmic biogenic monoamine neurotransmitters into the storage vesicles of presynaptic neurons and blood platelets. Complementary DNA (cDNA) synthesized from platelet VMT mRNA was analyzed in 17 patients meeting DSM-III-R diagnostic criteria for major depressive or bipolar disorder and in four healthy controls, using polymerase chain reaction (PCR) amplification and direct sequencing. PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain VMT (approximately 36,000 base pairs sequence screened). The results indicate that alterations in the primary structure of the VMT are not generally involved in the pathogenesis of unipolar depression and manic depressive illness.

Adult↗
PubMed2003

Rising rates of hospital admissions for atrial fibrillation.

BACKGROUND: Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study). METHODS: The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years. We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods. Changes in admission rates were analyzed using Cox proportional hazard models. RESULTS: During the 2 7-year periods, 379 subjects were admitted with a hospital diagnosis of atrial fibrillation. The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period (relative risk = 1.6; 95% confidence interval = 1.3-1.9 [adjusted for age, sex, prior myocardial infarction, arterial hypertension, diabetes mellitus, electrocardiographic left ventricular hypertrophy, decreased lung function, smoking, height, and weight]). CONCLUSION: During the latest 10 to 20 years, there has been a 60% increase in hospital admissions for atrial fibrillation independent of changes in known risk factors. This increase could result from changes in admission threshold or coding practices, or it could reflect a genuine increase in the population incidence of atrial fibrillation.

Adult↗
PubMed1998

Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue.

The question of a possible role for JC virus (JCV) genomic rearrangements in the pathogenesis of progressive multifocal leukoencephalopathy (PML) was addressed by analysis of the genomic complexity and the transcriptional control region (TCR) of the JCV DNA population in persistently infected CNS and kidney tissue. After cloning of full-length viral DNA, no extensive changes were detected in the coding regions of the JCV genome by restriction analysis suggesting an intact JCV DNA population. For further analysis of the distribution of JCV subtypes, the non-coding region was amplified by PCR. Molecular analysis revealed homogeneous JCV TCR populations in almost 50% of the individuals. Heterogeneity was found in two CNS samples with three and five different JCV subtypes, respectively, and in four kidney specimens with two TCR subtypes. Altogether, seven TCR subtypes were identified. One in each group represented single promoter element TCRs without duplication of sequences. The TCR of the major variant JCV-W1 was comparable in sequence and structure to that of the PML prototype JCV Mad-1 DNA. The identification of dominant PML-derived JCV TCR subtypes in most persistently infected individuals suggests that rearrangements of the JCV TCR can be associated with the persistent state of infection. However, it appears unlikely that PML-associated JCV subtypes are generated anew in each individual host in the course of persistence. The findings rather suggest that a limited number of stable JCV subtypes circulate in different geographical regions of the world.

Adult↗
PubMed2007

Intrahost evolution of HBe antigen-negative hepatitis B virus genomes ascribed to the F genotype: a longitudinal 3 year retrospective study.

The intrahost hepatitis B virus (HBV) genomic evolution process of an HBe antigen (HBeAg)-negative chronic HBV patient (designated RI) was studied. Two nearly full-length direct sequences obtained in 1995 (RI95) and 1998 (RI98) showed: (a) a mutation rate of 2.7x10(-3) nucleotides per site per year; (b) nucleotide changes mainly located at single coding regions (P=0.002); (c) mixed populations; and (d) a predominance of non-synonymous substitutions (P=0.0036). Population heterogeneity was assessed by cloning and sequencing of a fragment spanning nearly half the genome. Two-thirds of the analysed clones exhibited long nucleotide deletions. Pairwise genetic diversity revealed that diversity was higher for RI95 than for RI98 cloned sequences. In conclusion, a highly heterogeneous genomic population circulated within patient RI, which might support the persistence of HBV. Finally, the structure of the deletant genomes suggests that they might serve as intermediates for integration to the host-cell genome.

Evolution, Molecular↗
PubMed1994

Hepatitis C virus and liver diseases.

Hepatitis C virus (HCV) was identified molecularly and a procedure for its diagnosis was developed. In Japan, 70-80% of all cases of chronic liver disease, including hepatocellular carcinoma, are associated with HCV infection. Hepatitis C virus is a typical RNA virus with a high mutation rate. At least six variants of HCV have been identified by their nucleotide sequences. These variants are still classified into three types each containing at least two subtypes; that is, 1a (type I) and 1b (type II), 2a (type III) and 2b (type IV), and 3a (type V) and 3b (type VI). Type 1b (type II) is the predominant HCV in Japan. Even HCV cDNA clones isolated from a single patient showed mutations of HCV, especially in envelope-coding regions. Thus HCV may change during the course of chronic hepatitis due to the high mutation rate of HCV itself and elimination of some clones by immune reactions or interferon therapy. These findings explain the higher rate of chronic HCV infection and indicate that production of an effective vaccine is difficult.

Amino Acid Sequence↗
PubMed1998

The Australian mortality decline: cause-specific mortality 1907-1990.

This review describes the changes in composition of mortality by major attributed cause during the Australian mortality decline this century. The principal categories employed were: infectious diseases, nonrheumatic cardiovascular disease, external causes, cancer, 'other' causes and ill-defined conditions. The data were age-adjusted. Besides registration problems (which also affect all-cause mortality) artefacts due to changes in diagnostic designation and coding are evident. The most obvious trends over the period are the decline in infectious disease mortality (half the decline 1907-1990 occurs before 1949), and the epidemic of circulatory disease mortality which appears to commence around 1930, peaks during the 1950s and 1960s, and declines from 1970 to 1990 (to a rate half that at the peak). Mortality for cancer remains static for females after 1907, but increases steadily for males, reaching a plateau in the mid-1980s (owing to trends in lung cancer); trends in cancers of individual sites are diverse. External cause mortality declines after 1970. The decline in total mortality to 1930 is associated with decline in infection and 'other' causes. Stagnation of mortality decline in 1930-1940 and 1946-1970 for males is a consequence of contemporaneous movements in opposite directions of infection mortality (decrease) and circulatory disease and cancer mortality (increase). In females, declines in infections and 'other' causes of death exceed the increase in circulatory disease mortality until 1960, then stability in all major causes of death to 1970. The overall mortality decline since 1970 is a consequence of a reduction in circulatory disease, 'other' cause, external cause and infection mortality, despite the increase in cancer mortality (for males).

Adolescent↗
PubMed1992

Identification of mutations in the pigment cell-specific gene located at the brown locus in mouse.

The pigment cell-specific gene, located at the brown (b)-locus in mouse, encodes the protein that determines the type of melanin synthesized. This protein is known as tyrosinase-related protein, but here we tentatively term it b-locus protein to avoid confusions with the related sequence cross-hybridizing to the tyrosinase gene. In order to identify the mutation at the b-locus, we have cloned and characterized the b-locus protein gene of BALB/c mouse (b/b, c/c). The gene is about 18 kb long and organized into 8 exons and 7 introns. Sequence analysis of the b-locus protein gene reveals four base changes within the protein-coding regions: two missense mutations and two silent mutations. Two missense mutations result in the Cys to Tyr substitution at position 86 (codon 110) and the Arg to His substitution at position 302 (codon 326) of a b-locus protein molecule. Using allele-specific amplification, we confirmed that these missense mutations are actually present in the genomic DNA of two b-mutant strains examined, BALB/c and DBA/2 (b/b, C/C) mice, suggesting that these mutations are specific for the mutant mice at the b-locus. Moreover, we are able to show that the b-locus protein containing Tyr 86 is not reactive with the anti-b-locus protein monoclonal antibody, TMH-1, in transient expression assays.

Amino Acid Sequence↗
PubMed2006

A direct voxel tracking method for four-dimensional Monte Carlo dose calculations in deforming anatomy.

In this work we present a method of calculating dose in deforming anatomy where the position and shape of each dose voxel is tracked as the anatomy changes. The EGSnrc/DOSXYZnrc Monte Carlo code was modified to calculate dose in voxels that are deformed according to deformation vectors obtained from a nonlinear image registration algorithm. The defDOSXYZ code was validated by consistency checks and by comparing calculations against DOSXYZnrc calculations. Calculations in deforming phantoms were compared with a dose remapping method employing trilinear interpolation. Dose calculations with the deforming voxels agree with DOSXYZnrc calculations within 1%. In simple deforming rectangular phantoms the trilinear dose remapping method was found to underestimate the dose by up to 29% for a 1.0 cm voxel size within the field, with larger discrepancies in regions of steep dose gradients. The agreement between the two calculation methods improved with smaller voxel size and deformation magnitude. A comparison of dose remapping from Inhale to Exhale in an anatomical breathing phantom demonstrated that dose deformations are underestimated by up to 16% in the penumbra and 8% near the surface with trilinear interpolation.

Algorithms↗
PubMed2000

Accurate condensed history Monte Carlo simulation of electron transport. I. EGSnrc, the new EGS4 version.

In this report a new EGS4 version, called EGSnrc to reflect the substantial changes made to the original code is reported, which incorporates a new any-angle multiple elastic scattering theory, an improved electron-step algorithm, a correct implementation of the fictitious cross section method for sampling distances between discrete interactions, a more accurate evaluation of energy loss, as well as an exact boundary crossing algorithm. It is demonstrated that EGSnrc allows for an artifact free Monte Carlo simulation of ion chamber response and backscattering, situations that have been considered in the past as the two of the most stringent tests of condensed history Monte Carlo codes. A detailed discussion of the effect of the various components of the condensed history simulation of electron transport on the simulated ion chamber response is given in the accompanying paper.

Algorithms↗
PubMed1994

Differential flagellin expression in a flaA flaB+ mutant of Campylobacter jejuni.

Campylobacter jejuni 81116 has two genes coding for flagellin, flaA and flaB. Fully motile wild-type C. jejuni bacteria express the flaA gene, with no flaB message being detected. A nonmotile flaA flaB+ mutant, R1, produced detectable levels of flagellin B which was incorporated into truncated flagella. After R1 had invaded INT-407 cells, a variant with increased motility, R1-V2, was isolated. R1-V2 produced full-length flagella and an increased amount of flagellin B. Transcriptional analysis showed that R1-V2 contained more flaB mRNA than its parental strain, R1. The flaB gene promoter sequence and primer extension experiments confirmed that transcription of the flaB gene is initiated from a sigma 54 promoter. Neither the promoter sequence nor the coding sequence of flaB had changed in R1-V2. In contrast to R1, R1-V2 no longer produced (truncated) flaA mRNA. The sigma 28 flaA promoter sequence was not changed in R1-V2. We propose that expression of the two flagellin genes in C. jejuni 81116 is regulated at the transcriptional level, in such a way that predominantly one gene at a time is transcribed. We compared the levels of invasiveness of the wild-type strain, R1, and R1-V2 for INT-407 cells. The shift in expression from flaA to flaB occurred not only during invasion assays but also under different conditions in the absence of eukaryotic cells.

Bacterial Proteins↗
PubMed1999

Genetic basis for immunological aberrations in poliovirus Sabin serotype 3 strains imported in the netherlands.

During the characterization of poliovirus type 3 strains imported in The Netherlands, Sabin serotype 3 strains that reacted with both specific antisera against Sabin-like (vaccine) and non-Sabin-like (wild-type) strains by the intratypic strain differentiation assay have been found. The present study was done to determine the pathogenic potential of these virus strains for humans. Characterization of these so-called double-reactive strains with neutralizing monoclonal antibodies (MAbs) against the major antigenic sites of serotype 3 Sabin virus led to the identification of two groups with different antigenic properties. Six of the seven strains were resistant to neutralization with MAbs against sites 2B and 3B and one strain was neutralized by all the MAbs in a manner similar to that for the Sabin serotype 3 virus. Partial sequencing of the coding regions confirmed the antigenic changes for all six antigenically distinct strains. By inoculation of these viruses into transgenic mice which express the human poliovirus receptor, one strain was identified as highly neurovirulent, three were identified as intermediate, and three were identified as attenuated. Sera from vaccinated persons efficiently neutralized the mutants. Our data suggest that some double-reactive strains are a potential risk to the unvaccinated community but not to the vaccinated population.

Animals↗