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Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and changes of dipeptidyl peptidase IV mRNA levels during cell differentiation.

A cDNA (DPCR1) specific for human intestinal dipeptidyl peptidase IV (DPP IV) has been isolated. This 1.7-kilobase cDNA, together with a previously published partial sequence, covers the entire open reading frame of human DPP IV plus 67 base pairs of the 3'-untranslated end. Human DPP IV is a 766-amino acid polypeptide with a high degree of homology with the rat liver protein. The characterization of this molecular probe allowed us to definitively confirm the identity of DPP IV with CD 26, a mouse thymocyte activation antigen, a conclusion strengthened by the fact that we observed identical patterns on Southern blot of human genomic DNA hybridized either with human DPP IV or mouse CD 26 cDNA probe. Using this new tool, we have investigated the expression of DPP IV during the onset of enterocytic differentiation of two cultured human colon cancer cell lines, HT-29 and Caco-2. Whatever the cell line and the culture conditions, DPP IV expression strictly correlates with the presence of a differentiated phenotype, as shown by enzyme activity and the steady state amount of the protein measured by indirect immunofluorescence and Western blot. Accordingly, DPP IV biosynthesis exclusively increases in cells that display an enterocytic differentiation. Neither the glycosylation nor the stability of the protein appear to be dependent on the state of enterocytic differentiation. The DPP IV mRNA level remains very low in undifferentiated cell populations and specifically increases in cells that undergo an enterocytic differentiation. These results strongly suggest that DPP IV gene expression is controlled at the transcriptional or posttranscriptional level during intestinal differentiation.

Amino Acid Sequence↗

[Assessment of health risk in view of changes in labor code and methods used for protecting the environment].

In view of the present and proposed amendments to the Labor Code as well as bearing in mind anticipated harmonization of regulations in this area with those of EEC, the authors emphasize the need for well developed methodology for assessing chemical safety in an occupational environment with special reference to health effects in people exposed to chemicals. Methods for assessing health risk induced by work under conditions of exposure to chemicals were divided into: methods for assessing technological/processing risk, and methods for assessing health risk related to the toxic effect of chemicals. The need for developing means of risk communication in order to secure proper risk perception among people exposed to chemicals and risk managers responsible for prevention against chemical hazards was also stressed. It is suggested to establish a centre for chemical substances in order to settle down all issues pertaining to human exposure to chemicals. The centre would be responsible, under the provisions of the Chemical Substances Act, for the qualitative and quantitative analysis of the present situation and for the development of guidelines on assessment of health risk among persons exposed to chemicals.

Hazardous Substances↗

A privacy challenge to longitudinal study methods: patient-derived codes.

Recent changes to privacy legislation in Australia have resulted in more stringent requirements with respect to maintaining the confidentiality of patient health information. We describe a method employed to de-identify health information collected in a longitudinal study using codes. Using a patient-derived code that did not change during the life of the study follow-up resulted in errors in a quarter of the follow-up surveys. This may introduce bias that could compromise the validity of the study. Alternative methods of coding may alleviate some of these issues. However, removal of some of the constraints imposed by interpretations of privacy legislation may be the best way forward.

Cohort Studies↗

Evolutionary changes in the genetic code.

1. The genetic code was thought to be identical ("universal") in all biological systems until 1981, when it was discovered that the coding system in mammalian mitochondria differed from the universal code in the use of codons AUA, UGA, AGA and AGG. 2. Many other differences have since been discovered, some in mitochondria of various phyla, others in bacteria, ciliated protozoa, algae and yeasts. 3. The original thesis that the code was universal and "frozen" depended on the precept that any mutational change in the code would be lethal, because it would produce widespread alterations in the amino acid sequences of proteins. Such changes would destroy protein function, and hence would be intolerable. 4. The objection was "by-passed" by nature. It is possible for a codon to disappear from mRNA molecules, often as a result of directional mutation pressure in DNA: thus all UGA stop codons can be replaced by UAA. 5. The missing UGA codon can then reappear when some UGG tryptophan codons mutate to UGA. The new UGA codons will be translated as tryptophan, as is the case in non-plant mitochondria and Mycoplasma. Therefore, no changes have taken place in the amino acid sequences of proteins. 6. Variations of this procedure have occurred, affecting various codons, and discoveries are still being made. The findings illustrate the evolutionary interplay between tRNA, release factors and codon-anticodon pairing.

Animals↗

Is the apparent rise in cancer mortality in the elderly real? Analysis of changes in certification and coding of cause of death in England and Wales, 1970-1990.

The effect of changes in recording and coding of cause of death on trends in cancer mortality in England and Wales in persons aged 45 and over during 1970-1990 is reviewed. During this period, all-cancer mortality rates increased only at ages over 75 in males and over 55 in females. Rises in cancer mortality were largely due to increases in cancer of lung, prostate and unspecified site in men, and of lung, breast and unspecified site in women. Death coding and certification artefacts were much larger in older persons. In those aged 75-84, a change in the position of recording cancer on the death certificate could potentially account for 46% of the recorded increase in prostate-cancer mortality and 28% of the increase in breast-cancer mortality. The decrease in recorded mortality from ill-defined terminal events was far greater than the increase in cancer mortality in this age group. The rise in all-cancer mortality in the elderly was partly due to an increase in lung-cancer mortality, and data artefacts explained a large proportion of the increase in the other common specified cancers in those aged 75-84. The use of routine mortality statistics to chart progress against cancer lacks validity at older ages because of imprecision in certification of cause of death.

Aged↗

[Evolutionary changes in the genetic code, predictable on basis of the hypothesis of physical predetermination of the structure of codon bases].

According to the earlier proposed hypothesis on the structural correspondence between amino acids and doublets from the first codon bases (Sukhodolets 1980), the UGA triplet corresponds to tryptophan and the AGX triplets - to the termination codons. It is notably this sense of the UGA and AGA, AGG, respectively, that was reported for mitochondrial codes. Thereby, a proposal is indirectly confirmed that meanings of the UGA (nonsense) and AGA, AGG (arginine) in the normal cytoplasmic code is the result of evolutionary changes.

Amino Acids↗

Comparison of observer reliability in assessing alveolar bone changes from color-coded with subtraction radiographs.

OBJECTIVES: To assess intra- and interobserver agreement on marginal changes in periodontal bone from color-coded compared with subtraction radiographs. METHODS: Sequential radiographs from patients undergoing periodontal treatment were acquired using direct digital intra-oral radiography. Fifty-one pairs of color-coded and subtraction radiographs were produced and evaluated twice by six dentists for changes in marginal bone. Intra- and interobserver agreement were calculated. RESULTS: Intra-observer agreement was significantly higher for the color-coded radiographs (P < 0.05). Interobserver agreement was significantly higher for color-coded radiographs at the second (P < 0.001) but not the first (P = 0.34) evaluation. CONCLUSIONS: Color coding of radiographic differences by means of image addition may be a feasible alternative to the subtraction technique for evaluating periodontal bone changes.

Alveolar Bone Loss↗

Payment for procedural sedation.

PURPOSE OF REVIEW: As surgical procedures become less invasive and medical procedures become more invasive, the role of procedural sedation has become more important. The resulting proliferation of settings for procedural sedation and providers rendering sedation has brought attention to the economics of this service from nonanesthesia specialists and payers. Rapidly escalating expenditures for sedation have led to scrutiny from public and private insurance carriers. The review will summarize these trends and predict changes in coding and payment for procedural sedation. RECENT FINDINGS: Changes in coding for sedation by proceduralists have raised questions about the value of procedural sedation that have implications for anesthesiologists and other specialists administering sedatives for their own or others' procedures. The emerging literature on the role of registered nurses in administering new sedative agents has led to a re-examination of the role of anesthesiologists and other physicians in providing this care. Workforce projections demonstrating an ongoing shortage of anesthesia and nursing personnel have created a dilemma about the availability of professionals to meet the growing need for sedation. A proliferation of Medicare medical necessity rules may limit the availability of payment for monitored anesthesia care in many settings. SUMMARY: Coding, payment rules and fees for procedural sedation are likely to change in the coming 2-5 years. Those responsible for providing such services must consider the economic, clinical and workforce issues underlying these changes when planning to undertake or expand a commitment to sedation.

Journal Article↗

Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding region.

Changes in histone acetylation at promoters correlate with transcriptional activation and repression, but whether acetylation of histones in the coding region of genes is important for transcription is less clear. Here, we show that cells lacking the histone acetyltransferases Gcn5 and Elp3 have widespread and severe histone H3 hypoacetylation in chromatin. Surprisingly, severe hypoacetylation in the promoter does not invariably affect the ability of TBP to bind the TATA element, or transcription of the gene. By contrast, similar hypoacetylation of the coding region correlates with inhibition of transcription, and inhibition correlates better with the overall charge of the histone H3 tail than with hypoacetylation of specific lysine residues. These data provide insights into the effects of histone H3 hypoacetylation in vivo and underscore the importance of the overall charge of the histone tail for transcription.

Acetylation↗

Twenty-year trends in mortality from chronic obstructive pulmonary disease: the Honolulu Heart Program.

There is evidence of a rising trend in COPD mortality. Whether this is due to changes in coding or diagnostic practices, increase in disease incidence or severity, or other causes is unknown. The Honolulu Heart Program (HHP) has followed a cohort of 11,136 Japanese-American men, 45 to 65 yr of age at onset, from 1965 to 1984. Following a fixed protocol, study physicians assigned cause of death after review of hospital records, pathology and autopsy reports, the death certificate, and, in doubtful cases, after interview with family and personal physician. The eighth revision of the international Classification of Diseases was used throughout. During 20 yr of follow-up, 2,624 men died, 113 from COPD by HHP coding and 105 from COPD by State Health Department (HD) coding. There was no change in age-adjusted or age-specific COPD mortality rates from 1965 to 1984 by HHP coding (tests for trend, p greater than 0.05). In contrast, when HD coding was used there was a significant decline in COPD mortality over the same time period. The frequency with which COPD was found on the death certificate decreased significantly for diagnoses listed in Section 1 and increased for those in Section 2. Current smokers showed increasing trends and past smokers decreasing trends in COPD mortality. When HHP and HD codings were compared, there was agreement in only 46% (69 of 149) of the cases. Agreement was greater in 1965-1974 than in 1975-1984. This study found no evidence of increasing mortality rates from 1965 to 1984 in this cohort of Japanese-American men.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Mutation and evolutionary analyses identify NR2E1-candidate-regulatory mutations in humans with severe cortical malformations.

Nuclear receptor 2E1 (NR2E1) is expressed in human fetal and adult brains; however, its role in human brain-behavior development is unknown. Previously, we have corrected the cortical hypoplasia and behavioral abnormalities in Nr2e1(-/-) mice using a genomic clone spanning human NR2E1, which bolsters the hypothesis that NR2E1 may similarly play a role in human cortical and behavioral development. To test the hypothesis that humans with abnormal brain-behavior development may have null or hypomorphic NR2E1 mutations, we undertook the first candidate mutation screen of NR2E1 by sequencing its entire coding region, untranslated, splice site, proximal promoter and evolutionarily conserved non-coding regions in 56 unrelated patients with cortical disorders, namely microcephaly. We then genotyped the candidate mutations in 325 unrelated control subjects and 15 relatives. We did not detect any coding region changes in NR2E1; however, we identified seven novel candidate regulatory mutations that were absent from control subjects. We used in silico tools to predict the effects of these candidate mutations on neural transcription factor binding sites (TFBS). Four candidate mutations were predicted to alter TFBS. To facilitate the present and future studies of NR2E1, we also elucidated its molecular evolution, genetic diversity, haplotype structure and linkage disequilibrium by sequencing an additional 94 unaffected humans representing Africa, the Americas, Asia, Europe, the Middle East and Oceania, as well as great apes and monkeys. We detected strong purifying selection, low genetic diversity, 21 novel polymorphisms and five common haplotypes at NR2E1. We conclude that protein-coding changes in NR2E1 do not contribute to cortical and behavioral abnormalities in the patients examined here, but that regulatory mutations may play a role.

Animals↗

The development and validation of a coding protocol to measure change in tobacco-control newspaper coverage.

The national ASSIST newspaper coding protocol model was used as a template to adapt a system for measuring tobacco-related newspaper coverage in Colorado newspapers. Over a 3-month period, tobacco-related articles were clipped from 180 daily and weekly newspapers. Variables coded included adaptations of the original ASSIST categories. During development and testing, additional variables were added to make the protocol more comprehensive and sensitive to tobacco policy media coverage. Inter-coder reliabilities were calculated for all non-static variables using Cohen's kappa. Disagreements were resolved through group discussions. Two rounds of testing achieved ratings above .70 for all variables. The protocol improves dramatically upon the ASSIST model by providing greater breadth and depth of analysis and more sensitivity to the nuances of newspaper coverage of tobacco-related issues. Given its simplicity, the protocol could also prove valuable for anti-tobacco advocacy groups who wish to track the changes in public and media opinions.

Bibliometrics↗