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A new electrocardiographic classification for post-myocardial infarction clinical trials.

A new electrocardiographic code was developed for clinical trials involving patients with acute myocardial infarction (AMI). In the Multicenter Post-Infarction Program (MPIP), the electrocardiogram, classified by the Minnesota code, was not useful as a clinical predictor and played almost no role in subsequent analysis. To test its value the new code was applied to the electrocardiograms of 653 of the 866 patients in the MPIP data base who had sustained a first AMI. The MPIP code identifies AMI by region and severity. The 4 regions are anterior, lateral, inferior and posterior, defined by traditional criteria. Severity codes include Q-wave and non-Q-wave AMI, ST depression and no ischemic changes. The interpretation for each of 4 regions results in a 4-digit location severity code that is amenable to sorting and analysis. Fourteen separate and mutually exclusive groups were identified. Mortality gradients were found within the inferior AMI groups, but not within the anterior AMI groups. Mean ejection fraction was 50% for patients with isolated anterior infarction and decreased progressively (p less than 0.0003) as the extent of lateral wall involvement increased. For isolated inferior AMI, mean ejection fraction was 53%; lateral or posterior involvement did not significantly change this. The MPIP code is easy to apply, correlates acceptably well with clinically relevant variables of left ventricular function and permits the electrocardiogram to be used as a clinical predictor in large clinical trials.

Clinical Trials as Topic↗

Proteolytically induced changes in the molecular form of the carbamyl phosphate synthetase-uracil-aspartate transcarbamylase complex coded for by the URA2 locus in Saccharomyces cerevisiae.

When a uracil-auxotrophic yeast strain is grown under uracil-limiting conditions, the aspartate transcarbamylase activity found in crude extracts shows a variation in sensitivity to feedback inhibition by uridine 5'-triphosphate. In this study we correlated this variation with changes in the molecular form of the carbamyl phosphate synthetase-uracil-aspartate transcarbamylase complex. Carbamyl phosphate synthetase-uracil (molecular weight, 240,000) and uridine 5'-triphosphate-insensitive aspartate transcarbamylase (molecular weight, 140,000) were present separately in extracts from cells collected in the early exponential phase; this was in contrast to the presence of a single high-molecular-weight form (molecular weight, about 900,000) bearing both activities in extracts from stationary-phase cells. The lack of sensitivity to uridine 5'-triphosphate by aspartate transcarbamylase was delayed by adding uridine 5'-triphosphate before cell disruption and was prevented completely by adding phenylmethylsulfonyl fluoride. Thus, this event was attributed to a transient serine protease activity detected only in early exponential-phase cell extracts. However, even in the presence of phenylmethylsulfonyl fluoride, a sucrose density gradient analysis in the absence of uridine 5'-triphosphate revealed a change in the aggregation state of the complex which might have occurred in vivo. None of these events was observed in extracts from cells that lacked protease B activity (strain HP232-2B).

Aspartate Carbamoyltransferase↗

e-Health Code of Ethics (May 24).

The Internet is changing how people receive health information and health care. All who use the Internet for health-related purposes must join together to create an environment of trusted relationships to assure high quality information and services; protect privacy; and enhance the value of the Internet for both consumers and providers of health information, products, and services. The goal of the e-Health Code of Ethics is to ensure that people worldwide can confidently and with full understanding of known risks realise the potential of the Internet in managing their own health and the health of those in their care. The final e-Health Code of Ethics, presented in this paper, has been prepared as a result of the "e-Health Ethics Summit," which convened in Washington DC on 31 January 2000 - 2 February 2000. The summit, organized by the Internet Healthcare Coalition and hosted by the World Health Organisation/Pan-American Health Organisation (WHO/PAHO), was attended by a panel of about 50 invited experts from all over the world and produced the foundation for a draft code, which was released 18 February [1] for an online public consultation period which ended on 14 April 2000. The final Washington e-Health Code of Ethics sets forth guiding principles under eight main headings: candor; honesty; quality; informed consent; privacy; professionalism in online health care; responsible partnering; and accountability.

Ethics, Medical↗

Regulation of the nuclear-coded peptides of yeast cytochrome c oxidase.

We have analyzed the catabolite regulation of cytochrome oxidase by assaying changes in the synthesis of precursors of the nuclear-coded peptides (IV--VII) of cytochrome c oxidase in an in vitro reticulocyte cell-free system programmed with RNA isolated from cells grown in either glucose or raffinose. As a first step, we have characterized antibodies which bind to the precursors of subunits V and VI. Initial translation products for subunits IV and VII have also been tentatively identified by utilizing these antibodies. The messenger RNAs coding for the precursors of the nuclear-coded subunits fall in the expected size range of 8--15 S. Catabolite repression of the nuclear-coded oxidase peptides appears to be regulated by the abundance of their messenger RNAs. Translation of messenger RNA isolated from yeast cells grown on glucose indicates a coordinate and uniform increase in precursor synthesis during glucose derepression. In contrast, when RNA isolated from raffinose (derepressed) grown cells is used to direct cell-free translation, precursor abundance is high throughout growth, although the synthesis of some of the species changes in a complex pattern of ratio and abundance. These data indicate that the abundance of the messengers for the nuclear-coded precursors is regulated in a fashion dependent on the physiologic state of the cell.

Electron Transport Complex IV↗

Rates and dates of divergence between AIDS virus nucleotide sequences.

The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being approximately 1.7 X 10(-3) nucleotide substitutions/site/year. The nonsynonymous rate is extremely high (14 X 10(-3] in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10(-3) and 7 X 10(-3). The average synonymous rate for the HIV genome is 10 X 10(-3). These rates are 10(6) times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.

Base Sequence↗

In vivo 31P NMR OSIRIS of bioenergetic changes in rabbit kidneys during and after ischaemia: effect of pretreatment with an indeno-indole compound.

Changes in energy phosphates of rabbit kidneys subjected to ischaemia-reperfusion have been measured in vivo with volume selective 31P NMR spectroscopy. The effects of pretreatment with a new lipid peroxidation inhibitor (indeno-indol derivate--code name H290/51) on the bioenergetic changes were analysed. The left kidney was moved to a subcutaneous pocket to facilitate exact positioning over the surface coil. A 1H NMR image was acquired and a 3.5-mL cube selected for 31P NMR spectra. 31P NMR spectra were recorded before occlusion of the left renal artery, during 1 h of ischaemia and 2 hours of reperfusion. Ischaemia induced drastic changes in the levels of inorganic phosphates and ATP as well as intracellular acidosis. A normalization was observed during reperfusion. Two hours after reperfusion significantly higher values for beta-ATP/Pi and intracellular pH were recorded in the animals pretreated with H290/51. The present technique allows quantitative analyses of changes in kidney bioenergetics in vivo during different experimental conditions. The importance of ischaemia-reperfusion induced lipid peroxidation for mitochondrial function is emphasized.

Adenosine Triphosphate↗

Femtosecond silicon K alpha pulses from laser-produced plasmas.

Ultrashort bursts of silicon K alpha x-ray radiation from femtosecond-laser-produced plasmas have been generated. A cross-correlation measurement employing a laser-triggered ultrafast structural change of a CdTe crystal layer (320 nm) shows a K alpha pulse duration between 200 fs and 640 fs. This result is corroborated by particle in cell simulations combined with a Monte-Carlo electron stopping code and calculations on the structural changes of the crystal lattice.

Journal Article↗

Changes in judgment of duration with different patterns of auditory information for individuals confined to bed.

A theoretical proposition that changes in the organization and structure of auditory information result in changes in temporal experience was tested in this study. Changes were measured in the judgment of duration of a 40-second interval that occurred in three different patterns of auditory information among individuals confined to bed. The sample consisted of 90 men and 90 women aged 18 to 35 years who had no known physical or mental health problems. Subjects rested in bed in a comfortable room for two and one-half hours. Each subject received one of three forms of auditory information-called decoded, coded, and ambient auditory information. At four periods during the 150 minutes of auditory information (25 minutes, 75 minutes, 120 minutes, 150 minutes) the subject was directed by a lighted sign to produce a 40-second interval by depressing a button. The button was connected to a microtimer which timed the interval to the nearest tenth second. None of the three hypotheses-1) that time would seem to pass more slowly in the coded than in the decoded condition: 2) that time would pass more slowly in the decoded than ambient condition: and 3) that as the period of bedrest progressed differences in duration experience would occur among the three groups--was supported by the data. The produced interval for ambient auditory information was expected to be the longest of the three groups, but the opposite effect occurred; it was the shortest. The significant overestimation that occurred in the ambient condition relative to the decoded condition appeared to be related to the methodological imposition of vigilance, lack of structuring information, and the condition of waiting. The coded auditory input did not effect changes in duration relative to the decoded and ambient auditory information as subjects were able to reorder the coded information.

Acoustic Stimulation↗

Minimizing resolution of isotopically coded peptides in comparative proteomics.

Stable isotopes are now widely used to quantify concentration changes in proteomics. This paper focuses on the resolution of isotopically coded peptides and how isotope effects occurring during chromatographic separations can be minimized. Heavy isotope derivatizing agents used in this work were the commercially available 2H8-ICAT reagent and 13C4-succinic anhydride. The ICAT reagent derivatizes cysteine-containing peptides, whereas the succinic anhydride reacts with primary amine groups in peptides. It was observed during reversed-phase chromatography of peptides from a BSA tryptic digest differentially labeled with the 2Hr and 2H8-ICAT reagents that resolution of the isoforms exceeded 0.5 with 20% of the peptides in the digest. Three-fourths of the peptides in this group contained two cysteine residues and were doubly labeled. Only 23% of the peptides labeled with a single ICAT residue had a resolution greater than 0.4. The resolution of peptides differentially labeled with 13C- and 12C-succinate never exceeded +/- 0.01, even in the case of peptides from the BSA digest labeled with 2 mol of succinate. Because this value is within the limits of the method used to determine resolution, it was concluded the 13C- and 12C-coded isoforms of labeled peptides did not resolve. The isotope ratio in the case of 13C/12C coding could be determined from a single mass spectrum taken at any point in the elution profile. This enabled isotope ratio analysis to be completed early in the elution of a peptide from chromatography columns.

Carbon Isotopes↗

Morbidity coding in general practice.

If research is to be of any use the phenomena being studied must be clearly defined. Almost 30 years ago the difficulty of classifying primary care problems using the International Classification of Diseases (ICD-8) was demonstrated. This led to the development of the International Classification of Health Problems in Primary Care-2-Defined which is based on ICD-9. Despite the work that has gone into the development of ICHPPC-2-Defined, relatively little work has been undertaken to assess the validity and reliability of its use. This paper describes the results of such a study conducted as a preliminary to the use of ICHPPC-2-Defined in a study of consulting patterns in general practice. The participating general practitioners were trained in the use of ICHPPC-2-Defined and then coded problems which they identified in a set of clinical vignettes. Following the coding exercise, a review session was held in which difficulties and errors in the use of ICHPPC-2-Defined were discussed. Subsequently, the general practitioners were required to code two more sets of vignettes, which included some problems repeated from the preceding sets. Comparisons were then made of changes in the validity and reliability of coding from one round to the next. The results of the study suggest that the reliability and validity of morbidity data collected using ICHPPC-2-Defined can be increased by training sessions for the coders which focus on the main sources of error in the use of ICHPPC-2-Defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗

Acoustic and electrical pattern analysis of consonant perceptual cues used by cochlear implant users.

It is hypothesized that for postlingually deafened adult cochlear implant (CI) users, a significant source of their perceptual performance variability is attributable to differences in their ability to discriminate the basic perceptual cues that are important in speech recognition. Previous research on 'electric hearing' has identified consistent perceptual cues for vowel recognition. However, the results on consonant perception by CI users are less clear. The primary purpose of this study is to present a quantitative method of evaluating potential 'electric cues' used by CI users in consonant identification. Since the actual input signals to the auditory periphery of CI users are electric in nature, we elected to measure the CI electric discharge patterns in addition to the original acoustic waveforms. The characteristics of the electric discharge patterns in response to intervocalic consonants were quantified and correlated with the dimensions of CI patients' perceptual spaces, which were computed from multidimensional scaling analyses of their consonant confusion matrices. The results agree with most, but not all, commonly accepted acoustic cues used by normal-hearing listeners. The correlation findings also suggest that CI users employ different sets of 'electric cues' in perceiving consonants that differ in their manner of articulation. Specifically, spectral and temporal cues associated with slowly changing formant structures and transitions, and features associated with frication and high-frequency noise, are all highly correlated with the perceptual dimensions of all CI users. However, rapidly changing formant transitions, such as those present in stop consonants, did not appear to play a significant role in consonant recognition by more poorly performing CI subjects. The perceptual results were consistent with our physical findings that the SPEAK coding strategy partially degraded the rapidly changing formant transitions.

Acoustic Stimulation↗

Preoperative imaging of lower extremity varicose veins: color coded duplex sonography or venography.

We prospectively examined 137 limbs in 112 consecutive patients with clinical evidence of severe varicosis by color coded duplex sonography and ascending venography (including varicography in 48 limbs) to evaluate the diagnostic capabilities of color coded duplex sonography in the assessment of venous anatomy, variant varicosis, postthrombotic changes, and incompetence of the superficial and perforating venous system. Additionally, descending venography was performed in the first 52 limbs and compared to color coded duplex sonography in the diagnosis of deep and superficial venous reflux. Variant venous anatomy (21 cases) was missed in two limbs and misinterpreted in one limb by ascending venography compared to surgery. Color coded duplex sonography was inconclusive in two cases. Variant varicosis (59 cases) was missed in seven surgically proved cases by venography and in one case by color coded duplex sonography. Color coded duplex sonography was inconclusive in five cases. Ascending venography was slightly superior to color coded duplex sonography in the detection of postphlebitic changes. Good agreement was found between color coded duplex sonography and descending venography in the grading of superficial (k = 0.75) and deep venous reflux (k = 0.79). Excellent agreement was found between ascending venography in the grading of long (k = 0.96) and short (k = 0.94) saphenous vein reflux. More incompetent perforating veins were detected by ascending venography, (and varicography) than by color coded duplex sonography, but the latter technique allows direct preoperative marking of the skin, which is beneficial for the surgeon. We conclude that color coded duplex sonography is a valuable imaging tool before venous stripping and is capable of replacing invasive ascending and descending venography. Only patients with inconclusive color coded duplex sonographic results (e.g., complex variant venous anatomy) should proceed to venography.

Adult↗

[Profiles of expression of genes coding kininogen and kinin receptors as a marker of tissue pathology in cervical cancer coexisting with HPV infection].

Kinins are peptides involved in inflammatory processes, vascular permeability, proliferation and mitogenesis of tumor cells. The majority of kinins actions are mediated through an interaction with cell surface bradykinin receptors BR1 and BR2. Kinins precursor is kininogen (kng). The changes in proteins are initiated by changes in the expression of genes coding these proteins, thus can be a valuable diagnostic markers of malignant processes including cervical carcinoma. The paper presents an analysis of kininogen-kinins receptor genes expression in women treated surgically because of a carcinoma of uterine cervix. Among the studied women in 5 cases previously brachyHDR therapy was applied. In all studied cases HPV 18 infection and in 2 cases a co-infection HPV 16/18 by use of Consensus Primers MY09, MY 11 and type specific primers for HPV 16, 18 was ascertained. In RNA extracts the number of the mRNA copies for kiningen, BR1 and BR2 was assessed using QRT-PCR Taq Man. The higher expression of BR1 than BR2 was marked in the tissue with cancer cells. In the patients after brachytherapy higher expression of BR2 than BR1 mRNA was found. The higher BR1 expression was also shown in iliac lymph nodes in patients with active neoplastic process, opposite to the patients after brachytherapy in whom higher BR2 expression was ascertained. The lack of expression of kng mRNA was found only in 3 specimens. The high expression of kinin receptors especially BR1 in infiltrating carcinoma margin can be a marker of pathology intensity: proliferative potential of neoplasms cells or chronic inflammatory state in the presence of invasive carcinoma.

Adult↗

Altered taste responses in adult NST after neonatal chorda tympani denervation.

Anatomic and behavioral changes have been observed in the taste system after peripheral deafferentation, but their physiological consequences remain unknown. Interestingly, a recent behavioral study suggested that peripheral denervation could induce central plasticity. After neonatal chorda tympani (CT) transection, adult rats demonstrated a marked preference for a normally avoided salt, NH(4)Cl. In the present study, taste responses were recorded from the nucleus of the solitary tract (NST) in similarly CT-denervated rats to investigate a physiological basis for this behavioral phenomenon. We hypothesized that alterations in functional connectivity of remaining afferent nerves might underlie the behavioral change. Specifically, if NST neurons formerly activated by sodium-selective CT fibers were instead driven by more broadly tuned glossopharyngeal (GL) afferents, neural coding of salt responses would be altered. Such a change should be accompanied by a shift in orotopic representation and increased NH(4)Cl responses. This hypothesis was not supported. After CT denervation, orotopy was unaltered, NH(4)Cl responsiveness declined, and no other changes occurred that could simply explain the behavioral effects. Indeed, the most pronounced consequence of CT denervation was a 68% reduction in NaCl responses, supporting previous evidence for a critical role of this nerve in coding sodium salts. In addition, we found "reorganizational" changes similar to, albeit smaller than, those observed in other sensory systems after deafferentation. There was a trend for increased responses elicited by stimulation of receptor subpopulations innervated by the GL and greater superficial petrosal nerves. In addition, the spontaneous rate of nasoincisor duct-responsive cells increased significantly. This effect on spontaneous rate is opposite to that produced by CT anesthesia, suggesting that acute versus chronic denervation may affect central taste neurons differently. In conclusion, the taste system at the medullary level seems more resistant to large-scale plasticity than other sensory systems, but nevertheless reacts to lost afferent input. Because the most robust plastic changes have been documented at cortical levels in other sensory pathways, the substrate for the behavioral effect of neonatal CT transection may be located more centrally in the gustatory system.

Afferent Pathways↗

A simplified explanation for the frameshift mutation that created a novel C-terminal motif in the APETALA3 gene lineage.

BACKGROUND: The evolution of type II MADS box genes has been extensively studied in angiosperms. One of the best-understood subfamilies is that of the Arabidopsis gene APETALA3 (AP3). Previous work has demonstrated that the ancestral paleoAP3 lineage was duplicated at some point within the basal eudicots to give rise to the paralogous TM6 and euAP3 lineages. This event was followed in euAP3 orthologs by the replacement of the C-terminal paleoAP3 motif with the derived euAP3 motif. It has been suggested that the new motif was created by an eight-nucleotide insertion that produced a translational frameshift. RESULTS: The addition of 25 eudicot AP3 homologs to the existing dataset has allowed us to clarify the process by which the euAP3 motif evolved. Phylogenetic analysis indicates that the euAP3/TM6 duplication maps very close to the base of the core eudicots, associated with the families Trochodendraceae and Buxaceae. We demonstrate that although the transformation of paleoAP3 into euAP3 was due to a frameshift mutation, this was the result of a single nucleotide deletion. The use of ancestral character state reconstructions has allowed us to demonstrate that the frameshift was accompanied by few other nucleotide changes. We further confirm that the sequence is evolving as coding region. CONCLUSION: This study demonstrates that the simplest of genetic changes can result in the remodeling of protein sequence to produce a kind of molecular 'hopeful monster.' Moreover, such a novel protein motif can become conserved almost immediately on the basis of what appears to be a rapidly generated new function. Given that the existing data on the function of such C-terminal motifs are somewhat disparate and contradictory, we have sought to synthesize previous findings within the context of the current analysis and thereby highlight specific hypotheses that require further investigation before the significance of the euAP3 frameshift event can be fully understood.

Amino Acid Sequence↗

Fibroadenomatosis (fibroadenomatoid mastopathy): a benign breast lesion with composite pathologic features.

A benign breast lesion with the composite histologic features of a fibroadenoma and fibrocystic changes has been referred to previously as fibroadenomatosis or fibroadenomatoid mastopathy; this lesion is distinct from the typical well circumscribed fibroadenoma that may have fibrocystic changes. The purpose of our study was to ascertain the frequency of this change among 200 consecutive breast biopsies and excisions with a coded pathologic diagnosis of fibroadenoma and/or "fibrocystic disease"; we identified these changes in 23 (11.5%) specimens. The lesion was characterized by microscopic fibroadenomatoid foci intermingled with dilated ducts, epitheliosis, and adenosis. It is suggested that fibroadenomatosis is yet another pattern in the complex morphologic spectrum known as benign proliferative breast disease. From our experience, this particular lesion was often appreciated as a unique finding, but the appropriate diagnostic designation was in question. The natural history of fibroadenomatosis is essentially unknown. It may represent a morphologic stage in the development of fibroadenoma(s).

Adenofibroma↗