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PubMed1988

Ischemia induces changes in the level of mRNAs coding for stress protein 71 and creatine kinase M.

Hyperthermia, hypoxia, and other conditions induce the appearance of heat shock or stress proteins in cells. We have previously shown that in the ischemic dog myocardium the level of a messenger RNA (mRNA) coding for a protein with migration characteristics similar to heat shock/stress protein 71 increases. Using a human heat-shock protein (hHSP) 70 genomic clone and anti-HSP70 antibodies as probes, we demonstrate in this report that heart stress protein (SP) 71 mRNA and its translational products (71 kDa polypeptides) are members of the stress protein family. In rabbit hearts, the ischemia-induced mRNAs translate into three isoforms with different isoelectric points (6.0, 6.1, and 6.15), in contrast to dog heart mRNA that translates into a protein with a pI of 5.8. The levels of SP71 mRNA in the dog and rabbit ischemic myocardium increased by sixfold and 18-fold, respectively. In the same samples, the levels of creatine kinase M mRNA decreased by about 40%, whereas those of myosin heavy chain mRNA remain unaltered. Our comparative analysis of three different mRNAs indicates that ischemia manifests its effects by differentially changing the levels of specific mRNAs coding for proteins with separate and distinct roles in the cell.

Animals↗
PubMed2007

KLF6: mutational analysis and effect on cancer cell proliferation.

Kruppel-like factor 6 (KLF6/Zf9/CPBP), a member of the Kruppel-like family of zinc finger transcription factors, has recently been suggested to be a mutated tumor suppressor in selected human cancers. Initially, we investigated whether the KLF6 gene was altered in 36 paired non-small cell lung cancers (NSCLC), 89 brain tumors, 7 normal brains, 46 cancer cell lines from a large variety of tissues, and 144 peripheral blood cells from healthy individuals using single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. Changes in the coding region of KLF6 were found in brain tumors (missense changes, 8%; silent polymorphisms, 2%), lung cancers (missense changes, 3%; silent polymorphisms, 6%) and cancer cell lines (missense changes, 2%; silent polymorphisms, 2%). All of the nucleotide changes in the lung tumor samples were present in their matched normal samples, suggesting that these changes were germline polymorphism. Many of the altered KLF6 genes found in the brain tumors were cloned into an expression vector and placed into a GBM cell line, and cell growth was monitored. Wild-type, deleted exon 3, or E30G missense KLF6 significantly reduced cell growth; in contrast, forced expression of KLF6 having either the S92R, P183L or A276G missense substitution did not alter the growth of transfected GBM cells (p > 0.05). Expression levels of KLF6 were higher in normal brain samples than in glioma samples as measured by real-time RT-PCR (p < 0.05). To our surprise, nucleotide changes were found at -4, -5, and -6 upstream of the start of translation in 45% of brain tumors, and 10% of normal blood samples. Focusing on the most frequent alteration (-4 C > A), the nucleotide change did not affect translation of KLF6. Taking together, KLF6 coding sequences are altered in 10% brain tumors, 8% NSLC, and 4% of cancer cell lines. All of those observed in lung cancer are germline polymorphisms. Several additional ones identified in GBM, have lost their ability to slow the growth of glioma cells; furthermore, a proportion of GBM have decreased expression of KLF6 as compared to normal brain tissue. Dysfunction of this gene may contribute to oncogenesis in the brain.

Base Sequence↗
PubMed1990

[A method for the quantitative evaluation of the probability of ischemic heart disease in epidemiological research on workers exposed to harmful effects].

A method for quantitative evaluation of the probability for ischaemic disease of the heart in epidemiological studies is recommended and the state of risk is determined by riskogram, including 3 parts: 1. Assessment of the electrocardiographic changes after Minnesota code. 2. Integral quantitative interpretation of ECG-changes with the data from the Rose test. 3. Classified quantitative assessment of the probability for ischaemic disease of the heart. The quantitative interpretation of the probability for ischaemic disease of the heart allows the use of various statistical methods, mathematical models and computer processing of data, received at the epidemiological studies. By tracing the dependences "dose-effect" and "dose-response" the maximum admissible duration of the length of service could be predicted in specific conditions of professional exposure, in order to prevent injury of the cardiovascular system from harmful industrial factors.

Bulgaria↗
PubMed2006

The number of genes changing expression after chronic exposure to code division multiple access or frequency DMA radiofrequency radiation does not exceed the false-positive rate.

Experiments with cultured C3H 10T 1/2 cells were performed to determine if exposure to cell phone radiofrequency (RF) radiations induce changes in gene expression. Following a 24 h exposure of 5 W/kg specific adsorption rate, RNA was extracted from the exposed and sham control cells for microarray analysis on Affymetrix U74Av2 Genechips. Cells exposed to 0.68 Gy of X-rays with a 4-h recovery were used as positive controls. The number of gene expression changes induced by RF radiation was not greater than the number of false positives expected based on a sham versus sham comparison. In contrast, the X-irradiated samples showed higher numbers of probe sets changing expression level than in the sham versus sham comparison.

Animals↗
PubMed2006

Creating a code of conduct to enable organizational change.

This article provides an overview of the elements that were involved in developing a comprehensive change management strategy at a large, multi-site laboratory as it readied for a major environmental change in the clinical laboratory. A multi-year strategic and tactical plan was created based on an organization-wide employee satisfaction survey, an environmental survey, business needs, and internal/external pressures. The goal was to build a collaborative, team-oriented, and respectful place to work, and to ensure that the workplace became a vibrant environment focused on both individual growth and business improvement and efficiency. This article presents the strategy and outcome of the change, including external and internal environmental influences, challenges, and successes. It also discusses the dissemination of information and engagement of staff, clarification of roles and responsibilities, code of conduct, career laddering and career self-management, and a review of deficiencies impacting efficiency and productivity.

Accreditation↗
PubMed2002

Role of nondiagnostic exercise-induced ST-segment abnormalities in predicting future coronary events in asymptomatic volunteers.

BACKGROUND: Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. METHODS AND RESULTS: We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression > or =1 mm; 11:2 (n=66), flat or downsloping ST depression > or =0.5 mm and <1 mm; 11:4 (n=124), ST-J depression > or =1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression > or =1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P<0.0001), male sex (RR=1.98, P=0.009), plasma cholesterol (RR=1.02/mg per dL, P<0.0001), hypertension (RR=2.23, P=0.002), duration of exercise (RR=0.71/min, P=0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P=0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P<0.0001), male sex (RR=2.76, P=0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P<0.0001), duration of exercise (RR=0.87/min, P=0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P=0.0005) or 11:5 (RR=2.73, P=0.04) were independent predictors of CE. CONCLUSIONS: Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels > or =1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic.

Age Distribution↗
PubMed1990

Production of transgenic mice and application to immunology and autoimmunity.

During the last decade, transgenic animal technology has assumed an increasingly important role as a critical tool in animal biology, biomedical research, and pharmaceutical development. This technology allows virtually any fragment of DNA large enough to contain an entire gene to become integrated into the germline of the recipient animal. The newly inserted DNA will be inherited like endogenous genes, and will be expressed as RNA and protein at tissue locations and abundance depending on regulatory elements attached to the coding DNA. It is possible to clone a particular gene, change a regulatory coding sequence, and reinsert the gene to determine the effect of the change on expression and function of the gene.

Allergy and Immunology↗
PubMedDate not supplied

Musical training enhances automatic encoding of melodic contour and interval structure.

In music, melodic information is thought to be encoded in two forms, a contour code (up/down pattern of pitch changes) and an interval code (pitch distances between successive notes). A recent study recording the mismatch negativity (MMN) evoked by pitch contour and interval deviations in simple melodies demonstrated that people with no formal music education process both contour and interval information in the auditory cortex automatically. However, it is still unclear whether musical experience enhances both strategies of melodic encoding. We designed stimuli to examine contour and interval information separately. In the contour condition there were eight different standard melodies (presented on 80% of trials), each consisting of five notes all ascending in pitch, and the corresponding deviant melodies (20%) were altered to descending on their final note. The interval condition used one five-note standard melody transposed to eight keys from trial to trial, and on deviant trials the last note was raised by one whole tone without changing the pitch contour. There was also a control condition, in which a standard tone (990.7 Hz) and a deviant tone (1111.0 Hz) were presented. The magnetic counterpart of the MMN (MMNm) from musicians and nonmusicians was obtained as the difference between the dipole moment in response to the standard and deviant trials recorded by magnetoencephalography. Significantly larger MMNm was present in musicians in both contour and interval conditions than in nonmusicians, whereas MMNm in the control condition was similar for both groups. The interval MMNm was larger than the contour MMNm in musicians. No hemispheric difference was found in either group. The results suggest that musical training enhances the ability to automatically register abstract changes in the relative pitch structure of melodies.

Acoustic Stimulation↗
PubMed1982

Changing faces: visual and non-visual coding processes in face recognition.

Two experiments examined the effect of recognition accuracy and latency of changing the view of faces between presentation and test. In Expt 1, all the faces were unfamiliar to the subjects. Faces at test were either unchanged, or changed in angle (e.g. full face to 3/4), expression (e.g. smiling to unsmiling) or both. Unchanged faces were recognized more quickly and accurately than faces with a change in angle or expression which were in turn better than faces with both changed. In Expt 2, half the faces were highly familiar to the subjects, and at test unfamiliar and familiar faces were either unchanged or changed in both angle and expression. Unfamiliar faces were recognized more slowly and less accurately if changed at test, while familiar faces were recognized more slowly though no less accurately if change (though performance was effectively at ceiling). Familiar faces were recognized more quickly and accurately than unfamiliar, though false positive rates and rejection latencies were similar for familiars and unfamiliars. The results are discussed in terms of the combination of information from "pictorial', "structural', and "semantic' and "name' codes.

Discrimination Learning↗
PubMed2006

High resolution analysis and phylogenetic network construction using complete mtDNA sequences in sardinian genetic isolates.

For mitochondrial phylogenetic analysis, the best result comes from complete sequences. We therefore decided to sequence the entire mitochondrial DNA (mtDNA) (coding and D-loop regions) of 63 individuals selected in 3 small Ogliastra villages, an isolated area of eastern Sardinia: Talana, Urzulei, and Perdasdefogu. We studied at least one individual for each of the most frequent maternal genealogical lineages belonging to haplogroups H, V, J, K, T, U, and X. We found in our 63 samples, 172 and 69 sequence changes in the coding and in the D-loop region, respectively. Thirteen out of 172 sequence changes in the coding region are novel. It is our hypothesis that some of them are characteristic of the Ogliastra region and/or Sardinia. We reconstructed the phylogenetic network of the 63 complete mtDNA sequences for the 3 villages. We also drew a network including a large number of European sequences and calculated various indices of genetic diversity in Ogliastra. It appears that these small populations remained extremely isolated and genetically differentiated compared with other European populations. We also identified in our samples a never previously described subhaplogroup, U5b3, which seems peculiar to the Ogliastra region.

DNA, Mitochondrial↗
PubMedDate not supplied

Dynamic typology clustering within the stages of change for smoking cessation.

Dynamic typology clustering was employed to find homogeneous subgroups of smokers within each of three early stages of change (precontemplation, contemplation, preparation) in a representative sample of smokers. Individual change profiles were created by coding the stage of change for each subject at five consecutive assessment points over a 2-year period (baseline and 6, 12, 18, and 24 months). A total of 446 unique change profiles were found in the sample of 2,088 smokers who had complete data for all five time points. The sample was initially split into three groups determined by baseline stage of change. Within each initial stage, subgroups that shared similar patterns of change were interpreted by examining the shape and elevation of the change profiles. Four major types of profiles emerged: a stable profile, a progressing profile, a vacillating profile, and a regressing profile. External validation revealed significant differences among the dynamic typology subtypes on key transtheoretical model constructs (processes of change, decisional balance, situational temptations). These results both support and complement key construct relationships within the transtheoretical model and can provide important predictive information to direct and enhance treatment interventions for smoking cessation.

Adult↗
PubMedDate not supplied

The 13 errors.

The reality is that most change efforts fail. McKinsey & Company carried out a fascinating research project on change to "crack the code" on creating and managing change in large organizations. One of the questions they asked--and answered--is why most organizations fail in their efforts to manage change. They found that 80 percent of these failures could be traced to 13 common errors. They are: (1) No winning strategy; (2) failure to make a compelling and urgent case for change; (3) failure to distinguish between decision-driven and behavior-dependent change; (4) over-reliance on structure and systems to change behavior; (5) lack of skills and resources; (6) failure to experiment; (7) leaders' inability or unwillingness to confront how they and their roles must change; (8) failure to mobilize and engage pivotal groups; (9) failure to understand and shape the informal organization; (10) inability to integrate and align all the initiatives; (11) no performance focus; (12) excessively open-ended process; and (13) failure to make the whole process transparent and meaningful to individuals.

Humans↗
PubMed1997

The PMAC code of marketing practices: time for improvement? Pharmaceutical Manufacturers Association of Canada.

In this issue (see pages 351 to 356) Dr. Joel Lexchin proposes reforms that could help the Pharmaceutical Manufacturers Association of Canada (PMAC) adapt its Code of Marketing Practices to changing times. The PMAC code reflects the ethical concerns of drug manufacturers and speaks to the need for high standards in promotional activities. The code is a commendable beginning, but it does not go far enough in ensuring ethical practice. The PMAC should take this opportunity to address the concerns raised by Lexchin. For example, proactive assessment of advertising would improve the current system.

Advertising↗
PubMed2003

Trends in mortality rates comparing underlying-cause and multiple-cause coding in an English population 1979-1998.

Until recently, national coding and analysis of routine mortality statistics in most countries included only underlying cause of death. There were changes in the rules for selection and coding of underlying cause in England in 1984 and 1993. We report on trends in mortality rates in an English region from 1979 to 1998, comparing multiple-cause and underlying-cause coded rates, for individual diseases that were affected by coding changes. Among many others, these include pneumonia, venous thromboembolism, heart failure, respiratory distress syndrome, tuberculosis, diabetes, dementia, alcohol and drug abuse, epilepsy, multiple sclerosis, stroke, asthma, peptic ulcer, appendicitis, and cancers of the breast, colon and prostate. Comparisons over time of mortality rates based on underlying cause alone will be misleading when the time-period crosses years in which rules changed for selecting underlying cause.

Cause of Death↗
PubMed1985

Development and evolution of electrocardiographic Minnesota Q-QS codes in patients with acute myocardial infarction.

The development of ECG Minnesota Q-QS codes and their subsequent evolution were studied in the first 692 subjects to enter the POSCH program who had had one MI. The mean interval from MI to entry into the study was 2.2 years. Sixty-three percent of the subjects developed the most significant code with the infarction. By the time the subjects entered the study, the codes had commonly regressed to a lower level, disappearing altogether in 34%. The likelihood of complete regression varied inversely with the significance of the code. There was no significant difference between the groups with disappearance and with retention of a Q-QS code as to time since MI, the extent of coronary arterial disease, or the age or sex of the subject. In about half of the subjects the original code did not change with time and in 21% to 44% the code increased to one of a higher level of significance.

Adult↗
PubMed2002

Improvement of the movement and host range properties of a plant virus vector through DNA shuffling.

Virus expression vectors based on the tobacco mosaic virus (TMV) genome are powerful tools for foreign gene expression in plants. However, the inclusion of increased genetic load in the form of foreign genes limits the speed of systemic plant invasion and host range of these vectors due to reduced replication and movement efficiencies. To improve these properties of TMV vectors, the gene encoding the 30-kDa movement protein was subjected to mutagenesis and DNA shuffling. A vector that expresses the green fluorescent protein was used to allow simple visual discrimination of mutants with enhanced movement phenotypes. An initial round of mutagenesis produced 53 clones with a faster local movement phenotype. Two subsequent rounds of DNA shuffling produced additional clones that showed further increased rates of cell-to-cell movement and degrees of systemic invasion in restrictive hosts. Surprisingly, sequence analysis of the best performing shuffled genes revealed alterations resulting in coding and silent changes in the movement protein gene. Separation of these coding and silent alterations into distinct gene backgrounds revealed that each contributes to improved movement protein function to differing degrees. The resulting vectors demonstrate that the complex activities of the movement protein genes of viruses can be evolved to have improved movement phenotypes, as evidenced by cell-to-cell and systemic invasion. The experiments produced improved vectors that will be of use both for in planta functional screening and for therapeutic protein production and demonstrated the power of shuffling for plant virus vector improvement.

DNA, Recombinant↗
PubMed1997

Resource-Based Relative Value Scale (RBRVS), coding, and Medicare reimbursement.

Many changes occurred during 1996 in the Resource-Based Relative Value Scale that determines physician payment for services to Medicare beneficiaries in 1997. These issues include the 5-year review of physician work values, the Correct Coding Initiative, changes in the surgical Conversion Factor, and a new Medicare payment formula. Likewise, several more changes on the horizon in 1997 will dramatically impact the 1998 Medicare Fee Schedule, primarily the upcoming resource-based Practice Cost Relative Value Scale, and possible elimination of the separate surgical Conversion Factors. There are also several new Current Procedural Terminology codes that will receive Medicare payment in 1997 and 1998. This article summarizes these events and issues from a vascular surgical perspective.

Centers for Medicare and Medicaid Services, U.S.↗