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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↗
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↗
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↗
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.↗
PubMed2001

Assessment of radiocontrast media induced renal vasoconstriction by color coded duplex sonography.

INTRODUCTION: Changes in renal hemodynamics are suspected to be one of the major pathogenetic correlates in radiocontrast media-induced nephrotoxicity. We investigated whether color-coded duplex sonography is an appropriate method to document changes in intrarenal vascular resistance, after intravenous injection of the low-osmolar contrast material lopamidol. METHODS: Intrarenal arterial doppler wave forms were analyzed every minute after intravenous injection of 100 mL lopamidol in 10 patients during a voiding cystourogram-procedure. The Resistive Index (RI) of each flow curve, reflecting intrarenal flow resistance, was calculated and compared to the mean of four RI measurements taken before contrast media application. RESULTS: One minute after injection of Iopamidol the RI remained unchanged compared to the baseline standard of 0.70. In measurements obtained 2, 3, 4, and 5 minutes after lopamidol injection a statistically significant rise was seen: (minute 2: 0.74, p < 0.001/minute 3: 0.75, p = 0.001/minute 4: 0.72, p =0.018/minute 5: 0.74, p = 0.031). During the further course, the resistive indices decreased progressively and showed no significant difference in comparison with the baseline standard value. CONCLUSION: Color coded duplex sonography is a simple method to detect changes in renal flow resistance after application of radiocontrast media. Based on our results, we believe that the analysis of intrarenal arterial doppler flow profiles constitutes an ideal method to investigate pathophysiologic mechanisms of radiocontrast media-induced nephrotoxicity, as well as pharmacological concepts in nephroprotectivity.

Contrast Media↗
PubMed1991

Integrating behavior and cardiovascular responses: the code.

The next revolution in biology is predicted to be in the integrative domain, and the need to involve physiologists in this kind of research has been recognized. This paper represents an approach to providing some of the tools required for dealing with integrative physiology at the behavioral level. Video tape recordings are made of the activities of a group of five baboons (Papio hamadryas) while simultaneous recordings of arterial blood pressure, heart rate, renal blood flow, and mesenteric or iliac blood flow are telemetered from two of the members of the group. The telemetered cardiovascular information is recorded on the two audio channels of the videotape. Subsequently the videotape is viewed, and a two-dimensional code is used to record the behavior of the two animals with the telemetry equipment. The first dimension of the code categorizes the behavior changes precisely regarding those aspects of behavior that are related to cardiovascular dynamics and does so with an accuracy of 16 ms. The second dimension codes relevant environmental changes. The paper describes the code and presents illustrations of how the code reflects the cardiovascular dynamics associated with the behavioral changes.

Animals↗
PubMed1997

Brain aging: changes in the nature of information coding by the hippocampus.

Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information.

Aging↗
PubMed2000

Homocysteine-induced changes in mRNA levels of genes coding for cytoplasmic- and endoplasmic reticulum-resident stress proteins in neuronal cell cultures.

Elevated homocysteine levels have been suggested to contribute to various pathological states of the brain. However, the basic mechanisms underlying homocysteine-induced neurotoxicity have not yet been fully elucidated. In the present series of experiments, we investigated the effect of homocysteine on mRNA levels of genes coding for cytoplasmic- or endoplasmic reticulum-resident stress proteins. Primary neuronal cell cultures were exposed to different homocysteine levels for 1-24 h. Cell injury was evaluated using the MTT assay, protein synthesis was studied by measuring the incorporation of L-[4,5-3H]leucine into proteins, mRNA levels of hsp70, gadd153, grp78, and grp94 were evaluated by quantitative PCR, and changes in protein levels of hsp70, grp78 and grp94 were analyzed by immunoblotting. Exposure of cells to 5 or 10 mM homocysteine for 24 h induced marked cell injury (decrease of viability to 58 or 45% of control respectively). After 6 h treatment, gadd153, grp78 and grp94 mRNA levels increased markedly, but only when cells were exposed to levels of homocysteine high enough to induce cell injury. In addition, hsp70 mRNA levels and protein synthesis were significantly reduced. At earlier (1 or 3 h) or later (12 or 24 h) time intervals, homocysteine exposure induced a marked increase in mRNA levels of all genes studied. GRP78 and GRP94 protein levels were increased in cells exposed to 5 mM homocysteine for 24 h but not in cells exposed to 10 mM homocysteine. HSP70 protein levels, in contrast, were decreased in cells exposed to homocysteine for different periods. The expression of genes coding for ER-resident stress proteins is specifically activated under conditions of ER stress. The close relationship between the extent of cell injury and increase in grp78 mRNA levels suggests that ER dysfunction may contribute to the pathological process. The results imply that the ER is an intracellular target of homocysteine toxicity.

Animals↗
PubMed1985

The mitochondrial genome of the fission yeast Schizosaccharomyces pombe. 7. Continuous gene for apocytochrome b in strain EF1 (CBS 356) and sequence variation in the region of intron insertion in strain ade 7-50h.

The third BamHI fragment, containing most of gene for apocytochrome b, has been cloned and sequenced in the Schizosaccharomyces pombe strain EF1 (CBS 356). In contrast to strain ade 7-50h- (50) from the Leupold collection, in which the gene is interrupted by an intron of group II (Lang et al. 1984), the homologous gene in strain EF1 is continuous. This demonstrates that the intron in the gene for apocytochrome b is optional. Aligning the EF1 sequence with the homologous regions in strain 50, 2 base pair changes were found in the leader and 14 in the coding region. These changes led to 12 altered triplets, but 9 of them specify the same amino acid. Seven base changes were clustered within a stretch of 30 base pairs in the region in which the intron is inserted in strain 50. Five out of the resulting six triplet changes were also silent. These sequence variations around the highly conserved splice point region may be linked to the insertion or excision of the intron.

Ascomycota↗
PubMed1995

Nucleotide and deduced amino acid sequences of the nucleocapsid protein of the virulent A75/17-CDV strain of canine distemper virus.

Virus persistence is essential in the chronic inflammatory canine distemper virus (CDV)-induced demyelinating disease. In the case of CDV there is a close association between persistence and virulence. Virulent CDV isolated from dogs with distemper shows immediate persistence in primary dog brain cell cultures (DBCC) and in different cell lines. We have evidence that the nucleocapsid (NP) protein plays an important role in the development of persistence. The NP-protein, the most abundant structural virus protein, also influences virus assembly and has some regulatory functions in virus transcription and replication. In this study we compared the nucleotide and deduced amino acid sequence of a virulent CDV strain (A75/17-CDV) to a culture-attenuated non-virulent strain (OP-CDV). Viral RNA was extracted from DBCC infected with virulent CDV. Virulent CDV retains its in vivo properties, such as virulence and ability to cause demyelination, when propagated in these DBCC. The viral RNA was reverse transcribed and the resulting cDNA amplified by polymerase chain reaction for subsequent cloning. The nucleotide sequences of these clones were determined by the dideoxy chain termination method. The number of nucleotides and the putative NP-protein of the virulent strain matched the attenuated CDV strain. We observed a total of 105 nucleotide differences. Three were localised within the 3' and five within the 5' non-coding region of the NP-gene. The 97 nucleotide changes within the coding region resulted in 22 amino acid differences. 10 of these amino acid (AA) modifications were within the N-terminal region (AA 1 to 159) and 12 within the C-terminal area (AA 351 to 523).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2001

Antimicrobial resistance mechanisms: what's hot and what's not in respiratory pathogens.

Community respiratory tract pathogens comprise Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and a few other select, but less frequent, species such as atypical bacteria, staphylococci, and some gram-negative organisms. In addition to an array of virulence factors, these bacteria have also developed a propensity to withstand a range of antimicrobial agents. These resistance mechanisms occur as either target site or antibiotic modifications or antibiotic transportation changes (prevention of cell entry or agent efflux). The genetic coding for these changes can be transmitted to progeny every 20 minutes or can be acquired from the normal flora via transformation. Presently, it is this acquisition of naked DNA by pneumococci that is a "hot" topic and the realization that unless antimicrobials are used more thoughtfully, then new agents can be rapidly rendered redundant. Other potential, but as yet unfounded, resistance scenarios include the acquisition of extended spectrum beta-lactamases by H. influenzae and the development of ribosomal changes to obviate the ketolides and oxazolidinones. To prevent the continued escalation of antimicrobial resistance, new approaches to antimicrobials must be implemented soon.

Drug Resistance, Microbial↗
PubMed1992

Metabolic, molecular genetic and toxicological aspects of the acetylation polymorphism in inbred mice.

Over the past 10 years, much fascinating information has been obtained concerning the biochemistry, genetics, toxicological implications and molecular genetics of the N-acetylation polymorphism in mice. Using C57BL/6J (B6) mice as representative of rapid acetylation and A/J (A) mice as representing slow acetylation, it has been shown that the polymorphism observed in N-acetyltransferase (NAT) activity in liver also occurs in kidney, bladder, blood, and other tissues. The development of congenic acetylator mouse lines derived from B6 and A, have provided the necessary tools to study the role of the acetylation polymorphism, on either the B6 or A genetic background, free of nearly all other genetic differences between these strains. Eliminating genes which modify and complicate the differences due to the acetylator genes make the congenic lines very useful in toxicology studies, particularly those involving carcinogenesis. The molecular genetic basis of the acetylator polymorphism in B6 and A mice involves two Nat genes. Nat-1 encodes a protein termed NAT1 which is identical in rapid and slow acetylator strains. Nat-2, however, differs between rapid and slow strains by a single nucleotide change in the coding region. The corresponding NAT2 proteins differ by a single change at amino acid 99: an hydrophilic asparagine in rapid acetylator NAT2 to an hydrophobic isoleucine in NAT2 from slow acetylators. The mechanistic basis for the differences between rapid and slow acetylation in mice appears to be that NAT2 from the rapid B6 strain is 15-fold more stable at 37 degrees C and is transcribed/translated with a maximal efficiency twice that of the enzyme from slow acetylator A mice. Results discussed in this review indicate that mice provide an excellent system for studying the N-acetyltransferase polymorphism and also are useful for modelling several aspects of the human N-acetyltransferase polymorphism.

Acetylation↗
PubMed1987

Evolution of anticodons: variations in the genetic code.

Clues to evolution of the genetic code can be found by comparing usage of anticodons in various organisms and organelles. GC content of DNA varies, as a result of directional mutation pressure (AT/GC pressure), especially in bacteria. Low GC in Mycoplasma is accompanied by use of UGA for tryptophan and, in ciliated protozoa, by use of UAA and UAG for glutamine. These are examples of "stop codon capture," which has been preceded by duplication of tRNA genes followed by nucleotide substitutions in their sequences, including mutational changes in their anticodons. Evolutionary changes in the code may have resulted from disappearance of codons and anticodons resulting from GC pressure and from their reappearance when the direction of the pressure was reversed. In this manner, codon UGA and anticodon UCA for tryptophan could have disappeared under GC pressure and reappeared in Mycoplasma under AT pressure. Stop codon UGA may have been the third of the three stop codons to appear, originating from mutations in UAA. Changes in the code are adaptive and nondeleterious. We propose that the number of anticodons has increased and that evolution continued until three existing forms of the universal code were produced: eukaryotic, eubacterial, and the code for halobacteria and methanococci. These three codes are distinguished from each other by their anticodon pattern. The eukaryotic code contains eight INN (ANN) anticodons that have replaced GNN anticodons as a result of AT pressure. Mitochondrial and chloroplast codes have evolved from the eubacterial code through genomic economization and AT pressure, leading to losses of GNN and CNN anticodons.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗