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At least 1,207 records · Page 67Linked to original sources
PubMed1989

Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial.

A positive exercise electrocardiogram (ECG) has been proved to predict cardiovascular events in asymptomatic normolipidemic men. To study whether it is also predictive for hypercholesterolemic men, data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed. All the men had performed a submaximal treadmill exercise test at baseline, before they were assigned to the cholestyramine or placebo treatment group. Because of missing or inconclusive data, 31 men were excluded from the analyses. A test was positive if the ST segment was displaced by greater than or equal to 1 mm (visual code) or there was greater than or equal to 10 microV-s change in the ST integral (computer code), or both. The prevalence of a positive test was 8.3%. During the 7 to 10 year (mean 7.4) follow-up period, the mortality rate from coronary heart disease was 6.7% (21 of 315) in men with a positive test and 1.3% (46 of 3,460) in men with a negative test (placebo and cholestyramine groups combined). The age-adjusted rate ratio for a positive test, compared with a negative test, was 6.7 in the placebo group and 4.8 in the cholestyramine group. With use of Cox's proportional hazards models, it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age, smoking history, systolic blood pressure, high density lipoprotein cholesterol and low density lipoprotein cholesterol. A positive test was not significantly associated with nonfatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed2000

The compositional evolution of vertebrate genomes.

The compositional evolution of vertebrate genomes is characterized: (i) by one predominant conservative mode, in which nucleotide changes occur, but the base composition of DNA sequences in general, and of coding sequences in particular, does not change; and (ii) by three different shifting or transitional modes, in which nucleotide changes are accompanied by changes in the base composition of sequences. Investigations on these evolutionary modes have shed new light on a central problem in molecular evolution, namely the role played by natural selection in modulating the mutational input. This review will present first the intragenomic shifts, the 'major shifts' and the 'minor shift', and then the 'whole-genome', or 'horizontal', shift. In each case, the shifts were preceded and followed by a conservative mode of evolution. This review expands on a previous one [Bernardi, Gene 241 (2000) 3-17], and summarizes the evidence that the changes of the compositional patterns of the genome and their maintenance are controlled by Darwinian natural selection.

Animals↗
PubMed1997

Two missense mutations of H type alpha(1,2)fucosyltransferase gene (FUT1) responsible for para-Bombay phenotype.

BACKGROUND AND OBJECTIVES: Rare individuals (Bombay and para-Bombay phenotypes) fail to express the A, B and H antigens on erythrocyte membranes because of a lack in the H gene (FUT1)-encoded alpha(1,2)fucosyltransferase activity. In this study, we have found a para-Bombay individual (Bmh) who expressed B and H antigens in saliva but not on red blood cells. The FUT1 alleles of this person contained two single base changes (T460C and G1042A) in the coding region relative to the wild type allele. These substitutions may result in changes in two amino acid residues (Y154H and E348K). MATERIALS AND METHODS: Since the T460C and G1042A mutations destroy endonuclease RsaI and AvaI sites, respectively, we tested for these mutations using PCR-RFLP. RESULTS: Our findings indicated that this para-Bombay person was homozygous for the T460C and G1042A mutations, and that neither of these mutations was found in 136 randomly selected Japanese individuals. The measurement of the alpha(1,2)fucosyltransferase activity after transient expression of the FUT1 alleles in COS-7 cells indicated that the H-deficient allele-encoded enzyme had no detectable activity. Moreover, transfection by chimera FUT1 allele contains only the T460C mutation, or only the G1042A mutation, and yielded 1.0 or 9.3%, respectively, of the activities compared to transfection by the wild type allele. CONCLUSIONS: These results suggest that the two mutations in combination are responsible for the inactivation of the FUT1-encoded enzyme activity.

ABO Blood-Group System↗
PubMed1999

How does replication-associated mutational pressure influence amino acid composition of proteins?

We have performed detrended DNA walks on whole prokaryotic genomes, on noncoding sequences and, separately, on each position in codons of coding sequences. Our method enables us to distinguish between the mutational pressure associated with replication and the mutational pressure associated with transcription and other mechanisms that introduce asymmetry into prokaryotic chromosomes. In many prokaryotic genomes, each component of mutational pressure affects coding sequences not only in silent positions but also in positions in which changes cause amino acid substitutions in coded proteins. Asymmetry in the silent positions of codons differentiates the rate of translation of mRNA produced from leading and lagging strands. Asymmetry in the amino acid composition of proteins resulting from replication-associated mutational pressure also corresponds to leading and lagging roles of DNA strands, whereas asymmetry connected with transcription and coding function corresponds to the distance of genes from the origin or terminus of chromosome replication.

Amino Acid Sequence↗
PubMed1998

What differentiates declarative and procedural memories: reply to Cohen, Poldrack, and Eichenbaum (1997)

CPE claim that procedural and declarative representations differ on two important dimensions: flexibility and compositionality. I have proposed that the apparent flexibility of a memory depends entirely on the transfer conditions. Any retest is, in some sense, a test of flexibility, because something has changed since the original encoding episodic. I have argued that if one changes something that does not provide support to memory performance, the memory will appear flexible, and resistant to changes in the environment. If one changes the very thing that the representation codes, the memory will appear inflexible and easily disrupted by changes in the environment. This principle is equally true for procedural and declarative memory. CPE contend that procedural representations lack compositionality. An ideal test of this claim would examine the representation of a task that is widely agreed to be procedural (e.g. that has been demonstrated to be learned normally by amnesic patients, and in the absence of awareness by neurologically intact subjects). Such experiments appear not to have been conducted, and the fact is that many tasks that are widely agreed to be procedural probably are not compositional. They appear to be, as CPE contend, biases in a processing system; it is hard to imagine how repetition priming could be compositional. Nevertheless, this is not true of all procedural memories. There is a good deal of evidence that motor behaviour is organised hierarchically and has compositionality. There is every reason to think that most if not all motor behaviour is procedural; motor behaviour might be driven by goals that are declarative, but the low-level operations that actually manipulate effectors are closed to consciousness, do not depend on the medial temporal lobe or diencephalon, and would therefore be classified as procedural. CPE framed their theory of differences between procedural and declarative memory systems as an account of the deficit in amnesic patients. They therefore predict that the learning of amnesic patients should not show flexibility or compositionality. There is already at least one study showing learning in amnesic patients that is as flexible as that of control participants (Knowlton & Squire, 1996). There are not, to my knowledge, data on whether the motor skill learning of amnesic patients shows compositionality, but one might expect that it would, given that it does in neurologically intact participants, and given that motor skill learning appears unimpaired in amnesic patients. Thus, the conception of declarative and procedural memory provided by CPE may not provide a complete account of amnesic performance. The anatomic distinction between procedural and declarative memory systems appears quite strong, and there is therefore reason to believe that there are accompanying computational differences. There does not, however, appear to be sufficient evidence to support those differences proposed by CPE.

Amnesia↗
PubMedDate not supplied

[Complete nucleotide sequence of Rous sarcoma virus variants adapted to duck cells].

Subgroup C avian sarcoma viruses efficiently infect and transform but poorly replicate in duck cells. Nucleotide sequence analysis of Prague strain of Rous sarcoma virus adapted by numerous passages on duck embryonic fibroblasts (daPr-RSV-C) showed that adaptation of originally chicken virus to duck cells correlated with changes in viral genome, first of all in gp85-coding domain of env-gene. Besides, changes in LTR and src-gene sequences could play a role in widening of host range for this virus. The major changes of daPr-RSV-C in comparison with original Pr-RSV-C appeared to be the result of homologous recombinations with corresponding regions of chicken endogenous retroviruses.

Amino Acid Sequence↗
PubMed1996

After 4 years' work, revised Code of Ethics goes to General Council for decision.

The CMA's Committee on Ethics will present a revised Code of Ethics for consideration by General Council during the annual meeting in Sydney, NS, later this month. This article outlines the reasons for updating the current (1990) version of the code and explains some of the significant changes and omissions. If approved by General Council, the revised code will take effect immediately.

Canada↗
PubMed2005

An assessment of pregnancy-related mortality in the United States.

Deaths from pregnancy complications remain an important public health concern. Nationally, two systems collect information on the number of deaths and characteristics of the women who died from complications of pregnancy. The Centers for Disease Control and Prevention's (CDC) National Center for Health Statistics (NCHS) reports maternal mortality through the National Vital Statistics System (NVSS); CDC National Center for Chronic Disease Prevention and Health Promotion's Pregnancy Mortality Surveillance System (PMSS) conducts epidemiological surveillance of pregnancy-related deaths. The numbers of deaths reported by these two systems have differed over the past two decades; our objective was to determine the magnitude and nature of these differences. For 1995-97, we compared maternal deaths in the NVSS with pregnancy-related deaths in PMSS for the 50 States, Washington DC and New York City. Pregnancy-related deaths whose underlying cause was assigned to ICD-9 codes 630-676 by NVSS were classified as maternal deaths; those coded outside 630-676 were not. There were 1387 pregnancy-related deaths in PMSS and 898 maternal deaths in the NVSS; 54% of these deaths were reported in both systems, 40% in PMSS only, and 6% in NVSS only. Pregnancy-related deaths due to haemorrhage, embolism, and hypertensive complications of pregnancy were proportionately more often identified by NVSS as maternal deaths than those from cardiovascular complications, medical conditions or infection. From the 1471 unduplicated deaths classified as maternal or pregnancy-related from either reporting system, we estimated a combined pregnancy-related mortality ratio of 12.6/100,000 live births for 1995-97, compared with 11.9 for PMSS only and 7.5 for NVSS only. The identification and classification of these events is dependent on the provision of complete and accurate cause-of-death information on death certificates. Changes in the guidelines for coding maternal deaths under ICD-10 may change the relationship in the number of deaths resulting from pregnancy reported by these two systems.

Adolescent↗
PubMed2004

Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: evolutionary evidence for differences in molecular effects.

Most Mendelian diseases studied to date arise from mutations that lead to a single amino acid change in an encoded protein. An increasing number of complex diseases have also been associated with amino acid-changing single-nucleotide polymorphisms (coding SNPs, cSNPs), suggesting potential similarities between Mendelian and complex diseases at the molecular level. Here, we use two different evolutionary analyses to compare Mendelian and complex disease-associated cSNPs. In the first, we estimate the likelihood that a specific amino acid substitution in a protein will affect the protein's function, by using amino acid substitution scores derived from an alignment of related protein sequences and statistics from hidden Markov models. In the second, we use standard Ka/Ks ratios to make comparisons at the gene, rather than the individual amino acid, level. We find that Mendelian disease cSNPs have a very strong tendency to occur at highly conserved amino acid positions in proteins, suggesting that they generally have a severe impact on the function of the protein. Perhaps surprisingly, the distribution of amino acid substitution scores for complex disease cSNPs is dramatically different from the distribution for Mendelian disease cSNPs, and is indistinguishable from the distribution for "normal" human variation. Further, the distributions of Ka/Ks ratios for human and mouse orthologs indicate greater positive selection (or less negative selection) pressure on complex disease-associated genes, on average. These findings suggest that caution should be exercised when using Mendelian disease as a model for complex disease, at least with respect to molecular effects on protein function.

Biological Evolution↗
PubMed2003

Evolution of transcription factor function.

Functional assays in Drosophila melanogaster with orthologous transcription factors from other species suggest that changes in the protein-coding sequence may play a larger role in the evolution of transcription factor pathways than was previously believed. Interestingly, recent studies provide evidence that changes in transcription factor protein sequence can affect the regulation of only a subset of target genes, even in the same cells of a developing animal.

Animals↗
PubMed1996

Mutational analysis of the CDKN2 gene in metastases from patients with cutaneous malignant melanoma.

We analysed 26 metastases from 25 patients with sporadic cutaneous malignant melanoma for alterations in the CDKN2 gene by a combined polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3' non-coding sequence of the exon 3 region) were concordantly and independently detected by both SSCP and nucleotide sequence analysis. Two of the exon 2 changes and the five changes in the non-coding exon 3 region are likely to represent natural polymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and belonged to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore revealed no sign of homozygous deletions of the CDKN2 exon 2 region. The results support an involvement of the CDKN2 product in the development of a subgroup of sporadic melanomas and encourage the search for alterations in additional genes of the 9p21 region.

Alleles↗
PubMed2003

Generation of an infectious clone of VR-2332, a highly virulent North American-type isolate of porcine reproductive and respiratory syndrome virus.

A full-length cDNA clone of the prototypical North American porcine reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332 was assembled in the plasmid vector pOK(12). To rescue infectious virus, capped RNA was transcribed in vitro from the pOK(12) clone and transfected into BHK-21C cells. The supernatant from transfected monolayers were serially passaged on Marc-145 cells and porcine pulmonary alveolar macrophages. Infectious PRRSV was recovered on Marc-145 cells as well as porcine pulmonary macrophages; thus, the cloned virus exhibited the same cell tropism as the parental VR-2332 strain. However, the cloned virus was clearly distinguishable from the parental VR-2332 strain by an engineered marker, a BstZ17I restriction site. The full-length cDNA clone had 11 nucleotide changes, 2 of which affected coding, compared to the parental VR-2332 strain. Additionally, the transcribed RNA had an extra G at the 5' end. To examine whether these changes influenced viral replication, we examined the growth kinetics of the cloned virus in vitro. In Marc-145 cells, the growth kinetics of the cloned virus reflected those of the parental isolate, even though the titers of the cloned virus were consistently slightly lower. In experimentally infected 5.5-week-old pigs, the cloned virus produced blue discoloration of the ears, a classical clinical symptom of PRRSV. Also, the seroconversion kinetics of pigs infected with the cloned virus and VR-2332 were very similar. Hence, virus derived from the full-length cDNA clone appeared to recapitulate the biological properties of the highly virulent parental VR-2332 strain. This is the first report of an infectious cDNA clone based on American-type PRRSV. The availability of this cDNA clone will allow examination of the molecular mechanisms behind PRRSV virulence and attenuation, which might in turn allow the production of second-generation, genetically engineered PRRSV vaccines.

Animals↗
PubMed2002

New considerations in analyzing stroke and heart disease mortality trends: the Year 2000 Age Standard and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision.

BACKGROUND: Monitoring of trends and patterns of stroke mortality will be of utmost importance in the coming decade. Two innovations in vital statistics may complicate this task and must be brought to the attention of both researchers and readers of research reports: the new Year 2000 Age Standard and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). SUMMARY OF REVIEW: For cerebrovascular diseases, the age-adjusted death rate is 2.4 times higher with the use of the year 2000 standard than with the use of the old 1940 standard. However, if rates for all years are computed with the use of the same age standard, the percent change from 1979 to 1995 is similar according to the 1940 standard (-35.8%) or the year 2000 standard (-34.3%). Another important effect of the change to the year 2000 standard is to reduce black/white differentials in age-adjusted death rates. Major discontinuities are not observed for mortality trends in cerebrovascular disease or heart disease between International Classification of Diseases, Ninth Revision (ICD-9) (1979-1998) and ICD-10 (1999 and following years) classifications. CONCLUSIONS: All data users must exercise caution to specify the age standard used when assessing or presenting age-adjusted rates over time or between groups. The comparability of ICD codes chosen for years before 1999 versus 1999 or following years must be checked to distinguish changes due to coding from true changes in mortality levels.

Epidemiologic Measurements↗
PubMed2005

Host range mutants of Minute Virus of Mice with a single VP2 amino acid change require additional silent mutations that regulate NS2 accumulation.

Two host range switch mutants of the immunosuppressive strain of parvovirus Minute Virus of Mice (MVMi) were isolated from plaques on A9 fibroblasts. Both carried a single coding mutation at residue D399 in VP2, to alanine and glycine in hr105 and hr107, respectively, and a second, non-coding, guanine-to-adenine change at nucleotide 1970 in hr105 and 1967 in hr107. These mutations were recreated in a wild type MVMi infectious plasmid clone, both alone and as pairs, in either the original or switched combinations. All single mutants failed to replicate productively in fibroblasts, but the two pairs of changes were functionally equivalent. Single D399 mutations allowed the viruses to initiate infection in fibroblasts, but NS2 expression was severely restricted and correlated with poor accumulation and release of progeny virus. Mutations at 1967 or 1970 enhanced NS2 accumulation, and allowed efficient progeny production and release. Conversely, the D399 mutations destroyed the viruses' ability to infect EL4 lymphocytes. In all productive EL4 infections, NS2 was expressed at high ratios even in the absence of upstream mutations, and progeny accumulation was efficient. However, EL4 cells lack a mechanism for early progeny release, potentially explaining why virus amplification in these cells is slow.

Amino Acid Sequence↗
PubMedDate not supplied

p53 gene mutation spectrum in human unknown primary tumors.

Mutations affecting the p53 gene are associated with many human malignancies, but little is known about changes in p53 in unknown primary tumors (UPTs), which are characterized as tumors with advanced stages of malignancy. We therefore investigated the frequency of p53 mutations in a series of 15 unknown primary tumor biopsies and eight cell lines established from UPTs. Mutations in the conserved regions of the p53 gene were verified by single-strand conformation polymorphism analysis of exons 5-9 and were verified by direct DNA sequencing of polymerase chain reaction products. A point mutation leading to an amino acid change in the p53 protein was found in six cases, and a mutation causing a change to termination was found in one case. A frameshift mutation was observed in one cell line. In one patient and one cell line we observed more than one mutation in the p53 coding sequence. Overall, the frequency of mutations that changed the p53 coding sequence in the UPTs we studied was 26% (6/23). Mutations were distributed in eight codons of the p53 gene. Seven of these tumors showed a reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. We conclude that although UPTs represent highly metastatic advanced tumors that are expected to have a high incidence of p53 mutations, the frequency of p53 mutations is relatively low, suggesting that p53 mutations may not play a major role in the development and progression of this unique tumor type.

Amino Acid Sequence↗
PubMed1999

A neurocorrective approach for MMPI-2 use with brain-damaged patients.

Conventional administration of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) to aetiologically distinct brain-damaged out-patients (n = 137) revealed significant indications of psychological maladjustment. An adjustment for the endorsement of aetiology-specific items pertaining to traumatic brain injury (TBI), stroke, and whiplash was considered necessary, however, because these items may represent potentially valid symptoms or manifestations of neurological damage or dysfunction. These so-called neurologically relevant items (NRIs) were identified in a previous study. With this corrective approach, based on the complete MMPI-2 item pool, it was shown that T-score elevations could at least in part be attributed to symptoms associated with brain injury, regardless of the type of brain damage. Similarly, after prorated correction for the endorsement of NRIs, code-typing appeared to be substantially changed with respect to both occurrence and content of the MMPI-2 defined code-types. The validity of the NRI concept was supported by comparing NRI/non-NRI endorsement ratios of traumatically brain-injured patients with those of non-neurological patients, and with those having anxiety and somatoform disorders. To prevent unjustified interpretations when administering the MMPI-2 to brain-damaged patients, an adjustment procedure for NRI-endorsement is proposed, and difficulties in interpretation are discussed.

Adolescent↗
PubMed2005

Neural correlates of consciousness: a definition of the dorsal and ventral streams and their relation to phenomenology.

The paper presents a hypothesis for a neural correlate of consciousness. A proposal is made that both the dorsal and ventral streams must be concurrently active to generate conscious awareness and that V1 (striate cortex) provides a serial link between them. An argument is presented against a true extrastriate communication between the dorsal and ventral streams. Secondly, a detailed theory is developed for the structure of the visual hierarchy. Premotor theory states that each organism-object interaction can be described by the two quantitative measures of torque and change in joint position served by the basal ganglia and cerebellum, respectively. This leads to a component theory of motor efference copy providing a fundamental tool for categorizing dorsal and ventral stream networks. The rationale for this is that the dorsal stream specifies spatial coordinates of the external world, which can be coded by the reafference of changes in joint position. The ventral stream is concerned with object recognition and is coded for by forces exerted on the world during a developmental exploratory phase of the organism. The proposed pathways for a component motor efference copy from both the cerebellum and basal ganglia converge on the thalamus and modulate thalamocortical projections via the thalamic reticular nucleus. The origin of the corticopontine projections, which are a massive pathway for cortical information to reach the cerebellum, coincides with the area typically considered as part of the dorsal stream, whereas the entire cortex projects to the striatum. This adds empirical support for a new conceptualization of the visual streams. The model also presents a solution to the binding problem of a neural correlate of consciousness, that is, how a distributed neural network synchronizes its activity during a cognitive event. It represents a reinterpretation of the current status of the visual hierarchy.

Animals↗
PubMedDate not supplied

Colour-coded mapping technique in impression cytology - findings in soft contact lens wearers and patients with other external eye diseases.

This study aimed to demonstrate metaplastic changes in a wide area of conjunctival epithelium using the mapping technique by colouring different stages of metaplastic changes after marking them on a millimetric scale paper under a light microscope. Data of 23 patients were studied: 19 contact lens wearers, 2 cases with dry eyes, 1 with lagophthalmus, 1 with conjunctivitis, and 13 normal subjects as controls. Cellulose acetate paper cut into crescents was applied to nasal and temporal quadrants of the conjunctiva. After evaluating the collected cells under light microscopy, they were marked on a millimetric scale. Almost all the patients had varying degrees of squamous metaplasia; however, significant differences were observed in the distribution and the percentage ratio of these changes. In conclusion the colour-coded mapping method yields valuable information in a broader perspective for determining the distribution and degree of the ocular surface changes caused by different physiological and pathological circumstances.

Conjunctiva↗