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At least 19 recordsLinked to original sources

The prognostic significance of quantitative signal-averaged variables relative to clinical variables, site of myocardial infarction, ejection fraction and ventricular premature beats: a prospective study.

A prospective study was undertaken of the prognostic significance of quantitative signal-averaged electrocardiographic (ECG) variables relative to clinical variables, site of myocardial infarction, left ventricular ejection fraction and characteristics of ventricular premature beats in 115 patients (mean age 62 +/- 12 years) studied 10 +/- 6 days after myocardial infarction. Signal-averaged variables included the root mean square voltage of the terminal 40 ms, the duration of the filtered signal-averaged QRS complex and low amplitude signals less than 40 microV determined at 25 and 40 Hz high pass filtering in all patients. Of the 115 patients, 51 (44%) had an abnormal signal-averaged ECG (one or more abnormal signal-averaged variables), 51 (44%) at 25 Hz and 48 (42%) at 40 Hz high pass filtering. A higher proportion of patients with an inferior wall infarction had an abnormal signal-averaged ECG as compared with patients with anterior wall infarction (58% versus 31%). Over a 14 +/- 8 month follow-up period 16 patients (14%) had an arrhythmic event. An abnormal signal-averaged ECG at 40 Hz high pass filtering had a higher sensitivity (81% versus 75%) and specificity (65% versus 61%) than at 25 Hz high pass filtering. The predictive value of the signal-averaged ECG was superior to that of the ejection fraction (40% versus 20%) in anterior wall myocardial infarction, whereas in patients with inferior wall infarction, the predictive values of the two tests were equivalent. The prognostic power of 27 clinical and noninvasive variables was determined with the Cox proportional hazards regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Risk indicators for future clinical attachment loss in adult periodontitis. Tooth and site variables.

In an earlier report, we examined the relationship of patient-derived clinical and epidemiological variables to the risk for future clinical attachment loss (CAL) in chronic adult periodontitis. We determined that the extent of the patient's existing periodontal disease as measured by mean attachment loss (MAL) and the patient's age were the most important patient-derived risk indicators for CAL among those factors evaluated. In this study, we examined the tooth and site variables that were associated with CAL. Seventy-five patients with chronic adult periodontitis were followed for 6 months. Clinical data at baseline, including attachment level and probing depth, were obtained from six sites per tooth. The hazard rate for CAL at all sites was 2.0%, and 4.1% of teeth displayed at least one site with CAL. Mandibular and maxillary molars and maxillary premolars displayed the highest incidence of CAL (6.1%, 5.6%, 5.5%, respectively), while maxillary anterior teeth (1.8%) and mandibular premolar teeth (2.1%) demonstrated the lowest incidence. The greatest number of sites demonstrating CAL had an existing attachment level of 4 to 7 mm and a probing depth of less than or equal to 5 mm. When the data were converted to hazard rates, however, an increase in hazard rate was seen with increasing existing attachment loss or probing depth. When MAL was considered, patients with mild and moderate periodontitis demonstrated a relatively low incidence of CAL at sites with less than or equal to 7 mm of existing attachment loss. Patients with severe periodontitis exhibited greater hazard rates for sites with 0 to 3, 4 to 5 and 6 to 7 mm of existing attachment loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Site variability in the solubility of collagen of human fetal membranes.

The extractability of collagen was examined in different sites of amnion and chorion from term deliveries. Sequential extraction with NaCl, acetic acid and CaCl2 showed that soluble collagen accounted for 1.5% of the proteins extracted. Saline extracted more collagen from the amnion than from the chorion. Acetic acid and CaCl2 extracted decreasing and increasing amounts of collagen from the amnion and chorion respectively. The concentration of collagen decreased linearly in the chorion as the rupture site was approached. The results indicate differences in the nature of collagen between amnion and chorion as well as in various sites in the latter.

Acetates

Age and site variability of skin blood perfusion in the hairless mouse ear determined by laser Doppler flowmetry.

Laser Doppler Flowmetry (LDF) was used to characterize skin blood perfusion variations present within the Homozygous Hairless mouse ear microvasculature as a function of 1) arteriolar level within the microvasculature, 2) animal age and 3) LDF probe distance above the tissue being studied. To this end blood perfusion measurements (arbitrary perfusion units) were made in the ear at vascular sites in the vicinity of primary vessels (site A), secondary vessels (site B), tertiary vessels (site C), and peripheral zones distant from larger vessels. These were done without any invasive procedures save anesthesia administration and were carried out at three different tissue-probe distances (0.5, 0.75 and 1.0 mm) on three groups of eight mice each with ages of three, five and eight weeks. Results show a significant gradient in perfusion from sites A to D in each age group and a significant increase in perfusion with increasing age. The effect of probe-tissue distance variations on perfusion values was found to be significant between 0.5 mm and 1.0 mm but overall differences were small. In addition to these specific findings the present results demonstrate the potential of LDF as a means of detecting, evaluating and correlating perfusion changes, either by itself or as a complementary method to detailed microvascular measurements using conventional in vivo microscopy.

Age Factors

Variable site of airway narrowing among obstructive sleep apnea patients.

The purpose of this was to determine whether the site of physiological narrowing within the upper airway was uniform or differed among patients with obstructive sleep apnea. Inspiratory pressures were measured with an esophageal balloon catheter and three catheters located at different sites along the upper airway: supralaryngeal airway, oropharynx, and nasopharynx. Peak inspiratory pressure differences between catheters allowed assessment of pressure gradients across three airway segments: lungs-larynx-retroepiglottal airway (esophageal-supralaryngeal pressure), hypopharynx (supralaryngeal-oropharynx pressure), and transpalatal airway (oropharynx-nasopharynx pressure). In five patients, hypopharyngeal obstruction was present, and in four patients no hypopharyngeal obstruction existed. In these four patients the site of obstruction was located at the level of the palate. In a given subject, the site of obstruction was the same during repeated measurements. The presence or absence of hypopharyngeal narrowing during sleep was not predictable from gradients measured across different segments of the upper airway during wakefulness. We conclude that the site of physiological upper airway obstruction varies among patients with obstructive sleep apnea and is not predictable from pressure measured during wakefulness. We speculate that uvulopalatopharyngoplasty may not relieve obstructive apneas in patients with hypopharyngeal obstruction.

Adult

Assessment of relationships between site-specific variables.

The assessment of relationships between site-specific variables has been a matter of controversy because of the claim that periodontal sites within individuals can be used as independent observations in statistical models. One problem with this approach is the unreliability of the calculated Type I and Type II error rates. Another problem is that such inappropriate analysis may prohibit a correct assessment of causal relationships between site-specific variables. The host-factor can act as an effect modifier and modulate the magnitude of the site-specific effects and/or the host-factor can act as a confounder by superimposing a patient-effect on the studied site-specific effects leading to bias. As a result, site-specific biological mechanisms of disease progression may be misinterpreted. Sites can be used as the experimental unit of analysis, but the sampling design from which the site-specific data originated should not be ignored.

Causality

Molecular organization of ribosomal RNA genes clustered at variable chromosomal sites in Triturus vulgaris meridionalis (Amphibia, Urodela).

The ribosomal RNA genes of Triturus vulgaris meridionalis (Amphibia, Urodela) show the peculiar feature of being clustered not only at the nucleolar organizer, present in the species at a definite chromosome location, but also at "additional ribosomal sites" which are highly variable in number and chromosomal distribution among individuals. The additional ribosomal sites are most often found at specific chromosome regions, such as telomeres, C-bands and centromeres, in virtually all the chromosomes. With increasing numbers of additional clusters, the genomic dosages of ribosomal RNA genes are found to increase over a tenfold range, though not linearly. At a molecular level, the ribosomal DNA repeats differ in size because of discrete variations in the length of the non-transcribed spacers. However, the resulting length heterogeneity of the gene family is rather limited within a single genome as well as within the species. Many of the ribosomal loci appear to be internally homogeneous with respect to the repeat length. Moreover, separate clusters from distant genomic regions can share the same size class of ribosomal repeats even in the same specimen. The nucleolar organizer is mostly endowed with "shorter" ribosomal repeating units, ranging in size from 13.7 X 10(3) to 15.2 X 10(3) base-pairs. The additional ribosomal sites are characterized by the occurrence of "longer" repeats, ranging in size from 16.2 X 10(3) to 19.7 X 10(3) base-pairs. The "shorter" class of ribosomal repeats is always detected in the amplified ribosomal DNA, suggesting that the nucleolar organizer locus is involved in the amplification process in most oocytes. "Longer" ribosomal repeats are also detectable in the amplified ribosomal DNA of a few females.

Animals

Estimating the fraction of invariable codons with a capture-recapture method.

A codon-based approach to estimating the number of variable sites in a protein is presented. When first and second positions of codons are assumed to be replacement positions, a capture-recapture model can be used to estimate the number of variable codons from every pair of homologous and aligned sequences. The capture-recapture estimate is compared to a maximum likelihood estimate of the number of variable codons and to previous approaches that estimate the number of variable sites (not codons) in a sequence. Computer simulations are presented that show under which circumstances the capture-recapture estimate can be used to correct biases in distance matrices. Analysis of published sequences of two genes, calmodulin and serum albumin, shows that distance corrections that employ a capture-recapture estimate of the number of variable sites may be considerably different from corrections that assume that the number of variable sites is equal to the total number of positions in the sequence.

Biological Evolution

Radiotherapy and hyperthermia. Analysis of clinical results and identification of prognostic variables.

Site- and tumor-specific data obtained from two groups of patients with head and neck and melanoma lesions, respectively, showed that both immediate response and response duration were enhanced by the addition of heat. Two important variables, however, such as tumor volume and "isoeffect thermal dose" appeared to influence local tumor control. The volume effect was less pronounced in the lesions treated with radiotherapy plus heat than in those treated with radiotherapy alone, suggesting that the addition of heat was more damaging to the large than to the small lesions. Furthermore, a striking isoeffect thermal dose-response relationship was shown in head and neck lesions. Those data were collected and used to design a mathematical model relating the probability of local control to clinical and treatment variables. The analysis shows that, by using the same radiation parameters, the probability of local tumor control is a function of both "isoeffect thermal dose" and tumor volume.

Carcinoma, Squamous Cell

Expectation maximization algorithm for identifying protein-binding sites with variable lengths from unaligned DNA fragments.

An Expectation Maximization algorithm for identification of DNA binding sites is presented. The approach predicts the location of binding regions while allowing variable length spacers within the sites. In addition to predicting the most likely spacer length for a set of DNA fragments, the method identifies individual sites that differ in spacer size. No alignment of DNA sequences is necessary. The method is illustrated by application to 231 Escherichia coli DNA fragments known to contain promoters with variable spacings between their consensus regions. Maximum-likelihood tests of the differences between the spacing classes indicate that the consensus regions of the spacing classes are not distinct. Further tests suggest that several positions within the spacing region may contribute to promoter specificity.

Algorithms

Co-mutation Based Genetic Networks to Infer Temporal Mutation Dynamics in Ancient Human Mitochondrial Genomes.

The evolutionary history of Homo sapiens is marked by complex interactions between environmental, cultural, and genetic factors. To investigate the molecular signatures of these processes, we analyzed ancient mitochondrial DNA (mtDNA) across temporal and geographic contexts using principles of co-occurrence of minor alleles defined as co-mutation, through spatiotemporal co-mutation networks of variable sites. Haplogroup-based assessments of variable sites revealed a major transition from foraging to agrarian lifestyles during the Copper-Bronze Age. Genetic network analyses demonstrated that COX and CYB loci exhibited distinct temporal dynamics, with their interactions modulated by NADH dehydrogenase genes in a geological age-dependent manner. To complement the network approach, we constructed phylogeny-based gene interaction networks and assessed polymorphism-to-divergence from chimpanzee ratios. The tree-based networks displayed topologies consistent with co-mutation analyses but showed reduced gene-gene connectivity. Polymorphism/divergence analysis further indicated that the CYB gene has been under long-term purifying selection, whereas ATP6, COX, and NADH dehydrogenase genes experienced episodic purifying selection aligned with distinct historical phases. Collectively, our findings demonstrate that network-based analysis of ancient mtDNA provides insights into early human lifestyle transitions and haplogroup diversification, contributing to the evolutionary foundations of modern human populations.

Ancient humans

Identification of five new variable restriction sites in HSV-1 DNA.

Restriction endonuclease analysis of herpes simplex virus type 1 (HSV-1) DNA has shown that individual strains differ from one another. The differences can be recognized by the presence or absence of cleavage sites due to base changes, small insertions and occasional deletions. In a study in which 13 HSV-1 isolates from South Africa were analysed, a total of 5 new variable restriction sites were identified using the restriction endonucleases Hind III, Eco RI and Bgl II.

Bacterial Proteins

Apolipoprotein B amino acid 3611 substitution from arginine to glutamine creates the Ag (h/i) epitope: the polymorphism is not associated with differences in serum cholesterol and apolipoprotein B levels.

A G- to A-DNA sequence change in exon 26 of the human apolipoprotein B (apo B) gene leads to a glutamine substitution for arginine at codon 3611 of the mature apolipo-protein B100 and causes a loss of an MspI site. In 106 Finnish individuals, a complete correspondence exists between this MspI polymorphic site and the Ag (h/i) immunochemical polymorphism. Linkage disequilibrium was found between this MspI polymorphic site and the apo B XbaI and EcoRI variable sites and the Ag (al/d) and (c/g) epitope pairs; there is apparent linkage equilibrium with the apo B PvuII variable site. Based on three population studies (samples from London. Finland and Italy), no significant association was found between this RFLP and serum cholesterol and apo B levels. These data suggest that the arginine 3611----glutamine 3611 substitution has no significant effect on apo B function.

Adult

Metastatic adenocarcinomas of unknown primary site. Prognostic variables and treatment results.

As part of a Phase II chemotherapy trial using mitomycin-C, adriamycin, and vindesine, 57 patients with adenocarcinoma of unknown primary site were assessed for prognostic variables predictive of response and survival. They were also evaluated for response and toxicity, usefulness of screening techniques, and eventual definition of primary site and pattern of progression. Only gender predicted response, with women being more likely to respond than men. Visceral metastases below the diaphragm, or the presence of liver metastases, predicted poor survival. Responding patients were highly likely to relapse first at sites of initial disease. Hemolytic-uremic syndrome was the most severe toxicity; other side effects were moderate. The response rate was 30% (three complete responders), which is similar to other current regimens. This study suggests that patients with better prognosis characteristics of single site of disease and without intraabdominal tumor may benefit from a policy of expectant observation after local control has been established. Patients with multiple sites of disease and/or intraabdominal tumor are appropriate candidates for investigational chemotherapy.

Adenocarcinoma

Genetic control over fragile X chromosome expression.

The cytogenetic expression of fragile sites is highly variable. Sites are seen in differing proportions of cells. To determine if part of this variability is genetic, the proportions of lymphocytes manifesting the fragile X were examined in a large cohort of males with the fragile X chromosome. The number of fragile X cells was solely determined by genetic factors: the heritability as determined from the correlation between brothers as well as between cousins was 99.6% and 94.4%, respectively, as compared with 0% in unrelated males with the fragile X. This is consistent with pure genetic determination without any environmental influence over the expression of the fragile X chromosome in males.

Alleles

Antigenic analysis of African measles virus field isolates: identification and localisation of one conserved and two variable epitope sites on the NP protein.

Measles virus isolates from epidemics in the Cameroons (1983) and Gabon (1984) were analysed by a panel of monoclonal antibodies against four of the virion proteins. We observed no antigenic variation in the haemagglutinin, the fusion glycoprotein, or in the matrix protein. However, both inter- and intra-epidemic variation was observed in the nucleoprotein (NP). On the basis of strain reactivity and a competition binding assay, three epitopic sites were designated on the NP. One site was found on all the measles virus strains examined, whereas the other two were variable. Examination of proteolytic cleavage of the NP in situ (on the ribonucleoparticle) showed that the conserved site is located on a large fragment which remains bound to the viral genome. The peptide removed by proteolysis contained the two variable epitopes. The variability of the NP is discussed in relationship to its biological activity.

Animals

Phylogenetic studies of ribosomal RNA variation in higher moths and butterflies (Lepidoptera: Ditrysia).

The selection of exemplars has been shown both theoretically and empirically to affect tree topology, but the importance of the number and nature of taxa used to represent higher taxonomic lineages in molecular studies is rarely stressed. In our rRNA study of higher moths and butterflies (Lepidoptera: Ditrysia), the selection of different exemplars and outgroups caused major tree rearrangements. We also examined the effectiveness with which conserved rRNA regions track the diversification of Lepidoptera. Homoplasy is as prevalent at the few variable sites of conserved regions (18E, 18J, 28F) as at the many variable sites of a more rapidly evolving region (28B). Finally, 28B sequence variation differs qualitatively among lepidopteran superfamilies of presumed comparable age, the Papilionoidea (true butterflies) and Noctuoidea (cutworm moths and relatives).

Animals

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies.

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma