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DNA synthesis index: higher for human gallbladders with cholesterol gallstones than with pigment gallstones.

[3H]dThd uptake by the gallbladder epithelium was estimated in 33 patients with cholesterol stones, in 13 patients with pigment stones, and in 12 gallbladders without stones. Proliferative parameters were estimated by autoradiography after in vitro incubation with [3H]-dThd. Stones were identified by quantitative infrared spectroscopy. The degree of inflammation of the gallbladder wall was estimated by a histologic scoring method. In the gallbladders containing cholesterol stones the DNA synthesis index (1.39 +/- 0.28%) was higher (P less than .01) than in the gallbladders without stones (0.19 +/- 0.04%). No significant increase in proliferative parameters was found in the gallbladders with pigment stones (0.24 +/- 0.06%). No correlation was found between total stone number, weight or volume, and the DNA synthesis index. No evidence was observed that inflammation could influence the epithelial cell proliferation. Something in the bile of patients with cholesterol stones rather than the physical presence of stones may be the cause of the variations observed.

Autoradiography↗

Pulmonary pneumaticity in the postcranial skeleton of extant aves: a case study examining Anseriformes.

Anseriform birds were surveyed to examine how the degree of postcranial pneumaticity varies in a behaviorally and size-diverse clade of living birds. This study attempts to extricate the relative effects of phylogeny, body size, and behavioral specializations (e.g., diving, soaring) that have been postulated to influence the extent of postcranial skeletal pneumaticity. One hundred anseriform species were examined as the focal study group. Methods included latex injection of the pulmonary apparatus followed by gross dissection or direct examination of osteological specimens. The Pneumaticity Index (PI) is introduced as a means of quantifying and comparing postcranial pneumaticity in a number of species simultaneously. Phylogenetically independent contrasts (PICs) were used to examine the relationship between body size and the degree of postcranial pneumaticity throughout the clade. There is a high degree of similarity (i.e., clade-specificity) within most anseriform subgroups. As a whole, Anseriformes demonstrate no significant relationship between relative pneumaticity and body size, as indicated by regression analysis of body mass on PI. It is apparent, however, that many clades of diving ducks do exhibit lower PIs than their nondiving relatives. By exclusion of diving taxa from analyses, a significant positive slope is observed and the hypothesis of relatively higher pneumaticity in larger-bodied birds is only weakly supported. However, low correlations indicate that factors other than body size account for much of the variation observed in relative pneumaticity. Pneumaticity profiles were mapped onto existing phylogenetic hypotheses. A reduction in the degree of postcranial pneumaticity occurred independently in at least three anseriform subclades specialized for diving. Finally, enigmatic pneumatic features located in distal forelimb elements of screamers (Anhimidae) result from invasion of bone by a network of subcutaneous air sac diverticula spreading distally along the wings.

Animals↗

The effects of geology and the impact of seasonal correction factors on indoor radon levels: a case study approach.

Geology has been highlighted by a number of authors as a key factor in high indoor radon levels. In the light of this, this study examines the application of seasonal correction factors to indoor radon concentrations in the UK. This practice is based on an extensive database gathered by the National Radiological Protection Board over the years (small-scale surveys began in 1976 and continued with a larger scale survey in 1988) and reflects well known seasonal variations observed in indoor radon levels. However, due to the complexity of underlying geology (the UK arguably has the world's most complex solid and surficial geology over the shortest distances) and considerable variations in permeability of underlying materials it is clear that there are a significant number of occurrences where the application of a seasonal correction factor may give rise to over-estimated or under-estimated radon levels. Therefore, the practice of applying a seasonal correction should be one that is undertaken with caution, or not at all. This work is based on case studies taken from the Northamptonshire region and comparisons made to other permeable geologies in the UK.

Air Pollutants, Radioactive↗

Analysis of factors associated with variability in haemodialysis adequacy.

BACKGROUND: Delivered dialysis dose measured as Kt/V is widely accepted as an important factor affecting mortality on haemodialysis. It is currently measured relatively infrequently in most units for pragmatic reasons. We have previously shown that significant variation occurs within individuals which often makes the difference between dialysis that would be considered adequate, and inadequate. The aim of this study is to delineate which factors are responsible for the observed variation. METHODS: We studied 1109 treatments in 109 patients, mean age 59.9 years, mean dry weight 71.8 kg. Depurated volume (Kt) was measured by ionic dialysance for each treatment. Kt and other relevant treatment-related variables were automatically recorded on a central server. Multivariate analysis using mixed models with backwards elimination was used to analyse the determinants of Kt. Kt/V was not used, in order to avoid introducing error in the determination of V. RESULTS: The analysis indicated that the following were independent determinants of Kt: blood pump speed, time, minimum and mean arterial line pressure, both maximum and minimum venous line pressures and total ionic mass balance. CONCLUSION: This analysis suggests that the variation in adequacy that occurs within an individual is multifactorial. It confirms the importance of effective vascular access, prescription of and adherence to adequate time on dialysis, and reinforces the impact of degree of sodium removal. In clinical practice absolute control of these variables is not possible in every dialysis session and some degree of variability in Kt is therefore inevitable. Monitoring of adequacy thus requires more frequent assessment of Kt than is currently performed. Online monitoring of ionic dialysance achieves this.

Adult↗

Approaching the Lower Limits of Transgene Variability.

The inclusion of chicken lysozyme matrix-associated regions (MARs) in T-DNA has been demonstrated to reduce the variation in [beta]-glucuronidase (GUS) gene expression among first-generation transformed plants. The residual variation observed between transgenic plant lines with MARs at the T-DNA borders was investigated. By definition, any phenotypic variance between or within genetically identical plants is caused by random or environmental variation. This variation therefore sets a lower limit to the variation in GUS activities. The variance of GUS activity in offspring plant populations of genetically identical individuals was used as an estimate of environmental variation. For transgenic plants with MARs at the T-DNA borders, the variation between independent transformants could not be distinguished from the environmental variation. The variation could be attributed mainly to the variation in the GUS activity measurement. Therefore, the MAR element approached the maximal possible reduction of transgene variability given current technology and sample sizes. The role of MARs in offspring plants was evaluated by comparing such populations of transgenic plants for the magnitude of and variation in GUS activity. Pairwise comparisons showed that the presence of MARs reduced variation in offspring generations in the same manner as demonstrated for primary transformants. The populations carrying a doubled cauliflower mosaic virus 35S promoter-GUS gene tended to be more variable than the Lhca3.St.1 promoter-GUS gene-carrying populations. This tendency indicated an intrinsic susceptibility of the doubled cauliflower mosaic virus 35S promoter to variation. Homozygous plants were approximately twice as active as the corresponding hemizygous plants and tended to be more variable than the hemizygous plants. We hypothesized that the magnitude of environmental variations is related to a higher susceptibility to transgene silencing.

Journal Article↗

Direct electrochemistry of the enzyme, methylamine dehydrogenase, from bacterium W3A1.

The electrochemical response of methylamine dehydrogenase from bacterium W3A1 at edge-plane-oriented pyrolytic graphite (epg) and modified gold electrodes has been investigated. Quasi-reversible electron transfer has been observed. Variations in concentration of different cations and anions gave rise to both promotion and inhibition of the direct response. A catalytic response of the enzyme in the presence of methylamine has been observed at both an epg electrode and a 2,2'-dithiodiglycolic-acid-modified gold electrode surface, and the effects of various cations and anions on the catalytic peak current have been investigated. The spectroelectrochemical results obtained at an optically transparent thin-layer electrode, modified with 2,2'-dithiodiglycolic acid, are also reported. In the presence of 1,1'-dimethylferrocene-3-(1-ethanol-2-amine) (14.8 microM), the results reveal a midpoint potential of -148 mV for methylamine dehydrogenase from bacterium W3A1. This is in very close agreement to the value obtained in the cyclic voltammetric investigations of -140 mV.

Anions↗

Amino acid transport in human ciliary epithelium.

A statistical study of the co-variation of the concentrations of 19 amino acids and related compounds from 21 persons was performed as a factor analysis of Caq/Cpl and of Caq. Six factors explained about 83% of the observed variation. Factor 1 showed a correlation to alpha-amino-N-butyric acid, valine, methionine, isoleucine, leucine, tyrosine and phenylalanine, factor 2 to lysine, histidine, arginine and glutamine (containing serine), factor 3 to taurine and proline, factor 4 to glycine and cystine, factor 5 to urea and factor 6 to glutamic acid. Only alanine and threonine showed a correlation to different factors in the Caq/Cpl- and the Caq-matrix. This correlation of groups of substances to different and independent factors is considered to be an argument in favour of the existence of six transport systems in the ciliary epithelium for the investigated substances.

Amino Acids↗

Tissue variation in the control of oxidative phosphorylation: implication for mitochondrial diseases.

Metabolic control analysis has often been used for quantitative studies of the regulation of mitochondrial oxidative phosphorylations (OXPHOS). The main contribution of this work has been to show that the control of mitochondrial metabolic fluxes can be shared among several steps of the oxidative phosphorylation process, and that this distribution can vary according to the steady state and the tissue. However, these studies do not show whether this observed variation in the OXPHOS control is due to the experimental conditions or to the nature of the mitochondria. To find out if there actually exists a tissue variation in the distribution of OXPHOS control coefficients, we determined the control coefficients of seven OXPHOS complexes on the oxygen-consumption flux in rat mitochondria isolated from five different tissues under identical experimental conditions. Thus in this work, only the nature of the mitochondria can be responsible for any variation detected in the control coefficient values between different tissues. The analysis of control coefficient distribution shows two tissue groups: (i) the muscle and the heart, controlled essentially at the level of the respiratory chain; and (ii) the liver, the kidney and the brain, controlled mainly at the phosphorylation level by ATP synthase and the phosphate carrier. We propose that this variation in control coefficient according to the tissue origin of the mitochondria can explain part of the tissue specificity observed in mitochondrial cytopathies.

Animals↗

Age-specific fitness components and their temporal variation in the barn owl.

Theory predicts that temporal variability plays an important role in the evolution of life histories, but empirical studies evaluating this prediction are rare. In constant environments, fitness can be measured by the population growth rate lambda, and the sensitivity of lambda to changes in fitness components estimates selection on these traits. In variable environments, fitness is measured by the stochastic growth rate lambda(S), and stochastic sensitivities estimate selection pressure. Here we examine age-specific schedules for reproduction and survival in a barn owl population (Tyto alba). We estimated how temporal variability affected fitness and selection, accounting for sampling variance. Despite large sample sizes of old individuals, we found no strong evidence for senescence. The most variable fitness components were associated with reproduction. Survival was less variable. Stochastic simulations showed that the observed variation decreased fitness by about 30%, but the sensitivities of lambda and lambda(S) to changes in all fitness components were almost equal, suggesting that temporal variation had negligible effects on selection. We obtained these results despite high observed variability in the fitness components and relatively short generation time of the study organism, a situation in which temporal variability should be particularly important for natural selection and early senescence is expected.

Age Factors↗

Do attending or resident physician practice styles account for variations in hospital resource use?

Prospective payment has created incentives for hospitals to identify physicians who are responsible for high or excessive rates of resource use. However, at teaching hospitals it is unclear whether individual attending or resident physicians account for a substantial portion of the observed variations in hospital resource use. To explore this issue, case-mix adjusted hospital length of stay and ancillary resource use at a university teaching hospital for 7,667 consecutive discharges on general medicine wards and 7,566 discharges on medical subspecialty wards were evaluated. After controlling for case mix and patient characteristics (patients' age, sex, marital status, insurance status, and ward service), only 2% of the length of stay variance (log transformed) was attributable to the attending physician on general medicine wards (P = 0.06) and 1% on subspecialty medicine wards (P < 0.01). For total ancillary resource use, about 2% of the variance was attributable to general medicine and subspecialty ward attendings. Similar associations were found for resident physicians, although the overlap of attending and resident physicians' month-long rotations prevented critical appraisal of their independent contributions to resource use. Furthermore, labeling attending physicians as high or low hospital resource utilizers based on data from one month of attending duty (mean admissions = 33 +/- 7) would be scarcely better than randomly classifying them (kappas ranged from -0.05 for length of stay on subspecialty services to 0.18 for pharmacy use on general medicine services). In conclusion, in this university teaching hospital, attendings and residents account or a small, although statistically significant, amount of the variation in hospital resource use. It would be impractical for the hospital to reliably profile the resource use intensity of individual physicians.

Analysis of Variance↗

Respiratory sinus arrhythmia and cardiovascular responses to stress.

The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses.

Adaptation, Physiological↗

Interobserver reliability of skinfold measurements in infants and young children.

Interobserver reliabilities were determined for the triceps, biceps, subscapular, suprailiac, and abdominal skinfolds in 77 children, 9-24 months of age. Technical errors of measurement (replicate variances) and coefficients of variation were compared to data on 12-17-year-olds from the U.S. Health Examination Survey (HES) to 2.5-7-year-old Guatamalan children. Of the five skinfolds, the between-observer variation was not significantly different from zero in four; in the case of the biceps fold, F-ratio was significant at p less than .01. Errors of measurement are less for these data than for the HES or Guatemalan studies. This difference is attributed to the larger means of the older children and youth, as well as to the greater error of measurement shown to exist for larger skinfolds.

Adolescent↗

The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma.

Osteosarcoma (OS) is characterized by chromosomal instability and high copy number gene amplification. The breakage-fusion-bridge (BFB) cycle is a well-established mechanism of genome instability in tumors and in vitro models used to study the origins of complex chromosomal rearrangements and cancer genome amplification. To determine whether the BFB cycle could be increasing the de novo rate of formation of cytogenetic aberrations in OS, the frequency of anaphase bridge configurations and dicentric chromosomes in four OS cell lines was quantified. An increased level of anaphase bridges and dicentrics was observed in all the OS cell lines. There was also a strong association between the frequencies of anaphase bridges, dicentrics, centrosomal anomalies, and multipolar mitotic figures in all the OS cell lines, indicating a possible link in the mechanisms that led to the structural and numerical instabilities observed in OS. In summary, this study has provided strong support for the role of the BFB cycle in generating the extensive structural chromosome aberrations, as well as cell-to-cell cytogenetic variation observed in OS, thus conferring the genetic diversity for OS tumor progression.

Anaphase↗

Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. II. Relationship to baseline SCE frequency.

Environmental and genetic factors have been implicated as important sources of individual variation in baseline sister-chromatid exchange (SCE) frequency in humans. The current study was designed to test whether the frequency of baseline SCEs in 58 normal blood donors is associated with previously observed variations in SCE frequencies induced by diepoxybutane (DEB). Because 12 subjects were current cigarette smokers and smoking is known to be an in vivo inducer of baseline SCE frequencies, we specifically tested whether higher baseline SCE frequencies in smokers would be associated with in vitro sensitivity to SCE induction by DEB. Analysis of variance showed that DEB-induced SCE frequencies were significantly associated with baseline SCE frequencies; those who were sensitive to SCE induction by DEB were more likely to have higher baseline SCE frequencies. This effect, however, was independent of in vivo induction of SCE by smoking. Chromosomal sensitivity to the induction of SCE by DEB explained approx. 15-20% of the variation in baseline SCE. This was similar in magnitude to the effect of cigarette smoking. Because increased sensitivity to DEB-induced SCEs is common in normal blood donors (approx. 24%) and is associated with an increase in baseline SCEs, it should be investigated as a source of bias and/or a potential marker of sensitivity to environmental mutagens in future cytogenetic studies.

Adult↗

Effect of naturally occurring nematode infections on growth performance of first-season grazing calves.

Liveweight of calves on 89 dairy farms was measured at the end of the grazing season and related per herd to the level of exposure to nematode infection during the grazing season. There were significant between-herd variations in antibody titres against Ostertagia spp., Cooperia spp. and Dictyocaulus viviparus as well as in pepsinogen values. All but six herds (93.1%) had gastrointestinal nematode infections, as measured by faecal egg counts in September. Faecal samples of 17 herds (19.3%) contained lungworm larvae in September. Liveweight of calves per herd deviated from -68.1 kg to +84.1 kg from the age-adjusted population mean after their first grazing season. Growth performance up to the time of liveweight measurements was significantly correlated negatively with several serological and parasitological parameters. Data could be fitted by means of both linear and segmented curvilinear regression. Antibody titre against Cooperia spp. and gastrointestinal nematode egg output measured in September accounted for 3.1% (P less than 0.10) and 6.7% (P less than 0.05), respectively, of the variation in growth performance among herds. Certain infection parameters, when combined, accounted for 9.2% of this variation; these were antibody titre against Cooperia spp. and larval counts for both gastrointestinal nematodes and lungworm. Adding certain management factors to these infection parameters resulted in a model explaining 27.6% of the observed variation in growth performance among herds. These factors were supplementary feeding, lungworm vaccination, anthelmintic treatment at housing, date of housing and herd age.

Age Factors↗

Melanoma is not caused by sunlight.

When comparisons are made of cutaneous melanoma with cutaneous squamous cell cancer (SCC) and basal cell cancer (BCC) of the skin with respect to age dependence, sex ratio, distribution on the body, association with sun exposure, and variation with latitude, it is clear that SCC is due almost entirely to sun exposure, that BCC is partly due to sun exposure, and that melanoma is not due to sun exposure. For melanoma, it is only latitudinal variation that favours the hypothesis of sun exposure causation. However, an examination of the latitudinal variation of SCC incidence reveals that this is several fold greater than can be accounted for by variation of exposure to UV-B. The other factor operating appears to be skin temperature. For melanoma, it is postulated that the latter factor by itself may suffice to account for the observed variation with latitude. The higher incidence of melanoma in the higher social classes and its increasing incidence with age may be readily explained by the hypothesis that melanoma incidence increases with increase in skin temperature.

Adult↗

Study of the spread of a cold instantaneous heavy gas release with surface heat transfer and variable entrainment.

Air quality models help in developing relationships between the amount of pollutant released into the ambient atmosphere by a source and the corresponding incremental contribution in the atmospheric concentration. Of the various dispersion models, the heavy gas models help in predicting the concentrations due to release of gases heavier than air and the risks associated with the increased concentrations. Several differences exist among the various models developed to study the heavy-gas dispersion phenomena. These differences mainly arise because of the varied treatment given to physical processes involved in the dispersion mechanism. One of these processes, which have not been fully considered in many of the existing models, is the effect of ground heating on the movement of a cloud under windy conditions. In this study, the box model developed by Kunsch and Fannelop (J. Hazard. Mater. 43 (1995) 169) is extended to incorporate variable air entrainment on the dispersion of a heavy gas cloud spreading in a channel under windy conditions. The air entrainment was assumed to be proportional to the cloud frontal velocity. The semi-analytical equations developed were then solved by numerical methods to provide a heavy gas cloud dispersion profile. The popular Runge-Kutta fourth order technique was adopted to solve the differential equations numerically. The model was applied on a cold cloud released instantaneously and the results indicated that the model behavior follows closely the expected dispersion trends and observed cloud characteristics reported in a laboratory study. The trial run carried out in order to model the scenario of no heat transfer, by equating the source temperature to the ambient temperature, followed variations observed in the field. The analysis of cloud behavior indicated that the cloud length is strongly influenced by source density and initial cloud temperature.

Air Movements↗

No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters.

Opioid drugs reportedly regulate the immune system via their effects on the hypothalamic- pituitary-adrenal (HPA) axis. The present study was carried out to assess the effects of chronic exposure to buprenorphine on HPA axis activation, corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and the immune system. Results show that buprenorphine, delivered by osmotic pump subcutaneously in C57BL/6 male mice during a 10-day period, caused a marked decrease in total corticosterone (CORT) levels at day 1 of exposure. CORT levels then increased with maximal values observed at day 5 of exposure. After day 5, total CORT levels gradually decreased and returned to control values. No significant changes were observed in CBG protein levels and mRNA expression in the liver. Since CBG levels remained unchanged, the percentage of free CORT values in buprenorphine mice did not differ from control values. Thus, the variations observed in the amount of free CORT were related only to changes measured in total CORT. These endocrine changes did not have a significant impact on the immune parameters measured. Total CD(4)+ and CD(8)+ splenic and thymic populations were not modulated by buprenorphine. However, splenocytes from mice exposed to buprenorphine after 5 days exhibited greater proliferation upon anti-TCR monoclonal antibody stimulation than saline-exposed mice. These results indicate that buprenorphine can be safely used because it did not have significant effects on GC availability for immune corticosensitive cells.

Analgesics, Opioid↗