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Loss of complement receptor type 1 (CR1) on ageing of erythrocytes. Studies of proteolytic release of the receptor.

Complement receptor type 1 (CR1) is a glycoprotein of Mr about 250 000 present on erythrocytes and other cell types. CR1 acts as a cofactor in the factor I-mediated breakdown of complement fragment C3b to form iC3b. Using an assay of cofactor activity, a wide variation in mean CR1 levels between erythrocytes from individual donors is observed. CR1 levels also decrease on ageing of erythrocytes in vivo, and again the rate of loss is widely variable between individuals. However, variable loss of CR1 during ageing of erythrocytes is likely to make only a minor contribution to the observed variation in mean CR1 levels. CR1 is very sensitive to proteolysis, and random proteolytic removal of CR1 from erythrocytes is likely to be an important factor in loss of CR1 on ageing of red cells in vivo. In vitro, mild trypsin treatment, plasmin or thrombin digestion of erythrocytes results in the loss of the factor I cofactor activity from the cell surface, and appearance of this activity in the supernatant. We conclude that an active fragment of CR1 is released from the cell surface on proteolysis. Subsequent prolonged trypsin treatment destroys most of the activity of this fragment. Proteolytic removal of CR1 from red cells may account not only for loss on ageing of cells, but also for the acquired CR1 deficiencies observed by others in systemic lupus erythematosus.

Erythrocyte Aging↗

Microsatellite DNA population structure and stock identification of steelhead trout (Oncorhynchus mykiss) in the Nass and Skeena rivers in northern British Columbia.

Population structure and the application to genetic stock identification for steelhead (Oncorhynchus mykiss) in the Nass and Skeena Rivers in northern British Columbia was examined using microsatellite markers. Variation at 8 microsatellite loci (Oki200, Omy77, Ots1, Ots3, Ssa85, Ots100, Ots103, and Ots108) was surveyed for approximately 930 steelhead from 7 populations in the Skeena River drainage and 850 steelhead from 10 populations in the Nass River drainage, as well as 1550 steelhead from test fisheries near the mouth of each river. Differentiation among populations within rivers accounted for about 1.9 times the variation observed among years within populations, with differences between drainages less than variation among populations within drainages. In the Nass River, winter-run populations formed a distinct group from the summer-run populations. Winter-run populations were not assessed in the Skeena River watershed. Simulated mixed-stock samples suggested that variation at the 8 microsatellite loci surveyed should provide relatively accurate and precise estimates of stock composition for fishery management applications within drainages. In the Skeena River drainage in 1998, Babine River (27%) and Bulkley drainage populations (31%) comprised the main components of the returns. For the Nass River in 1998 steelhead returning to Bell-Irving River were estimated to have comprised 39% of the fish sampled in the test fishery, with another 27% of the returns estimated to be derived from Cranberry River. The survey of microsatellite variation did not reveal enough differentiation between Nass River and Skeena River populations to be applied confidently in estimation of stock composition in marine fisheries at this time.

Journal Article↗

Effects of solvent density on retention in gas-liquid chromatography. I. Alkanes solutes in polyethylene glycol stationary phases.

Gas-liquid chromatographic columns were prepared coating silica capillaries with poly(oxyethylene) polymers of different molecular mass distributions, in the range of low number-average molar masses, where the density still varies significantly. A novel, high-temperature, rapid evaporation method was developed and applied to the static coating of the low-molecular-mass stationary phases. The analysis of alkanes retention data from these columns reveals that the dependence of the partition coefficient with the solvent macroscopic density is mainly due to a variation of entropy. Enthalpies of solute transfer contribute poorly to the observed variations of retention. Since the alkanes solubility diminishes with the increasing solvent density, and this variation is weakly dependent with temperature, it is concluded that the decrease of free-volume in the liquid is responsible for this behavior.

Alkanes↗

Robust parameter estimation techniques for stochastic within-host macroparasite models.

We present a stochastic model of the within-host population dynamics of lymphatic filariasis, and use a simulated goodness-of-fit (GOF) method to estimate immunological parameters and their confidence intervals from experimental data. A variety of deterministic moment closure approximations to the stochastic system are explored and compared with simulation results. For the maximum GOF parameter estimates, none of the methods of closure accurately reproduce the behaviour of the stochastic model. However, direct analysis of the stochastic model demonstrates that the high levels of variation observed in the data can be reproduced without requiring parameters to vary between hosts. This indicates that the observed aggregation of parasite load may be dynamically generated by random variation in the development of an effective immune response against parasite larvae.

Animals↗

Kinetics of hydrolysis of 4-methoxyphenyl-2,2-dichloroethanoate in binary water-cosolvent mixtures; the role of solvent activity and solute-solute interactions.

Rate constants are reported for the pH-independent hydrolysis of 4-methoxyphenyl-2,2-dichloroethanoate in aqueous solution as a function of the concentration of added cyanomethane (acetonitrile), polyethylene glycol (PEG 400) and tetrahydrofuran (THF). The concentration of water was varied between ca. 25 and 55.5 M. It was found that the variation in water activity yields only a minor contribution to the observed variation in rate constants. Interestingly, for both cyanomethane and PEG 400 log(k) varies approximately linearly with the molar concentration of water. Medium effects in highly aqueous solutions ([H(2)O] > 50 M) of ethanol, 1-propanol, 2-propanol, 1-butanol and 2-methyl-2-propanol have also been determined. Unexpectedly, in this concentration range the alcohols induce significantly smaller effects per unit volume than cyanomethane. The present results are discussed in terms of pairwise interaction parameters. Isobaric activation parameters have been determined and reveal remarkable differences in the nature of the induced medium effects.

Journal Article↗

Can right ventricular performance be assessed by equilibrium radionuclide ventriculography?

Although right ventricular function may be examined by following the passage (first pass) of a bolus of radionuclide through the right heart before it reaches the left heart, the counts detected with conventional gamma cameras in such a short time interval are low; moreover, repeated determinations would result in an unacceptable radiation burden to the patient. We have modified the gated equilibrium blood pool method to allow repeated assessment of the right ventricular ejection fraction (RVEF) and have compared the results with the first-pass method in 43 patients. Good agreement was obtained between the two methods (r = 0.91, p less than 0.001). The mean difference between the two methods was 0.04 with an intra-observer variation for the equilibrium studies of 0.03 and an inter-observer difference of 0.04. The mean difference in RVEF for seven patients studied on two separate occasions 30 minutes apart was only 0.02. In four patients the mean RVEF measured at rest was 0.44 +/- 0.05 (SEM) and after exercise it was 0.48 +/- 0.06. After infusion of isoprenaline at 1 microgram/min the mean rose to 0.64 +/- 0.04 (p less than 0.02) and after infusion of a new beta 1-sympathomimetic agent, prenalterol, at doses of 1 and 2 mg it was 0.56 +/- 0.02 (p less than 0.02) and 0.59 +/- 0.03 (p less than 0.01) respectively, where the significance levels are relative to the resting values. In nine patients with good ventricular function the vasodilator nifedipine caused right and left ventricular ejection fractions to increase by the same amount; while in six patients with severe impairment of left ventricular function due to ischaemic heart disease the RVEF increased from 0.58 +/- 0.03 to 0.73 +/- 0.03 (p less than 0.01) after 2 mg of prenalterol, but the left ventricular ejection fraction increased only from 0.22 +/- 0.04 to 0.26 +/- 0.04. We conclude that repeated estimation of right ventricular performance is possible by equilibrium radionuclide ventriculography.

Adrenergic beta-Agonists↗

Early systole in the healthy kidney: variability of Doppler US waveform parameters.

PURPOSE: To determine the sampling variability of intrarenal Doppler ultrasound (US) indexes of early systole in a screened population of healthy individuals. MATERIALS AND METHODS: Doppler US measurements were obtained in the superior, middle, and inferior regions of 132 kidneys in 66 healthy, potential kidney donors. All individuals subsequently underwent angiography. Systematic measurement differences and random effects were estimated for sampling from a particular parenchymal region, from a kidney in a subject, from an individual in a population, and from a vascular territory. RESULTS: Coefficients of variations ranged from 20% to 30%. Most (55%-66%) of the observed variation was attributable to random differences between repeated measurements in the same kidney. No systematic variations attributable to kidney region, vascular territory, right versus left kidney, or subject age were found for acceleration time, acceleration, or waveform shape. Some evidence of fixed variation between kidneys and between regions was found for peak systolic velocity, but the magnitude of this variation was small. Averages of repeated measurements may decrease the probability of exceeding the normal threshold for acceleration but not for acceleration time. CONCLUSION: Measurements of Doppler parameters of the early systole have substantial intrinsic variability. Thus, caution is needed when interpreting small changes in these measurements within a kidney or between individuals.

Adult↗

Relation between rise times and amplitudes of GABAergic postsynaptic currents.

1. We recorded rise times and amplitudes of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) in melanotropes of Xenopus laevis. Average rise times did not vary with amplitude, but the rise times of larger IPSCs were less variable. A simple linear one-step Markov model for channel opening following the binding of a transmitter molecule can quantitatively account for the average rise time and its coefficient of variation as a function of amplitude. Our results indicate that the observed variations in the rise times are not due to variations in transmitter concentrations, but result from stochastic variations in the opening of the receptor channels.

Animals↗

Variability and conservation in hepatitis B virus core protein.

BACKGROUND: Hepatitis B core protein (HBVc) has been extensively studied from both a structural and immunological point of view, but the evolutionary forces driving sequence variation within core are incompletely understood. RESULTS: In this study, the observed variation in HBVc protein sequence has been examined in a collection of a large number of HBVc protein sequences from public sequence repositories. An alignment of several hundred sequences was carried out, and used to analyse the distribution of polymorphisms along the HBVc. Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid. The relationship between HBVc diversity and HBV genotype was examined. The position of variable amino acids along the sequence was examined in terms of the structural constraints of capsid and envelope assembly, and also in terms of immunological recognition by T and B cells. CONCLUSION: Over three quarters of amino acids within the HBVc sequence are non-polymorphic, and variation is focused to a few amino acids. Phylogenetic analysis suggests that core protein specific forces constrain its diversity within the context of overall HBV genome evolution. As a consequence, core protein is not a reliable predictor of virus genotype. The structural requirements of capsid assembly are likely to play a major role in limiting diversity. The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.

Amino Acid Sequence↗

The prevalence of stillbirths: a systematic review.

BACKGROUND: Stillbirth rate is an important indicator of access to and quality of antenatal and delivery care. Obtaining overall estimates across various regions of the world is not straightforward due to variation in definitions, data collection methods and reporting. METHODS: We conducted a systematic review of a range of pregnancy-related conditions including stillbirths and performed meta-analysis of the subset of studies reporting stillbirth rates. We examined variation across rates and used meta-regression techniques to explain observed variation. RESULTS: We identified 389 articles on stillbirth prevalence among the 2580 included in the systematic review. We included 70 providing 80 data sets from 50 countries in the meta-analysis. Pooled prevalence rates show variation across various subgroup categories. Rates per 100 births are higher in studies conducted in less developed country settings as compared to more developed (1.17 versus 0.50), of inadequate quality as compared to adequate (1.12 versus 0.66), using sub-national sample as compared to national (1.38 versus 0.68), reporting all stillbirths as compared to late stillbirths (0.95 versus 0.63), published in non-English as compared to English (0.91 versus 0.59) and as journal articles as compared to non-journal (1.37 versus 0.67). The results of the meta-regression show the significance of two predictor variables - development status of the setting and study quality - on stillbirth prevalence. CONCLUSION: Stillbirth prevalence at the community level is typically less than 1% in more developed parts of the world and could exceed 3% in less developed regions. Regular reviews of stillbirth rates in appropriately designed and reported studies are useful in monitoring the adequacy of care. Systematic reviews of prevalence studies are helpful in explaining sources of variation across rates. Exploring these methodological issues will lead to improved standards for assessing the burden of reproductive ill-health.

Journal Article↗

The cell cycle of symbiotic Chlorella. III. Numbers of algae in green hydra digestive cells are regulated at digestive cell division.

Regression analysis of the relationship between the size of interphase and mitotic digestive cells of green hydra, and the numbers and total volume of the symbiotic Chlorella algae they contain showed a partial correlation only, suggesting that numbers of algae per cell are not regulated by limiting them to a specific proportion of the host cell, and that the variation observed in numbers of algae per cell is not due to variation in host cell size. After hydra were fed, which stimulates algae and digestive cells to divide at the same time, numbers of algae per cell were higher in prophase than in interphase cells, and numbers increased as mitosis proceeded. In excised regenerating peduncles algae divide before digestive cells, and at the onset of digestive cell division mitotic cells were found to contain almost twice the number of algae as before excision. Thus, almost all of the algal cell division necessary to maintain a constant population size was associated with digestive cell division. Analysis of variance in numbers of algae in telophase mother and daughter cells suggested that the proportion of algae dividing as a result of host cell mitosis was greater in digestive cells with few algae than in those with many algae. The fact that the mechanism controlling the proportion of algae dividing in host cells is expressed at host cell division and is manifested in the daughter cells may contribute to wide variation in numbers of algae per cell.

Animals↗

Environmental factors affecting the start of pollen season and concentrations of airborne Alnus pollen in two localities of Galicia (NW Spain).

Alnus pollen is an early component of the annual atmospheric aerosol of the north-west regions of Spain, which causes the first occurrence of allergic symptoms. Seasonal and intra-daily variation of Alnus pollination, and the influence that main meteorological parameters exert, was studied in this paper. Monitoring was carried out from 1993-2002, by using two Lanzoni VPPS 2000 volumetric samplers. Once the atmospheric behaviour of this pollen had been identified, the final objective was to elaborate predictive models to determine the onset of the Alnus pollen season and its concentrations during the pollination period in two localities of north-west Spain (Santiago and Ourense). Winter chilling required to overcome the bud-dormancy period was similar in both cities, with around 800 Chilling Hours (C.H.) and 5.5 degrees C threshold temperature. Calculation of heat requirement for bud growth was carried out with maximum temperature, with around 50 Growth Degree Days (G.D.D. degrees C) needed, with 6 degrees C threshold temperature. Data from 2002 were used in order to determine the real validity of the models. This year was not taken into account to establish the aforementioned models. The variation between the predicted start of the pollen season and the observed season was smallest in Ourense. Verifying the proposed models for predicting daily mean concentrations of Alnus pollen during the pollen season shows that the predicted curves fits the observed variations of daily mean concentrations.

Air Pollution↗

Comparison of spermatozoal movement and semen characteristics with fertility in stallions: 64 cases (1987-1988).

Information pertaining to evaluation of single ejaculates of semen and records for 2 consecutive breeding seasons were obtained. In all, data for 99 individual breeding seasons (n = 43 Standardbreds and 56 Thoroughbreds) were evaluated. Included in each semen evaluation was examination of semen characteristics and computer-aided analysis of spermatozoal movement characteristics. On the basis of the analysis of breeding records for 4,175 mares (7,017 estrous cycles), a per-estrous cycle fertility rate was calculated from data for 96 of the breeding seasons. Stallions with lower fertility than the mean overall season fertility had significantly (P less than 0.01) lower mean values for subjective appraisal of the percentage of motile and progressively motile spermatozoa and for percentage of morphologically normal spermatozoa. Lower mean values were obtained for computer-aided movement analysis of the percentage of motile and progressively motile spermatozoa, and for mean velocity of motile spermatozoa. Semen characteristics, including spermatozoal movement characteristics, and fertility were significantly (P less than 0.05) correlated for Thoroughbred and Standardbred stallions when analyzed individually and when data for both breeds were combined. Characteristics most highly correlated (P less than 0.01) with fertility data for both breeds combined were: subjective appraisal of the percentage of motile (r = 0.40) and progressively motile (r = 0.46) spermatozoa; percentage of morphologically normal spermatozoa (r = 0.36); and computer-aided analysis of percentage of motile spermatozoa (r = 0.34). However, on the basis of evaluation of a single ejaculate for each stallion, the variation in these characteristics only accounted for approximately 20% of the observed variation in fertility rate.

Animals↗

Receptor-mediated inositol phosphate formation in relation to calcium mobilization: a comparison of two cell lines.

Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid mobilization of Ca2+ from internal stores of both cell types. Paradoxically, alpha 1-adrenergic agonists did not rapidly increase inositol trisphosphate (Ins-P3) formation in BC3H-1 cells, in distinction to the rapid increase in Ins-P3 accumulation observed in 1321N1 cells after muscarinic stimulation. To determine whether the variations observed in the Ins-P3 response could be ascribed to differences in the relative amounts of inositol 1,4,5-trisphosphate, inositol 1,3,4-trisphosphate, and inositol tetrakisphosphate (respectively, Ins-1,4,5-P3, Ins-1,3,4-P3, and Ins-P4), we have separated the individual inositol phosphates by high-performance liquid chromatography and examined the rates of conversion of individual inositol phosphates in the two types of cells. Muscarinic stimulation of 1321N1 cells resulted in increased Ins-1,4,5-P3 production, as well as the rapid production of Ins-1,3,4-P3 and Ins-P4. Application of alpha 1-agonist to BC3H-1 cells produced a modest but delayed increase in accumulation of Ins-1,4,5-P3. Adrenergic stimulation also resulted in a smaller and even slower production of Ins-1,3,4-P3, and Ins-P4 could not be detected in BC3H-1 cells under any conditions employed. Thus, over a 30-sec interval in which Ca2+ is mobilized to a maximum extent, increases in Ins-1,4,5-P3, Ins-1,3,4-P3, or Ins-P4 amounted to less than 10% over basal values in BC3H-1 cells. These results indicate that the regulation of Ins-P3 isomer formation and conversion may vary substantially between different cell types. In addition, if inositol 1,4,5-trisphosphate is the sole mediator of intracellular Ca2+ release, it is necessary to propose that an increase in Ins-1,4,5-P3 sufficient to mobilize Ca2+ rapidly may occur only within discrete cellular localities in some cell types. According, it may not be possible to detect the increases in Ins-1,4,5-P3 over basal concentrations when measuring total cellular inositol phosphates.

Animals↗

Blood flow fluctuations in cerebral cortex microvessels.

Studies on the dynamics of the blood flow in cerebral microvessels with the diameter of erythrocyte flow (5-13 micron) carried out by the cinema-TV method showed that the linear velocity of the blood flow in microvessels experienced considerable fluctuations the amplitude of which varied within 10 to 1500 micron/s and the period within 0.2 to 7 s. It was established that variations in linear velocity of the blood flow were most frequently observed during 0.5-1 s. The autocorrelation analysis showed there was periodicity in the blood flow fluctuations in most microvessels which varied within a wide range of 0.3 to 3 s. A linear dependence was found between the amplitude and the period of fluctuations. The observed variations in the blood flow are likely to be caused by the changes in local resistance when leukocytes and erythrocyte aggregates passed through microvessels.

Animals↗

Small area variation analysis: a tool for primary care research.

Small area variation analysis is a research tool used by health services researchers to describe how rates of health care use and events vary over well-defined geographic areas. Significant variation has been shown to exist in the rates of hospitalization for chronic obstructive lung disease, pneumonia, hypertension, and in surgical procedures, such as hysterectomy, cholecystectomy, and tonsillectomy. Potential sources of variation include differences in underlying morbidity, access to care, physician judgment, quality of care delivered, patient demand for services, and random variation. Small area variation studies have been used to determine if significant variation exists across geographic areas and to describe relationships between the observed variation and potential causal factors. Methodologic concerns include the definition of small areas, defining the at-risk population within each small area, sample size, case mix adjustments, and stability of rates over time. The use of small area analysis in primary care will require definition of appropriate small areas for ambulatory care, description of the variation in ambulatory events across small areas, development of appropriate measures for ambulatory case mix, and development of appropriate tools to measure the outcomes of ambulatory care.

Episode of Care↗

Factors influencing the development and carbohydrate metabolism of Echinococcus granulosus in dogs.

Echinococcus granulosus adult worms, 35 days postinfection, were measured for dispersion in the intestines of 10 dogs, a range of morphological characters, and the excreted end products of carbohydrate catabolism following 4 hr incubation in vitro. Most worms were found in the proximal sections of the small intestine, but the pattern of dispersion differed between dogs. Worm development varied both between dogs and between different regions of the small intestine of individual dogs. Overall there was a high level of variability with no simple patterns. Worm metabolism was related to worm development and, also independently, to local population density within the intestine. Larger, more mature worms produced less lactate and, at higher densities, worms tended to produce more acetate and succinate (pathways with a higher energy yield than lactate) and less ethanol. Thus, both more developed worms and high population density are associated with a shift from cytosolic to mitochondrial metabolism. The variation between worm populations along the small intestine along with the observed variation between worm populations from sibling dogs infected with genetically identical parasites suggests that the local host environment has a significant effect on parasite development.

Acetates↗

[Can case-mix explain differences in involuntary admissions?].

BACKGROUND: The proportion of patients admitted involuntarily varies considerably among Norwegian psychiatric hospitals. We tested the hypothesis that these variations are the result of differences in case-mix. MATERIAL AND METHODS: The observed differences in involuntary admissions to Norwegian psychiatric hospitals were compared to those expected on the basis of their case-mix, as predicted by our multivariate model (multinomial logistic regression). The material was based on a cross-sectional registration of hospitalized patients in Norwegian psychiatric hospitals as of 1 November 1999. Thirty-two hospitals (all Norwegian hospitals that take involuntary admissions) supplied data on a total of 1,500 patients. RESULTS: The analysis shows that a large amount of the observed variation in involuntary admissions is related to differences in case-mix. However, for patients involuntarily admitted for observation, the case-mix was found to have less explanatory effect. Age, sex, previous admissions and diagnoses were used to operationalize hospital case-mix. INTERPRETATION: The analysis also indicated that other explanatory factors should be explored, such as differences in admission threshold and in medical decision in explaining variation in involuntary psychiatric admissions.

Adolescent↗