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PubMed1994

Might stochasticity and sampling variation be a possible explanation for variation in clonal population survival curves.

Biogerontological survival analysis attempts to understand, through the use of mathematical and computer models, how biological and environmental processes affect the dynamics of survival. The survival model parameters are assumed to reflect an average or mean response to some intervention. Further, these parameters are usually assumed to be constant over the time course of the experiment and across the elements of the experimental cohort. In this paper, we introduce stochastic (random) features to the survival curve parameters and we observe how this might affect our interpretation of the biology; as reflected in the estimates of the model parameters. In particular, we provide a possible explanation for variation in parameter estimates within sample populations drawn from a population of genetic clones.

Computer Simulation↗
PubMed1984

Sodium lauryl sulfate irritant patch tests. II. Variations of test responses among subjects and comparison to variations of allergic responses elicited by Toxicodendron extract.

Inflammation was induced on the forearms of volunteers by twenty-four closed patch tests to either the irritant 10% sodium lauryl sulfate (SLS) or Toxicodendron extract. Each chemical was tested at eight sites on the ventral forearms of each volunteer in order to assess the variability of response among test sites in individual subjects. Inflammation was assessed about 10 minutes after patch tests were removed. The degree of inflammation elicited by both Toxicodendron and SLS was variable among subjects, but variation among individual test sites was much more marked in subjects tested with SLS (p less than 0.002). The marked variability of responses to irritation that occur in any single subject may explain why irritant patch test responses do not reliably identify the irritation-prone individual.

Adolescent↗
PubMed1986

Isoelectric focusing in low-denaturing media: visualization in renal disease of variation of the isoelectric point of albumin not related to a remarkable conformational variation.

The isoelectric properties of serum and urinary albumin from normal subjects and patients with nephrotic syndrome have been investigated in various conditions of denaturation, obtained by using urea (0-8 M) as a support in isoelectric focusing. In normal human serum, albumin is rather acidic (pI = 4.7) when focused in glycerol while the denatured form obtained by exposing the protein to 8 M urea has a much higher pI (6.1). Albumin from nephrotic patients is acidic in glycerol but at very low levels of urea (2M) it shifts from pI 4.7 to pI 6.1; the same effect has been induced by treating albumin with activated charcoal at low pH. In order to obtain more information on urea-induced changes, we have recorded the circular dichroic spectra of albumin when exposed to the concentration of urea used in gels, and we found that no conformational transition occurs for urea concentrations less than 5 M. Taken together, these observations reveal that variation of the pI of albumin in nephrotic syndrome occurs mainly due to a dissociating effect of urea on charged substances bound to this protein.

Albumins↗
PubMed1975

The relationship of variations in children's growth rates to seasonal climatic variations.

The growth rates in stature of 300 children in the Orkney Islands, measured at monthly intervals over 2 years, were negatively correlated with various measures of light and temperature. All correlations were small but statistically significant, the highest being with the mean of the maximal daily temperatures (-0.32) for the boys and with hours of bright sunshine (-0.29) for the girls. The children's mean growth rates reached maxima at midwinter and minima at midsummer but the maximum in the winter 1971-72 was much lower than those at the beginning of 1971 and at the end of 1972. The climatic variables were not appreciably different in the two years. Only about 35 per cent of children showed cycles of growth rates which could be regarded as seasonal in that they rose to peak values at approximately the same time in the two successive years. The difference between the maximal and minimal rates exhibited by Orkney children (5.26+/-0.12 cm/yr for boys; 5.46+/-0.14 cm/yr for girls) was almost identical to that in London children. The synchronization of the maximal growth rates was no more precise in Orkney than in London. It is concluded that seasonal variations in light and temperature exert at most only a small effect on growth rate and perhaps none at all. The influence of other factors, as yet unidentified, is greater.

Child↗
PubMed2003

Regional variations of blood pressure in the United States are associated with regional variations in dietary intakes: the NHANES-III data.

Compared with other regions in the United States, the southern region has had the highest stroke mortality rate and a more prevalent and resistant hypertension. We designed this analysis of the data obtained from the National Health and Nutritional Examination Survey III (NHANES-III), which is a community-based cross-sectional survey, to describe regional variations in blood pressure and the reported consumption of nutrients, focusing on those linked to blood pressure, in the United States. We selected the following variables from the NHANES-III data for this analysis: systolic and diastolic blood pressures, protein, carbohydrates, total fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, fiber, sodium, potassium, calcium, magnesium, zinc, copper, iron, riboflavin, niacin, thiamin, alcohol and vitamins C, E, B-6 and B-12. Of the 17,752 participants in the survey who were 18 y of age or older, the south had the highest systolic and diastolic blood pressures (P < 0.005 for each) and reported the highest consumption of monounsaturated fatty acids, polyunsaturated fatty acids and cholesterol (P < 0.05 for all) and the least amount of fiber in the multivariate analysis (P < 0.005). The highest reported sodium consumption was in the south region (3.4 +/- 0.02 g), and the lowest was in the west (3.2 +/- 0.03 g; P < 0.05). The south also consumed the least potassium, calcium, phosphorous, magnesium, copper, riboflavin, niacin, iron and vitamins A, C and B-6 (P < 0.005). There was no difference among the four regions in frequency of "adding salt on the table." The region of the United States that includes the "stroke belt" has dietary patterns that may contribute to the high prevalence of hypertension and cardiovascular disease.

Adult↗
PubMed2006

Variation in the pulmonary hypertensive responsiveness of broilers to lipopolysaccharide and innate variation in nitric oxide production by mononuclear cells.

Variability among broilers in their pulmonary hypertensive (PH) responsiveness to lipopolysaccharide (LPS) appears to reflect innate variation in the types or proportions of vasodilators and vasoconstrictors released by leukocytes and endothelial cells. Two experiments were designed to evaluate possible correlations between the PH responsiveness to LPS in vivo and the quantities of nitric oxide (NO; a potent pulmonary vasodilator) produced by mononuclear cells in vitro. In Experiment 1, blood samples were collected from male broilers from a base population (control group) and from survivors of a 60% lethal dose i.v. injection of cellulose microparticles (MP survivor group). In Experiment 2, blood samples were collected from male broilers from a relaxed line and from lines known to be susceptible or resistant to pulmonary hypertension syndrome. Peripheral mononuclear cells (PMNC) from each blood sample were cultured at 2 million cells per well, remained unstimulated, or were stimulated with LPS to elicit the expression of inducible NO synthase, and the 24-h production of NO was measured. In both experiments, unstimulated PMNC cultures did not produce consistently detectable levels of NO, whereas LPS-stimulated cultures produced quantities of NO that varied widely among individuals. Nitric oxide production by cultured PMNC also was evaluated by flow cytometry, demonstrating that LPS-stimulated PMNC produced substantially more NO than did unstimulated cells in all of the groups evaluated. Moreover, NO-producing PMNC were identified to be monocytes. The same broilers from which PMNC had been isolated were catheterized subsequently to record pulmonary arterial pressure, LPS was injected i.v. to assess the amplitudes of peak and postpeak PH responses, then N(omega)-nitro-L-arginine methyl ester was injected to inhibit ongoing NO production. In Experiment 1, the amplitude of the peak and postpeak PH responses to LPS were correlated with the quantity of NO produced by LPS-stimulated cultured PMNC from broilers in the control group but not for MP survivors. In Experiment 2, the postpeak PH response to LPS was correlated with the quantity of NO produced by LPS-stimulated PMNC from broilers in the relaxed line, but not in the susceptible or resistant lines. In all groups, N(omega)-nitro-L-arginine methyl ester injections triggered substantial increases in pulmonary arterial pressure (> or = 8 mm Hg), thereby revealing a significant ongoing modulation by NO of the PH response to LPS. We concluded that most of the modulatory NO generated in vivo during the acute PH response to LPS (within 60 min postinjection) likely is produced by constitutive NO synthase in the vascular endothelium. In addition, the NO produced by inducible NO synthase in PMNC appeared to have modulated the LPS-stimulated PH responses of unselected broilers having the broadest range of pulmonary vascular capacities (control broilers and relaxed line), but not in broilers whose pulmonary vascular capacities had been selected to represent the higher (MP survivors, resistant line) or lower (susceptible line) extremes of the population.

Animals↗
PubMed1986

Seasonal variation in the total volume of Leydig cells in stallions is explained by variation in cell number rather than cell size.

Stereological methods were employed in two studies with stallions 1) to determine if seasonal variation in the total volume of Leydig cells is a function of cell number or cell size and 2) to characterize the annual cycle of the Leydig cell population. In the first study, numbers of Leydig cells were calculated for 28 adult (4-20 yr) stallions in the breeding or nonbreeding seasons from nuclear volume density (percentage of the decapsulated testicular volume), parenchymal volume (decapsulated testicular volume), and the volume of individual Leydig cell nuclei. The average volume of the individual Leydig cells was calculated as the total Leydig cell volume/testis (volume density of Leydig cells in the parenchymal volume times parenchymal volume) divided by the number of Leydig cells. The average volume of an individual Leydig cell varied within each season, but means were almost identical for the nonbreeding (6.94 +/- 0.61 picoliter) and breeding (6.91 +/- 0.45 picoliter) seasons. However, Leydig cell numbers per testis were 57% higher in the breeding season, which also had a 58% higher total volume of Leydig cells per testis. In the second study, the numbers of Leydig cells were determined for 43-48 adult horses in each 3-mo period for 12 mo. The number of Leydig cells per testis in May-July was higher (p less than 0.05) than in August-October or February-April, and higher (p less than 0.01) than in November-January. Thus, seasonal fluctuations in the total volume of Leydig cells in adult stallions is a function of the number of Leydig cells that cycle annually.

Animals↗
PubMed1998

A method to compare costs of drugs and supplies among anesthesia providers: a simple statistical method to reduce variations in cost due to variations in casemix.

BACKGROUND: Comparison of costs among anesthesia providers using "cost per case" does not adjust for variations in casemix (such as the type of procedure and patient condition). The authors propose an alternative method for comparing costs using the American Society of Anesthesiologists' Relative Value Scale (ASARVS) system, which incorporates basic units (for the procedure), modifier units (for the patient's physical condition), "other" units (such as for the placement of invasive monitors), and time units (proportional to the case duration). METHODS: Data were obtained from a series of 3,340 anesthetics performed at a tertiary hospital. Administered and discarded drug, supply, and fluid costs were used. RESULTS: Costs expressed as dollars per ASARVS unit had 54% less variability than costs expressed as dollars per case (P < 0.0001). Pearson correlations between demographic variables and cost per ASARVS unit ranged from -0.10 to 0.13. Total (e.g., quarterly) costs for simulated sets of cases were predicted within 0.0 +/- 2.3% by multiplying (1) their sum of units and (2) a like set of case's sum of costs divided by sum of units. CONCLUSIONS: Costs of anesthetic supplies and drugs of a case were more accurately reported as "cost per unit" than as "cost per case." This method of calculating the cost of anesthetic drugs and supplies has several applications, including (1) comparison of costs among anesthesia providers and (2) benchmarking costs among hospitals and anesthesia groups. By design, anesthesia providers' time is quantified by their ASARVS units. Together anesthesia costs (personnel, supplies, and drugs) are better reported as "cost per unit" than as "cost per case."

Adult↗
PubMed2000

Estimating the dose variation in a volume of interest with explicit consideration of patient geometric variation.

A method to measure the effects of internal organ motion and deformation and patient setup error on cumulative dose variation in a volume of interest is proposed. The method uses multiple CT scans and electronic portal images of a single patient to numerically simulate dose-volume effects over the entire course of the patient's external beam treatment. The results are expressed in the form of a novel dose-volume histogram, called an expected dose-volume histogram (EDVH).

Humans↗
PubMed1975

Diurnal variations in plasma corticosterone and growth hormone as corrlelated with regional variations in norepinephrine, dopamine and serotonin content of rat brain.

Statistically significant diurnal variations in plasma growth hormone (GH) were found to occur in handled male rats. Peak GH values (at miday) appeared to be inversely correlated with the diurnal peak of plasma corticosterone(CS) which occurred after the onset of darkness. Brain amines were examined in the following regions: cortex, striatum, septum, amygdala, pons, midbrain, and hypothalamus. Statistically significant diurnal cycles of serotonin (5-HT) concentration were found in the amygdala and midbrain, significant diurnal alterations in norepinephrine (NE) levels. Ultradian dopamine (DA) cycles were significant in all regions examined. Plasma GH changes were found to be directly correlated with midbrain and amygdala 5-HT levels and with DA levels of all areas except the amygdala, Plasma CS was found to be inversely correlated with striatal and cortical DA and with 5-HT levels of amygdala.

Amygdala↗
PubMed1986

The myocardial signature: absolute backscatter, cyclical variation, frequency variation, and statistics.

This paper studies the absolute myocardial backscatter as a function of the frequency and phase of the cardiac cycle. This was achieved by calibration of the ultrasonic instrumentation and the random diffraction process. We have discovered a first-order model in which the scattering from the myocardium is Rayleigh scattering with a cardiac cycle variation in the scattering cross section. Furthermore, the statistics are approximately those of a radio frequency waveform with two independent Gaussian components (Rayleigh envelope). Deviations from the first-order model suggest measurable fine structure related to myocardial ultrastructure. This model has profound effects on the choice of optimal radiation patterns and signal processing schemes for preparing diagnostic parameters (e.g., integrated backscatter).

Animals↗
PubMed2005

Age at onset of Huntington disease is not modulated by the R72P variation in TP53 and the R196K variation in the gene coding for the human caspase activated DNase (hCAD).

BACKGROUND: TP53 is an attractive candidate for modifying age of onset (AO) in Huntington disease (HD): The amino-terminus of the mutated huntingtin (htt) exon 1 translation product has functional properties which may affect critically the TP53 pathway in HD neurons. The pathogenic domain of mutant htt interacts with nuclear transcription factors, and it potentially modulates TP53-induced transcriptional events. A single nucleotide polymorphism (SNP) resulting in the R72P exchange in TP53 protein might modulate the variation in AO. In addition, also the R196K replacement in human caspase activated DNase (hCAD) may theoretically affect the AO. METHODS: We have genotyped the polymorphisms R72P and R196K in a well established cohort of 167 unrelated HD patients. RESULTS: The expanded CAG repeat explained 30.8% of the variance in AO. Adding the genotypes of the SNPs investigated did not affect the variance of the AO variance explained. CONCLUSION: In this replication study, no association was found explaining a significant amount of the variability in AO of HD thus contradicting a recent report.

Age of Onset↗
PubMed1996

Diurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity.

To study possible mechanisms controlling diurnal changes in corticosterone (CORT) levels, we tested the CORT responses to ACTH in the morning (AM) and evening (PM) in male Wistar and Sprague-Dawley rats. Rat ACTH-(1-39) or human ACTH-(1-24) (3.75-15 ng/rat) was given as an iv bolus or an intraarterial infusion to (un)anesthetized rats treated with dexamethasone (0.1-0.5 mg/kg, 2-6 h before ACTH). In all conditions studied, no AM/PM differences in CORT responses were found when ACTH was given in vehicle (pH 4.3-7). This contrasts with earlier studies in which ACTH was given in a strongly acid vehicle (pH 1-1.9). Administration of ACTH in such acid vehicle confirmed the reported AM/PM differences in CORT responses (P < 0.05). Because alterations in splanchnic nerve activity can modulate ACTH-induced CORT secretion, we studied the effect of splanchnic nerve transection (SPLNX) on the diurnal change in resting CORT levels in unilaterally adrenalectomized rats. SPLNX reduced resting CORT concentrations in the PM (approximately 50%; P < 0.05), but not in the AM. SPLNX did not abolish the acid vehicle-associated AM/PM differences in CORT responses to ACTH. We conclude that 1) diurnal variation in adrenal responsiveness to ACTH per se does not exist in this rat model; 2) the strongly acid vehicle interacts with ACTH-induced CORT secretion; 3) the PM rise in plasma CORT depends on the integrity of the sympathetic neural input to the adrenal gland.

Adrenal Glands↗
PubMed1978

Variation in dental occlusion and arches among Melanesians of Bougainville Island, Papua New Guinea. II. Clinical variation, geographic microdifferentiation and synthesis.

Patterns of geographic microdifferentiation for dental occlusion and the size and shape of the dental arches are described for 14 villages on Bougainville Island, Papua New Guinea. Occlusal variables, such as overjet, overbite, molar relationships, crowding or spacing, and malalignment vary less among villages than do arch length and width. Arch length and width decrease in size from north to south. The pattern of biological distance among villages for occlusal variables and arch size correspond poorly to anthropometric, linguistic, geographic and migrational distances. The value of occlusal variables and arch size for discriminating among populations, the biological interpretation of multivariate data and the objectives of research on geographic microdifferentiation are discussed.

Black People↗
PubMed2003

Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry.

Leptin is secreted primarily by the adipocytes and plays an important role in the regulation of food intake and energy expenditure. In addition to its adipostatic function, it has been demonstrated that leptin directly enhances stromal cell differentiation to osteoblasts, and since such precursor cells are potential targets for leptin, the latter could possibly mediate the relationship between obesity and bone mass and size. To address this question, we studied phenotypic and genetic correlations between the circulating levels of leptin and hand bone size (BS) and geometry (BG) of the radiographic hand in a healthy and ethnically homogeneous sample of pedigrees. We also attempted to evaluate to what extent potential leptin/BS/BG correlations are modified by an individual's obesity traits, specifically his/her BMI. Our research has shown that leptin, BMI and the corresponding bone measures are clearly inherited traits (0.46+/-0.11, 0.35+/-0.16, 0.62+/-0.12 and 0.51+/-0.09, respectively). The bivariate variance component analysis revealed very strong and significant genetic and environmental correlations between circulating leptin and BMI ( r(G)=0.86+/-0.09, r(E)=0.75+/-0.05, P<0.001). Furthermore, genetic correlations between leptin and hand bone characteristics proved inverse and statistically significant ( r(G)=-0.35+/-0.01 and -0.45+/-0.10 for BS and BG, respectively), while corresponding environmental correlations were low ( r(E)=-0.14+/-0.15 and -0.07+/-0.14) and they could be constrained to zero without significant deterioration of the model fit to the data ( P>0.10). However, despite the extremely strong relationship between leptin and BMI, we failed to detect phenotypic or genetic correlations between BMI and our two hand bone measures. Thus our study provided evidence that plasma leptin levels may be statistically significant predictor of hand bone size and geometry, and may play a physiological role in maintaining bone mass as well as in regulation of hand bone proportions.

Adolescent↗
PubMed2002

Combinatorial variation in coding and promoter sequences of genes at the Tri locus in Pisum sativum accounts for variation in trypsin inhibitor activity in seeds.

Cultivars of Pisum sativum that differ with respect to the quantitative expression of trypsin/chymotrypsin inhibitor proteins in seeds have been examined in terms of the structure of the corresponding genes. The patterns of divergence in the promoter and coding sequences are described, and the divergence among these exploited for the development of facile DNA-based assays to distinguish genotypes. Quantitative effects on gene expression may be attributed to the overall gene complement and to particular promoter/coding sequence combinations, as well as to the existence of distinct active-site variants that ultimately influence protein activity. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00438-002-0667-4.

Genetic Markers↗