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PubMed1996

[Normal values of calcium and oxalate excretion in children].

Aim of the study was to establish normal values for calcium/creatinine (Ca/cr) and oxalate/creatinine (Ox/cr) ratio in infants and children. Urine probes of 416 healthy children (25 infants aged 1-7 days and 391 children aged 1 month-14.5 years) were analysed. Oxalate was measured by ion-chromatography. Urinary Ca2+/cr was normally distributed, Ox/cr had log-normal distribution. Ca/cr was the lowest in the first days of life, the highest between 7 month-1.5 years (mean +/- SD = 0.39 +/- 0.28 mmol/mmol), a slight decrease could be observed until 14 years (0.34 +/- 0.18). The highest Ox/cr values were measured during the first month of life (geometric mean/range/ = 133 /61-280 mmol/mmol/), followed by gradual decrease until 14 years (25/6-73/). The measurement of Ca2+/cr and Ox/cr in first morning urine samples is suitable for screening of hypercalciuria and hyperoxaluria. The interpretation of the values requires age specific reference values. Both calcium and oxalate determinations should be the part of the evaluation of patients with hematuria, hypercalciuria or nephrolithiasis.

Adolescent↗

PubMed1982

The multivariate reference range: an alternative interpretation of multi-test profiles.

To test the utility of multivariate interpretation of laboratory data, we developed a multivariate reference range based of the Mahalonobis distance (D2) measure. Results for 20 commonly measured clinical chemistry analytes were collated for two sophomore medical-school classes (118 and 143 individuals in 1979 and 1980, respectively). The data for each test were examined for fit to a gaussian (normal) distribution by using a Kolmogorov--Smirnov test. Those results discovered to have a non-normal distribution were "normalized" by used the of a two-stage log-exponential transform. After this transformation, the D2 distance for each student group followed the expected chi-square distribution with 20 degrees of freedom. For each student's D2 distance an associated chi-square percentile was derived, and a cutoff percentile (95%) was selected to differentiate multivariately the "normal" from "abnormal" test results. Whereas more than two-thirds of the students had univariate test abnormalities, fewer than 7% had abnormal multivariate D2 scores. Analysis showed that the multivariate reference range could sensitively detect minor variations of multiple analytes but could also be quite insensitive to highly abnormal results for a single analtye. The multivariate approach has promise as a tool to avoid unnecessary followup of falsely abnormal test results, but further study and validation in a clinical setting are required.

Adult↗

PubMed1997

Neuronal and macrophagic nitric oxide synthase isoforms distribution in normal rat retina.

A detailed study about the distribution of nitric oxide synthase (NOS) isoforms, neuronal NOS (nNOS) and macrophagic NOS (mNOS), in normal rat retina was performed using immunocytochemistry by employing specific antibodies. The nNOS immunocytochemistry showed immunoreactive amacrine cells, fibres in inner and outer plexiform layers (IPL and OPL) and an immunostained band corresponding to inner photoreceptor segments (IPS). This was in agreement with NADPH-d histochemical results. mNOS immunoreactivity was found in cell somas localized in both, inner nuclear layer (INL) and ganglion cell layer (GCL), in slender Müller cell processes along IPL and GCL and also in the band corresponding to IPS. A different distribution of nNOS and mNOS was found in rat retina although both isoforms of NOS are co-localized in IPS.

Animals↗

PubMed1998

Detection and utilization of single genes without DNA assays.

Quantitative traits are often assumed to be controlled by a large number of loci that each have a small effect. Under this assumption, the distribution of genotypic and phenotypic values can be adequately modeled by a multivariate normal distribution. Thus, most genetic analyses are based on mixed linear models. Evidence is accumulating, however, for the presence of loci that have large effects on traits of economic importance. If the genotypes for such loci can be observed without error, then--conditional on these observed genotypes--genotypic and phenotypic values follow a multivariate normal distribution, and data from very large pedigrees can be analyzed using a mixed linear model that includes the genotypic effects for these loci as fixed effects. However, when the major genotype is not observed, the genotypic and phenotypic values follow a mixture of multivariate normal distributions, and analyses based on fitting a mixed linear model may not be optimum, especially for populations undergoing selection and nonrandom mating. Several approaches are discussed for the genetic analysis of data when the major genotypes are not known.

Algorithms↗

PubMed1994

Graded changes in the response of individual human basophils to stimulation: distributional behavior of early activation events.

These studies examine the distribution of single-cell responses in basophil preparations in the context of four events that may be associated with early activation by anti-immunoglobulin E (IgE) antibody and the bacterial peptide fMet-Leu-Phe (fMLP). In general, we measured the single-cell response distributions after challenge with a concentration of stimulus that resulted in an optimal response and compared this with the distribution that occurred after challenge with suboptimal concentrations of the same stimulus. The elevation in cytosolic calcium, as detected in Fura-2-labeled basophils, after challenge with anti-IgE or fMLP showed graded characteristics in that the distributions were unimodal under conditions of optimal or suboptimal challenge with little skewing from a normal distribution. Similarly, the up-regulation of the cell surface adhesion molecule CD11b, as determined by flow cytometry, showed graded unimodal increases after challenge with anti-IgE antibody at optimal and suboptimal concentrations. In addition, stimulation of basophils led to increased F-actin polymerization. After challenge with an optimal concentration of anti-IgE antibody, the F-actin content of basophils increased to a maximum between 10 and 15 min and returned to near prechallenge levels by 60 min. There was a close correlation between the maximum increase in F-actin content and histamine release regardless of the stimulus; anti-IgE antibody, fMLP, and phorbol ester (PMA) responses lay on the same regression line. The single-cell F-actin polymerization distributions were also unimodal and graded according to the magnitude of the histamine release response. During measurements of the calcium response under the microscope we noted that basophils underwent significant changes in morphology after challenge with any stimulus. These changes were related to both degranulation and nondegranulation events and could be quantitated by a series of image-processing algorithms, which are presented. The kinetics of the morphological change, measured as a change in cell perimeter, paralleled degranulation. Single-cell distributions of the morphologic changes were also unimodal under conditions of both optimal and suboptimal stimulation. Therefore, no evidence of all-or-nothing responses could be observed in the context of these four early activation events. In general, the response distributions resembled normal distributions at both optimal and suboptimal levels of stimulation, which indicated that single basophils responded in a graded manner.

Basophils↗

PubMed1995

A nonparametric approach for mapping quantitative trait loci.

Genetic mapping of quantitative trait loci (QTLs) is performed typically by using a parametric approach, based on the assumption that the phenotype follows a normal distribution. Many traits of interest, however, are not normally distributed. In this paper, we present a nonparametric approach to QTL mapping applicable to any phenotypic distribution. The method is based on a statistic ZW, which generalizes the nonparametric Wilcoxon rank-sum test to the situation of whole-genome search by interval mapping. We determine the appropriate significance level for the statistic ZW, by showing that its asymptotic null distribution follows an Ornstein-Uhlenbeck process. These results provide a robust, distribution-free method for mapping QTLs.

Animals↗

PubMed1983

The relationship between pressure and flow in the normal pig renal pelvis. An experimental study of the range of normal pressures.

The renal pelvis pressure flow relationship of 40 normal pig upper urinary tract was investigated. During standardized studies it was disclosed that the resting pressure has a normal distribution with wide 95% confidence limits (0.3-14.7 cmH2O). When perfusion was introduced, pelvic pressure increased, the normal distribution was lost, and the 95% confidence limits were broadened to more than 30 cmH2O. A normal distribution was regained at higher flow rates. The mean increment beyond 8 ml/minute was small, only 3.7 cmH2O from 8 ml/minute to 20 ml/minute. The wide variation found in pressure responses to high flow rates and the spread of pressures at higher flow rates imply major difficulties in distinguishing, between normal and abnormal pressure flow relationships in renal pelvis.

Animals↗

PubMed2000

The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

Previous reports indicate that the mRNA for the cardiac isoform of the voltage-gated L-type calcium channel (alpha(1C)) is elevated in colon cancer. The aim of these experiments was to verify that the mRNA for alpha(1C) was significantly increased in tumors of two separate populations of patients when compared to normal adjacent mucosa. The second aim was to measure the distribution of alpha(1C) using immunocytochemistry in normal human colon and in colon cancer and to determine what might regulate the channel expression. Biopsies were taken from patients with various stages of colon cancer and nearby normal mucosa were used as control. RNA was prepared and mRNA level measured by semiquantitative reverse transcriptase-polymerase chain reaction. The mRNA of the calcium channel was compared with other markers including beta-actin. The mRNA for alpha(1C) was increased significantly in colon cancers compared to nearby adjacent mucosa. Using confocal microscopy alpha(1C) was localized mainly at the apical membrane in the surface epithelium of normal human colon with less distribution on the lateral and basal membranes. The channel was localized on the lateral and basal membranes in crypt cells. Calcium channel localization appeared to be nearer nuclei in colon cancer samples, in part because of the smaller size of the cells. Likewise, cultured Caco-2 and T84 cells showed a membrane distribution. Western blotting indicated that alpha(1C) protein was increased in nonconfluent cultures of colonic carcinoma cells compared to confluent cells and immunocytochemistry confirms that there is more calcium channel protein in cells that are nonconfluent. We conclude that the increase in mRNA of alpha(1) subunit of the cardiac isoform of the L-type calcium channel may be a useful marker of colon cancer compared to other markers because the increase is large and this increase can be documented on small samples using a simple semiquantitative reverse transcriptase-polymerase chain reaction. We found that alpha(1C) protein is increased when colonic cells are nonconfluent or dividing which may account for the increase in cancer.

Blotting, Western↗

PubMed2001

Dynamic finite-size scaling of the normalized height distribution in kinetic surface roughening.

Using well-known simple growth models, we have studied the dynamic finite-size scaling theory for the normalized height distribution of a growing surface. We find a simple functional form that explains size-dependent behavior of the skewness and kurtosis in the transient regime, and obtain the transient- and long-time values of the skewness and kurtosis for the models. Scaled distributions of the models are obtained, and the shape of each distribution is discussed in terms of the interfacial width, skewness, and kurtosis, and compared with those for other models. Exponents eta(+) and eta(-), which characterize the form of the distribution, are determined from an exponential fitting of scaling functions. Our detailed results reveal that eta(+)+eta(-) approximately 4 for a model obeying usual scaling in contrast to eta(+)+eta(-)<4 with eta(-)=1 for a model exhibiting anomalous scaling as well as multiscaling. Since we obtain eta(+)+eta(-) approximately 4 for a model exhibiting anomalous scaling but no multiscaling, we conclude that the deviation from eta(+)+eta(-) approximately 4 is due to the presence of multiscaling behavior in a model.

Journal Article↗

PubMed2001

Melatonin production in healthy infants: evidence for seasonal variations.

The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy full-term infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8- (n = 317) and 16-wk-old (n = 93) infants over the nocturnal period (19:00-08:00 h). In addition, 6SMT was assessed in 8-wk-old (n = 35) healthy infants over the entire 24-h period. 6SMT was determined by an ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations with (mean +/- SD) 61 +/- 18% of the daily production excreted during the nocturnal period regardless of season. The nocturnal 6SMT values in the entire cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov test). A normal distribution was obtained using a natural base logarithmic (ln) transformation of the data. The normal range (2.5-97.5 percentile of the ln 6SMT excretion per night) was thus defined as 4.66-8.64 (106-5646 ng/night) for 8-wk-old and 5.19-9.67 (180-15,820 ng/night) for 16-wk-old infants. A significant effect of the month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p < 0.002) with maximal levels produced by infants born in June (summer solstice) and minimal excretion in infants born in December (winter solstice). Short-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p = 0. 01). The seasonal variations were no longer present at 16 wk of age. No effect of breast-feeding at the time of sampling on seasonality of 6SMT was found. Normal ranges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 and 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor for child development. The strong effect of season on the normal excretion of nocturnal 6SMT at 8 but not 16 wk of age suggests prenatal influence of the photoperiod on the ontogeny of melatonin.

Analysis of Variance↗

PubMed2003

Glutathione distribution in normal and oxidatively stressed cells.

Glutathione is the most abundant of the low-molecular-mass molecules that provide reducing equivalents that protect cells from oxidative stress. We used immunoelectron microscopy to investigate glutathione distribution in normal and oxidatively stressed cells. Here, for the first time, we show that reduced glutathione is distributed relatively evenly throughout the cell, with the exception of the lumen of the rough endoplasmic reticulum, where little is detected. Oxidant exposure, either to 0.1 mM diamide or ethycrinic acid, eventually caused cellular glutathione depletion. However, despite entering a cell within seconds, both oxidants required hours to dramatically affect glutathione levels in the majority of cells in a population. Interestingly, cells within a homogeneous cell line population lost glutathione at different rates. Structural changes associated with oxidative stress, such as increased vacuolization and membrane blebbing, were correlated with glutathione depletion. Oxidant-exposed cells that appeared normal had higher glutathione levels than those within the same population that appeared stressed. The last reserves of cellular glutathione were found within mitochondria.

Cell Line↗

PubMed1993

A new look at the limits of detection (LD), quantification (LQ) and power of definition (PD)

The relationship between the concentration of the analyte and the imprecision of an analytical method can be displayed by the precision profile in which the coefficient of variation (relative standard deviation) is plotted against the concentration of the analyte. The function of the curve of the profile and its confidence limits can easily be assessed by a computer program developed by W.A. Sadler & M.H. Smith (Clin. Chem. 36 (1990), 1346-1350). For the assessment of limits of detection and of quantification the following procedure is proposed: The lower (and upper) limit of the measuring interval is defined by the point at which an acceptable CV-line intersects the confidence limit. If, in the variance function one sets the concentration to zero, the normal distribution of the random errors of the blank will result. The mean of the next adjacent normal distribution, following the variance formula and overlapping the "zero-distribution" by a defined amount, represents the limit of detection. Within the described measuring interval, or within a fraction of it, one might construct overlapping normal distributions in an analogous manner. Their number represents the "power of definition" (PD) (instead of the "analytical sensitivity"), which also depends on the concentration of the determinand according to the variance function. We tested these hypotheses by a comparison of two methods for the determination of cyclosporin A (ciclosporin, INN). Our results demonstrate that the data of the lower limits of the measuring interval and of the limit of detection agree well with data from the literature obtained in extensive interlaboratory surveys.

Algorithms↗

PubMed1978

Growth related changes in the content of heparin and 5-hydroxytryptamine of mast cells.

Heparin and 5-hydroxytryptamine (5-HT) were quantitated cytofluorometrically in individual mast cells from rats of various ages and body weights. Mast cells were studied in animals 35-200 days of age (150-575 g) representing a period of major body growth and about a quarter of the life span of the rat. Mast cell numbers as well as the content of both heparin and 5-HT in the mast cells was found to be strongly related to body weight and age of the animals. The number of mast cells increased about 3.5 times, the content of heparin in mast cells was doubled and the content of 5-HT increased at least three times during the growth period studied. There were great variations in the content of heparin and 5-HT within the cell populations of both young and old animals. The heparin content in the mast cell populations appeared to be either approximately normally distributed or slightly positively skewed. The skewness was not as marked as in a log-normal distribution. The 5-HT distribution profiles, on the other hand, were more strongly positively skewed. Except in the youngest age group, the 5-HT content appeared to be log-normally distributed within the mast cell population. A strong positive correlation was found between the median values of 5-HT and heparin content in the mast cell populations of growing rats.

Aging↗

PubMed1999

Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy.

OBJECTIVE: To test the hypothesis that changes in the normal regional distribution of potassium and calcium currents contribute to the different regional changes in action potential duration in isoprenaline-induced hypertrophy in rats. METHODS: Hypertrophy was elicited in rats by seven daily injections of isoprenaline. Left ventricular myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial tissue. Membrane currents were measured using the whole-cell patch-clamp technique at 35 +/- 1 degrees C. RESULTS: Cell membrane capacitance was similar in all three groups and was increased by 17% in hypertrophy (P < 0.001, t-test). Changes in the calcium-independent transient outward current (Ito1) density in hypertrophy were different in the three regions (P < 0.05, ANOVA). Ito1 was reduced in sub-epicardial (control, 23.4 +/- 2.0 pA pF-1; hypertrophy, 15.8 +/- 1.5 pA pF-1, P < 0.01 ANOVA) and in mid-myocardial myocytes (control, 24.0 +/- 2.8 pA pF-1; hypertrophy, 13.8 +/- 1.3 pA pF-1, P < 0.01 ANOVA) and was not significantly altered in sub-endocardial myocytes (control, 8.5 +/- 0.7 pA pF-1; hypertrophy, 7.4 +/- 1.8 pA pF-1). Steady-state background current density was reduced in hypertrophy (P < 0.05, ANOVA). The regional difference in steady-state background current in control hearts (P < 0.05, ANOVA) was altered in hypertrophy. Calcium current (ICa) density was similar in the three regions studied in both control and hypertrophied hearts. ICa was reduced in hypertrophy (P < 0.05, ANOVA). CONCLUSION: The normal regional differences in Ito1 are reduced, in steady-state background current are altered and in ICa are unchanged in catecholamine-induced hypertrophy in the rat left ventricle. These data may in part explain the reduction in the normal regional differences in APD observed in hypertrophy.

Action Potentials↗

PubMed2000

Normal and abnormal day-to-day variability of urinary albumin excretion in control and diabetic subjects.

Urinary albumin excretion (UAE) is very variable from day to day. This variability, more or less potent, might by itself have a patho-physiological significance. We analyzed day-to-day UAE in 207 elderly (60-75 years) inpatients (134 with and 73 without diabetes mellitus) attending the department of internal medicine of the Angers University hospital. Twenty-four-hour urine was collected 3 times during a 5-10 day hospitalization period. One-hundred-fifty-one patients (73%) displayed normoalbuminuria (UAE<30 mg/24 h in 2 or 3 measures) while 56 patients (27%) had microalbuminuria (UAE within 30-300 mg/24 h in 2 or 3 measures). As the raw data of UAE was not normally distributed, we transformed UAE into the variable z=log (log (k + UAE)) where k is an integer and looked for a k value for which z might be normally distributed. We found that z was actually normally distributed for k=2. Mean value and coefficient of variation of z in the 3 measurements were used to define the level and the temporal intra-individual variability of UAE. Expressed in term of z, the day-to-day intra-individual variability of UAE showed a potent change (from large variability to small variability) at the particular level z=1.25, corresponding to UAE=30.8 mg/24 h. This value is precisely the level currently used to define microalbuminuria in diabetic subjects. It is remarkable that the day-to-day variability of UAE collapses when UAE crosses the level which has been used to define microalbuminuria.

Aged↗

PubMed1982

In vitro modulation of the distribution of normal human plasma high density lipoprotein subfractions through the lecithin: cholesterol acyltransferase reaction.

The effect of the lecithin: cholesterol acyltransferase reaction on the chemical composition, morphology and distribution of normal human plasma high density lipoprotein (HDL) subclasses was studied in vitro. Incubation of plasma in the presence of polyenephosphatidylcholine (PPC) resulted in a 45 +/- 11% (n = 6) decrease in unesterified cholesterol after 20 h. This effect was abolished by prior heating of the plasma at 56 degrees C or by the addition of diisopropyl fluorophosphate (DIFP). Plasma triacylglycerol levels were constant. Analysis of the plasma lipoproteins by zonal ultracentrifugation and isopycnic equilibrium banding revealed a bimodal distribution of the HDL of native plasma and both heat-inactivated or DIFP-treated samples with peak maxima at d = 1.084 g/ml and d = 1.110 g/ml. Following the lecithin:cholesterol acyltransferase reaction essentially all of the HDL material had flotation characteristics typical of HDL2. The peak maximum was d = 1.086 g/ml. There were no apparent changes in the distribution of the lipoproteins of d less than 1.063 g/ml. The newly formed HDL were poor in PC and unesterified cholesterol but rich in cholesteryl ester, sphingomyelin and lyso-PC. The HDL apolipoprotein pattern was unaltered. HDL morphology was not affected by the lecithin:cholesterol acyltransferase reaction. Similar results were obtained in the absence of PPC. However, under these conditions the total phospholipid content of the HDL was reduced and lyso-PC was not demonstrable as a product of the lecithin:cholesterol acyltransferase reaction after 20 h. The results are interpreted to indicate that lecithin:cholesterol acyltransferase is involved in the transformation of HDL3 into HDL2.

Female↗

PubMed1976

An approach to numerical identification of bacterial species.

The distribution of matching coefficients (M values) for strains of a species to their own 'hypothetical mean organism' (HMO) or to HMO patterns of other organisms was studied in 754 strains of 19 mycobacterial species, testing for 91 discriminating characters. The M values of strains of a species to the HMO of other species usually showed a normal distribution, and M values to their own HMO showed either a normal distribution of a binomial distribution, depending on the mean of M values. If the number of test characters was large, the binomial distribution usually resembled the normal distribution. After preparation of the HMO for every species and estimation of the mean of the M values (M) and the standard deviation (s), numerical identification could be carried out: if a test strain had an M value to the HMO of species chi that only fell within the range (M +/2s) for species chi, the strain would be identified as a member of that species.

Bacteria↗

PubMed1986

Relation between signs and symptoms in Paget's disease of bone.

The relation between signs and symptoms of Paget's disease of bone was studied in 180 patients consecutively submitted for treatment. In these patients 826 lesions were identified by scintigraphy. The intensity of scintigraphic uptake was correlated with long-term calcium uptake in bone. The frequency distribution of lesions over the patients was compatible with a 65 per cent chance of local disease once the patient had been exposed to an extraneous agent. The spatial distribution within a skeleton was related to the local density of the osteoclast population. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Within lesions, increases in numbers of osteoclasts and osteoblasts were proportional and these too had a log-normal distribution. Increases of alkaline phosphatase levels and hydroxyproline excretion were closely related and reflected anatomical spread on the one hand and local activity on the other. They were also closely correlated with overall calcium fluxes. It was shown that alkaline phosphatase is the more sensitive and hydroxyproline the more accurate of the biochemical signs. Maximum values, corresponding to total skeletal disease, were approximately 25 times the upper limit of normal. Equilibrium between bone formation and resorption was not always maintained. There were, indeed, wide variations of urinary calcium, which were significantly related to the difference between bone formation and resorption, but the extracellular calcium homeostasis was generally maintained. This may explain the frequent occurrence of normocalcaemic and hypercalcaemic hyperparathyroidism. The hypercalciuria constitutes an additional risk for urolithiasis in men. The most frequent complaint was pain (86 per cent). Extent of lesions was important, but a major decisive factor was the specific nature of the bone affected. The findings allowed assessment of the relative importance of the various signs, symptoms and locations as criteria of disease severity and as indications for treatment.

Adult↗