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PubMed1977

Osteoclast counting in crista biopsies.

A description is given of a modified method of counting osteoclasts both per section area and also relative to the remaining trabeculae surface area in crista biopsies. The material consisted of normal individuals, patients with clinical osteoporosis, and patients with chronic renal failure undergoing haemodialysis. The number of osteoclasts in the biopsies from normal and osteoporotic individuals showed a normal distribution with the same mean. In the haemodialysis patients there was a marked skew distribution. In normal individuals, there was a significant decrease in the number of osteoclasts per section area with age, but this was not significant when calculated relative to the bone surface area.

Adolescent↗
PubMed1985

Quantitative analysis of ultradian luteinizing hormone secretion in normal men.

Basal pulsatile secretion of luteinizing hormone (LH) was studied in 8 healthy adult men and analyzed by mathematical and statistical techniques. LH pulses previously defined by semiquantitative criteria resisted the data-smoothing techniques employed. LH values were shown to have normal distribution in normal men. No correlation was found between mean LH and testosterone levels for the same individual. On the basis of analysis of variance it was shown that the individual variability and not the collection time is important in determining each isolated LH value. The LH levels were located within a particular channel for each individual for each collection time.

Activity Cycles↗
PubMedDate not supplied

Fetal hemoglobin biosynthesis in clonal cell culture.

Availability of the clonal erythropoietic cell culture methods provided a unique opportunity to study human hemoglobin biosynthesis under controlled conditions. Observations in several laboratories during the last four years fundamentally agree and can be summarized as follows: (1) Biosynthesis of fetal hemoglobin (HbF) is markedly augmented in cultures of adult erythropoietic precursors. (2) HbF biosynthetic capabilities inversely parallel the maturational stages of adult erythropoietic precursors in the marrow. (3) Adult circulating precursors (BFU-e) are also capable of augmented HbF biosynthesis in culture. (4) The pattern of Hb synthesized by fetal erythropoietic precursors corresponds very closely to the Hb compositions in the mature erythrocytes of the donors. (5) Burst-promoting activities (BPA) rather than erythropoietin (Ep) appear to stimulate HbF biosynthesis by augmentation of proliferation of precursors which are programmed to produce F cells in vivo. (6) Individual BFU-e are heterogeneously committed to HbF biosynthesis and their frequency distributions reveal normal distributions. (7) Increase in HbF production in culture is primarily due to increased production of the number of cells containing Hbf. (8) Commitment to produce HbF continues during subcolony formation in culture. (9)HbF synthesized in culture of adult and umbilical cord blood BFU-e reveal "adult" and "intermediate" values of G gamma:A gamma ratios, respectively. (1)) Frequency distributions of individual bursts varying in relative G gamma synthesis (G gamma/[G gamma+A gamma]) reveal unimodal distributions. (11) Positive correlations exist between gamma/(gamma+beta) and G gamma/(G gamma + A gamma) values in individual bursts.

Bone Marrow↗
PubMed1983

Microregional blood flow and high energy phosphates under conditions of high O2 supply in left ventricular subendocardium.

Blood flow and high energy phosphate (HEP) content were determined simultaneously in multiple microregions of the left ventricular subendocardium in 49 anaesthetized open-chest rabbits, to determine the relationship between the parameters during high O2 supply with hypercapnia and chromonar treatment. ATP and CP content were quantitated in quick-frozen hearts by fluorometry in 1-2 mg sites where perfusion was measured by H2 clearance employing bare-tipped platinum electrodes. Both hypercapnia and chromonar elevated subendocardial tissue perfusion approximately 30% and O2 supply 45% above control. Blood flow was normally distributed with either treatment, but was more homogeneous with hypercapnia. Neither treatment altered absolute levels of either HEP, but the variance of ATP was less than control. CP distribution was normal in both treatments. There was no significant linear correlation between blood flow and HEP under hypercapnia or chromonar treatment. We conclude that tissue HEP content is a variable not only dependent on O2 supply and blood flow, but also on the size of the ATP and CP pool and the energy demand of the local microregion. The variability of ATP in microregions of the rabbit subendocardium is reduced under conditions of high O2 supply.

Adenosine Triphosphate↗
PubMed1983

A simple method for the approximation of the behaviour of marker constituents in density-fractionated red blood cells by means of normalized cumulative distribution functions.

The present paper proposes a mathematical approach for the approximation of the relation between the concentration (or activity) of a cell constituent and the cumulative red cell distribution after density gradient centrifugation by means of normalized cumulative distribution functions (NCDF). With only one parameter (easily obtained on a programmable pocket calculator) and the mean concentration of the substance in the total red cell population this functional relation can be described in good approximation. The goodness of fit expressed by v2 (= square of correlation coefficient) to the experimentally obtained data is demonstrated for the cell constituents creatine (v2 = 0.85-0.97), RNA (v2 = 0.82-0.87) and G-6PD (v2 = 0.60-0.95). The method of NCDF is shown to be superior to an exponential function. It permits the estimation of a concentration (or activity) of a cell constituent for any chosen density-fractionated cell portion and thus gives information on the ratio of standardized portions of young: old cells.

Cell Separation↗
PubMed1995

Antiphospholipid antibodies in a healthy population: methods for estimating the distribution.

OBJECTIVE: To determine the distribution of antibodies to cardiolipin (IgG, IgM and IgA) in a healthy population. To classify subjects according to a cutpoint in order to determine what level of antibody measurement would yield 95% specificity. METHODS: Antiphospholipid (aPL) antibodies were measured using a conventional ELISA technique, with isotype specific antibody, to determine levels of IgG, IgM and IgA binding to cardiolipin. The subjects were 282 Red Cross blood donors, 82 undergraduate medical and nursing students, and 13 laboratory volunteers. RESULTS: The distribution of aPL antibodies measured in units of optical density is significantly skewed, while the distribution of aPL antibodies measured on the log scale is nearly symmetric. Neither distribution is normally distributed. There was no evidence that aPL antibodies differed significantly by age (up to age 50) or sex. We estimate the 90th, 95th, and 99th percentiles for IgG, IgM and IgA antibodies for the optical densities and binding indices. CONCLUSION: For 95% specificity we conclude that an adjusted IgG optical density above 0.386, an adjusted IgM optical density above 0.301, or an adjusted IgA optical density above 0.085 be considered positive.

Adult↗
PubMed1995

Statistical considerations regarding the use of ratios to adjust data.

OBJECTIVE: The use of ratios to adjust data (i.e. 'index' variables) is common in obesity and related research. The rationale for the use of ratios often seems to be the desire to control or eliminate the influence of the variable in the denominator. The purpose of this paper is to gain a greater appreciation of the statistical assumptions underlying ratios and their impact on data interpretation. RESULTS: We demonstrate the limitations of the indiscriminant use of ratios to adjust data. Specifically, we show that: (1) given linearity, a zero intercept between the numerator and denominator are necessary and sufficient conditions for a ratio to remove the confounding effects of the denominator; (2) seemingly minor departures from a zero intercept can have major consequences on the ratio's ability to control for the denominator; (3) the ratio of two normally distributed variables cannot be normally distributed, and this may violate the assumptions of subsequent parametric statistical analyses; (4) the use of ratios affects the error distribution of the data which may also violate the assumptions of subsequent parametric statistical analyses; (5) the use of ratios cannot easily take nonlinear effects between the numerator and denominator into account; (6) the use of ratios can introduce spurious correlations among the ratios and other variables; (7) the use of ratios can create interpretive difficulties. We also clarify that the mean of ratios is not necessarily equivalent to the ratio of the means of the numerator and denominator. Finally, we present and discuss formulae for the reliability of ratios and residuals. CONCLUSION: Because of the above issues, we question the indiscriminant use of ratios and advocate that investigators consider regression-based approaches as alternatives.

Body Constitution↗
PubMed1988

HLA DR and DQ distribution in normal human ocular structures.

HLA DR and DQ distribution was investigated in normal human ocular tissues, together with class I antigens and immunocompetent cell subsets, by immunofluorescence and immunoperoxidase procedures. In the anterior segment, our findings, consistent with those of previous reports, showed the wide distribution of class I antigens, specially in the corneal epithelium, while class II antigens were restricted to very rare cells scattered in the conjunctiva, the peripheral cornea and the stroma of the ciliary processes. Some non pigmented epithelial cells of the ciliary processes were HLA DR and DQ positive. In the posterior segment, class I antigens were abundantly represented in the choroid and the retinal layers. Few HLA DR and DQ positive cells were seen in the choroid, similar to those found in the anterior segment. Normal RPE did not react with any monoclonal antibody, but numerous cells located in the retina were strongly HLA DR and DQ positive, all around the blood vessels, and not at the sites of endothelial cells. The characterization of those cells, which could be hypothetized as pericytes needs further studies but suggests close relationships between neuroretina and the immune system. This study may provide insight in the implication of the immune system in many poorly understood ocular diseases.

Adult↗
PubMed2001

Statistical power of QTL mapping methods applied to bacteria counts.

Most QTL mapping methods assume that phenotypes follow a normal distribution, but many phenotypes of interest are not normally distributed, e.g. bacteria counts (or colony-forming units, CFU). Such data are extremely skewed to the right and can present a high amount of zero values, which are ties from a statistical point of view. Our objective is therefore to assess the efficiency of four QTL mapping methods applied to bacteria counts: (1) least-squares (LS) analysis, (2) maximum-likelihood (ML) analysis, (3) non-parametric (NP) mapping and (4) nested ANOVA (AN). A transformation based on quantiles is used to mimic observed distributions of bacteria counts. Single positions (1 marker, 1 QTL) as well as chromosome scans (11 markers, 1 QTL) are simulated. When compared with the analysis of a normally distributed phenotype, the analysis of raw bacteria counts leads to a strong decrease in power for parametric methods, but no decrease is observed for NP. However, when a mathematical transformation (MT) is applied to bacteria counts prior to analysis, parametric methods have the same power as NP. Furthermore, parametric methods, when coupled with MT, outperform NP when bacteria counts have a very high proportion of zeros (70.8%). Our results show that the loss of power is mainly explained by the asymmetry of the phenotypic distribution, for parametric methods, and by the existence of ties, for the non-parametric method. Therefore, mapping of QTL for bacterial diseases, as well as for other diseases assessed by a counting process, should focus on the occurrence of ties in phenotypes before choosing the appropriate QTL mapping method.

Algorithms↗
PubMed1996

On modeling longitudinal pulmonary function data.

In this paper we have discussed how random effects can be included in linear models to accommodate the analyses of longitudinal pulmonary function (REM) and categorical (GEE) types of respiratory data. It was suggested that REM analysis be used for continuous observations that are normally distributed or that can be transformed to have near normal distributions and that GEE be used for categorical or non-normally distributed data. Two methods were reviewed, parallel plots and within-subject regression fitting, which can assist in determining the order of random effects to be included. Using a sample data set of longitudinal FEV1 measures, we outlined the steps that should be taken for selecting the within-subject error structure, the order of random effects, elements of the between-subject covariance matrix, and selecting the most important or predictive fixed effects. Lastly, two different types of residual plots were illustrated, conditional and marginal, which can be used to detect outliers and possible trends from underfitting the observed data. All options discussed herein are not available in all the programs currently available for doing the REM and GEE modeling.

Computer Simulation↗
PubMedDate not supplied

Latent trait standardization of the benzodiazepine dependence self-report questionnaire using the Rasch scaling model.

The aim of the present study was to obtain standardized scores that correspond with the raw scores on the four Rasch scales of the Benzodiazepine Dependence-Self Report Questionnaire (Bendep-SRQ). The eligible normative group for standardization of the Bendep-SRQ scales consisted of 217 general practice (GP) patients, all using benzodiazepines. Two standardization methods were used and compared: "classical standardization," which transforms raw scores into standard scores on the unit normal distribution, and "latent trait standardization," which transforms raw scores into latent trait scores. The latter requires the Rasch model with the additional assumption of a normally distributed latent trait, which held true for the scales "problematic use," "lack of compliance," and "withdrawal," but not for "preoccupation." The observed unequal item spacing on the "preoccupation" scale was hypothesized to induce a response tendency of nondeviation, causing a local violation of the assumption of a normally distributed latent trait. Nevertheless, comparison of the results of the two standardization methods revealed such a high degree of resemblance, that latent trait standardization could be used for "preoccupation" just as well as classical standardization. The presented standard scores and corresponding percentile ranks make raw Bendep-SRQ scores clinically interpretable in relation to the normative GP sample. Incorporation of the Rasch scaling methodology into the development of the Bendep-SRQ marks the adoption of the item response theory in the field of applied test methodology. In this process, it appears that equal item spacing has to be taken into account to prevent local violations of the Rasch model with the additional assumption of a normally distributed latent trait.

Adolescent↗
PubMedDate not supplied

Theophylline tissue partitioning and volume of distribution in normal and dietary-induced obese rats.

Theophylline tissue distribution was examined in normal and dietary-induced obese Sprague-Dawley rats following constant infusion to steady-state. Theophylline distribution was linear among all tissues and uniform throughout body water spaces. The apparent distribution coefficient, Kd,app (tissue: serum concentration) ranged from 0.55 to 0.69 for all lean tissues, but averaged 0.08 in fat. Obese rats had a consistently higher Kd,app in several tissues including muscle, heart, and liver caused by reduced (from 42 to 33 per cent) serum protein binding. Muscle slice uptake of theophylline from buffer was similar in normal and obese animals, confirming serum binding as the factor altering Kd,app. The conceptual and applied bases of calculating and measuring steady-state volume of distribution (VSS) by various methods were explored. The physiological perturbations of theophylline VSS by obesity can be accounted for by alterations in serum binding and expanded lean and fat tissue masses, rather than changes in tissue partitioning.

Animals↗
PubMed1988

Simulated percentage points for the null distribution of the likelihood ratio test for a mixture of two normals.

We find the percentage points of the likelihood ratio test of the null hypothesis that a sample of n observations is from a normal distribution with unknown mean and variance against the alternative that the sample is from a mixture of two distinct normal distributions, each with unknown mean and unknown (but equal) variance. The mixing proportion pi is also unknown under the alternative hypothesis. For 2,500 samples of sizes n = 15, 20, 25, 40, 50, 70, 75, 80, 100, 150, 250, 500, and 1,000, we calculated the likelihood ratio statistic, and from these values estimated the percentage points of the null distributions. Our algorithm for the calculation of the maximum likelihood estimates of the unknown parameters included precautions against convergence of the maximization algorithm to a local rather than global maximum. Investigations for convergence to an asymptotic distribution indicated that convergence was very slow and that stability was not apparent for samples as large as 1,000. Comparisons of the percentage points to the commonly assumed chi-squared distribution with 2 degrees of freedom indicated that this assumption is too liberal; i.e., one's P-value is greater than that indicated by chi 2(2). We conclude then that one would need what is usually an unfeasibly large sample size (n greater than 1,000) for the use of large-sample approximations to be justified.

Biometry↗
PubMed2002

Characterization of the distribution of the cocaine priming threshold and the effect of SCH23390.

The cocaine-induced reinstatement (priming) of cocaine self-administration occurs when the cumulative concentration of cocaine reaches a threshold level that we have previously termed the cocaine priming threshold. The present studies used a modified procedure to measure the cocaine priming threshold over 4-8-month periods in individual rats. The values for the priming threshold varied between days but there was no evidence of a systematic change in the priming threshold over time, indicating that neither tolerance nor sensitization occurred. The frequency distribution of the priming threshold was significantly different from a normal distribution but was not significantly different from a log-normal distribution. Therefore, the geometric mean with its associated variance estimates, but not the arithmetic mean, appropriately describe the distribution of the cocaine priming threshold. The estimate of the geometric mean value of the priming threshold for this group of Sprague-Dawley rats was 284 (CI(95): 234-344) microg/kg of cocaine. The log-normal distribution of equieffective doses of cocaine is typical of agonist-induced pharmacological responses. In the presence of the D(1) dopamine receptor-selective antagonist SCH23390, the geometric means of the cocaine priming threshold were significantly increased in a dose-dependent manner, implying a role for D(1) dopamine receptors in the priming response. This technique provides a quantitative method for the measurement of antagonist-induced increases in the cocaine priming threshold.

Algorithms↗
PubMed2001

Hair density, hair diameter and the prevalence of female pattern hair loss.

BACKGROUND: Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated. OBJECTIVES: To determine the prevalence of female pattern hair loss and to relate the clinical findings to hair density and hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented to a general dermatology clinic with complaints unrelated to hair growth (the unselected sample). A second group of 47 women referred with typical female pattern hair loss was included in analyses of the relationships between hair density, hair diameter and the clinical diagnosis. Hair density was measured using a photographic method. In each subject the major and minor axis diameters were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged under 50 years were diagnosed as having female pattern hair loss, increasing to 38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/- 61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70 years. Hair density showed a normal distribution in the unselected sample. Most women classified as having female pattern hair loss had hair densities within the lower half of the normal distribution. The perception of hair loss was determined mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair density between women classified as having Ludwig I hair loss and the no hair loss group, which was partly accounted for by differences in mean hair diameter (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all diameters. CONCLUSIONS: Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.

Adolescent↗
PubMed2000

Expression of the platelet-activating factor receptor in human spermatozoa: differences in messenger ribonucleic acid content and protein distribution between normal and abnormal spermatozoa.

OBJECTIVE: To determine the expression and distribution of the platelet-activating factor (PAF) receptor in normal and abnormal specimens of human spermatozoa. DESIGN: Prospective analysis of membrane-bound PAF receptors by immunofluorescence and PAF receptor messenger RNA by quantitated reverse transcription-polymerase chain reaction in normal and abnormal spermatozoa. SETTING: University-based reproductive genetics laboratory. PATIENT(S): Men undergoing routine semen analysis. INTERVENTION(S): Normal and abnormal spermatozoa were exposed to rabbit anti-PAF receptor antibody, fluorescein isothiocyanate-conjugated goat anti-rabbit antibody, and fluorescent microscopy or subjected to RNA isolation by acid-phenol extraction and quantitated (MIMIC Construction Kit [Clontech Laboratories, Inc., Palo Alto, CA]) reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Fluorescent intensities at six locations along spermatozoa (end piece, principal tail, midpiece, neck, proximal head, and acrosomal region) and PAF receptor expression (messenger RNA) levels. RESULT(S): Immunofluorescence demonstrated a significant difference in PAF receptor distribution between normal and abnormal human spermatozoa, specifically at the neck region. Additionally, abnormal spermatozoa were found to have statistically significantly more PAF receptor messenger RNA than normal spermatozoa. CONCLUSION(S): Platelet-activating factor receptor expression and distribution are significantly altered in abnormal spermatozoa and this may be the result of some defect in gene transcription.

Animals↗
PubMed1997

Factors determining the size frequency distribution of beta-amyloid (A beta) deposits in Alzheimer's disease.

The size frequency distributions of discrete beta-amyloid (A beta) deposits were studied in single sections of the temporal lobe from patients with Alzheimer's disease. The size distributions were unimodal and positively skewed. In 18/25 (72%) tissues examined, a log normal distribution was a good fit to the data. This suggests that the abundances of deposit sizes are distributed randomly on a log scale about a mean value. Three hypotheses were proposed to account for the data: (1) sectioning in a single plane, (2) growth and disappearance of A beta deposits, and (3) the origin of A beta deposits from clusters of neuronal cell bodies. Size distributions obtained by serial reconstruction through the tissue were similar to those observed in single sections, which would not support the first hypothesis. The log normal distribution of A beta deposit size suggests a model in which the rate of growth of a deposit is proportional to its volume. However, mean deposit size and the ratio of large to small deposits were not positively correlated with patient age or disease duration. The frequency distribution of A beta deposits which were closely associated with 0, 1, 2, 3, or more neuronal cell bodies deviated significantly from a log normal distribution, which would not support the neuronal origin hypothesis. On the basis of the present data, growth and resolution of A beta deposits would appear to be the most likely explanation for the log normal size distributions.

Aged↗
PubMed1996

Genetic contributions to LDL-C, Apo-B and LDL-C/Apo-B ratio in a sample of Israeli offspring with a parental history of myocardial infarction.

One hundred and forty sibships consisting of 280 brothers and 256 sisters with a family history of myocardial infarction were investigated for the possible involvement of a major gene in the determination of LDL-C, Apo-B and LDL-C/ Apo-B ratio (as a surrogate for LDL subclasses). The mean ages were 29.5 years (range 15-48) and 29.2 years (range 15-47), for brothers and sisters, respectively, and values were initially adjusted for age effects through multiple regression analysis. Results from commingling analysis indicated that for LDL-C a single normal distribution fitted the data as well as a mixture of two distributions. For Apo-B, a mixture of two normal distributions fitted the data significantly better than a single distribution (chi 2 = 7.8, df = 2, p = 0.02). For LDL-C/ Apo-B ratio a mixture of three normal distributions fitted the data significantly better than two distributions (chi 2 = 9.2, df = 2, p = 0.01). A regression analysis applied to the logarithm of the sex- and age-adjusted mean and variance within sibship, showed no indication of a major gene involvement for LDL-C. For Apo-B and LDL-C/Apo-B ratio, there existed, however, significant linear relationships between the logarithmically transformed means and within sibship variances which support the involvement of major genes. In addition, the Bartlett test applied to the data of within-sibship variances also rejected the null hypothesis of multifactorial transmission for Apo-B and LDL-C/Apo-B ratio (p < 0.0001). Lastly, the results from sib-pair linkage analyses provided significantly positive evidence for linkage between ApoB levels and the Apo-B XbaI restriction site.

Adolescent↗