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PubMed1978

A comparative study of the buoyant density distribution of normal and malignant lymphocytes.

Density distribution patterns of normal and malignant lymphocytes were compared following centrifugation to equilibrium on linear density gradients. For normal lymphocytes differences in the distribution patterns were observed between: (1) B and T cells, (2) central and peripheral cells, and (3) resting and activated cells. The findings suggested that cell density is determined by cell lineage the degree of differentiation and the stage of functional activation. Marked differences in the density distribution profiles were also observed among certain types of morphologically distinguishable lymphoproliferations. To some extent density analyses enabled the discrimination between CLL, follicular lymphomas and lymphoblastic lymphomas as well as between O-ALL and T-ALL. Density profiles of malignant lymphocytes failed to disclose any features specific for malignancies. But they revealed some similarities with distinct subsets of normal lymphocytes, i.e. between: (1) CLL and bone marrow lymphoid cells, (2) follicular lymphomas and follicular centre cells, and (3) lymphoblastic lymphomas and activated lymphocytes. These findings are further evidence supporting the hypothesis that the malignant transformation of phenotypically different lymphoproliferations takes place at different levels of lymphocyte differentiation.

B-Lymphocytes↗

PubMed1989

Microvascular distribution in normal human synovium.

The distribution of vessels in normal human synovium has been investigated using frozen sections and staining with Ulex Europaeus lectin by an indirect immunoperoxidase technique. The presence of a vascular net close to the tissue surface was confirmed. Quantitative analysis showed the majority of vessel profiles to be small venules with a peak density 25-100 microns beneath the tissue surface. A smaller number of capillaries was present with a peak density within 25 microns of the tissue surface. It is suggested that important functions of the numerous venules seen in synovium may include the provision of a source of fresh monocytes to replace surface macrophages and provision of nutrients for the surface layer of cells as a whole, and that the density of the vascular net may reflect angiogenic signals from this cell layer.

Anthropometry↗

PubMed1983

Intrauterine growth retardation detected in several species by non-normal birthweight distributions.

The statistical distribution of birthweights in 64 litters of pigs, 48 litters of dogs, 59 litters of rabbits, 130 litters of rats and 46 litters of mice was examined. Birthweight followed a Gaussian or normal distribution in about two-thirds of the litters inspected, as judged visually using a normal probability plot, and by the W-test statistic. In the remainder, a single outlying observation in an otherwise normal sample was detected by Dixon's test, and/or a separate sub-population of low birthweight animals could be identified by fitting two normal populations to the observed samples. In the non-Gaussian litters, the average proportion of affected members was 40% of the litter. These results suggest that growth-retarded neonates should not be regarded simply as the tail-end of a normal distribution.

Animals↗

PubMed1988

Assessment of polyclonal antibody binding of ligand by Sips' equation or by the exact polyclonal equation. Comparison of models.

Different possibilities of modelling equilibrium data on polyclonal antibody binding of ligand were investigated. The binding curves of the exact polyclonal model, based upon the mass-action law, and the Sips' model were compared. The basic assumption was that the free energy of binding is distributed according to the Gauss normal distribution. Using a few equations, the values of binding site concns and affinity constants of the individual clones were converted to the parameters of Sips' equation (that is, A = Ab binding site concn, K0 = average affinity, Hi = heterogeneity index). It was demonstrated that the binding curves from the exact polyclonal and the Sips' equations were very similar for simulated, approximately normally distributed antibody populations. Even when only two or three Ab-clones are involved, the Sips' and the exact polyclonal binding curves are very similar as long as the ratio between affinity constants does not exceed 10. Equilibrium data plotted as bound ligand concn on a linear scale vs free ligand concn on a logarithmic scale (or alternatively after logarithmic transformation of free ligand concn) form the well known sigmoid saturation curve. A mathematical relationship was demonstrated between half-height slope of such curves, resulting from approximately normally distributed antibody populations, and parameters of Sips' equation. The half-height slope is Hi X A/4 when natural logarithms are used. The ideas described were illustrated by weighted nonlinear curve-fittings applied to actual equilibrium data on anti-DNP antibodies. Tested in this way, the Sips' and a 2-clonal model gave equally good fit but somewhat different average affinities. It was concluded that it is often impossible to distinguish between a 2-clonal, a 3-clonal or an approximately normally distributed antibody population by curve-fitting to experimental equilibrium data.

2,4-Dinitrophenol↗

PubMed1987

Secretory ameloblasts and calcium distribution during normal and experimentally altered mineralization.

The distribution of calcium in relation to secretory ameloblasts of the rat incisor was studied. An experimental model system in which enamel mineralization was temporarily inhibited by injecting sodium fluoride and cobalt chloride was used. Potassium pyroantimonate (PPA) cytochemistry, electron energy loss spectroscopy (EELS), and energy dispersive X-ray spectrometry (EDS) were used to clarify the role of the ameloblast in controlling calcium distribution during normal and experimentally altered enamel mineralization. Secretory ameloblasts chemically-preserved in glutaraldehyde either with or without PPA were analyzed for calcium; those preserved with PPA showed higher concentrations of calcium than did those preserved with glutaraldehyde only. Freeze-dried control and experimental tissues showed an increasing gradient of calcium from stratum intermedium cells to the distal ends of the ameloblasts. Calcium levels were reduced near the distal ends of the cells following fluoride and cobalt injections, while magnesium levels were increased markedly in the same region. This multi-method approach showed correlated calcium localization in specific regions of this cell in relation to changes in function. The study thus provides additional evidence for active involvement of the ameloblasts in enamel mineralization.

Ameloblasts↗

PubMed1995

Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid.

The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and their phenotypic characteristics were extensively investigated in a group of 18 healthy individuals using two- and three-color flow cytometry. Generally, CD3+ T lymphocytes constituted the vast majority of CSF lymphocytes while the number of B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype of memory/primed cells in both the CD4+ and CD8+ subpopulations. Two markers for recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated when compared with peripheral blood (PB) in the majority of CSF T lymphocytes. However, a fraction of T lymphocytes co-expressing the NK cells markers CD56 and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with PB. This study documents that the cellular composition of the normal CSF differs profoundly from PB regarding all major lymphocyte subpopulations. This has to be taken into account in studies addressing questions regarding cellular immune reactions in the central nervous system under pathological conditions.

Adult↗

PubMed1984

Estimation of response slopes in respiratory control.

The ventilatory response to changes in alveolar (arterial) CO2 is widely used as an index of respiratory control behavior. Methods for estimating these response slopes should incorporate the possibility that there may be errors in both the independent (partial pressure of CO2) and dependent (ventilation) variables. In a recent paper Daubenspeck and Ogden (J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 45:823-829, 1978) have suggested problems inherent in the traditional technique of reduced major axis and have suggested a more contemporary technique of directional statistics. We have previously analyzed both techniques and developed a method to overcome the problems of reduced major axis and problems inherent in the use of directional statistics. Under the assumption of a bivariate normal distribution, we demonstrate that our slope estimate is similar to the maximum likelihood estimate proposed by Mardia et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 309-313, 1983) for this problem. In addition, we demonstrate a bootstrap statistical approach when the distributions are not normally distributed. These concepts are illustrated using O2-CO2 interaction data.

Carbon Dioxide↗

PubMed1994

Ribosome distribution in normal and infarcted rat hearts.

Distribution of ribosomes throughout the myocardium of normal and infarcted rat hearts was studied by immunofluorescence and laser confocal scanning microscopy. In addition, sections were labelled with peroxidase or immunogold particles for electron microscopic examination. Ligation of the proximal free left coronary artery produced severe myocardial ischaemia, and after 6 days of ligation most of the left ventricular wall was necrotic and partially replaced by granulation tissue. Immunofluorescence microscopy revealed the presence of ribosomes throughout the non-necrotic myocardium. Some cardiac muscle cells located in subendocardial areas and in the border areas surrounding the infarct were particularly intensely stained. Cells constituting the granulation tissue frequently exhibited strong ribosomal immunostaining. Within longitudinally sectioned cardiac muscle cells, ribosomes were organized in strands oriented along the long axis of the cell as well as in a cross-striated pattern. By double labelling of muscle cells with antibodies against ribosomes and Z-line-associated proteins (desmin or alpha-actinin), it was shown that the cross-striated bands of anti-ribosomal staining coincided with the I-bands along the myofibrils. Immunoelectron microscopy confirmed a wide distribution of ribosomes throughout the intermyofibrillar and subsarcolemmal sarcoplasm, and some labelling was also observed within the I-band. The present results indicate that ribosomes are distributed in a characteristic pattern throughout the sarcoplasm of cardiac muscle cells in association with the myofibrils. Furthermore, it is suggested that within viable cardiac muscle cells located adjacent to the infarct, protein synthesis is increased; this might be an important factor in regional development of compensatory hypertrophy of the surviving cardiac muscle cells.

Animals↗

PubMed1995

Estimation of quantitative genetic parameters under non-normal models.

In traditional quantitative genetics, the relationship between the observed value of a quantitative trait in a set of families and its genetic and environmental contributions can be described as a linear additive relationship. Generally, it is assumed that the genetic and environmental effects are independent and normally distributed. Consequently, the quantitative trait also has a normal distribution. However, there are some situations where the phenotype does not follow the normal distribution. To deal with this problem the author suggests the families of distributions that belong to the Johnson Translation System (JTS). As an example, two dependent quantitative traits, weight and height, are investigated assuming that they have a lognormal and normal distribution, respectively. Computational methods for estimating the genotypic variances and covariances are presented.

Finland↗

PubMed1994

A quantitative method for cost reimbursement and length of stay quality assurance in multiple trauma patients.

OBJECTIVE: To develop a statistically valid method for trauma reimbursement and quality assurance (QA) length-of-stay filters. This is needed because diagnosis related group (DRG)-based trauma payment systems assume a random sampling of injury severities from a normally distributed population and thus result in economic disincentives to level I trauma centers. METHODS: 142 trauma patients with MVC blunt multisystem injuries (MSI) (ISS > or = 16) were studied concurrently during their hospital course. SETTING: Level I regional trauma center. OUTCOME MEASURES: Outcome measures were (dependent variables) length of stay (LOS) and state-approved hospital charges (COST). RESULTS: Mean acute care COST was $74,310, but the distribution of COST was log normal, rather than Gaussian normal as assumed by DRGs. The LOS for MSI was more than twice the average for all trauma (22 vs. 9 days), reflecting skewed severities of level I patients and was related to COST (r2 = 0.802; p < 0.0001). The ISS alone was a weak determinant of COST or LOS (r2 = 0.05; p < 0.0001). The best single determinant of COST and LOS was survival (r2 = 0.15; p < 0.0001): as it increased, it increased LOS. The most costly injuries (all p < 0.0001) involved the lower extremity (LE) or hip joint (HIP), whereas sepsis and pulmonary and surgical complications constituted the most costly complications (all p < 0.0001). Regression models that accounted for the log-normal distribution of the dependent variable and based on binary variables for survival, LE and HIP injuries, and the complications of sepsis, ARDS, pulmonary failure, MOFS, plus ISS, explained nearly two thirds of the variability in COST (r2 = 0.621; p < 0.0001) or LOS (r2 = 0.687; p < 0.0001) and the residuals were normally distributed. CONCLUSIONS: These models provide a valid method of reimbursement for MSI trauma for level I trauma centers, since the data imply that good care associated with survival from specific complications of MSI are the major determinants of COST, rather than the specific type of injury or the resultant ISS. Moreover, using survival and ISS plus the disease-related complications as determinants of LOS, this method can be applied to any U.S. region since local factors can be used to adjust hospital COST as a highly correlated function of LOS. This method also permits identification of LOS outliers for QA, taking into account the influence of injury complications.

Accidents, Traffic↗

PubMed1996

Interindividual variations in susceptibility and sensitivity: linking risk assessment and risk management.

In the past few years, our knowledge of mammalian genomes has increased enormously. Our understanding of the molecular basis of the normal cellular processes of DNA replication and repair and cell cycle control, together with how their fidelity malfunctions as part of tumor development, has increased in parallel. This has led to a clearer appreciation that there are subpopulations that have been generically described as being genetically or otherwise susceptible to the induction of cancer or birth defects. The term susceptibility is a default option, since there clearly will be a very broad range of sensitivities among the so-called susceptible populations, dependent upon the specific underlying mechanism. This could lead to the conduct of risk assessments for each specific situation, involving both genotypes of individuals and agents of concern. This would ideally take into account the effects on response of various modifying factors, genetic and other. One advantage to be gained from this approach is the ability to determine if a particular susceptibility places subpopulations at extreme risk as compared to the overall normal distribution of risk in the population, or whether such a susceptible population presents a slight extension of the upper bound of the risk distribution or lies within the normal distribution. In addition, the specific mechanism of the susceptibility as related to exposure scenarios and the magnitude and demographics of the susceptible populations need to be taken into account. Thus, the management of risk has to be linked to the specific risk assessment. For many of the so-called susceptible populations an uncertainty factor of less than 10, even including 1, would be predicted to bring the risk within the normal distribution. It is hoped that as more mechanistic information on susceptibility becomes available and a specific risk can be defined, the practice of risk management will be considerably improved.

Animals↗

PubMed1981

Examination of a lognormal distribution equation for describing distributions of diameters of bovine adipocytes.

Samples of subcutaneous, intermuscular and mesenteric adipose tissues from beef steers were fixed with osmium tetroxide, and freed adipocytes were counted with an automatic particle counter to determine whether a lognormal distribution function would describe adipocyte size distributions more accurately than a normal distribution function. Modes and medians of size distributions generally were larger than means for adipocyte size distributions modeled with a lognormal distribution function. Normalized third and fourth moments of predicted lognormal distributions often were close to 0 and 3, respectively, which are expected values for a normally distributed population. Considerable variation was observed in the skewness of adipocyte size distributions. Both normal and lognormal models for adipocyte size distribution yielded similar means. The lognormal model yielded a greater standard deviation than the normal model for adipocyte size distributions. Smaller chi-square values were found for size distributions modeled with a lognormal than with a normal distribution function. Results suggest that a lognormal distribution function more accurately models the size distributions of bovine adipocytes.

Adipose Tissue↗

PubMed1996

Sonographic appearance and distribution of normal cervical lymph nodes in a Chinese population.

In 100 normal subjects who had a sonographic examination of the neck, 1211 lymph nodes were detected. In all the subjects, at least five lymph nodes were seen. The distribution, number, echogenicity, shape, presence or absence of echogenic hilus, and the sharpness of nodal borders of normal cervical lymph nodes were determined. The usefulness of these sonographic features in understanding the normal distribution and characteristics of the nodes in the Chinese population is discussed. The relationship between the shape and size of lymph node also was assessed.

Adolescent↗

PubMed1978

The correlation between relatives with assortative mating.

The equilibrium correlation between various close relatives is calculated for phenotypic assortative mating for a character determined by additive loci without dominance and an uncorrelated environment. It is supposed that the phenotypes of spouses have a bivariate normal distribution and environment and heredity are normally distributed. Heredity is Gaussian if either there are many alleles with approximately normally distributed effects at each of an arbitrary number of loci or the trait is controlled by many loci, each of which makes only a small contribution. It is also assumed that the regression of the phenotype or genotype of an individual on the phenotype or genotype of any one of his relatives is linear. The results show that with the above assumptions Fisher's formulae for the correlation between relatives hold with no restrictions on the linkage map.

Female↗

PubMed1982

A multi-stage Gaussian transformation algorithm for clinical laboratory data.

We have developed a multi-stage computer algorithm to transform non-normally distributed data to a normal distribution. This transformation is of value for calculation of laboratory reference intervals and for normalization of clinical laboratory variates before applying statistical procedures in which underlying data normality is assumed. The algorithm is able to normalize most laboratory data distributions with either negative or positive coefficients of skewness or kurtosis. Stepwise, a logarithmic transform removes asymmetry (skewness), then a Z-score transform and power function transform remove residual peakedness or flatness (kurtosis). Powerful statistical tests of data normality in the procedure help the user evaluate both the necessity for and the success of the data transformation. Erroneous assessments of data normality caused by rounded laboratory test values have been minimized by introducing computer-generated random noise into the data values. Reference interval endpoints that were estimated parametrically (mean +/- 2 SD) by using successfully transformed data were found to have a smaller root-mean-squared error than those estimated by the non-parametric percentile technique.

Adult↗

PubMed1986

Distributional expectations and the induction of category structure.

Previous research on how categories are learned from observation of exemplars has largely ignored the possible role of prior expectations concerning how exemplars will be distributed. The experiments reported here explored this issue by presenting subjects with category-learning tasks in which the distributions of exemplars defining the categories were varied. In Experiments 1 and 2 the distributional form of a category was found to affect speed of learning. Learning was faster when a category's distribution was normal than when it was multimodal. Also, subjects in the early stages of learning a multimodal category responded as if it were unimodal. These results suggested that subjects enter category-learning tasks with expectations of unimodal, possibly normal, distributions of exemplars. Experiments 3 and 4 attempted to manipulate subjects' prior expectations by varying the distribution of exemplars in the first of two consecutive category-learning tasks. Learning a multimodal category was influenced by the shape of a previously learned distribution and was facilitated when the earlier distribution was either multimodal or skewed, rather than normal. These results are interpreted as support for a dual-process model of category learning that incorporates the effects of prior expectations concerning exemplar distributions.

Adolescent↗

PubMed1994

Computing the central location of immunofluorescence distributions: logarithmic data transformations are not always appropriate.

The idea of the "average" intensity of immunofluorescence data is often poorly defined, with such terms as average, mean, and peak used interchangeably. In addition, the common use of logarithmic amplifiers with immunofluorescence data further complicates the problem. Log amplifiers permit the display of a wider range of fluorescence intensities. At the same time, they effect a log transformation of the data. This transformation decreases the variance resulting in narrower fluorescence distributions, which are assumed to approximate normal distributions. When the log transform is used, the distribution mean is the geometric mean of the untransformed data, which is computed simply as the mean of the channel values. This mean value serves as a simple indicator of the population center. Despite the prevalence of log transformations in flow cytometry, this transformation may not yield normally distributed immunofluorescence data, whereas the square root or other fractional power transformations can yield normal distributions.

Flow Cytometry↗

PubMed1976

Differential transglutaminase distribution in normal rat liver and rat hepatoma.

Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule.

Animals↗