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PubMed1990

The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans.

Cytoskeleton inhibitors were used to study morphogenesis in the pathogenic and dimorphic fungus Candida albicans. Nocodazole is a specific microtubule inhibitor and chloropropham (CIPC), at high concentrations, is an inhibitor of microtubules and microfilaments. Distribution of microtubules and microfilaments was studied by immunofluorescence techniques using anti-tubulin antibody with FITC-conjugated secondary antibody, and by staining with Rh-phalloidin. Nocodazole did not arrest apical cell elongation at a concentration (20 micrograms ml-1) that inhibited nuclear division and migration. Cytoplasmic and nuclear microtubules disappeared within 30 min in filamentous cells under these conditions. However, the Rh-phalloidin-stained actin granules which were localized in the tips of filamentous cells, and the microfilaments, were arranged normally at this concentration of nocodazole. Growth, and normal distribution of microtubules and microfilaments, were inhibited by a high concentration (200 micrograms ml-1) of CIPC. At a concentration (100 micrograms ml-1) of CIPC that permitted nuclear division, apical cell elongation was arrested, and filamentous growth was converted into yeast growth. At this concentration of CIPC, microtubules were distributed normally in filamentous cells. Long microfilaments were not observed, and actin granules did not localize in the tips of filamentous cells, but were distributed throughout the cytoplasmic cortex. Our results show that cytoplasmic microtubules are not essential for the elongation of filamentous cell tips but that microfilaments are apparently essential for this process.

Actin Cytoskeleton↗

PubMed1988

Bromine levels in human serum, urine, hair. Short communication.

Much is known about the essentiality of the halogens fluorine (F), chlorine (Cl), and iodine (I), but very little has been discussed with respect to bromine (Br). As a member of the halogen family its chemical properties are comparable to those of other halogens, but its presence has been masked by the presence of I and Cl in chemical analyses. By virtue of new technology and a special computerized machine called the Kevex Model 0600 Energy Dispersive X-Ray Induced X-Ray Fluorescence Spectrometer (EDXRF), we can specifically identify bromine in different compartments and verify its concentration accurately. In order to establish standard values of Br concentrations and evaluate the nature of its presence in humans, samples of serum, urine, and hair were collected from ten healthy adult males and analyzed for bromine content. Our samples had normal distributions, with serum bromine levels ranging from 3.2 to 5.6 micrograms/mL, urine levels between 0.3 to 7.0 micrograms/mL, and hair levels determined from 1.1 to 49.0 micrograms/mL. These levels, especially those of serum bromine, have been encountered by other examiners whose samples also had normal distributions. These findings suggest to us that bromine may well be an essential trace element, as are its other halogen family members.

Adult↗

PubMed1987

Human plasma protein Z antigen: range in normal subjects and effect of warfarin therapy.

In contrast to the other well-studied vitamin K-dependent proteins that circulate in plasma, protein Z antigen is much more variable. The concentration in plasmas collected in EDTA from 455 normal, healthy donors is normally distributed with a mean of 2.9 micrograms/mL (46 nmol/L) and a SD of 1.0 microgram/mL (95% interval of 32% to 168% of the mean). No significant correlation to age or sex could be detected. In comparison, the concentration of protein C antigen measured with the same type of assay on the same 455 samples has a log normal distribution with a mean of 4.0 micrograms/mL (65 nmol/L) and a 95% interval of 70% to 138% of the mean. Also in marked contrast to other plasma vitamin K-dependent proteins, the total protein Z antigen level is extremely low in patients on stable warfarin therapy (range 1% to 16% of normal). Moreover, even though greater than 95% of the antigen in normal plasmas adsorbs to barium citrate (a crude reflection of the presence of gamma-carboxyglutamic acid (Gla) residues), in the patients taking warfarin almost all of the small amount of the antigen failed to adsorb, suggesting that virtually no protein Z had its full complement of Gla residues. Total protein C antigen in the same 25 patients averaged 53% of normal (34% to 72%) and 54% (average) of the total remaining antigen still adsorbed to barium citrate. The concentration of protein Z antigen in the plasma of a normal individual given a loading dose of warfarin fell at an initial rate of approximately 20% a day, indicating a plasma half-life (t1/2) of 2 to 3 days.

Antibodies, Monoclonal↗

PubMed2002

Alterations of nPKC distribution, but normal Akt/PKB activation in denervated rat soleus muscle.

Denervation has been shown to impair the ability of insulin to stimulate glycogen synthesis and, to a lesser extent, glucose transport in rat skeletal muscle. Insulin binding to its receptor, activation of the receptor tyrosine kinase and phosphatidylinositol 3'-kinase do not appear to be involved. On the other hand, it has been shown that denervation causes an increase in the total diacylglycerol (DAG) content and membrane-associated protein kinase C (PKC) activity. In this study, we further characterize these changes in PKC and assess other possible signaling abnormalities that might be related to the decrease of glycogen synthesis. The results reveal that PKC-epsilon and -theta;, but not -alpha or -zeta, are increased in the membrane fraction 24 h after denervation and that the timing of these changes parallels the impaired ability of insulin to stimulate glycogen synthesis. At 24 h, these changes were associated with a 65% decrease in glycogen synthase (GS) activity ratio and decreased electrophoretic mobility, indicative of phosphorylation in GS in muscles incubated in the absence of insulin. Incubation of the denervated soleus with insulin for 30 min minimally increased glucose incorporation into glycogen; however, it increased GS activity threefold, to a value still less than that of control muscle, and it eliminated the gel shift. In addition, insulin increased the apparent abundance of GS kinase (GSK)-3 and protein phosphatase (PP)1 alpha in the supernatant fraction of muscle homogenate to control values, and it caused the same increases in GSK-3 and Akt/protein kinase B (PKB) phosphorylation and Akt/PKB activity that it did in nondenervated muscle. No alterations in hexokinase I or II activity were observed after denervation; however, in agreement with a previous report, glucose 6-phosphate levels were diminished in 24-h-denervated soleus, and they did not increase after insulin stimulation. These results indicate that alterations in the distribution of PKC-epsilon and -theta; accompany the impairment of glycogen synthesis in the 24-h-denervated soleus. They also indicate that the basal rate of glycogen synthesis and its stimulation by insulin in these muscles are diminished despite a normal activation of Akt/PKB and phosphorylation of GSK-3. The significance of the observed alterations to GSK-3 and PP1 alpha distribution remain to be determined.

Animals↗

PubMedDate not supplied

Sequential decision making with continuous disease states and measurements: I. Theory.

The question of whether to perform a continuous valued test to assess a continuous valued health state such as blood pressure or serum cholesterol is explored by decision analysis. Principal assumptions are that the underlying health state and measurement variability are both normally distributed, and that the impact of treatment on the utility of outcomes varies linearly with the underlying health state. Using Bayes' theorem, an expression for the expected utility of performing the test is derived and compared with immediate treatment or decision to withhold treatment. The calculations can be carried out with a pocket calculator and a table of the normal distribution. Iterating the analysis, a sequential decision making process is developed, leading to a series of no treat/test again and test again/treat thresholds with which a running average of independently obtained measurements can be compared to produce stepwise optimal results. The thresholds are readily calculated on a microcomputer. Finally, the conjugate-normal-linear model is extended to encompass the correlated observations that may be made on a single visit. This paper concentrates on the mathematics of decision making with continuous variables. The companion paper illustrates its application to diastolic blood pressure.

Bayes Theorem↗

PubMed2003

Polydisperse adsorbability composition of several natural and synthetic organic matrices.

The polydisperse composition of nine dissolved organic materials (DOMs) from two river water sources, one ground water source, two biologically treated wastewater sources, and two commercial sources was analyzed based on their adsorbabilities by activated carbon. For each DOM, batch adsorption isotherms measured for both TOC and UV260 were analyzed using an overall isotherm model derived from the IAST-Freundlich expression. By accounting for the heterogeneity of each DOM with a log-normal distribution of the Freundlich parameter (K), its adsorption behavior was characterized with only four parameters (including three fitting ones). The average adsorptive strength (KM) and heterogeneity (sigma) determined for all DOMs, which were defined by the mean value and the standard deviation of the log-normal distribution of the Freundlich K, changed over the ranges 2.5-62.2 and 0.22-0.97 (mg/g)/(mg/l)(1/n), respectively, when the TOC index was used. Among all DOMs studied, a river water DOM at the upper stream was found least heterogeneous: the Freundlich K of its organic constituents varied in the range 10.8-190 (mg/g)/(mg/l)(1/n), as compared to a commercial humic acid that exhibited the broadest Freundlich K distribution of 0.01-1494.3 (mg/g)/(mg/l)(1/n). KM and sigma, along with other two parameters (the Freundlich exponent 1/n and the nonadsorbable organic fraction parameter Cnon/CT0), changed with both indices of TOC and UV260 in a regular manner, indicating that UV-absorbing organic molecules possessed adsorbabilities different from non-UV-absorbing ones. Also based on HPSEC chromatograms measured for solutions before adsorption, the molecular weight composition of all DOMs was also assessed and the molecular size impacts on adsorption characteristics of DOMs were briefly discussed.

Adsorption↗

PubMed1996

Transmission electron microscopy of cementum crystals correlated with Ca and F distribution in normal and carious human root surfaces.

Root-surface caries, like enamel caries, develops as a subsurface type of mineral loss. Very little is known about the composition of the surface zone covering the body of the lesion, and the ultrastructure and composition of carious cementum are not known. The aim of this study was to correlate the ultrastructure and arrangement of the cementum crystals with the distribution of fluoride and calcium in root cementum from human teeth with sound, unexposed, or exposed root surfaces as well as in early stages of root-surface caries. Microradiographically, unexposed specimens showed a relatively homogeneous mineral distribution contrasting with the formation of an apparently highly mineralized surface layer in exposed and, in particular, in carious cementum. The electron-probe findings showed a substantial fluoride peak corresponding to the surface layers in carious tissues in particular, whereas the calcium profile in the surface did not reflect the apparent increase in mineralization. A substantial increase in size of the cementum crystals was found in specimens with formation of the fluoride-rich, well-mineralized surface zone. The crystal lattice intervals when observed along the (001) plane showed a hydroxyapatite spacing. The findings indicated that a significant crystal growth can be achieved in human cementum concomitant with fluoride accumulation.

Adult↗

PubMed1983

Mapping of cell cycle distribution in normal human urinary bladder epithelium.

A method is described by which urothelial cells from well defined areas in the urinary bladder mucosa can be obtained. At cystoscopy epithelial cells are aspirated by means of a ureteral catheter. The cells obtained by this selective sampling technique are well suited for morphology and for quantitative single cell measurements by flow cytometry (FCM). In the present study the cell cycle distribution has been measured by FCM. Twenty-five patients (13 males and 12 females) had urothelial cells collected from well defined areas in the mucosa and the DNA content measured from different sites separately. The distribution of bladder mucosa cells in the different parts of the cell cycle (G1, S-phase and G2 + M) is reported. No significant differences were found with regard to sex and age of the patients. Also, a low regional variation was found in the bladder mucosa indicating that the method should enable the discrimination of even small abnormal cell populations in tumour disease. No evidence of polyploidy in the human urothelium was found.

Adult↗

PubMed2004

Clinical trials and p-values, beware of the extremes.

BACKGROUND: In randomized controlled trials, prior to statistical analysis, the data are checked for outliers and erroneous data. Statistical tests are, traditionally, not very good at distinguishing between errors and outliers, but they should be able to point out main endpoint results closer to expectation than compatible with random sampling. OBJECTIVES: To explain from hypothesized and published examples why extreme p-values like p>0.95 and p<0.0001 may indicate that sampling was not completely random. RESULTS: Extreme p-values can be readily observed in recent issues of high-impact journals. A p-value >0.95 literally means that we have a >95% chance of finding a result less close to expectation and, consequently, a <5% chance of finding a result this close or closer. Often in studies a statistical power of 80% is agreed upon, corresponding with a p-value of approximately 0.01. The ultimate p-value may then be a bit larger or smaller. However, a p-value much smaller than 0.01 will be rarely observed, because it would indicate that the study is overpowered. If the p-values can be assumed to follow a normal distribution around 0.01, then we will have a less than 5% chance of observing a p-value of <0.0001. CONCLUSIONS: In randomized controlled trials, main endpoint p-values larger than p=0.95 will be rare, because they would indicate similarities closer than compatible with a normal distribution of random data samples. Also very low p-values like p<0.0001 will be rarely encountered, because it would mean that the trial was overpowered and should have had a smaller sample size. It would seem appropriate, therefore, to require investigators to explain such results and to consider rejecting the research involved. So far, in randomized controlled trials the null-hypothesis is generally rejected at p<0.05. Perhaps we should consider rejecting the entire study if the main endpoint p-values are >0.95 or <0.0001.

Area Under Curve↗

PubMed1993

Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual variability.

1. The rate of conjugation of benzoic acid with glycine was measured in the homogenates of 110 specimens of human liver and in 67 specimens of human renal cortex. 2. The assay for the formation of benzoyl glycine consisted of measuring the formation of benzoyl glycine from (14C) benzoic acid and glycine in the presence of coenzyme A and ATP. 3. In human liver, the mean (+/- SD) and coefficient of variation for the formation rate of benzoyl glycine were 254 +/- 90.5 nmol min-1 per g liver and 36%, respectively. There was a weak, but significant, negative correlation (r = -0.339, p < 0.001) between the rate of formation of benzoyl glycine and the liver donor's age. 4. In the human kidney, the rate of benzoyl glycine formation was normally distributed. The mean (+/- SD) and coefficient of variation were 321 +/- 99.3 nmol min-1 per g kidney and 31%, respectively. 5. These in vitro results are consistent with the view that the in vivo rate of conjugation of carboxylic acid with glycine varies among subjects and is normally distributed.

Adult↗

PubMedDate not supplied

[Statistical analysis of repetitive nerve stimulation test].

INTRODUCTION: Statistical properties of Repetitive Nerve Stimulation test (RNS) are studied for different variables (forth to first potentials ratio of CMAP) together with two new variables (trends of area and amplitude for series of CMAP) OBJECTIVE: To compare the variables commonly used, in order to define the best statistical properties and, in the other hand, investigate if the new variables (trends in area and amplitude) could be useful for the study of neuromuscular transmission pathology. SUBJECTS AND METHODS: Statistical properties of voltage (V4/V1(V)), area of CMAP (V4/V1(a)) and slopes of regression lines of voltage (m(V)) and area (m(a)) measures are determined for runs of 3, 10, 15 and 20 Hz series of stimuli in 13 men and 17 women healthy volunteers. RESULTS: 1) The sample fits well to a normal distribution; 2) The variables that measure tendencies in CMAP series, can be reasonably fitted to linear regression functions; 3) Differences between sex and age have been not found; 4) Variables measuring tendencies have been the most stables, specially m(a); 5) The variable that fits better to normal distribution is m(V); 6) All variables behave linearly with respect frequency of stimulation. CONCLUSIONS: 1) Neuromuscular transmission is a particularly stable physiologic function; 2) The most used variable in clinical neurophysiology laboratories, V4/V1(V) have the worst statistical properties, showing a very significant variability; 3) Trends measures (m(a)) and m(V)) show very satisfactory statistical properties; this implies that these could be very useful for the study of neuromuscular transmission diseases.

Data Interpretation, Statistical↗

PubMed1985

Relationship between adhesion of Escherichia coli to uro-epithelial cells and the pathogenesis of urinary infection: problems in methodology and analysis.

Escherichia coli strains isolated from patients with urinary infections were tested for their ability to adhere to human uro-epithelial cells. In any single experiment, the numbers of bacteria adhering to individual uro-epithelial cells showed great variations; some cells had hundreds of bacteria adhering to them whereas other cells had few or none. This non-Normal distribution of bacterial attachment must be taken into account when carrying out statistical analyses of the results. The wide discrepancies reported in the literature regarding bacterial adhesion to uro-epithelial cells must, in part, be related to the type of statistical analysis used. In many cases, a Normal rather than a non-Normal distribution has been assumed. We found that even when all variables were kept constant, the experiment was still not reproducible. Therefore the technique shows a high degree of both inter- and intra-experimental error. Adhesion depended on such factors as the type of fimbriae produced by the bacteria, differing viability of uro-epithelial cells and varying pH of the medium used for a particular experiment. It is concluded that the results of in-vitro experiments demonstrating adhesion of E. coli to uro-epithelial cells are difficult to relate to bacterial adhesion in vivo but better results could be obtained if more attention were paid to standardisation of methods and their analysis.

Adhesiveness↗

PubMed1991

Quantitative electroencephalography in dogs anesthetized with 2.0% end-tidal concentration of isoflurane anesthesia.

Quantitative electroencephalography was assessed in dogs under controlled, 2% end-tidal isoflurane anesthetic conditions, and each variable at each electrode site was tested for normal distribution. With the quantitative electroencephalographic system used, 16 values for each of 21 electrode sites were evaluated. Absolute power ratios also were evaluated. The methods for quantitative electroencephalographic recording and analysis appear to be readily adaptable to the dog. Most of the data do not conform to a normal distribution. Therefore, distribution-free nonparametric statistics should be used when looking for differences under experimental or clinical conditions. Quantitative electroencephalography appears to be a sensitive noninvasive method that could be used to evaluate brain function under anesthetic, clinical, and experimental settings.

Acid-Base Equilibrium↗

PubMed2004

Sensitivity and specificity of new GDx parameters.

PURPOSE: The GDx is a scanning laser polarimeter that assesses peripapillary nerve fiber layer thickness. In addition to the 14 existing outcome parameters, four new parameters have been described recently: the Ellipse Standard Deviation (ESD), the Normalized Superior Area (NSA), the Normalized Inferior Area (NIA) and the Discriminant Analysis (DA). The aim of this study was to investigate the sensitivity and specificity of these four new parameters. METHODS: Only one randomly selected eye of 263 healthy volunteers and 241 glaucoma patients was considered. The healthy group was randomly divided into a reference set (n = 132) to calculate the tenth percentile of the normal distribution and a test set (n = 131) to calculate the specificity against these newly established cut-off points. Sensitivity was calculated for all glaucoma patients (n = 241) and again for three separate subgroups: early glaucoma (n = 90), moderate glaucoma (n = 93), and advanced glaucoma (n = 58). RESULTS: When the tenth percentile of the normal distribution was used as a cut-off point, the sensitivity and specificity pairs of the new parameters were 61.8% and 87.6%, 61.8% and 89.1%, 50.2% and 92.2% and 72.6% and 95.3% for the ESD, NSA, NIA, and the DA, respectively. The Area under the ROC curve was 0.86, 0.86, 0.87, and 0.90, respectively. Among the existing parameters, the Number discriminated best (sensitivity and specificity: 76.8% and 89.1%, respectively; area under the ROC curve: 0.90). When compared with The Number, the DA was equally good, whereas the other three new parameters performed statistically significantly worse. In general, the area under the ROC curve increased from early to moderate to advanced glaucoma. CONCLUSIONS: The new GDx parameters discriminated well between normal subjects and glaucoma patients. None of the new parameters discriminated better than The Number.

Adult↗

PubMed1987

On visual orientation of dot patterns.

Two-dimensional normally distributed random dot patterns were used in two experiments on visual orientation estimation. In the first experiment the patterns differed in their sample correlation and in dot number. In the second one the number of dots was maintained constant but the patterns were generated as a superposition of two normally distributed orthogonal sets composed of different number of dots. In both experiments the estimated orientation depended on stimuli correlation - with increasing correlation the estimated orientation gets closer to the orientation of the least square distance axis of the pattern. Even at very low unsignificant correlations there still remained a hint about stimulus orientation which was not estimated at random. Equalizing consecutively the number of dots in the two orthogonal dot patterns during the second experiment did not result in chance performance either. The bimodal angular distributions of the obtained responses permitted to approach the problem of orientation ambiguity. The results are discussed in terms of optimization processes taking place in the visual system.

Cybernetics↗

PubMed1984

Spectral analysis of the surface electromyogram as a tool for studying rate modulation: a comparison between theory, simulation, and experiment.

Theoretical work suggests that if the interpulse intervals ( IPIs ) of motor unit action potential trains ( MUAPTs ) are independently and normally distributed, then spectral analysis of the electromyogram could be a useful tool for studying rate modulation by virtue of the presence of a peak in the power spectrum at the average firing frequency of all active motor units. It is shown in this paper that IPIs need not be normally distributed, specifically that the results are very much the same if the IPIs are distributed according to a Gamma probability density function ( PDF ). Simulation of the electromyogram based on this theory proved the applicability of the method. Experimental results obtained for the masseter, biceps brachii and first dorsal interosseus (FDI) muscles, however, were in disagreement with both theory and simulation except for the biceps muscle at force levels up to 20% of the maximal force and for the masseter and FDI muscles in 1 out of 5 subjects. This indicates that the models for MUAPTs hitherto used might not be generally correct. Apart from this discrepancy, our results reveal differences between masseter and FDI muscles on the one hand and the biceps brachii on the other, which indicate that motor unit synchronisation is much more pronounced in the latter muscle.

Action Potentials↗

PubMed2002

Mathematical estimation of stress distribution in normal and dysplastic human hips.

By using a mathematical model of the adult human hip in the static one-legged stance position of the body, the forces acting on the hip, peak stress in the hip joint and other relevant radiographic and biomechanical parameters were assessed. The aims were to examine if the peak stress in dysplastic hips is higher than in normal hips and to find out which biomechanical parameters contribute significantly to higher peak stress. The average normalized peak stress in dysplastic hips (7.1 kPa/N) was markedly higher (to approximately 100%) than the average normalized peak stress in normal hips (3.5 kPa/N). The characteristic parameters that contributed to higher peak stress in dysplastic hips included the smaller lateral coverage of the femoral head, the larger interhip distance, the wider pelvis, and the medial position of the greater trochanter. These results are consistent with the hypothesis that stress distribution over weight-bearing surface of the hip joint is the relevant parameter for assessment of the risk for developing coxarthrosis.

Adolescent↗

PubMed1997

Evidence that male sexual orientation is a matter of degree.

Whether male sexual orientation is best represented by discrete categories or by a continuum has been the focus of much debate. These alternatives were compared in an analysis of 1,138 men's scores on the Minnesota Multiphasic Personality Inventory-2 Masculinity-Femininity Scale, an established correlate of male sexual orientation. Mixtures of 2 or 3 latent distributions did not fit the observed distribution of scores better than a single normal distribution, suggesting that the latent variable underlying male sexual orientation is not discrete. Additional taxometric analyses provided convergent support for continuity. The findings were inconsistent with accounts of male sexual orientation that invoke single preponderant causes, whether genetic or environmental, and call some forms of taxonomic theorizing about sexual orientation into question.

Adult↗