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PubMed1982

Temporal generalization.

Responses of 26 rats were reinforced following a signal of a certain duration, but not following signals of shorter or longer durations. This led to a positive temporal generalization gradient with a maximum at the reinforced duration in six experiments. Spacing of the nonreinforced signals did not influence the gradient, but the location of the maximum and breadth of the gradient increased with the duration of the reinforced signal. Reduction of reinforcement, either by partial reinforcement or reduction in the probability of a positive signal, led to a decrease in the height of the generalization gradient. There were large, reliable individual differences in the height and breadth of the generalization gradient. When the conditions of reinforcement were reversed (responses reinforced following all signals longer or shorter than a single nonreinforced duration), eight additional rats had a negative generalization gradient with a minimum at a signal duration shorter than the single nonreinforced duration. A scalar timing theory is described that provided a quantitative fit of the data. This theory involved a clock that times in linear units with an accurate mean and a negligible variance, a distribution of memory times that is normally distributed with an accurate mean and a scalar standard deviation, and a rule to respond if the clock is "close enough" to a sample of the memory time distribution. This decision is based on a ratio of the discrepancy between the clock time and the remembered time, to the remembered time. When this ratio is below a (variable) threshold, subjects respond. When three timing parameters--coefficient of variation of the memory time, the mean and the standard deviation of the threshold--were set at their median values, a theory with two free parameters accounted for 96% of the variance. The two parameters reflect the probability of attention to time and the probability of a response given inattention. These parameters were not influenced by stimulus manipulations but were affected by manipulations of reinforcement rate and by individual differences.

Animals↗

PubMed1997

[Geometrical distribution of newly formed blood vessels in diabetic retinopathy].

Outbreak sites of newly formed blood vessels (NFVs) in proliferative diabetic retinopathy (PDR) were analyzed geometrically. A montage was made of fluorescein fundus angiography photographs of 109 eyes and applied to a two dimensional x-y plane in which the center of the optic disc was taken as the origin. Thus each NFV acquired a coordinate value (x, y). After a coordinate transformation of this x-y plane designed to correct the parafoveal distortion of vascular distribution, a polar coordinate value (r, theta) of the NFV was calculated. The frequencies of NFVs were analyzed statistically relating to both theta, which is the angle around the origin, and r, which is the distance from the origin. The average theta was 2.74 +/- 1.72 (mean +/- standard deviation) radians and the outbreak frequency of NFVs showed a homogeneous distribution which was not influenced by any difference in theta. As for r, the frequency corrected as a truncated distribution at r = 0 showed a normal distribution with an average of 1.45 +/- 0.8. The outbreak of NFVs in PDR is a phenomenon in which accidental elements are strongly concerned and it is thought to be difficult to predict the site at early stage of retinopathy.

Adult↗

PubMed2003

Testicular expression and distribution of the rat bcl2 modifying factor in response to reduced intratesticular testosterone.

The Bcl2 modifying factor (Bmf) is a pro-apoptotic member of the Bcl2 family of apoptosis-related proteins that has been shown to initiate apoptosis in response to the loss of attachment of cells from their basal lamina (anoikis). Experimental reduction in intratesticular testosterone concentration brings about the death of spermatids as a consequence of their sloughing from Sertoli cells. Given the role of Bmf in anoikis in other systems, we hypothesized that Bmf would be expressed in germ cells and that its expression and normal distribution might be altered under conditions that induce widespread germ cell loss. To test these hypotheses, we demonstrated that Bmf indeed is expressed in the testis and cloned the full-length rat Bmf cDNA. Immunohistochemistry revealed that Bmf is present in the subacrosomal space of postmeiotic spermatids from step 4 to 16 of spermiogenesis. To test the hypothesis that Bmf expression and distribution are altered by conditions that elicit anoikis, intratesticular testosterone was reduced by implanting Silastic capsules containing testosterone and estradiol into adult rats for 8 weeks. As hypothesized, this resulted in a significant change in Bmf distribution relative to untreated animals. In particular, Bmf exhibited a loss of its normal subacrosomal distribution, becoming redistributed throughout the cytoplasm and nucleus, and appeared in cells in which it is not normally expressed (e.g., pachytene spermatocytes). Additionally, Bmf mRNA expression increased in response to lowered testosterone. These results suggest that Bmf may well be involved in germ cell apoptosis and/or anoikis in response to decreased intratesticular testosterone concentration.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Canine and feline hematology reference values for the ADVIA 120 hematology system.

BACKGROUND: The ADVIA 120 is a laser-based hematology analyzer with software applications for animal species. Accurate reference values would be useful for the assessment of new hematologic parameters and for interlaboratory comparisons. OBJECTIVE: The goal of this study was to establish reference intervals for CBC results and new parameters for RBC morphology, reticulocytes, and platelets in healthy dogs and cats using the ADVIA 120 hematology system. METHODS: The ADVIA 120, with multispecies software (version 1.107-MS), was used to analyze whole blood samples from clinically healthy dogs (n=46) and cats (n=61). Data distribution was determined and reference intervals were calculated as 2.5 to 97.5 percentiles and 25 to 75 percentiles. RESULTS: Most data showed Gaussian or log-normal distribution. The numbers of RBCs falling outside the normocytic-normochromic range were slightly higher in cats than in dogs. Both dogs and cats had reticulocytes with low, medium, and high absorbance. Mean numbers of large platelets and platelet clumps were higher in cats compared with dogs. CONCLUSIONS: Reference intervals obtained on the ADVIA 120 provide valuable baseline information for assessing new hematologic parameters and for interlaboratory comparisons. Differences compared with previously published reference values can be attributed largely to differences in methodology.

Animals↗

PubMed1993

1H-nuclear magnetic resonance studies of human synovial fluid in arthritic disease states as an aid to confirming metabolic activity in the synovial cavity.

1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison. 2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population. 3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis. 4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis. 5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation. 6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMedDate not supplied

Type of distribution of the test data of the optokinetic nystagmus.

In statistical analysis, the type of distribution of the population under study dictates the choice of analytical methods. Exploratory data analysis was undertaken to evaluate the type of distribution for several variables in optokinetic nystagmus: the total numbers of nystagmus (NYS), the algebraic sums of the slow-phase amplitude (AMP) and of the slow-phase velocity (VEL), and the means of the fast-phase velocity (FM). The samples were collected from 814 healthy subjects as reference data. The 5-number summaries were first calculated for each variable, and the mid-summaries for the six letter values were examined for fine structure to reveal the presence of some outliers. The upper and lower limits of the 5-number summaries were then defined to reject the outliers. After outlier rejection the distribution was examined by histogram and probability plots, and by evaluation with the chi-square test, the Kolomogorov-Smirnov test and also with skewness and kurtosis. All the variables proved to fit the normal distribution by at least three methods, except by skewness and kurtosis. Of all methods, the probability plot seems to be the best in the present evaluation.

Chi-Square Distribution↗

PubMed1997

Standardizing the immunological measurement of advanced glycation endproducts using normal human serum.

Advanced glycation endproducts (AGEs) have been linked to many sequelae of diabetes, renal disease and aging. To detect AGE levels in human tissues and blood samples, a competitive enzyme-linked immunosorbent assay (ELISA) has been widely used. As no consensus or standard research method for the quantitation of AGEs currently exists, nor a universally defined AGE unit available, the comparative quantitation of AGEs between research laboratories is problematic and restricts the usefulness of interlaboratory clinical data. By comparing the cross-reactivities of five different anti-AGE antisera with five different in vitro AGE-modified proteins, we found that the immunological recognition of AGEs by competitive ELISA is both AGE-carrier protein- and anti-AGE antibody-dependent. This suggests that in vitro AGE-modified proteins might not be appropriate standards for AGEs that occur naturally in vivo. Based on our observation that serum AGE levels in the normal human population are consistently within a narrow range and several folds lower than in diabetics, we propose a method to standardize AGE units against normal human serum (NHS). In this new method, one AGE unit is defined as the inhibition that results from 1:5 diluted NHS in the competitive AGE-ELISA; thus the AGE value in NHS is 5 units/ml. This NHS method requires a competitive AGE-ELISA with reasonable sensitivity such that 1:5 NHS produces a 25 to 40% inhibition of anti-AGE antibody binding to immobilized AGE-proteins. By using this standardized method we found that the AGE levels in normal human serum (5.0 +/- 2.2 units/ml; mean +/- SD, n = 34) fit a normal distribution (chi 2-test, p < 0.01), and the serum AGE levels in diabetic patients (20.3 +/- 3.8 units/ml, n = 7) are significantly higher than that of the normal population (p < 0.0001). Since AGE units can now be defined against a universally available standard, NHS, the results of quantitative AGE measurements using this method should be comparable between assays and between different laboratories. Taken together, standardizing the AGE-ELISA protocol as described here provides a simple and quantitative method that should facilitate the expanded application of clinical AGE data.

Adult↗

PubMed2006

Co-infection ratios versus inflammation, growth factors and progression of early atheromas.

Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP) antigens are encountered in complicated atheromas and may be implicated in the diversity of atherosclerotic lesions. Mycoplasma can downregulate the immune system, altering levels of inflammation, which may favor the proliferation of other co-infectious agents. In the present study we analyze whether initially stable human atheromas exhibit different ratios of MP/CP antigens compared to ongoing atheromatous lesions. Two groups were examined for the presence of inflammatory cells, macrophages, growth factors and infectious agents: Group I (GI), n=16, early stable atheromas, <4 CD68(+) macrophages/400 x field, showing a normal distribution and a fibrous cap; Group II (GII), n=14, growing atheromas, > or =4 CD68+ cells/400 x field, lacking a fibrous cap, showing a non-normal macrophage distribution. The amounts of CP (but not MP) antigens and lymphocytes in GI were significantly lower than in GII. MP/CP ratios were higher in GI. MP correlated with CP and PDGFB in GI (r=0.79 and r=0.83, p<0.001), but not in GII (r=-0.4 and r=-0.08, p=0.81). MP and CP antigens are already present in early atheromas, and a higher MP/CP ratio correlates with increased growth factors, lower inflammation and plaque stability.

Adult↗

PubMed1988

[Diagnosis of anterior perineal anus (APA)--significance of electromyographic evaluation of the external anal sphincter location].

APA is a common cause of constipation, and is the mild case of the imperforated anus. On diagnosing APA, anterior displacement of the anus and normal distribution of the external anal sphincter to the anus are essential. To determine the location of the anus in the perineum simple clinical technique was developed. In 61 normal cases, the result of measurement was almost same in each sex, but in 3 APA cases the location were anteriorly dislocated than normal cases. Distribution of the external anal sphincter was evaluated with electromyographic technique, and location map of the sphincter was made. In 3 APA cases, the anus was totally surrounded by the external anal sphincter, but in 17 ano-cutaneous fistula cases, the opening was anteriorly dislocated to the sphincter distribution map. As a conclusion, newly proposed simple clinical technique to determine anal location and electromyographic examination of the external and sphincter distribution are very useful in objective diagnosis of APA.

Anal Canal↗

PubMed1998

Proliferation and apoptosis in malignant and normal cells in B-cell non-Hodgkin's lymphomas.

We have examined apoptosis and proliferation in lymph node cell suspensions from patients with B-cell non-Hodgkin's lymphoma using flow cytometry. A method was developed which allowed estimation of the fractions of apoptotic cells and cells in the S-phase of the cell cycle simultaneously with tumour-characteristic light chain expression. Analysis of the tumour S-phase fraction and the tumour apoptotic fraction in lymph node cell suspensions from 95 B-cell non-Hodgkin's lymphoma (NHL) patients revealed a non-normal distribution for both parameters. The median fraction of apoptotic tumour cells was 1.1% (25 percentiles 0.5%, 2.7%). In the same samples, the median fraction of apoptotic normal cells was higher than for the tumour cells (1.9%; 25 percentiles 0.7%, 4.0%; P = 0.03). The median fraction of tumour cells in S-phase was 1.4% (25 percentiles 0.8%, 4.8%), the median fraction of normal cells in S-phase was significantly lower than for the tumour cells (1.0%; 25 percentiles 0.6%, 1.9%; P = 0.004). When the number of cases was plotted against the logarithm of the S-phase fraction of the tumour cells, a distribution with two Gaussian peaks was needed to fit the data. One peak was centred around an S-phase fraction of 0.9%; the other was centred around 7%. These peaks were separated by a valley at approximately 3%, indicating that the S-phase fraction in NHL can be classified as 'low' (< 3%) or 'high' (> 3%), independent of the median S-phase fraction. The apoptotic fractions were log-normally distributed. The median apoptotic fraction was higher (1.5%) in the 'high' S-phase group than in the 'low' S-phase group (0.8%; P = 0.02). However, there was no significant correlation between the two parameters (P > 0.05).

Adult↗

PubMed1986

MRI of brain iron.

A prominently decreased signal intensity in the globus pallidum, reticular substantia nigra, red nucleus, and dentate nucleus was routinely noted in 150 consecutive individuals on T2-weighted images (SE 2000/100) using a high field strength (1.5 T)MR system. This MR finding correlated closely with the decreased estimated T2 relaxation times and the sites of preferential accumulation of ferric iron using the Perls staining method on normal postmortem brains. The decreased signal intensity on T2-weighted images thus provides an accurate in vivo map of the normal distribution of brain iron. Perls stain and MR studies in normal brain also confirm an intermediate level of iron distribution in the striatum, and still lower levels in the cerebral gray and white matter. In the white matter, iron concentration is (a) absent in the most posterior portion of the internal capsule and optic radiations, (b) higher in the frontal than occipital regions, and (c) prominent in the subcortical "U" fibers, particularly in the temporal lobe. There is no iron in the brain at birth; it increases progressively with aging. Knowledge of the distribution of brain iron should assist in elucidating normal anatomic structures and in understanding neurodegenerative, demyelinating, and cerebrovascular disorders.

Adolescent↗

PubMed1984

[Glycogen distribution in rat hepatocyte populations after a single exposure to 4-dimethylaminoazobenzine and subsequent injections of phenobarbital].

7 day after a single interperitoneal injection of carcinogen 4-dimethylaminoazobenzen (DAB), a little number of cells with high glycogen contents was found in parallel with a decreased glycogen content in most isolated hepatocytes. 1.5 months after DAB injection, the normal distribution of glycogen content was seen restored in hepatocytes. The treatment of rats with phenobarbital (6 PhB injections 7 days after DAB application) blocked the restoration of the normal glycogen distribution. 2 months after the last PhB injection (3 months after DAB injection) an increased glycogen content was found in the smallest hepatocytes.

Animals↗

PubMed2005

Heterozygous insertions alter crossover distribution but allow crossover interference in Caenorhabditis elegans.

The normal distribution of crossover events on meiotic bivalents depends on homolog recognition, alignment, and interference. We developed a method for precisely locating all crossovers on Caenorhabditis elegans chromosomes and demonstrated that wild-type animals have essentially complete interference, with each bivalent receiving one and only one crossover. A physical break in one homolog has previously been shown to disrupt interference, suggesting that some aspect of bivalent structure is required for interference. We measured the distribution of crossovers in animals heterozygous for a large insertion to determine whether a break in sequence homology would have the same effect as a physical break. Insertions disrupt crossing over locally. However, every bivalent still experiences essentially one and only one crossover, suggesting that interference can act across a large gap in homology. Although insertions did not affect crossover number, they did have an effect on crossover distribution. Crossing over was consistently higher on the side of the chromosome bearing the homolog recognition region and lower on the other side of the chromosome. We suggest that nonhomologous sequences cause heterosynapsis, which disrupts crossovers along the distal chromosome, even when those regions contain sequences that could otherwise align. However, because crossovers are not completely eliminated distal to insertions, we propose that alignment can be reestablished after a megabase-scale gap in sequence homology.

Animals↗

PubMed1989

[A statistical study on distribution patterns of plasma free amino acids].

We investigated the distribution patterns of 23 plasma free amino acids in 875 healthy adults (375 males and 500 females, aged from 30 to 50 years), which were obtained after an overnight fast, using three statistical parameters of MLL (Maximum Logarithmic Likelihood), square root of b1, b2, and selected their patterns from the three of ordinary normal, log-normal and square root-normal distributions. The distribution patterns of the majority of plasma free amino acids were found to be either log-normal or square root-normal, and occasionally ordinary normal. We also evaluated the reliability of our selection system by a simulation model of 100 sets of values for plasma free amino acids that were randomly determined by the parameters of original data. Good reliability was observed for some amino acids. Our selection system may be useful for comparing the present results with the future results that will be obtained by other methods.

Adult↗

PubMed1999

[Visualization of normal organs in whole-body FDG-PET imaging].

It is important to know FDG accumulation in the normal distributions for interpreting whole-body PET imaging for tumor detection. Twenty-eight normal subjects were studied with whole-body PET imaging and were examined the intensity of FDG uptake in major organs and the factors which caused it's variety. Emission images were acquired and images were reconstructed without attenuation correction. The intensity of FDG uptake was classified into 4 grades visually. No accumulation was found in the thyroid, the esophagus and the spleen. The oral cavity, the liver, the stomach, and the colon were visualized in all subjects. The laryngeal muscle, the cervical muscle, and the heart accumulated FDG with various grade from 1 to 4 grades. No association was found between the intensity of uptake in the organs and volunteer's age. The fasting time was shorter in volunteers whose heart showed "high" grade than those showed less accumulation (p < 0.05). Serum concentration of free fatty acid was significantly lower in them, too (p < 0.05). Various FDG uptake was observed in many organs, especially the laryngeal muscle, the cervical muscle, and the heart. In our study, there was no facter which caused FDG uptake in organs except for the fasting time and the value of free fatty acid in the heart. Such analysis of whole-body FDG distributions in the normal subjects is valuable for tumor detection with FDG-PET.

Adult↗

PubMed1994

Sequential method of estimating the LD50 using a modified up-and-down rule.

In this paper, the original up-and-down method, modified up-and-down method, the Robbins-Monro method, and a fixed-sample Spearman-Kärber method are compared for the point estimator as well as the confidence interval of LD50. In particular, three different designs of the modified up-and-down approach based on the combination of experiments on one test space and reduced test space are investigated. The standard normal distribution and chi-square distribution are used as tolerance distributions. Simulation results indicate that the modified up-and-down method tends to be somewhat better than the original up-and-down method in terms of the mean squared error under normal tolerance distribution. In case of chi-square distribution, the modified method is shown to be substantially better when the test space is wide and the initial dose is further away from the LD50.

Lethal Dose 50↗

PubMed2001

Using Johnson's transformation and robust estimators with heteroscedastic test statistics: an examination of the effects of non-normality and heterogeneity in the non-orthogonal two-way ANOVA design.

The present study proposes a procedure that combines Johnson's transformation and the trimmed means method to deal with the problem of non-normality. An approximate test such as the Alexander-Govern test or Welch-James type test is then employed to deal with the heterogeneity of cell variance in the non-orthogonal two-way fixed effects completely randomized design. Both unweighted and weighted means analyses are considered. The empirical Type I error rates and the statistical power for comparing population means are investigated by Monte Carlo simulation. The simulated results show that Johnson's transformation with trimmed mean and the approximate test is valid in terms of Type I error rate control, and that the magnitude of the statistical power for non-normal distributions is better than that of conventional methods.

Analysis of Variance↗

PubMed2004

Theoretical analysis of drug release into a finite medium from sphere ensembles with various size and concentration distributions.

Release kinetics for heterogeneous sphere ensembles with a dissolved drug, i.e., initial drug loading below or equal to the drug solubility in the matrix, in a finite external medium was modeled with consideration of heterogeneity among and within spheres. Numerical solutions were obtained using the finite element method for sphere ensemble with normal or log-normal distribution of particle size or initial drug loading among spheres. Exact series solutions were derived for ensembles with various initial loading distributions within spheres, namely linear, quadratic, sigmoidal and uniform distribution, using their mean or average radii. Simplified solutions retaining only one term of the series for non-uniform distributions and three terms for uniform distribution were suggested because of their good approximation to the exact solution. The results of finite element analysis showed that the release rate of an ensemble decreased with increasing standard deviation of particle size. Using weight-average radii in the exact solution gave a prediction of release profile closer to that from the actual size distribution than using mean radii. The three non-uniform loading patterns within spheres all showed reduced initial burst and release rate, leading to more steady release rates than uniform loading, among which the sigmoidal distribution offered the best near-zero order release. Non-uniform initial loading among spheres seemed to have insignificant influence on the release profiles. The volume ratio of liquid to a sphere ensemble played an important role in release kinetics. The derived analytical solutions are applicable to multiple spheres or a single sphere in a finite medium or in a perfect sink.

Algorithms↗