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PubMed1983

Direct evaluation of fluorescence in single renal epithelial cells using a mitochondrial probe (DASPMI).

The study of distribution and quantitation of a fluorescent probe in living epithelia with the aid of an inverted microscope requires that individual cells can be analysed without optical interference from adjacent cells. This report describes the application of fluorescence microscopy and fluorometry to a recently developed in vitro culture system of renal epithelial cells. Epithelial cells derived from the mammalian renal cortical collecting tubule (CT) and the thick ascending loop of Henle (TAL) are cultivated as continuous monolayers in serum-free, hormone-supplemented media. A specific mitochondrial marker (DASPMI) is added to the medium and incorporated into the cytoplasm. The microscopic image reveals that the mitochondrial fluorescence distribution differs between CT and TAL cultures. The fluorometric quantitation shows a normally distributed histogram of medium-range intensity in TAL cell cultures while CT cultures exhibit a two-peak pattern of mitochondrial fluorescence distribution among epithelial cells.

Animals↗

PubMed1994

CD44 expression in alopecia areata and androgenetic alopecia.

CD44 is a widely distributed cell surface protein thought to be involved in multiple steps of normal immune cell function, including T-cell activation, and in cellular adhesion where it mediates cell attachment to hyaluronate. In normal skin, CD44 is found by immunohistochemical means to be primarily in eccrine coil cells. In this study, we have looked at the expression of CD44 in normal scalp and in two different hair disorders, androgenetic alopecia and alopecia areata. In normal scalp and androgenetic alopecia, CD44 was found in its normal distribution in eccrine coil cells. In scalp of 30 patients with alopecia areata, there was no expression of this glycoprotein. Patients were also assessed pre and post treatment for their alopecia areata, and even though they had no significant hair regrowth, 2 patients regained expression of CD44, indicating a variable expression of this protein in the alopecia areata disease process. The absence of CD44 expression in alopecia areata-affected scalp may give further information regarding the pathogenesis of this disease.

Adolescent↗

PubMed2003

Platelet hyperactivity after statin treatment discontinuation.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Adult↗

PubMed1990

Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus.

The diminished ability of insulin to promote glucose disposal and storage in muscle has been ascribed to impaired activation of glycogen synthase (GS). It is possible that decreased glucose storage could occur as a consequence of decreased glucose uptake, and that GS is impaired secondarily. Muscle glucose uptake in 15 diabetic subjects was matched to 15 nondiabetic subjects by maintaining fasting hyperglycemia during infusion of insulin. Leg muscle glucose uptake, glucose oxidation (local indirect calorimetry), release of glycolytic products, and muscle glucose storage, as well as muscle GS and pyruvate dehydrogenase (PDH) were determined before and during insulin infusion. Basal leg glucose oxidation and PDH were increased in the diabetics. Insulin-stimulated leg glucose uptake in the diabetics (8.05 +/- 1.41 mumol/[min.100 ml leg tissue]) did not differ from controls (5.64 +/- 0.37). Insulin-stimulated leg glucose oxidation, nonoxidized glycolysis, and glucose storage (2.48 +/- 0.27, 0.68 +/- 0.15, and 5.04 +/- 1.34 mumol/[min.100 ml], respectively) were not different from controls (2.18 +/- 0.12, 0.62 +/- 0.16, and 2.83 +/- 0.31). PDH and GS in noninsulin-dependent diabetes mellitus (NIDDM) were also normal during insulin infusion. When diabetics were restudied after being rendered euglycemic by overnight insulin infusion, GS and PDH were reduced compared with hyperglycemia. Thus, fasting hyperglycemia is sufficient to normalize insulin-stimulated muscle glucose uptake in NIDDM, and glucose is distributed normally to glycogenesis and glucose oxidation, possibly by normalization of GS and PDH.

Alanine↗

PubMed1995

Daily estimates of soil ingestion in children.

Soil ingestion estimates play an important role in risk assessment of contaminated sites, and estimates of soil ingestion in children are of special interest. Current estimates of soil ingestion are trace-element specific and vary widely among elements. Although expressed as daily estimates, the actual estimates have been constructed by averaging soil ingestion over a study period of several days. The wide variability has resulted in uncertainty as to which method of estimation of soil ingestion is best. We developed a methodology for calculating a single estimate of soil ingestion for each subject for each day. Because the daily soil ingestion estimate represents the median estimate of eligible daily trace-element-specific soil ingestion estimates for each child, this median estimate is not trace-element specific. Summary estimates for individuals and weeks are calculated using these daily estimates. Using this methodology, the median daily soil ingestion estimate for 64 children participating in the 1989 Amherst soil ingestion study is 13 mg/day or less for 50% of the children and 138 mg/day or less for 95% of the children. Mean soil ingestion estimates (for up to an 8-day period) were 45 mg/day or less for 50% of the children, whereas 95% of the children reported a mean soil ingestion of 208 mg/day or less. Daily soil ingestion estimates were used subsequently to estimate the mean and variance in soil ingestion for each child and to extrapolate a soil ingestion distribution over a year, assuming that soil ingestion followed a log-normal distribution.

Child, Preschool↗

PubMed2000

Rates of GDP referral of complete dentures to a teaching hospital.

PURPOSE OF STUDY: To identify areas and sites of excessive referral of complete dentures by GDPs, allowing for factors which might distort referral rates. METHODS: Two hundred and six consecutive valid referrals of patients over the age of 50 years with complete dentures to a local dental teaching hospital and originating from the 29 Sheffield electoral wards were audited from the beginning of 1995 to the end of 1997. The referring practitioner and electoral ward were recorded. RESULTS: Referral rates were calculated according to the size of the 50+ population within each ward and were found to be normally distributed, following exclusion of two wards with much higher referral rates than normal (3.5 and 6 SDs [standard deviations] from the mean). After calculating mean numbers referred per full-time equivalent (FTE) GDP for all wards, practices and practitioners originating excessive numbers of referrals within a high-referring ward could be identified. CONCLUSION: After taking into account factors which might permit a high referral rate to be acceptable, practices with inappropriately high referral rates can be identified and remedial teaching need pinpointed.

Aged↗

PubMed1999

Analysis of urinary nitric oxide metabolites in healthy subjects.

Nitric oxide (NO) has divergent actions under physiological and pathological conditions. NO is rapidly decomposed to nitrite (NO2-) and nitrate (NO3-). Since these metabolites are stable, they are good indices of NO production under various conditions. In the present study, we measured NO2- and NO3- concentrations in the urine collected from 62 hospital controls and 504 healthy subjects by means of a new HPLC system combined with Griess reaction. NOx was the sum of NO2- and NO3-. There was no considerable inter-day variation in urinary NO metabolite levels, and there was close correlation between NO2-, NO3- and NOx values in spot urine obtained in the early morning and those in 24-h stored urine in hospital controls. Urinary NO metabolite levels, which were corrected by creatinine (Cr) excretion and expressed on a logarithmic scale, showed normal distribution and were independent of sex and age in healthy subjects. The normal ranges of urinary NO2-, NO3- and NOx levels were estimated as 17-72 micromol/g Cr, 1,023-2,818 pmol/g Cr, and 1,071-2,951 micromol/g Cr, respectively. We also found that urinary NO metabolite levels were lower than normal range in patients with various diseases.

Adolescent↗

PubMed2000

Inference for the cost-effectiveness acceptability curve and cost-effectiveness ratio.

The aim of this article is to consider Bayesian and frequentist inference methods for measures of incremental cost effectiveness in data obtained via a clinical trial. The most useful measure is the cost-effectiveness (C/E) acceptability curve. Recent publications on Bayesian estimation have assumed a normal posterior distribution, which ignores uncertainty in estimated variances, and suggest unnecessarily complicated methods of computation. We present a simple Bayesian computation for the C/E acceptability curve and a simple frequentist analogue. Our approach takes account of errors in estimated variances, resulting in calculations that are based on distributions rather than normal distributions. If inference is required about the C/E ratio, we argue that the standard frequentist procedures give unreliable or misleading inferences, and present instead a Bayesian interval.

Antirheumatic Agents↗

PubMed2005

Error distribution for gene expression data.

We present a new instance of Laplace's second Law of Errors and show how it can be used in the analysis of data from microarray experiments. This error distribution is shown to fit microarray expression data much better than a normal distribution. The use of this distribution in a parametric bootstrap leads to more powerful tests as we show that the t-test is conservative in this setting. We propose a biological explanations for this distribution based on the Pareto distribution of the variables used to compute the log ratios.

Journal Article↗

PubMed1998

Preparation and characterization of oil-in-water type poly (D,L-lactic acid) microspheres containing testosterone enanthate.

Poly (D,L-lactic acid) (PLA) microspheres containing testosterone enanthate (ET) were prepared by using an oil-in-water (O/W) emulsion technique. The size distribution of the microspheres obtained could be explained by a log-normal distribution, and as a result, it was found that ET fully incorporates into microspheres even when the drug is loaded at up to 50%. On the other hand, the dissolution behavior of ET from microspheres was strongly dependent on particle size, suggesting that dissolution of the drug from microspheres can be easily controlled by controlling the preparative conditions.

Calorimetry, Differential Scanning↗

PubMed2004

A simple method for the estimation of recombination frequencies and genetic distances.

We have developed an alternative approach to the maximum likelihood method for calculating recombination values and linkage intensities. This new method is simpler than those in current use in that it obviates the need for formulae and tables. Maximum likelihood methods imply the use of iterative procedures over highly complicated estimation equations (at least second degree polynomials), whereas simplified methods use single-step procedures involving simple linear equations. The proposed method uses the frequencies of the distinguishable phenotypes that came from the union of at least one recombinant gamete with another gamete. We performed Monte-Carlo simulations for various combinations of genetic distance and offspring size. The recombination values obtained using the new method were compared with those derived by the maximum likelihood method on both simulated and experimental data. They were found to be nearly identical. The observed distribution of the recombination frequency values does not differ significantly from the Normal distribution, except for extreme values of the mean, as the Skewedness and kurtosis coefficients do not differ from zero. Our method has a similar accuracy to the maximum likelihood methods for recombination frequencies smaller than 25 cM and the difference does not increase greatly for greater frequencies.

Chromosome Mapping↗

PubMed1988

Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein.

Ultrastructural study of mucosal eosinophils in a case of eosinophilic gastroenteritis involving stomach, duodenum and ileum showed an altered structure in ulcerated duodenal areas. The electron core density of eosinophil granules was inverted or disappeared and tubulovesicular structures occurred. Using immunogold staining with specific antibodies, major basic protein was detected diffusely in the matrix of eosinophil granules and out of the granules in tight association with extragranular membrane formations. In contrast, eosinophil cationic protein and eosinophil peroxidase were normally distributed in the granule matrix. When compared with the eosinophils in macroscopically normal duodenal mucosa in the same patient, these changes support a role for major basic protein in tissue damage in eosinophilic gastroenteritis. The diffusion of one granule protein from the granules to the exterior of the cells favours the view of a selective release of eosinophil mediators.

Adult↗

PubMed1985

Line transect estimators for left-truncated distributions.

Left-truncated line transect data sets may occur when surveying with certain types of aircraft where the observer cannot look straight down. A general model of left-truncation in line transect sampling is developed and parametric estimators are derived in such cases when the underlying distribution of right-angle distances is either exponentially or half-normally distributed. Computer simulations demonstrate the validity of the derived estimators and the expected nonrobustness against alternative distributions. An aerial survey example using dolphin data is presented.

Animals↗

PubMed1977

[Use of various accordance measures in the study of sick leave frequency distribution per man-year].

In the studies of a wide number of phenomena very often an attempt to describe their distributions with the help of certain theoretical distributions is undertaken. Pearson's chi2 and Kolmogorovs lambda traditional tests, when applied to the evaluation of accordance between the empirical distribution and the distribution calculated on the basis of theoretical probability function, depend directly on the dimensions of population studied, and they are not useful in the case of big quantities. In the paper the author presents a great number of measures for two (empirical and theoretical) distributions accordance and their application to the study of sick-leave frequency distribution per man per year. On the basis of received results a high level of distributions accordance between the sick leave cases distribution and the negative binomial distribution has been observed. The distribution of sick leave shows a high accordance with the logarithmically-normal distribution. In the light of the above mentioned distribution study, the imperfection of Pearson's chi2 and Kolmogorov's lambda tests can be ascertained. In the case of big quantities the evaluation of distributions accordance seems to require the application of the accordance measures based on relative quantities.

Absenteeism↗

PubMed1996

Quasilikelihood estimation in measurement error models with correlated replicates.

We consider quasilikelihood models when some of the predictors are measured with error. In many cases, the true but fallible predictor is impossible to measure, and the best one can do is to obtain replicates of the fallible predictor. We consider the case that the replicates are not independent. If one assumes that replicates are independent and they are not, one typically underestimates the extent of the measurement error, leading to an inconsistent errors in variables correction. We devise techniques for estimating the measurement error covariance matrix. In addition, we discuss how one might perform a quasilikelihood analysis by computing the mean and variance functions of the observed data, both using approximations and also exactly through a Monte Carlo method. The methods are illustrated on a data set involving systolic blood pressure and urinary sodium chloride, where the measurement errors appear to be approximately normally distributed but highly correlated, and the distribution of the true predictor is reasonably modeled as a mixture of normals.

Analysis of Variance↗

PubMed1976

[Bivariate evaluation of laboratory findings: immunoglobulin G and albumin in cerebrospinal fluid (author's transl)].

Using radial immunodiffusion, albumin and immunoglobulin G were determined in non-preconcentrated cerebrospinal fluid from 127 controls and from 239 patients. In controls the concentrations of albumin and immunoglobulin G followed normal distribution. The two variables were correlated linearly (r = 0.60). The elliptic bivariate normal range was calculated, and was found to contain 95% of the paired values. As a clinical limit, this range discriminated more effectively between normal and altered pairs than the two one-dimensional normal ranges X+/-2 s, thus improving the evaluation of laboratory findings in the single case. Likewise in clinically defined groups of patients, bivariate evaluation of results provided additional evidence. In many distinct clinical syndromes, e.g. bacterial encephalomeningitis, polyneuropathy, amyotrophic lateral sclerosis, albumin and immunoglobulin G concentrations exhibited an especially close correlation, probably resulting from damage to the blood-cerebrospinal fluid barrier. However, no correlation of these two variables was detected in acute encephalomeningitis due to virus infection, and in multiple sclerosis: in these groups, immunoglobulin G concentrations were elevated independently of albumin. Since evidence is lacking as to the pathogenesis of multiple sclerosis, it seems noteworthy that the same phenomenon was observed in a well-defined group of viral infections.

Albumins↗

PubMed2005

Cluster aggregation and fragmentation kinetics model for gelation.

Gelation can occur in polymer, hydrogel, and colloid systems that undergo reversible aggregation-fragmentation (crosslinking accompanied by breakage). Gelation, characterized by rapid divergence of weight-average molecular weight and viscosity due to initial network formation, can be reversed if conditions change. In this paper, reversible aggregation and fragmentation in the pre-gelation time period are modeled with distribution kinetics. Moment equations are obtained from the population balance equation, and solved for eight different rate kernels. We identify the cases for which gelation is possible and obtain the critical values for the rate constants that allow gelation. The model provides a good simulation of published experimental data for aggregation and degradation of plasticized wheat gluten during thermo-mechanical treatments. We also evaluate two closure approximations based on Gamma and log-normal distributions, and conclude that log-normal closure predicts all five possible steady states, in agreement with the Vigil-Ziff criterion, and Gamma closure predicts only three. However, Gamma closure approximates the steady state either closely or exactly, whereas log-normal closure only poorly approximates the steady-state distribution.

Journal Article↗

PubMed1986

Prevalence of plaque, gingivitis and caries in 11-12-year-old children in South Wales.

The overall eruption and dental disease status of a group of 1015 11-12-yr-old schoolchildren in South Wales is presented. The mean number of teeth erupted was 21.8 with a distribution pattern reflecting continuing eruption of teeth at this age. Almost equal numbers of contralateral and opposing tooth types were present with exceptions including maxillary canines and lateral incisors. DMFT, DMFS, and DFS scores were consistent with other recent studies. The mean plaque score was 2.44 and showed a normal distribution for the group. All children had gingivitis at one or more sites as evidenced by bleeding on probing, and again the distribution pattern was a normal one. The mean pocketing was 1.24 mm and there was little clinical evidence of chronic periodontitis. As expected, plaque and gingivitis showed a very high and significant correlation, with plaque and pocketing and gingivitis and pocketing having lower correlation coefficients which were nevertheless highly significant.

Child↗