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Characterization of hydrophilic and lipophilic pathways of Hedera helix L. cuticular membranes: permeation of water and uncharged organic compounds.

The permeability of astomatous leaf cuticular membranes of Hedera helix L. was measured for uncharged hydrophilic (octanol/water partition coefficient log K(O/W) < or =0) and lipophilic compounds (log K(O/W) >0). The set of compounds included lipophilic plant protection agents, hydrophilic carbohydrates, and the volatile compounds water and ethanol. Plotting the mobility of the model compounds versus the molar volume resulted in a clear differentiation between a lipophilic and a hydrophilic pathway. The size selectivity of the lipophilic pathway was described by the free volume theory. The pronounced tortuosity of the diffusional path was caused by cuticular waxes, leading to an increase in permeance for the lipophilic compounds after wax extraction. The size selectivity of the hydrophilic pathway was described by hindered diffusion in narrow pores of molecular dimensions. A distinct increase in size selectivity was observed for hydrophilic compounds with a molar volume higher than 110 cm3 mol(-1). Correspondingly, the size distribution of passable hydrophilic pathways was interpreted as a normal distribution with a mean pore radius of 0.3 nm and a standard deviation of 0.02 nm. The increased permeance of the hydrophilic compounds by the removal of cuticular waxes was attributed to an increase in the porosity, a decrease in the tortuosity, and a widening of the pore size distribution. Cuticular transpiration resulted from the permeation of water across the hydrophilic pathway. The far-reaching implications of two parallel pathways for the establishment of correlations between cuticular structure, chemistry, and function are discussed.

Diffusion↗

Application of the anthropometric discriminant functions in estimation of carrier probabilities in Martin-Bell syndrome.

A method of estimating the likelihood ratio and the risk of an individual being affected with Martin Bell syndrome (MBS) from anthropometric measurements is described. The procedure is based on the discriminant functions (one for each sex), generated in our previous study in order to separate the individuals with MBS from the normal individuals. The procedure is illustrated by the examples of estimating the likelihood and the likelihood ratio in four individuals of either sex, belonging to MBS families, where the discriminant score value obtained from each individual is compared with the empirical (normalized) distribution of discriminant scores from the known MBS and normal subjects of a corresponding sex. The ways in which the risk of an individual being MBS is estimated in the general population or in members of the MBS families are indicated. The limitations of the discriminant diagnosis based on body measurements, as well as its particular applications in studies of the Martin-Bell syndrome, are discussed.

Anthropometry↗

Gangliosides in axolemmal and synaptic membrane fractions from developing rats: effects of maternal ethanol consumption on offspring.

Previous work from this laboratory has shown that in utero exposure to ethanol significantly alters the synthesis of glycoproteins in synaptic, axolemmal, and myelin membranes from developing rats. In an attempt to determine whether in utero exposure to ethanol similarly alters the synthesis of other glycoconjugates involved with cell-cell interactions, the present study examined the influence of chronic maternal ethanol consumption prior to parturition on the content and synthesis of gangliosides in axolemmal and synaptic plasma membranes from developing rats. The results demonstrate that, in contrast to central nervous system glycoproteins, synaptic and axolemmal glycolipids are minimally affected by in utero exposure to ethanol. At all ages examined (17 to 34 days of age), the offspring of control and ethanol-treated rats had a comparable distribution of radiolabel among synaptic and axolemmal gangliosides, a normal concentration of ganglioside sialic acid in synaptic plasma membranes, and a near-normal distribution of sialic acid among synaptic gangliosides. The present study provides evidence which indicates that the radiolabeling patterns of axolemmal and synaptic membrane gangliosides are similar. Specifically, the most heavily labeled synaptic and axolemmal gangliosides were GT1b (20-37% of the total radioactivity) and GD1a (20-32%). A smaller proportion of radioactivity was associated with GD1b (approximately 11-16%), GM1 (5-10%), and GQ1b (4-11%), as well as with GD3 and the other monosialogangliosides (less than 5%). During the age period examined the proportion of radioactive GT1b increased in both membrane fractions.

Animals↗

An analytical framework for relating dose, risk, and incidence: an application to occupational tuberculosis infection.

An adverse health impact is often treated as a binary variable (response vs. no response), in which case the risk of response is defined as a monotonically increasing function R of the dose received D. For a population of size N, specifying the forms of R(D) and of the probability density function (pdf) for D allows determination of the pdf for risk, and computation of the mean and variance of the distribution of incidence, where the latter parameters are denoted E[SN] and Var[SN], respectively. The distribution of SN describes uncertainty in the future incidence value. Given variability in dose (and risk) among population members, the distribution of incidence is Poisson-binomial. However, depending on the value of E[SN], the distribution of incidence is adequately approximated by a Poisson distribution with parameter mu = E[SN], or by a normal distribution with mean and variance equal to E[SN] and Var[SN]. The general analytical framework is applied to occupational infection by Mycobacterium tuberculosis (M. tb). Tuberculosis is transmitted by inhalation of 1-5 microns particles carrying viable M. tb bacilli. Infection risk has traditionally been modeled by the expression: R(D) = 1 - exp(-D), where D is the expected number of bacilli that deposit in the pulmonary region. This model assumes that the infectious dose is one bacillus. The beta pdf and the gamma pdf are shown to be reasonable and especially convenient forms for modeling the distribution of the expected cumulative dose across a large healthcare worker cohort. Use of the the analytical framework is illustrated by estimating the efficacy of different respiratory protective devices in reducing healthcare worker infection risk.

Cohort Studies↗

Modelling of reference values for size at birth.

Data from the Swedish Medical Birth Registration, 1977-1981 were used to apply methods of constructing reference standards for size at birth. Using clinical information a 'healthy' sub-population was extracted. The conditional distributions of birthweight (BW) and birthlength (BL) for each week of Gestational age, and the conditional distribution of birthweight given birthlength were modelled using truncated Normal distributions, after making use of Box-Cox power transformations. Spline functions were then used in conjunction with a multiplicative method to obtain appropriate percentage point curves. Examples of this analysis are given.

Birth Weight↗

Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes.

A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous.

Adolescent↗

Assessment of the thigh cuff technique for measurement of dynamic cerebral autoregulation.

BACKGROUND AND PURPOSE: Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique. METHODS: Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9. RESULTS: The ARI values for this sample population follow a normal distribution, with a mean+/-SD of 4.98+/-1.06 (n=15). Analysis of the cumulative mean ARI values of all subjects showed an exponential-type convergence of ARI toward the sample mean as the number of test iterations increased. The population average blood pressure drop on thigh cuff release was 26.4+/-7.1 mm Hg (n=16), occurring in 4.6+/-1. 7 seconds. The corresponding population average drop for CBFV was 15. 6+/-5.8 cm/s, taking 2.5+/-1.0 seconds. No significant trend was noted in the measurements as the number of test iterations increased. The correlation between the predicted and actual CBFV, having a mean value of 0.76+/-0.19, showed evidence of a nonlinear relationship to ARI values. Significant correlation was also found between ARI and (1) arterial blood pressure before cuff release and (2) the magnitude of the drop in CBFV on cuff release. CONCLUSIONS: The distribution of ARI values is not significantly different from normal. At least 3 iterations of the test procedure should be performed and averaged to obtain the mean ARI for each subject. There is no significant evidence of physiological accommodation as the number of test iterations increases. The effects of mean blood pressure and the magnitude of the change in CBFV should be considered as possible covariates when ARI data are analyzed.

Adult↗

Plasma and 24 h-urinary catecholamine concentrations in normal and patient populations.

Using a single HPLC-ECD methodology, plasma catecholamine data were compiled from 545 patients and 144 healthy subjects, and 24 h urinary free catecholamine data from 106 patients. From these data, normal reference ranges were derived for the clinical investigation of suspected phaeochromocytomas, specifically to address the question as to when a result is normal and when further investigation may be required. We have shown that noradrenaline and adrenaline concentrations in plasma and urine are not normally distributed, and basal plasma noradrenaline is significantly lower in normal volunteers than in hospital patients. We have also demonstrated that a reference range which does not take account of these factors will give a significant number of false-positive results. Age and sex did not appear to be significant variables for either plasma or urinary catecholamines. In the investigation of phaeochromocytoma, 95% confidence limits may be used as a warning to repeat sampling and 99% confidence limits as rendering the diagnosis extremely probable. In patients with phaeochromocytomas, urinary catecholamines had a 99.5% specificity and 100% sensitivity in the diagnosis, and thus provide for a rapid and efficient diagnostic screen.

Adolescent↗

Determining sensitivity of mammography from screening data, cancer incidence, and receiver-operating characteristic curve parameters.

OBJECTIVES: A mathematical model is presented that allows the computation of the sensitivity and specificity of breast screening based on receiver-operating characteristic (ROC) curve shape, the positive predictive value (PPV) of screening mammography, and the cancer incidence, f. METHODS: The normal and cancer populations are modeled as normal distributions with independent means and standard deviations. The distributions are scaled such that the area of the normal population is equal to 1-f and that of the cancer population is f. The PPV for screening mammography is used to determine the operating point on the ROC curve. Knowing this leads directly to the computation of sensitivity and specificity. The derivation is general and is applicable to both symmetrical and asymmetrical ROC curves. RESULTS: For symmetric ROC curves and typical values for the PPV of mammography (about 8%) and cancer incidence (f= 0.003), an A(z) value of 0.95 was required to achieve 63% sensitivity and an A. value of 0.98 led to 86% sensitivity. CONCLUSION: A model was developed that should allow researchers to deduce sensitivity and specificity for screening mammography based on ROC curve measurements and using realistic values of PPV and f. This model allows A. values to be related to the probability of breast cancer detection.

Breast Neoplasms↗

Interindividual variations in enzymes controlling organophosphate toxicity in man.

1 Interindividual variations in an unexposed population have been defined for five enzymes involved in organophosphate (OP) toxicity. The enzymes measured were: red blood cell acetylcholinesterase (AChE), lymphocyte neuropathy target esterase (NTE), serum cholinesterase (ChE), serum paraoxonase and serum arylesterase. 2 AChE and arylesterase were normally distributed in the population whilst the distribution of NTE, ChE and paraoxonase deviated significantly from normal. 3 Assay precision and intra-individual variability were measured for each of the enzymes; the effect on interindividual variation was assessed. 4 Variations in enzyme activities between individuals could have profound effects on susceptibility to OP toxicity. Prior determination of these enzymes may be predictive of susceptibility. 5 Lymphocyte NTE has some limitations as an indicator of exposure to neurotoxic OPs.

Acetylcholinesterase↗

Airborne exposure and soil levels associated with lead abatement of a steel tank.

This study reports on airborne exposure levels and soil concentrations of lead in regard to abatement of a steel structure (water tank). The tank was de-leaded by abrasive sand blasting. The ball of the tank had a lead surface level that exceeded the Environmental Protection Agency (EPA) definition of lead-based paint (LBP) (0.5% lead), but paint on stem and base was below this criterion. Personal and area airborne samples were collected during different activities of lead abatement of the tank. Summary results suggest during abrasive blasting of ball and stem/base personal exposure levels, as reported with arithmetic and geometric means, exceed the Occupational Safety and Health Administration (OSHA) permissible exposure limit (50 microg/m3). Highest personal exposure (occupational exposure) was associated with blasting of ball. Distribution of airborne and soil samples suggest non-normality and is best represented by a logarithmic form. Geometric standard deviations for air and soil lead support a non-normal distribution. Outlying values were found for personal and area air samples. Exposure levels associated with blasting stem/base section of tank support OSHA's policy requiring air monitoring of work at levels below the criterion established by EPA in identifying LBP. Area samples were statistically lower than personal samples associated with blasting ball and stem/base of tank. Exposure data suggest that workers performing abatement on steel structures have elevated lead exposure from surface lead. Respirator protection requirements are discussed. Soil lead concentration was suggested to decrease as distance increased from tank. Soil lead is suggested to be a result of deposition from LBP on tank surface. Minimal efforts were required to reduce average lead soil levels below EPA's upper acceptable criterion (1200 ppm Pb).

Air Pollutants, Occupational↗

Altered circadian blood pressure profile and prognosis.

BACKGROUND: In a previous analysis of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale we found a higher rate of cardiovascular morbid events among hypertensive nondippers than we did among dippers (5.86 versus 1.18 events per 100 person-years, P = 0.0002) for women, whereas the difference between the two groups was smaller and not statistically significant for men (4.15 versus 2.48 events per 100 person-years). These differences held in a multivariate analysis after adjustment for several confounders including average 24 h ambulatory blood pressure. In another analysis, the rate of occurrence of cardiovascular end-points was higher among nondippers than it was among dippers regardless of the definition of day and night (0600-2200 h and 2200-0600 h, awake and asleep, and 1000-2000 h and 2400-0600 h) and of the dividing line between dippers and nondippers (10 versus 0% day-night difference in blood pressure). OBJECTIVE: To test in a subsequent analysis based on a larger sample and a longer follow-up period, for both sexes, the prognostic value of a blunted diurnal rhythm of blood pressure. METHOD: We used the night: day ratio of ambulatory blood pressure, a continuous and normally distributed variable. RESULTS: A night: day systolic blood pressure ratio > 0.899 for men and > 0.909 for women (upper tertiles of distributions) identified a subset of subjects with greater than normal cardiovascular risk for any level of concomitant risk factors, wherease the hight:day diastolic blood pressure ratio was not statistically significant as an independent predictor. The excess risk for subjects in the upper tertile of the night: day systolic blood pressure ratio held after adjustment for several risk markers, including average 24 h ambulatory blood pressure. CONCLUSION: These data suggest that a blunted reduction in blood pressure from day to night predicts an increased cardiovascular morbidity at any level of concomitant risk factors including average 24 h ambulatory blood pressure. Nondippers can be defined in terms of a night: day ambulatory systolic blood pressure ratio > 0.899 for men and > 0.909 for women, regardless of the diastolic blood pressure profile.

Journal Article↗

[The increase and decrease of the total pollen counts of Sugi (Cryptomeria japonica) due to abnormal weather during pollen scattering season].

We investigated the changing total number of airborne pollen grains of Sugi (Cryptomeria japonica) due to abnormal weather during pollen scattering season. The pollen season was divided into 7 periods by the discrepancies in forest flowering time for observations. The observation forests were located at an altitude of 150 m, 220 m, 350 m, and 500 m, and 800 m in the Rokko mountains. These were located at equal spaces, when altitude was taken in the logarithm. The distribution percentage of pollen counts from 1993 to 1998 showed an almost normal distribution level. This was demonstrated by the Log-Normal Probability paper, with a middle level altitude of a 350 m forest. We could estimate the relative rate of 5 different altitude forests against the corresponding amount of pollen as shown under, 0.09 at 150 m forest, 0.34 at 220 m forest, 0.31 at 350 m forest, 0.16 at 500 m forest, 0.10 at 800 m forest. The percentage of pollen counts at the 500 m forest in 1994 and at the 350 m forest in 1995 were decreased from 95% confidence interval. We regarded the decrease in the percentage of pollen counts during these two time, as a cause weak wind velocity and wrong wind direction in Tanba mountains. It was shown that the method for dividing pollen season in different observation forests in which altitude differs, will be useful for pollen forecasts and the pollen source countermeasure.

Air Pollution↗

Analysis of life tables with grouping and withdrawals.

A number of individuals is observed at the beginning of a period. At the end of the period the number is surviving, the number who have died and the number who have withdrawn are noted. From these three numbers it is required to estimate the death rate for the period. All relevant quantities are supposed independent and identically distributed for the individuals. The likelihood is calculated and found to depend on two parameters, other than the death rate, and to be unidenttifiable so that no consistent estimators exist. For large numbers, the posterior distribution of the death rate is approximated by a normal distribution whose mean is the root of a quadratic equation and whose variance is the sum of two terms; the first is proportional to the reciprocal of the number of individuals, as usually happens with a consistent estimator; the second does not tend to zero and depends on initial opinions about one of the nuisance parameters. The paper is a simple exercise in the routine use of coherent, Bayesian methodology. Numerical calucations illustrate the results.

Actuarial Analysis↗

Scoliosis prevalence: a call for a statement of terms.

Recently published prevalence studies of scoliosis reveal a disconcerting variability, largely due to the use of different diagnostic "cutting points", which are frequently unstated. A statistical analysis of the prevalence of moderate and severe scoliotic curves shows that the distribution of scoliotic curves conforms best to a log normal distribution. Using this analysis, and using 10 degrees as the "cutting point" for the diagnosis, the adolescent scoliosis population consists of approximately 25 per 1,000.

Adolescent↗

Immunocytochemical studies of intermediate filament aggregates and their relationship to microtubules in cultured skin fibroblasts from patients with giant axonal neuropathy.

Giant axonal neuropathy (GAN) is a severe autosomal recessive disease affecting both the peripheral and central nervous systems. It is characterized by segmental axonal ballooning due to large neurofilamentous masses and abnormal aggregation of filaments in other cell types including glial cells. Coomassie blue staining of the detergent-resistant cytoskeleton of cultured skin fibroblasts from three patients with GAN revealed the presence of large cytoplasmic filamentous aggregates in the great majority of cells. The aggregates were birefringent when viewed under polarization microscopy and electron microscopy showed that they were composed of aggregates of 8 to 10 nm intermediate filaments. The aggregates stained with antisera specific for vimentin but did not stain with antibodies to actin, tubulin, or the high molecular weight (HMW) microtubule associated protein. Examination of the fibroblasts containing the vimentin aggregates with antibodies to tubulin and the HMW protein showed that they had a normal distribution of microtubules and that the microtubules present were normally associated with the HMW protein. The results suggest that giant axonal neuropathy is a generalized inborn error of organization of intermediate filaments and that a defect in microtubules or their association with HMW protein is not responsible for the observed aggregation of intermediate filaments in this disease. Further study of GAN may be useful in understanding the function of intermediate filaments.

Child↗

Immunohistochemical analysis of an additional case of focal myositis.

We present an additional case of focal myositis which, after surgical excision of the muscular mass, did not evolve to generalized polymyositis. To our knowledge immunological evaluations of this disease have never before been carried out. Immunohistochemical analysis of the muscular mass showed the presence of activated endothelial cells, CD4 and macrophage cells in the perivascular and endomysial areas, suggesting an immune-mediated mechanism of muscular damage. At the same time the normal distribution of the peripheral blood lymphocyte subpopulations and the normal levels of serum IL-1 beta, IL-6, TNF-alpha, soluble IL-2R and soluble CD8 underline the non-systemic nature of the disease.

Adolescent↗

Detection of Cryptosporidium-specific serum immunoglobulins in captive snakes by a polyclonal antibody in the indirect ELISA.

An indirect enzyme-linked immunosorbent assay (ELISA) was developed for the detection of systemic Cryptosporidium-specific antibodies (Ab) in the serum of captive snakes. An optimal concentration of Cryptosporidium soluble protein-cocktail antigen was 20 micrograms/mL. In a direct ELISA, alkaline phosphatase-labeled rabbit-anti-snake polyvalent Ab detected snake immunoglobulins at a dilution of 1:12800. It was possible to detect Cryptosporidium-specific Ab at a serum dilution of 1:1600. Nineteen of 26 (73%) captive snakes (eight species) were Cryptosporidium-seroconverted; however, the differences in Ab titer among species were not significant. The distribution of absorbance values did not conform to a normal distribution (P < 0.05); mean Ab titer of nine snakes with cryptosporidiosis was significantly higher than mean Ab titer of the remaining ten snakes (P < 0.01). The monoclonal Ab test showed that the stools of 17 (89%) of 19 seropositive snakes contained Cryptosporidium oocysts; nine of those 19 (47%) stools were positive by acid-fast-stained (AFS) direct wet smear (DWS). A significant positive relationship between Cryptosporidium-seroconversion and snake age was observed (P < 0.03); the mean age of seropositive snakes was significantly higher than the mean age of seronegative animals (P < 0.01). The proposed assay is fast, reproducible, could be used for retrospective and prospective seroepizootiological studies, and assist ophidian centers in establishing Cryptosporidium-free collections. After standardization, the assay can be used for large-scale screening of captive snakes.

Aging↗