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PubMed2000

Effects of PMCA and SERCA pump overexpression on the kinetics of cell Ca(2+) signalling.

The dynamic interactions of the main pathways for active Ca(2+) transport have been analysed in living cells by altering the expression of their components. The plasma membrane (PMCA) and the endoplasmic reticulum (ER) (SERCA) Ca(2+) pumps were transiently overexpressed in CHO cells, and the Ca(2+) homeostasis in the subcellular compartments was investigated using specifically targeted chimaeras of the Ca(2+)- sensitive photoprotein aequorin. In resting cells, overexpression of the PMCA and SERCA pumps caused a reduction and an increase in ER [Ca(2+)] levels, respectively, while no significant differences were detected in cytosolic and mitochondrial [Ca(2+)]. Upon stimulation with an inositol 1,4, 5-trisphosphate (IP(3))-generating agonist, the amplitude of the mitochondrial and cytosolic Ca(2+) rises correlated with the ER [Ca(2+)] only up to a threshold value, above which the feedback inhibition of the IP(3) channel by Ca(2+) appeared to be limiting.

Adenosine Triphosphatases↗
PubMed2004

Applicability of biomarkers in the early diagnosis of prostate cancer.

Early diagnosis of prostate cancer can increase the curative success rate for this disease. Although serum prostate-specific antigen measurement is regarded as the best conventional tumor marker available, there is little doubt that it has great limitations. The threshold above which biopsies are indicated has now decreased to a serum prostate-specific antigen value of 3 ng/ml, which results in a negative biopsy rate of 70-80%. This can readily be explained by the fact that prostate-specific antigen is not specific for prostate cancer. Clinicians need more sensitive tools to help diagnose prostate cancer and monitor progression of the disease. Molecular oncology is playing an increasing role in the fields of diagnosis and therapy for prostate cancer and has already been instrumental in elucidating many of the basic mechanisms underlying the development and progression of this disease. The identification of new prostate cancer-specific genes, such as DD3PCA3, would represent a considerable advance in the improvement of diagnostic tests for prostate cancer. This could subsequently lead to a reduction of the number of unnecessary biopsies.

Acyltransferases↗
PubMed1987

[Radioactivity levels of the air inhaled by personnel of a radioiodine therapy unit].

The mean activity concentration of 131I during inhalation by the nuclear medicine personnel was measured at therapeutic activity applications of 22 GBq (600 mCi) per week. The activity concentration reached its maximum in the exhaled air of the patients 2.5 to 4 hours after oral application. The normalized maximum was between 2 X 10(-5) and 2 X 10(-3) Bq X m-3 per administered Bq. The mean activity concentration of 131I inhaled by the personnel was 28 to 1300 Bq X m-3 (0.8 to 35 nCi X m-3). From this the 131I uptake per year was estimated to be 30 to 400 kBq/a (mean = 250, SD = 50%). The maximum permitted uptake from air per year is, according to the German and Austrian radiation protection ordinances 22/21 microCi/a (= 8 X 10(5) Bq/a). At maximum 50% and, on the average, 30% of this threshold value are reached. The length of stay of the personnel in the patient rooms is already now limited to such an extent that 10% of the maximum permissible whole-body dose for external radiation is not exceeded. Therefore, increased attention should be paid also to radiation exposure by inhalation.

Air Pollution, Radioactive↗
PubMed2004

Determination of detection and quantification limits for SNP allele frequency estimation in DNA pools using real time PCR.

The quantification of single nucleotide polymorphism (SNP) allele frequencies in pooled DNA samples using real time PCR is a promising approach for large-scale diagnostics and genotyping. The limits of detection (LOD) and limits of quantification (LOQ) for mutant SNP alleles are of particular importance for determination of the working range, which, in the case of allele-specific real time PCR, can be limited by the variance of calibration data from serially diluted mutant allele samples as well as by the variance of the 100% wild-type allele samples (blank values). In this study, 3sigma and 10sigma criteria were applied for the calculation of LOD and LOQ values. Alternatively, LOQ was derived from a 20% threshold for the relative standard deviation (%RSD) of measurements by fitting a curve for the relationship between %RSD and copy numbers of the mutant alleles. We found that detection and quantification of mutant alleles were exclusively limited by the variance of calibration data since the estimated LOD(calibration) (696 in 30 000 000 copies, 0.0023%), LOQ(20%RSD) (1470, 0.0049%) and LOQ(calibration) (2319, 0.0077) values were significantly higher than the LOD(blank) (130, 0.0004%) and LOQ(blank) (265, 0.0009%) values derived from measurements of wild-type allele samples. No significant matrix effects of the genomic background DNA on the estimation of LOD and LOQ were found. Furthermore, the impact of large genome sizes and the general application of the procedure for the estimation of LOD and LOQ in quantitative real time PCR diagnostics are discussed.

Calibration↗
PubMed2006

Urine protein-to-creatinine ratio in an untimed urine collection is a reliable measure of proteinuria in lupus nephritis.

OBJECTIVE: To evaluate the accuracy of urine protein-to-creatinine (P/C) ratio in an untimed urine specimen as compared with 24 h total protein excretion for measurement of proteinuria in patients with lupus nephritis. METHODS: Proteinuria in patients with lupus nephritis was assessed by 24 h total protein excretion and spot urine P/C ratio. Correlation and limits of agreement between the two methods were evaluated. The discriminant cutoff values for spot urine P/C ratio in predicting 24 h protein 'threshold' excretion of > or =0.3, > or =0.5, > or =1.0 and > or =3.5 g/day were determined using receiver operating characteristic curves. RESULTS: A total of 165 samples were available for assessment with 21.8% excluded due to inadequate collection. A strong correlation (r = 0.91, P < 0.0001) was found between spot urine P/C ratio and 24 h urine protein excretion. Bland-Altman plot showed the two tests had acceptable limits of agreement in low level of protein excretion (-0.86 to +0.92 g/day when protein excretion was <2.0 g/day). The limits became wider as the protein excretion increased. The spot urine P/C ratios of 0.45 (sensitivity 0.92; specificity 0.88), 0.7 (0.92; 0.89) and 1.84 (1.0; 0.86) mg/mg reliably predicted 24 h urine total protein equivalent 'thresholds' at > or =0.5, 1.0 and 3.5 g/day. CONCLUSION: This study supports the recommendation of using spot urine P/C ratio in screening and monitoring proteinuria in patients with lupus nephritis. However, in assessing the exact amount of proteinuria, the urine P/C ratio may have unacceptably wide limits of agreement in high protein excretion range.

Adult↗
PubMed2004

Detection of power changes between conditions using split-half resampling of synthetic aperture magnetometry data.

Synthetic Aperture Magnetometry (SAM) measures changes in task-related power using pseudo-t values which are affected by changes in both signal and noise. Detecting significant signal power changes between two separate experimental conditions should not be done directly due to possible fluctuation in the noise as well as the response. This study proposes a method to estimate the noise within a single condition, which is then used to test the null hypothesis of no difference between the conditions. The noise estimation is based on a split-half resampling technique. For each resampling, the data of a given condition is divided into two halves. The difference of the pseudo-t volumes between the pair of the datasets is calculated. After multiple resamplings, the confidence limits of the differences within this single condition are computed for a given p-value so that one can test the null hypotheses that the second condition is within the same distribution as the first. The limits are calculated using a bootstrap technique to correct for any bias in the estimated threshold. Power changes between the two conditions are considered significantly different if the difference of the pseudo-t value is larger than expected within conditions. To demonstrate the effectiveness of the technique, the proposed method was applied to MEG responses to two distinct visual stimuli recorded from a single subject. Major differences of brain activity between the two conditions were found in the occipital region. These results were validated using four pairs of split-half datasets, generated from either the odd or even trials in each condition. The method of split-half resampling should therefore be useful for localizing significant differences in brain activity between conditions within individual subjects.

Brain Mapping↗
PubMed1979

[Comments on the lateral load capacity of the phalangeal joints (author's transl)].

The article compares the load capacity of the collateral ligaments of the metacarpo-phalangeal and interphalangeal joints exposed to a laterally applied force. The tests were performed in vivo with 50 each female and male volunteers. It was found that the average load capacity of the metacarpo-phalangeal and interphalangeal joints in women was 5.8 kp and in men 12.3 kp. Furthermore, the bones of the long fingers with the preserved joint capsules and collateral ligaments of ten corpses were also examined, and the collateral ligaments exposed to a load which was increased to the point of their destruction. The average values found in this manner were 26.5 kp for the metacarpo-phalangeal collateral ligaments and 15.4 kp for the interphalangeal collateral ligaments. This means that the pain threshold is usually below the destruction limit, so that generally there will be no spontaneous overloading. It is important for the construction of endoprostheses that their stability level should always be above that of the pain threshold and should attain at least the values of the tear tests, since otherwise these endoprotheses will not function properly. These basic prerequisites enable a comparative study of endoprostheses, the results of which will be presented at a later date.

Adult↗
PubMed1985

Energy intake, body composition and reproductive performance of the gilt.

The relationship between age, live weight, body composition and energy status on the onset and maintenance of reproductive activity in females is reviewed. When possible, swine studies have been employed, although, of necessity, much data are drawn from other species. The relationship between age, weight and puberty is controversial. However, from the available data we conclude that neither age nor weight are reliable indices of reproductive development, but that minimum threshold values for these characteristics must be achieved before puberty can occur. Human data provides a strong indication that a minimum adipose to lean tissue ratio is a prerequisite for puberty onset. Limited data from swine support this contention and indeed it may be a superior measure of reproductive development than either age or weight. However, the value of this ratio remains to be defined in pigs, and again it is minimum threshold level, the attainment of which is necessary, but not in itself sufficient, for puberty onset. A positive energy balance seems to be necessary for puberty onset and the maintenance of estrous cycles in some species, but this has not been investigated in swine. The mechanisms whereby adiposity and energy status influences reproduction are discussed. Human studies demonstrate a negative correlation between energy status, body fatness and plasma gonadotrophin levels. Also, adipose tissue has the ability to metabolize sex steroids, aromatizing androgens to estrogens and changing the direction of estrogen metabolism to produce more or less biologically potent estrogens.

Adipose Tissue↗
PubMed1998

Determination of trinitrotoluene and metabolites in urine by means of gas-chromatography with mass detection.

Biological monitoring of chemicals and/or their metabolites has been a recent development in South Africa with the publication of the Hazardous Chemical Substance Regulations in 1995. Although trinitrotoluene (TNT) exposure has been included in recent legislative developments, only occupational exposure limits have been set. TNT does not have a biological exposure index in South Africa or internationally. This study was conducted to determine levels of TNT and its metabolite excretion in a sample of munition workers by using gas-chromatography with mass detection methodology. The metabolites 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT) in urine of exposed subjects, as well as total TNT (the sum of 4ADNT and 2ADNT), were used to determine absorption and excretion due to TNT exposure. Results indicated an increased absorption of TNT during the working week as compared to other published international studies. Post-shift values exceeded pre-shift levels in all samples. More reliable and specific research is necessary to set a biological threshold limit for TNT and its metabolites since monitoring indicated no definite symptoms, signs or biological effects due to increased excretion.

Chromatography, Gas↗
PubMedDate not supplied

Tympanometry:between ear symmetry and normative values.

Marked asymmetry of auditory function between left and right ears would normally be indicative of some abnormality. This study was designed to investigate the limits of tympanometric symmetry in normal individuals. A limiting ratio of 4/3 between left and right ear compliances is suggested. Applying this criterion and strict criteria for normality of middle ear pressure and reflex thresholds, a value for middle ear compliance was obtained with a considerably smaller range for "normality" than from previous studies. A marked difference between middle ear compliances of male and female subjects was observed, and evidence was adduced to suggest that this was due to differences in size of the ear canal and tympanic membrane.

Acoustic Impedance Tests↗
PubMed2000

C- and Adelta-fibre mediated thermal perception: response to rate of temperature change using method of limits.

Studies investigating the effect of rate of temperature change on thermal thresholds have used a variety of different methods and threshold combinations, and many display incomplete reporting of statistical analyses. It has been suggested that C- and Adelta-fibre mediated thresholds differ in their reaction to different rates of temperature change. Ten healthy female volunteers (aged 18-26 years; mean 21 +/- S.D. 2.53) undertook cold sensation (CS), warm sensation (WS), cold pain (CP) and heat pain (HP) threshold determinations on the thenar eminence of the dominant hand. Rates of temperature change of 0.5, 1, 2.5 and 4 degrees C/s were used, with a modified method of limits. Adaptation temperature was 32 degrees C and thermode size 3 cm x 3 cm. Results showed a significant increase in WS, HP and CP thresholds with increased rates of temperature change (all p < 0.001), but no significant change for CS (p = 0.653). These results suggest that thresholds with a C-fibre component (WS, HP and CP) and those that are Adelta-fibre mediated (CS) behave differently. A traditional explanation of measurement artefact alone is insufficient in rationalizing these results, with additional factors potentially involved. Slow rates of temperature change were shown to reduce mean intra-individual differences in recorded threshold values, and also to abolish ceiling effects with HP threshold determinations. Clinically, therefore, using slow rates of temperature change with method of limits has a range of benefits over and above simply minimizing measurement artefact.

Adaptation, Physiological↗
PubMed2006

Screening-level risk assessment of Di(2-ethylhexyl)phthalate for aquatic organisms using monitoring data in Japan.

Screening-level ecological risk assessments of di(2-ethylhexyl)phthalate (DEHP) for aquatic organisms in Japan were conducted using estimated statistical values based on surface water and sediment monitoring data and effect threshold values based on a large aquatic toxicity database. An alternative method is proposed to handle monitoring data that contain nondetects including multiple detection limits and to determine the statistical values of DEHP concentrations in Japanese surface waters. The No-Observed-Effect-Concentration (NOEC(water)) of DEHP for aquatic life of 77 micro g/L was determined giving equal importance to both physical effects probably caused by undissolved DEHP and to the intrinsic toxicity potentially caused by DEHP. The NOEC(sediment) of 615,000 micro g/kg was determined by the Equilibrium Partitioning (EqP) theory, conservatively assuming a threshold effect level in the water column as the water solubility of 3 micro g/L. The potential risks of DEHP in Japanese water environments were characterized simply by comparing the margin of exposure (MOE) with a specified uncertainty multiplier (UM). The MOE is expressed as the ratio of NOEC(water) or NOEC(sediment) to the expected environmental concentrations such as the 95th percentiles of the estimated DEHP concentration distributions for surface water or sediment. The results of risk characterization show that all MOE values calculated using the statistical values of DEHP concentrations in Japanese surface waters and sediments are above 10, indicating minimal risk. Although the DEHP concentrations of some surface water samples showed MOE values of less than 10, considering environmental chemistry such as bioavailable fractions and the form of existence of DEHP in a water environment, we conclude that the current levels of DEHP are of little concern to aquatic life in the majority of Japanese surface waters and sediments.

Animals↗
PubMed2003

Semiquantitative detection by real-time PCR of Aspergillus fumigatus in bronchoalveolar lavage fluids and tissue biopsy specimens from patients with invasive aspergillosis.

A real-time PCR method was developed and used to detect Aspergillus fumigatus mitochondrial DNA (mtDNA) in bronchoalveolar lavage (BAL) fluids and tissue biopsy specimens. The analytical sensitivity of the assay was one A. fumigatus conidium per reaction, and the assay was linear at least over 4 orders of magnitude above the detection limit. BAL fluids from 66 immunocompromised patients at risk of invasive pulmonary aspergillosis (IPA) and 33 immunocompetent controls and tissue biopsy specimens from 10 immunocompromised patients were analyzed. The results were related to the clinical diagnosis established according to recently published consensus criteria. A. fumigatus mtDNA positivity was encountered in 16 of 81 (20%) BAL fluid specimens from patients at risk and 1 of 33 (3%) specimens from immunocompetent controls. PCRs were positive in six of seven, two of four, and four of five of the patients with proven, probable, and possible IPA, respectively, as well as in four patients at risk but without any other evidence of IPA. With qualitative detection, the diagnostic sensitivity of PCR was 73%, specificity was 93%, and predictive values of positive (PPV) and negative (NPV) results were 73 and 95%, respectively. Using a threshold cycle of <35 as a limit for positive PCR, the specificity and PPV of PCR in the diagnosis of invasive aspergillosis were 100%, but its sensitivity was only 45% and NPV was 92%. PCR was positive in tissue biopsy specimens from all patients with invasive aspergillosis caused by A. fumigatus. Semiquantitative detection of A. fumigatus mtDNA in BAL fluid may be helpful in the diagnosis of IPA. PCR is well suited for the verification of the presence of A. fumigatus in tissue biopsy specimens.

Adolescent↗
PubMed1991

Properties of high-threshold mechanoreceptors in the oral mucosa. I. Responses to dynamic and static pressure.

1. Mechanical response properties of high-threshold mechanoreceptors (HTMs) of the goat oral mucosa were determined by single-unit recording from the palatine and alveolar nerves and from the trigeminal ganglion. The following observations were made. 2. HTMs of the oral mucosa could be separated into two subgroups on the basis of their threshold to mechanical stimulation. Intense pressure receptors (IPRs) comprised a group of A-delta afferents with thresholds of 2-16 g. Mechanonociceptors (MNs) comprised a group of relatively slowly conducting afferents (A-delta and C-fibers) with a higher threshold range (16-300 g). 3. In most instances, MNs lacked pressure-transducing capacity. Tests of reactivity to dynamically or statically applied stimuli revealed that significant functions were rarely fit between MN activity and pressure (4/20 cases). 4. IPRs differed from MNs by their pressure-transducing properties. The afferent response interval was in inverse proportion to the applied pressure. Significant pressure interval functions were fit in 16/20 cases. The relationship between pressure and response interval was best described by power functions. 5. Tests of reactivity to dynamically or statically applied stimuli revealed that IPRs preferred static pressure. Tighter fits and steeper slopes were observed in power functions fit to data generated by statically applied stimuli (mean fitted function, dynamic test: LnISI = -0.97 LnP + 3.4; mean fitted function, static test: LnISI = -1.6 LnP + 4.71). 6. Pressures-frequency thresholds (PFTs), asymptotes (PFAs), and mean response intervals (MRIs) were determined for IPRs from the static test series. The first two values are the pressures that produce the lower and upper limits of response frequency of mucosal HTMs (mean PFT, 1.48 N/mm2; mean PFA, 3.34 N/mm2). The MRI (28 ms) is simply computed from the function. When PFTs and PFAs are combined with activation threshold and power functions, they provide a relatively complete description of the range and form of reactivity of the IPR of the oral mucosa.

Animals↗
PubMedDate not supplied

Modern methods for measurement of basilar membrane displacements.

Basilar membrane displacements in response to sound at threshold intensities are in the fractional Angstrom range. Visual measurements, as used by Bekesy in his pioneering studies, are by definition limited to values above 10 000 A. The present paper discusses a number of modern techniques capable of taking measurements at lower Anstrom levels: One-point methods (capacitive probe, Mossbauer effect, laser interferometry, and optical heterodyne spectroscopy) and pattern-assessing methods (time-averaged and real-time holography). Advantages and disadvantages of these methods are being discussed.

Acoustic Stimulation↗
PubMedDate not supplied

B-vitamin status and intake in European adolescents. A review of the literature.

BACKGROUND: National and international recommendations for the intake of B vitamins in adolescents consist of estimates and extrapolations from adult values. Due to increasing growth and therefore relatively high energy and nutrient requirements adolescents are a vulnerable group from the nutritional point of view. In addition, a deficient intake of several B vitamins is strongly connected with the development of cancer, neural tube defects and cardiovascular diseases. OBJECTIVE: The aim of this work is to assess dietary intake and status of B vitamins and homocysteine of European adolescents on the basis of published data. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "Vitamin B", "homocysteine", "Europe", etc. Studies published between June 1980 and December 2004 were analysed for this review. Results of the intake of B vitamins were compared with the EAR or AI, respectively, as recommended by the U.S. Institute of Medicine. Due to lacking reference values for adolescents results of blood status as well as homocysteine were compared to different thresholds for adults. RESULTS: Considering the limitations of the comparability between the reviewed studies e.g. by different methodologies, sample size, age groups, the average intake of B vitamins surpassed the EAR and AI. Boys were better supplied with B vitamins than girls. The intake decreased with increasing age in both genders. A possible deficiency of folate was noticed and girls in particular seemed to be more at risk. Clear regional tendencies for the vitamin intake could not be observed. Results of vitamin B6, B12, folate in blood, and homocysteine were levelled in-between the thresholds. Though the great standard deviation of folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance. folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance.

Adolescent↗
PubMed2001

Pulse bifurcations and instabilities in an excitable medium: computations in finite ring domains.

We investigate the instabilities and bifurcations of traveling pulses in a model excitable medium; in particular, we discuss three different scenarios involving either the loss of stability or disappearance of stable pulses. In numerical simulations beyond the instabilities we observe replication of pulses ("backfiring") resulting in complex periodic or spatiotemporally chaotic dynamics as well as modulated traveling pulses. We approximate the linear stability of traveling pulses through computations in a finite albeit large domain with periodic boundary conditions. The critical eigenmodes at the onset of the instabilities are related to the resulting spatiotemporal dynamics and "act" upon the back of the pulses. The first scenario has been analyzed earlier [M. G. Zimmermann et al., Physica D 110, 92 (1997)] for high excitability (low excitation threshold): it involves the collision of a stable pulse branch with an unstable pulse branch in a so-called T point. In the framework of traveling wave ordinary differential equations, pulses correspond to homoclinic orbits and the T point to a double heteroclinic loop. We investigate this transition for a pulse in a domain with finite length and periodic boundary conditions. Numerical evidence of the proximity of the infinite-domain T point in this setup appears in the form of two saddle node bifurcations. Alternatively, for intermediate excitation threshold, an entire cascade of saddle nodes causing a "spiraling" of the pulse branch appears near the parameter values corresponding to the infinite-domain T point. Backfiring appears at the first saddle-node bifurcation, which limits the existence region of stable pulses. The third case found in the model for large excitation threshold is an oscillatory instability giving rise to "breathing," traveling pulses that periodically vary in width and speed.

Journal Article↗
PubMed2005

[Determination of electric current perception threshold in a sample of normal volunteers].

Reference values using the instrument Neurometer were determined and compared with those suggested by the manufacturer; the sensory thresholds for the different frequencies in different body segments were determined; the influence of age, level of education, gender and the reutilization of the electrodes in the different sites were also evaluated. Sensory threshold was determined in 101 normal volunteers (68 women), ages ranged from 17 to 87 years old. The procedure was fully automated with the sensory threshold being determined by the method of limits followed by the forced choice method. Analysis of the results revealed that: there was a significant difference between the values obtained for the index fingers and the halux; no difference was detected between both index fingers; gender and level of instruction had no effect on the results, age had a small influence after stimulation with 2000Hz and 250Hz; three reutilizations of the electrodes did not affect the results on the index fingers, however at the halux, the third utilization deteriorated the results from the 2000Hz stimulation. Except for the 2000Hz stimulation, significant differences were suggested between the values reported here and those provided by the manufacturer.

Adolescent↗