[Mushrooms--not always a happy acquaintance].
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Adult↗
Biomedical subjects
K Jensen
Publications and source records attributed to K Jensen.
The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, caused by mutations in the autoimmune regulator (AIRE) gene, is an autosomal recessive autoimmune disease characterized by the breakdown of tolerance to organ-specific antigens. The 545 amino acid protein encoded by AIRE contains several structural motifs suggestive of a transcriptional regulator and bears similarity to cellular proteins involved in transcriptional control. We show here that AIRE fused to a heterologous DNA binding domain activates transcription from a reporter promoter, and the activation seen requires the full-length protein or more than one activation domain. At the structural level AIRE forms homodimers through the NH(2)-terminal domain, and molecular modeling for this domain suggests a four-helix bundle structure. In agreement, we show that the common transcriptional coactivator CREB-binding protein (CBP) interacts with AIRE in vitro and in yeast nuclei through the CH1 and CH3 conserved domains. We suggest that the transcriptional transactivation properties of AIRE together with its interaction with CBP might be important in its function as disease-causing mutations almost totally abolish the activation effect.
Amino Acid Sequence↗
[Pericon interactions].
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Drug Interactions↗
Regional confidence bands for ROC curves.
The performance of a diagnostic test is characterised by its specificity and sensitivity. For a quantitative diagnostic test these criteria depend on the selected cut-off point. The receiver operating characteristic (ROC) curve of a quantitative diagnostic test is generated by plotting sensitivity against specificity as the cut-off point runs through the whole range of possible test values. In practice, the ROC curve is estimated from clinical data. One important goal is to select an optimal cut-off point. For this purpose the sample variability has to be taken into account. Recently, Campbell has introduced nonparametric asymptotic simultaneous confidence bands that are valid for the whole ROC curve. In this paper a nonparametric asymptotic approach for the construction of regional confidence bands for ROC curves is proposed. It can be applied for any specificity interval of interest. Our approach is based on the asymptotic theory of empirical and quantile processes. To investigate the small sample properties of the different approaches, a Monte Carlo study was conducted using normal and log-normal data. A method for sample size calculation is presented. Finally, the approaches are applied to a tumour marker in the diagnosis of bone marrow metastases.
Bone Marrow Neoplasms↗
The reliability of balance tests performed on the kinesthetic ability trainer (KAT 2000).
The Kinesthetic Ability Trainer (KAT 2000) is a balance platform designed for training and functional testing of the neuromuscular control system. Forty healthy and sports-active persons were tested and 1 month later retested to investigate the reliability of the KAT 2000 testing "one-leg static balance" and "two-leg dynamic balance". A significant improvement at retesting on the same day was seen in both tests; furthermore the dynamic test result improved significantly with retesting 1 month later. The data obtained made it possible to calculate the 95% confidence limits for an unchanged test result for a single person and a group of persons. The results show a clear learning effect when the persons are retested, especially in the dynamic test. The KAT 2000 can be used as a tool for testing groups of persons both in short- and long-term studies, but it cannot be used for testing single persons due to the great variance in the test results. Further investigations involving injured persons are needed to determine the range of improvement after intervention.
Adolescent↗
The effect of internal GTPgammaS on GABA-release in cultured hippocampal neurons.
The effects of presynaptic guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) on GABAergic inhibitory postsynaptic currents (IPSCs) were studied in cultured hippocampal neurons using whole-cell recordings. Inclusion of GTPgammaS (0.5-1 mM) in the presynaptic electrode reduced both the amplitude and paired-pulse depression of IPSCs, indicating that the probability of GABA-release had been reduced. Presynaptic GTPgammaS increased the depression of IPSCs by the GABA(B)-receptor-agonist baclofen (10 microM), and the effect of baclofen was poorly reversible after washing. Stimulation of the GABAergic neuron at 80 Hz for 1 s was accompanied by tetanic depression of the IPSCs by 52+/-6% and was followed by post-tetanic potentiation (PTP), reaching a peak value of 71+/-21% and lasting about 100 s. IPSCs evoked after tetanic stimulation were depressed and PTP was absent when tetanic stimulation was applied within 3 min after starting injection of GTPgammaS into the presynaptic neuron. At longer times, basal release underlying a single IPSC was depressed. This affected the ratios recorded in response to tetanic stimulations such that tetanic depression was abolished, while PTP increased to 117+/-34%. In conclusion, GTPgammaS reduces the probability of GABA-release in both a use- and time-dependent manner, most likely through an inhibitory action on presynaptic Ca2+-influx through voltage-gated Ca2+ channels or an interaction with small GTP-binding proteins in the nerve terminals.
Animals↗
Developmental increase in asynchronous GABA release in cultured hippocampal neurons.
Developmental changes in GABAergic synaptic transmission were examined in cultured hippocampal neurons using patch-clamp recordings and Ca(2+) imaging. In paired recordings, tetanization of the presynaptic GABAergic neuron with 80 pulses at either 40 or 80Hz was accompanied by tetanic depression of inhibitory postsynaptic responses. In neurons that had been cultured for more than two weeks, asynchronous inhibitory postsynaptic currents often appeared during the tetanus and continued for several seconds following stimulation. There was little asynchronous activity in neurons that had been cultured for shorter times. However, no age-related changes were observed in the amplitude of single synchronous inhibitory postsynaptic currents, paired-pulse depression or post-tetanic potentiation of inhibitory postsynaptic currents. Following equimolar replacement of extracellular Ca(2+) with strontium ions (Sr(2+)), single autaptic inhibitory postsynaptic currents were depressed in amplitude and asynchronous inhibitory postsynaptic currents were present on the decaying phase. Sr(2+)-induced asynchronous inhibitory postsynaptic currents showed no dependence on age in culture. Imaging of Ca(2+) in single GABAergic boutons was performed by including Fluo-3 in the patch pipette. During action potential firing induced by stimulating at 80Hz for 1s, intracellular calcium [Ca(2+)](i) increased rapidly in individual boutons. Following the stimulus, [Ca(2+)](i) decayed back to baseline within 10-15s. The half-time of decay increased from 1. 7+/-0.2s at 15days in vitro to 4.0+/-0.2s at 30days in vitro (P<0. 05), with a developmental profile that closely matched the increase in asynchronous inhibitory postsynaptic currents. We propose that the increase in tetanus-induced asynchronous GABA-release during the first month of synapse maturation in vitro is caused by a slowing of the Ca(2+)-clearing mechanisms in the GABAergic boutons. This results in larger and more prolonged elevations of [Ca(2+)](i) during tetanic stimulation, which leads to enhanced asynchronous transmitter release. We propose that the results of this study demonstrate a potentially important aspect of synapse maturation during development, and also imply that GABA release is up-regulated in conditions of decreased Ca(2+) buffering and clearing.
Action Potentials↗
Olfactory and quantitative analysis of aroma compounds in elder flower (Sambucus nigra L.) drink processed from five cultivars.
Fresh elder flowers (Sambucus nigra L.) were extracted with an aqueous solution containing sucrose, peeled lemon slices, tartaric acid, and sodium benzoate to make elder flower syrup. Aroma compounds emitted from the elder flower syrup were collected by the dynamic headspace technique and analyzed by GC-FID and GC-MS. A total of 59 compounds were identified, 18 of which have not previously been detected in elder flower products. The concentrations of the identified volatiles were measured in five elder cultivars, Allesoe, Donau, Sambu, Sampo, and Samyl, and significant differences were detected among cultivars in the concentration levels of 48 compounds. The odor of the volatiles was evaluated by the GC-sniffing technique. cis-Rose oxide, nerol oxide, hotrienol, and nonanal contributed to the characteristic elder flower odor, whereas linalool, alpha-terpineol, 4-methyl-3-penten-2-one, and (Z)-beta-ocimene contributed with floral notes. Fruity odors were associated with pentanal, heptanal, and beta-damascenone. Fresh and grassy odors were primarily correlated with hexanal, hexanol, and (Z)-3-hexenol.
Beverages↗
Applying phage display technology in aging research.
Filamentous bacteriophage offers the possibility of linking genotype with phenotype in one genetic package. By creating a library of different proteins as fusion to one of the coat proteins of filamentous bacteriophage it becomes possible to isolate proteins based on their binding characteristics. Phage displayed libraries of varying formats, ranging from small peptides to antibody fragments, have been selected successfully for ligands toward a large panel of targets. These peptides and antibody fragments are applicable in analysis of the behaviour of certain proteins with respect to changes in biological processes such as aging, thus providing valuable tools for a general understanding of the aging process. Alternatively, display of antibody fragments or peptides on filamentous bacteriophage can be instrumental in the discovery of novel antigens as exemplified by selections on cell surfaces or on complex protein mixtures such as sera from aging individuals. Although phage display has been applied successfully in a large number of studies relating to cancer, viral infections and other biological processes, its application in the field of aging research is yet to be realised.
Aging↗
[Superparamagnetic iron oxide enhanced MR angiography of the portal vein system].
PURPOSE: Superparamagnetic iron oxide (SPIO) is used for the detection of focal liver lesions. The current study examines whether the blood-pool effect of an approved substance is adequate for contrast-enhanced MR angiography of the portal venous system. METHODS AND MATERIALS: Fifteen patients [9 women, 6 men, mean age 57 (34-73)] were examined with a breathhold 3D-FISP sequence (TR/TE/FA; 5 ms/2 ms/25 degrees) at 1.5 Tesla (Vision; Siemens, Erlangen) during the last third of a half-hour Infusion of a standard dose (15 mumol Fe/kg) of AMI-25 (Endorem, Guerbet Co., France). The image quality of source images and 3D reconstructions was evaluated by two examiners using a 3-point scale. RESULTS: Large vessels (portal vein, left and right branch of the portal vein, superior mesenteric vein, splenic vein) are visualized well or adequately in 80-93% of the cases, while this was achieved in only 53-60% of the small veins (vessels of the first order emptying into the superior mesenteric vein and the spleen). Venous arcades of the mesenterium are not visible by this technique. CONCLUSION: SPIO-supported MRA of the portal venous system yields usable results in the majority of patients. A possible indication is preinterventional angiography together with an SPIO examination for the detection of focal liver lesions.
Adult↗
Genetic structure and AFLP variation of remnant populations in the rare plant Pedicularis palustris (Scrophulariaceae) and its relation to population size and reproductive components.
We investigated plant reproduction in relation to genetic structure, population size, and habitat quality in 13 populations of the rare biennial plant Pedicularis palustris with 3-28500 flowering individuals. We used AFLP (amplified fragment length polymorphism) profiles to analyze genetic similarities among 129 individuals (3-15 per population). In a cluster analysis of genetic similarities most individuals (67%) were arranged in population-specific clusters. Analysis of molecular variance indicated significant genetic differentiation among populations and among and within subpopulations (P < 0.001). Gene flow (N(e) m) was low (0.298). On average, plants produced 55 capsules, 17 seeds per fruit, and 42 seedlings in the following growing season. The number of seeds per capsule was independent of population size and of genetic variability. In contrast, the number of capsules per plant (P < 0.05) and the number of seedlings per plant (P < 0.05) were positively correlated with population size. The relation between population size and the number of seeds per plant was not significant (P = 0.075). The number of capsules and of seeds and seedlings per plant (P < 0.01) were positively correlated with genetic variability. Genetic variability was independent of actual population size, suggesting that historical population processes have to be taken into account, too. Stepwise multiple regressions revealed additional significant relationships of habitat parameters (soil pH, C:N ratio), vegetation composition, and standing crop on reproductive components. We conclude that populations of P. palustris are genetically isolated and that reproductive success most likely is influenced by population size, genetic variability, and habitat quality. Management strategies such as moderate grazing, mowing, and artificial gene flow should endeavor to increase population size as well as genetic variation.
Journal Article↗
[Methodology of diagnostic validation studies. Errors in study planning and evaluation].
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagnostic validation studies (Phase I to IV). The diagnostic value of a test can be described by indexes like sensitivity, specificity and predictive values. Sensitivity and specificity are so-called nosological probabilities whereas predictive values describe the probabilities of the disease given a positive or negative test result, respectively. These posterior probabilities depend on the prevalence of the disease in question. The methodological problems that arise in the planning of diagnostic studies differ from those encountered in treatment evaluation. This contribution presents an annotated checklist of the most important faults and shortcomings in the planning and the analysis of diagnostic validation studies. Avoiding these deficiencies may help that the study results are accepted by biostatisticians, clinicians and cost units.
Bias↗
Cytokeratin staining in Merkel cell carcinoma: an immunohistochemical study of cytokeratins 5/6, 7, 17, and 20.
Merkel cell carcinoma is an aggressive cutaneous neoplasm with neuroendocrine differentiation that carries a poor prognosis. Its homogeneous morphology is easily confused with lymphoma, leukemia, metastatic small cell carcinoma, and poorly differentiated cutaneous malignancies. Histopathologic diagnosis frequently requires support by immunohistochemistry. The authors investigated cytokeratins (CKs) 5/6, 7, 17, and 20 staining in paraffin sections of 26 Merkel cell carcinomas to expand the knowledge of the CK staining profile of this entity. Reactivity with anti-CK 20 was demonstrated in 23 of 26 Merkel cell carcinomas (88%). All three CK 20-negative tumors showed punctate staining with anti-keratin CAM5.2. Six of 26 tumors (23%) were positive for CK 7, a finding not previously reported. The staining patterns for both CKs 20 and 7 ranged from punctate (perinuclear) to localized (confined to half of the cytoplasm) to diffuse. Punctate CK 20 staining was seen in 17 of 26 cases but was the predominant pattern in only 10 cases. Antibodies to CKs 5/6 and 17 were each negative in the 13 cases for which these stains were performed. Both the positive and negative elements of the CK profile of this distinctive neoplasm provide additional useful diagnostic information for the differential diagnosis between Merkel cell carcinoma and other carcinomas that may simulate it. The authors note that the classically described perinuclear dotlike keratin staining pattern is not universally seen with CK 20 and that CK 7 staining may be seen in a subset of Merkel cell carcinomas.
Adult↗
[Visual fields defects following treatment with vigabatrin].
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Adult↗
[Recommendations for gastrointestinal decontamination].
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Antidotes↗
[Dilemma of the toxicologist].
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Denmark↗
[Methodology of diagnostic validation studies. Errors in planning and analysis].
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagnostic validation studies (Phase I to IV). The diagnostic value of a test can be described by indexes like sensitivity, specificity and predictive values. Sensitivity and specificity are so-called nosological probabilities whereas predictive values describe the probabilities of the disease given a positive or negative test result, respectively. These posterior probabilities depend on the prevalence of the disease in question. The methodological problems that arise in the planning of diagnostic studies differ from those encountered in treatment evaluation. This contribution presents an annotated checklist of the most important faults and shortcomings in the planning and the analysis of diagnostic validation studies. Avoiding these deficiencies may help that the study results are accepted by biostatisticians, clinicians and cost units.
Diagnostic Techniques and Procedures↗