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[Diagnosis and treatment of sarcoidosis (author's transl)].

With only a few exceptions, in sarcoidosis the lung is virtually always, the liver mostly and the spleen only occasionally involved. Therefore, thorax-X-ray is the most important screening procedure. Histological verification by laparoscopy, bronchoscopy (transbronchial lung biopsy and bronchial mucosa biopsy) or mediastinoscopy is essential. In order to decide the therapeutic regimen, particularly the use of corticosteroids, the staging according to Wurm seems less suitable than pulmonary function testing (pneumotachograph, plethysmograph, CO-transfer, compliance). Futher clinical trials will have to find out, whether enzyme analysis (ACE) is apt to monitor progression of disease or to diagnose sarcoidosis in clinical routine use.

Adult↗

[Esophagus: postoperative aspects].

Although endoscopy has replaced radiology for the diagnosis of diseases of the oesophagus, postoperative imaging still remains essential. The radiological investigation depends on the initial disease, and its technique is adapted to the suspected complication and the type of operation performed. Immediately postoperatively, a barium swallow allows verification of the surgery before reintroducing food. The early diagnosis of possible complications is based on the barium swallow and CT scan. At a longer interval after the operation, medical imaging, particularly barium swallow, allows anatomical and functional postoperative surveillance. Relapses of the initial disease, particularly neoplastic recurrences can be distinguished from an intercurrent disease or a mechanical complication due to the operation.

Esophageal Diseases↗

Acquired and developmental brain dysfunction in borderline personality disorder.

This paper examines the evidence that brain dysfunction causes borderline personality disorder (BPD). The rules of causation set forth by Sir Bradford Hill will be considered, which include the strength of association, consistency of findings, specificity, temporal relationship, biological gradient, biological plausibility, experimental verification and analogous evidence. Brain dysfunction, in this context, is considered to involve both acquired and developmental neurological (or "organic") brain injuries, as well as the evidence provided by neurological and neuropsychological testing, neurobehavioral models of brain functioning and response to treatment. Biochemical and genetic evidence will not be reviewed, but will be considered in proposing models of brain dysfunction in BPD. It is hoped that this review will provide both the stimulus and possible directions for future research and be of relevance to the clinician assessing and treating patients with BPD.

Borderline Personality Disorder↗

Verification of the role of PCP 4-monooxygenase in chlorine elimination from pentachlorophenol by Flavobacterium sp. strain ATCC 39723.

The bacterial enzyme PCP 4-monooxygenase from Flavobacterium sp. strain ATCC 39723 catalyzes the oxygenolytic removal of the first chlorine from pentachlorophenol. PCP 4-monooxygenase is an FAD binding, NADPH requiring oxygenase, with similar functional domains as other bacterial flavoprotein monooxygenases specific for phenolic substrates. However, the definitive proof for the singular role of an oxygenolytic elimination of the primary chlorine from pentachlorophenol by Flavobacterium sp. has awaited the development of a genetic system whereby targeted mutagenesis via allelic exchange could be carried out with the corresponding gene from PCP 4-monooxygenase, pcpB. We report the development of a genetic system for Flavobacterium sp. strain ATCC 39723, and its application in targeted mutagenesis of the pcpB allele for elimination of PCP 4-monooxygenase activity.

Blotting, Southern↗

Evaluation of several film/screen combinations for megavoltage radiation therapy treatment field verification.

The introduction of a lower cost alternative to a film commonly used for megavoltage radiation therapy port films led to a comparison of two films (Kodak X-TL and X-OMAT G) in four metal screen cassette configurations. In addition to determination of H-D curves and point spread functions, images of humanoid phantom sections were obtained and evaluated for clinical "usefulness." The X-OMAT G film-screen combinations compared favorably with the X-TL film combinations with respect to the H-D Curves and point spread functions but there was a slight preference for X-TL film. There were no differences noted whether the film was used in the standard "ready pack" or naked in the cassettes.

Evaluation Studies as Topic↗

Quantitative verification of the existence of high molecular weight protein aggregates in the intact normal human lens by light-scattering spectroscopy.

The method of quasi-elastic light-scattering spectroscopy was used to establish quantitatively the concentration of high mmolecular weight (HMW) aggregates present in the normal human intact lens as a function of age. The concentration of HMW proteins increases monotonically with age. HMW proteins are absent in the infant lens, but represent 3% of the total soluble lens protein at age 60 years. The percent concentration of HMW proteins measured in intact lenses of various ages by quasi-elastic light scattering is in striking agreement with values determined biochemically.

Adolescent↗

The mental representation of living and nonliving things: differential weighting and interactivity of sensorial and non-sensorial features.

Warrington and colleagues (Warrington & McCarthy, 1983, 1987; Warrington & Shallice, 1984) claimed that sensorial and functional-associative (FA) features are differentially important in determining the meaning of living things (LT) and nonliving things (NLT). The first aim of the present study was to evaluate this hypothesis through two different access tasks: feature generation (Experiment 1) and cued recall (Experiment 2). The results of both experiments provided consistent empirical support for Warrington and colleagues' assumption. The second aim of the present study was to test a new differential interactivity hypothesis that combines Warrington and colleagueS' assumption with the notion of a higher number of intercorrelations and hence of a stronger connectivity between sensorial and non-sensorial features for LTs than for NLTs. This hypothesis was motivated by previoUs reports of an uncrossed interaction between domain (LTs vs NLTs) and attribute type (sensorial vs FA) in, for example, a feature verification task (Laws, Humber, Ramsey, & McCarthy, 1995): while FA attributes are verified faster than sensorial attributes for NLTs, no difference is observed for LTs. We replicated and generalised this finding using several feature verification tasks on both written words and pictures (Experiment 3), including in conditions aimed at minimising the intervention of priming biases and strategic or mnemonic processes (Experiment 4). The whole set of results suggests that both privileged relations between features and categories, and the differential importance of intercorrelations between features as a function of category, modulate access to semantic features.

Analysis of Variance↗

A nonparametric maximum likelihood estimator for the receiver operating characteristic curve area in the presence of verification bias.

The efficacy of a diagnostic test can be represented by the area under the receiver operating characteristic (ROC) curve. In estimating the ROC curve area, a common problem is verification bias resulting from selectively verifying a subset of patients initially tested. This paper proposes a simple verification bias correction procedure for estimating the ROC curve area and its corresponding variance.

Bias↗

Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase.

The pyrG gene of Lactococcus lactis subsp. cremoris, encoding CTP synthase, has been cloned and sequenced. It is flanked upstream by an open reading frame showing homology to several aminotransferases and downstream by an open reading frame of unknown function. L. lactis strains harboring disrupted pyrG alleles were constructed. These mutants required cytidine for growth, proving that in L. lactis, the pyrG product is the only enzyme responsible for the amination of UTP to CTP. In contrast to the situation in Escherichia coli, an L. lactis pyrG mutant could be constructed in the presence of a functional cdd gene encoding cytidine deaminase. A characterization of the enzyme revealed similar properties as found for CTP synthases from other organisms. However, unlike the majority of CTP synthases the lactococcal enzyme can convert dUTP to dCTP, although a half saturation concentration of 0.6 mm for dUTP makes it unlikely that this reaction plays a significant physiological role. As for other CTP synthases, the oligomeric structure of the lactococcal enzyme was found to be a tetramer, but unlike most of the other previously characterized enzymes, the tetramer was very stable even at dilute enzyme concentrations.

Base Sequence↗

[Diagnostic studies of facial nerve function in bell's palsy (author's transl)].

In early Bell's Palsy the nerve excitability test (NET) still proves to be a very simple and reliable method for determining whether or not a decompression operation is necessary. However, two weeks after the onset of the paralysis, pathological findings in the NET may require verification by electromyography.

Bone Conduction↗

Assessing acetylation of NF-kappaB.

To achieve its full biological activity, NF-kappaB must undergo a variety of post-translational modifications, including acetylation. Acetylation plays a prominent role in regulating the nuclear action of NF-kappaB. The RelA subunit of NF-kappaB forms the major target of acetylation at several different sites. Acetylation of discrete lysine residues in RelA modulates distinct functions of NF-kappaB, including transcriptional activation, DNA binding, and assembly with its inhibitor IkappaBalpha. Here, we describe the experimental methods that have allowed the detection and functional analysis of acetylated forms of NF-kappaB. Acetylation of NF-kappaB can be studied both in vivo and in vitro. In vivo [3H]acetate labeling assays provides a useful, albeit rather insensitive, method for initial verification of acetylation of either over-expressed or endogenous subunits of NF-kappaB. A second valuable in vivo approach involves the use of anti-acetylated lysine antibodies for immunoblotting. However, the success of this approach varies with the specific antibody employed and the target protein studied. In vitro acetylation assays provide a rapid and sensitive method to validate the involvement of candidate histone acetyltransferases and to map the sites of acetylation. Anti-RelA antibodies that selectively react with site-specific acetylated forms of RelA are a singularly powerful tool for the study of NF-kappaB acetylation both in vivo and in vitro.

Acetates↗

Minimal cut sets in biochemical reaction networks.

MOTIVATION: Structural studies of metabolic networks yield deeper insight into topology, functionality and capabilities of the metabolisms of different organisms. Here, we address the analysis of potential failure modes in metabolic networks whose occurrence will render the network structurally incapable of performing certain functions. Such studies will help to identify crucial parts in the network structure and to find suitable targets for repressing undesired metabolic functions. RESULTS: We introduce the concept of minimal cut sets for biochemical networks. A minimal cut set (MCS) is a minimal (irreducible) set of reactions in the network whose inactivation will definitely lead to a failure in certain network functions. We present an algorithm which enables the computation of the MCSs in a given network related to user-defined objective reactions. This algorithm operates on elementary modes. A number of potential applications are outlined, including network verifications, phenotype predictions, assessing structural robustness and fragility, metabolic flux analysis and target identification in drug discovery. Applications are illustrated by the MCSs in the central metabolism of Escherichia coli for growth on different substrates. AVAILABILITY: Computation and analysis of MCSs is an additional feature of the FluxAnalyzer (freely available for academic users upon request, special contracts for industrial companies; see web page below). SUPPLEMENTARY INFORMATION: http://www.mpi-magdeburg.mpg.de/projects/fluxanalyzer

Algorithms↗

Comparative whole-genome analysis of virulent and avirulent strains of Porphyromonas gingivalis.

We used Porphyromonas gingivalis gene microarrays to compare the total gene contents of the virulent strain W83 and the avirulent type strain, ATCC 33277. Signal ratios and scatter plots indicated that the chromosomes were very similar, with approximately 93% of the predicted genes in common, while at least 7% of them showed very low or no signals in ATCC 33277. Verification of the array results by PCR indicated that several of the disparate genes were either absent from or variant in ATCC 33277. Divergent features included already reported insertion sequences and ragB, as well as additional hypothetical and functionally assigned genes. Several of the latter were organized in a putative operon in W83 and encoded enzymes involved in capsular polysaccharide synthesis. Another cluster was associated with two paralogous regions of the chromosome with a low G+C content, at 41%, compared to that of the whole genome, at 48%. These regions also contained conserved and species-specific hypothetical genes, transposons, insertion sequences, and integrases and were located adjacent to tRNA genes; thus, they had several characteristics of pathogenicity islands. While this global comparative analysis showed the close relationship between W83 and ATCC 33277, the clustering of genes that are present in W83 but divergent in or absent from ATCC 33277 is suggestive of chromosomal islands that may have been acquired by lateral gene transfer.

Bacterial Capsules↗

Linguistic processing during repetitive transcranial magnetic stimulation.

To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions.

Adult↗

Cause and evaluation of chronic dyspnea in a pulmonary disease clinic.

To test whether, in patients with chronic dyspnea, a diagnostic approach based on objective confirmation of suspected diagnoses would be superior to one based on clinical impression alone, we prospectively studied 85 patients with a primary complaint of dyspnea seen in a pulmonary subspecialty clinic. We achieved 100% success in determining the causes of dyspnea compared with only 66% accuracy based on clinical impression alone. Four groups of disorders, asthma, chronic obstructive pulmonary disease, interstitial lung diseases, and cardiomyopathy accounted for two thirds of the cases. Findings on the history and physical examination were too nonspecific to determine the specific diagnosis. Pulmonary function testing, including a methacholine bronchoprovocation challenge, were the most useful diagnostic tests, particularly for chronic obstructive pulmonary disease and asthma. Chest roentgenogram was most useful for interstitial lung disease, and comprehensive exercise testing for dyspnea due to psychogenic factors or deconditioning. Specific therapy was effective in reducing or eliminating dyspnea in the majority of cases. We conclude that a diagnostic approach to chronic dyspnea based on objective findings and verification, rather than clinical impression alone, will consistently lead to an accurate diagnosis and an improved therapeutic outcome.

Adolescent↗

Genome-wide identification and expression analysis of the UGT gene family in honeysuckle.

BACKGROUND: The UGT gene family plays critical roles in regulating plant growth, development, stress responses, and secondary metabolite synthesis. Although UGT proteins have been studied in numerous plant species, research on the UGT family in honeysuckle (Lonicera japonica Thunb.) remains limited. RESULTS: In this study, a comprehensive genome-wide analysis of the UGT gene family was performed in honeysuckle. A total of 224 unique LjUGT genes were identified and classified into 21 distinct subfamilies (T71-T92 without T77) based on the phylogenetic analysis. These genes were unevenly distributed on the 9 chromosomes. Eighteen segmental duplication events and 61 tandem duplications were identified, of which only 3 were positive selection. Integrated analysis of promoter cis-acting elements, transcription factors, targeted miRNAs, and interacting proteins suggested that the expression and function of the LjUGT genes may be regulated by transcription factors and proteins through binding to the various binding sites and cis-acting elements, thereby putatively participating in diverse biological processes, including hormone signaling, stress response, and metabolism. The expression pattern analysis of LjUGTs in different tissues and under stress conditions indicated that Lj2A1135G32, Lj5A236T61, Lj6A350T83, and Lj7A737T47 emerged as candidate genes potentially associated with development, 46 genes showed expression changes under all 6 abiotic stresses, suggesting broad stress responsiveness. Additionally, there 7 genes were identified as candidate hub genes that may correlate with the low temperature stress tolerance in honeysuckle according to the WGCNA results, and further verification by qRT-PCR confirmed that Lj4A99G61 and Lj9A591T82 can be regarded as key candidate genes for in-depth research. CONCLUSIONS: This study systematically identified 224 LjUGT genes in honeysuckle for the first time and characterized their physicochemical properties, phylogenetic relationship, and expression patterns. These findings provide a foundational resource for hypothesis-driven investigations into the functions and action mechanisms of LjUGTs.

Lonicera↗

Echocardiographic changes after myocardial infarction in a model of left ventricular diastolic dysfunction.

To determine the early and late effects of myocardial infarction on left ventricular (LV) diastolic function in the rabbit postinfarction model, male New Zealand White rabbits were randomly assigned to ligation of the circumflex artery or sham operation. Serial echocardiographic and Doppler studies were performed on both groups of animals at baseline and 1 h and 3 wk after surgery (n = 10 for each group) after verification of the reproducibility and repeatability of the measurements. At 1 h postinfarction, decreases in early mitral inflow velocity (E wave) and mitral inflow velocity with atrial contraction (A wave) and increases in the mean pulmonary venous systolic-to-diastolic ratio and A wave reversal velocities were observed, without changes in LV geometry. By 3 wk postinfarction, increases in the mitral E-to-A ratio (1.1 +/- 0.3 vs. 2.9 +/- 0.9, P < 0.001) and left atrial area (131 +/- 23 vs. 510 +/- 72 mm2, P < 0.001) and decreases in the pulmonary venous systolic-to-diastolic ratio (0.56 +/- 0.20 vs. 0.79 +/- 0.14, P = 0.008) were consistent with severe diastolic abnormalities (restricted physiology). The findings of this study demonstrate that coronary artery ligation in the rabbit provides a reproducible echocardiographic and Doppler model of LV diastolic dysfunction that is consistent with abnormalities found in humans with previous myocardial infarction, symptoms of heart failure, and preserved LV systolic function.

Animals↗

A functional neuroimaging investigation of the roles of structural complexity and task-demand during auditory sentence processing.

Using functional magnetic resonance imaging (fMRI), this study directly examined an issue that bridges the potential language processing and multi-modal views of the role of Broca's area: the effects of task-demands in language comprehension studies. We presented syntactically simple and complex sentences for auditory comprehension under three different (differentially complex) task-demand conditions: passive listening, probe verification, and theme judgment. Contrary to many language imaging findings, we found that both simple and complex syntactic structures activated left inferior frontal cortex (L-IFC). Critically, we found activation in these frontal regions increased together with increased task-demands. Specifically, tasks that required greater manipulation and comparison of linguistic material recruited L-IFC more strongly; independent of syntactic structure complexity. We argue that much of the presumed syntactic effects previously found in sentence imaging studies of L-IFC may, among other things, reflect the tasks employed in these studies and that L-IFC is a region underlying mnemonic and other integrative functions, on which much language processing may rely.

Adult↗