Similarities and differences of human and experimental mouse lymphangiomas.

Lymphangioma is a disfiguring malformation of early childhood. A mouse lymphangioma model has been established by injecting Freund's incomplete adjuvant (FIA) intraperitoneally, but has not been compared with the human disease. We show that, in accordance with studies from the 1960s, the mouse model represents an oil-granuloma, made up of CD45-positive leukocytes and invaded by blood and lymph vessels. Several markers of lymphatic endothelial cells are expressed in both mouse and human, like CD31, Prox1, podoplanin, and Lyve-1. However, the human disease affects all parts of the lymphovascular tree. We observed convolutes of lymphatic capillaries, irregularly formed collectors with signs of disintegration, and large lymph cysts. We observed VEGFR-2 and -3 expression in both blood vessels and lymphatics of the patients, whereas in mouse VEGFR-2 was confined to activated blood vessels. The experimental mouse FIA model represents a vascularized oil-granuloma rather than a lymphangioma and reflects the complexity of human lymphangioma only partially.     

Emergence of translocation t(9;11)-positive leukemia during treatment of childhood acute lymphoblastic leukemia

Therapy-related acute myeloid leukemia (t-AML) characterized by the t(9;11)(p22;q23) translocation is one of the most frequent secondary malignancies. The timing of the initiation of translocation and of development of the malignant t(9;11) clone during chemotherapy is presently unknown. In the present study, we backtracked bone marrow samples from three children during treatment for acute lymphoblastic leukemia (ALL). Two patients developed a t(9;11)-positive t-AML 19 and 30 months after therapy start, whereas the third patient, diagnosed with a rare t(9;11)-positive ALL, suffered from an ALL relapse 23 months after initial diagnosis. The genomic MLL-MLLT3 (MLL-AF9) fusion site was amplified by a multiplex, nested long-range PCR and used as a clonal marker for quantification of the MLL-MLLT3-positive cells during chemotherapy. The t(9;11)-positive clone was detectable 13 and 18 months after therapy start in both t-AML cases, which was 6-12 months before clinical diagnosis of the secondary malignancy. In the t(9;11)-positive ALL patient, the identical leukemic clone reoccurred during maintenance therapy after a short molecular remission, 8 months before clinically overt ALL relapse. The time course and characteristics of the genomic breakpoints in the present t-AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage.     

A novel isoform of the smooth muscle cell differentiation marker smoothelin

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease. Received: 25 August 1998 / Accepted: 19 October 1998     

Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis

The effects of statins on bone formation in periprosthetic osteolysis have not been determined to date. We investigated the effect of the HMG-CoA reductase inhibitor simvastatin on osteoblastic bone formation under conditions of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After 2 weeks, calvaria were processed for histomorphometry and stained with Giemsa dye. New bone formation was measured as osteoid tissue area within the midline suture. Bone thickness was quantified as indicator of net bone growth. Statistical analysis was performed using one-way ANOVA and a Student's t-test. New bone formation and bone thickness were significantly enhanced following simvastatin treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I), 0.015+/-0.012 mm2 after particle implantation without further intervention (group II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008). In conclusion, simvastatin treatment markedly promoted bone formation and net bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model. These new findings indicate that simvastatin may have favorable osteoanabolic effects on wear debris-mediated osteolysis after total joint arthroplasty, involving local stimulation of osteoblastic bone formation.     

Blurring artifacts in megavoltage radiography with a flat-panel imaging system: comparison of Monte Carlo simulations with measurements

Originally designed for use at medical-imaging x-ray energies, imaging systems comprising scintillating screens and amorphous Si detectors are also used at the megavoltage photon energies typical of portal imaging and industrial radiography. While image blur at medical-imaging x-ray energies is strongly influenced both by K-shell fluorescence and by the transport of optical photons within the scintillator layer, at higher photon energies the image blur is dominated by radiation scattered from the detector housing and internal support structures. We use Monte Carlo methods to study the blurring in a notional detector: a series of semi-infinite layers with material compositions, thicknesses, and densities similar to those of a commercially available flat-panel amorphous Si detector system comprising a protective housing, a gadolinium oxysulfide scintillator screen, and associated electronics. We find that the image blurring, as described by a point-spread function (PSF), has three length scales. The first component, with a submillimeter length scale, arises from electron scatter within the scintillator and detection electronics. The second component, with a millimeter-to-centimeter length scale, arises from electrons produced in the front cover of the detector. The third component, with a length scale of tens of centimeters, arises from photon scatter by the back cover of the detector. The relative contributions of each of these components to the overall PSF vary with incident photon energy. We present an algorithm that includes the energy-dependent sensitivity and energy-dependent PSF within a ray-tracing formalism. We find quantitative agreement (approximately 2%) between predicted radiographs with radiographs of copper step wedges, taken with a 9 MV bremsstrahlung source and a commercially available flat-panel system. The measured radiographs show the blurring artifacts expected from both the millimeter-scale electron transport and from the tens-of-centimeters length scale arising from the scattered photon transport. Calculations indicate that neglect of the energy-dependent blurring would lead to discrepancies in the apparent transmission of these wedges of the order of 9%.     

Predictability of Individual Differences in Activation Processes in a Field Setting Based on Laboratory Measures

The predictability of individual differences in activation processes was investigated in a multi-method laboratory-field study. Male students of physical education (N=58) were examined under various emotionally activating and physically demanding conditions (mental arithmetic, reaction time, free speech, cold pressor test, bicycle ergometer). The assessment included multi-channel recordings of pre-start phases in an athletic stadium and performance on a 1000 m run. Basal heart rate was also recorded during sleep. This multi-situational assessment was repeated after three weeks, three months, and, for most (N=42) subjects, after one year. Significant relationships exist between scores from corresponding conditions of relaxation, anticipation, and performance of physical exercise. However, with the exception of heart rate, correlation coefficients are rather small and seem to be of questionable predictive validity. A generalizability study further supports the general conclusion: To increase the practical relevance in psychophysiological investigations of stress/strain phenomena, such studies should directly assess individual differences in the criterion situations themselves.     

An adjective list for assessing emotional expressivity in psychotherapy research

Background: Several forms of psychotherapy aim at improving their patients' emotional expressivity, which is considered to contribute to mental health. Studies on the success of such attempts are virtually absent. Aim: To develop a measure for assessing changes of emotional expressivity in the course of psychotherapy. Method: In study 1 (N = 321), we generated a pool of German adjectives referring to emotional expressivity and reduced the number of those adjectives by means of factor‐analysis. In study 2 (N = 103), we determined how emotional expressivity is related to the Big Five personality factors. Results: An expressivity scale of 12 items with highly satisfactory psychometric properties was construed. Emotional expressivity is substantially related to Extraversion and moderately related to Agreeableness and Openness. Conclusion: The scale is ideally suited for repeated assessments in the course of psychotherapy in multi‐agent (e.g., inpatient) settings. Copyright © 2007 John Wiley & Sons, Ltd.     

Cross-reactive trinitrophenylated peptides as antigens for class II major histocompatibility complex-restricted T cells and inducers of contact sensitivity in mice. Limited T cell receptor repertoire

The induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major histocompatibility complex (MHC)-restricted, hapten-specific, CD4⁺ T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten-conjugated, MHC class II-associated peptides. This study for the first time directly demonstrates that hapten-peptides account for the majority of determinants recognized by trinitrophenyl (TNP)-specific CD4⁺ T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP-modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I-A^b or from λ represser with specificity to I-A^d as well as TNP-proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II-restricted hapten determinants for a number of TNP-specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP-specific helper T cells may cross-react with different TNP-peptides bound to identical class II molecules. Chemical treatment of antigen-presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements Vβ2 and Vα10 in I-A^b/TNP-specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93–105 (i.e. a clearly “non-self” sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP-peptide determinants defined by us as immuno-dominant are responsible for the induction of contact sensitivity to haptens.     

BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

Determining the health status of a population: role and quality of survey questions

Zusammenfassung Die Rolle und Güte von Befragungsdaten im Rahmen der Messung des Gesundheitszustands der Bevölkerung wird untersucht. Dabei werden zunächst die Informationsbedürfnisse im Gesundheitswesen abgesteckt und der Beitrag von Bevölkerungserhebungsdaten angegeben. Befragungsdaten stellen wiederum eine Untermenge dieser letzten Datengruppe dar.Zur Beurteilung von Rolle und Güte solcher Daten wird auf die methodischen Eigenschaften von Befragungsdaten eingegangen und gezeigt, da die Dokumentation der Methoden dieser Datenkörper nicht nur zur Gütebeurteilung notwendig ist sondern vielmehr deren Rolle im Kanon der Information im Gesundheitswesen wesentlich mitbestimmt. Wenn dieses so ist, müssen Anstrengungen zur Qualitätsverbesserung sich nicht nur um die Verbesserung traditionell berücksichtigter Methodikaspekte kümmern (wie z.B. Stichprobenziehung, Responseraten) sondern auch um die Verbesserung der methodischen Voraussetzungen für bessere Nutzungsmöglichkeiten von Befragungsdaten. Diese sind zu erreichen durch Erhöhung der Verknüpfungsmöglichkeiten, durch Einführung von einheitlichen Mindestdatensätzen, einheitliche Definitionen, einheitliche Ausdrücke und durch Beibehaltung von identischen Fragen in einem Erhebungstyp über längere Zeit hinweg. Güte von Befragungsdaten wird daher wesentlich durch ihre methodischen Eigenschaften und Rolle durch die Nutzungsmöglichkeiten dieser Daten bestimmt.

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Measuring population health levels: Role and quality of interview data

Summary Role and quality of interview data are examined with respect to their importance for the measurement of population health levels. Starting from general information requirements in health services, the contribution of population survey data is described. Interview data constitute just a subset of such survey data.When role and quality of interview survey data are to be judged, survey methods are of major importance. They not only determine the quality but also the role of health interview survey data in the framework of all information about the population's health. If this is so, efforts to improve health survey data quality should not only be directed towards improvement of traditional methodological aspects (such as sampling procedures and response rates) but also towards the implementation of prerequisites for wider usage of health interview data. This may be achieved by improving their linkage potential, by implementing uniform minimal basic data sets, by introducing identical terms and definitions and by keeping identical survey methods (including questions) for several years in a row.Quality of health interview data is, therefore, determined by the methodological standards underlying their collection and the potential for usage of these data sets determines the role they play as part of the information about the population's health.

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La mésure du niveau de la santé de la population: role et qualité de dates de questionnaires

Résume Cet article s'occupe du rôle et de la qualité des dates de questionnaires dans le domaine de l'état de santé de la population. On s'interesse d'abord à des besoins d'informations du système de la santé pour en déduire l'importance des enquêtes de la population. Des dates de questionnaires sont un sous-groupe des dates mentionnes ci-dessus.Pour juger le rôle et la qualité de telles dates on regarde de près les méthodes des dates de questionnaires tout en montrant que la documentation des méthodes de ce corps de dates n'est pas seulement nécessaires pour juger sa qualité mais également pour déterminer son rôle dans le cadre de l'information du système de la santé. Si c'est ainsi, il faut faire des efforts pour améliorer la qualité des aspects méthododiques auxquels on se réfère traditionellement et pour augmenter les suppositions de meilleurs possibilites d'emploi des dates d'enquêtes. Cet objectif est atteint par l'augmentation des possibilites de joindre les corps de dates, par l'introduction des dates minimes uniformes, des définitions et termes uniformes et par l'insistance en de mêmes questions pendant une certaine période. Or, la qualité des dates de questionnaires est deternminée essentiellement par ses charactéristiques méthodiques et le rôle de celles-ci par ses possibilités d'emploi.