FLT3 Length Mutations as Marker for Follow-Up Studies in Acute Myeloid Leukaemia

Length mutations within the FLT3 gene (FLT3-LM) can be found in 23% of acute myeloid leukaemia (AML) and thus are the most frequent mutations in AML. FLT3-LM are highly correlated with AML with normal karyotype and other cytogenetic aberrations of the prognostically intermediate group. This group is supposed to be a mixed group of AML with differences in the underlying pathogenesis. For more individualized treatment options it would be helpful to better characterize this large AML group not only by molecular mutations but also use these markers for the definition of minimal residual disease (MRD). However, so far the cytogenetically intermediate AML has been lacking suitable markers for PCR-based MRD detection like the fusion genes in the prognostically favourable subgroups. The suitability of the FLT3-LM as a target for PCR-based MRD was discussed controversially as it seemed to be a rather unstable marker. Thus, we aimed at the evaluation of FLT3-LM as a marker for residual disease in a large cohort of AML. Paired samples of 97 patients with AML at diagnosis and at relapse were analyzed. It could be shown that in only four cases a loss of the length mutation was detected. This is in the range of other well-characterized AML relapsing with a different geno- and/or phenotype. In contrast, a change in the ratio of the mutated allele in comparison to the wild-type allele was frequently observed. In detail, the FLT3-LM showed a tendency to accumulate during disease progression and was found more frequently at relapse than at diagnosis. In addition, 45 patients were analyzed at different time points during and after therapy. Using conventional PCR it clearly could be shown that for most of the patients positive at presentation FLT3-LM is a reliable PCR marker for monitoring treatment response. Even an early detection of relapse was possible in some cases. Copyright (C) 2004 S. Karger AG, Basel

First verbs : On the way to mini-paradigms

This 18th issue of ZAS-Papers in Linguistics consists of papers on the development of verb acquisition in 9 languages from the very early stages up to the onset of paradigm construction. Each of the 10 papers deals with first-Ianguage developmental processes in one or two children studied via longitudinal data. The languages involved are French, Spanish, Russian, Croatian, Lithuanien, Finnish, English and German. For German two different varieties are examined, one from Berlin and one from Vienna. All papers are based on presentations at the workshop 'Early verbs: On the way to mini-paradigms' held at the ZAS (Berlin) on the 30./31. of September 2000. This workshop brought to a close the first phase of cooperation between two projects on language acquisition which has started in October 1999: a) the project on "Syntaktische Konsequenzen des Morphologieerwerbs" at the ZAS (Berlin) headed by Juergen Weissenborn and Ewald Lang, and financially supported by the Deutsche Forschungsgemeinschaft, and b) the international "Crosslinguistic Project on Pre- and Protomorphology in Language Acquisition" coordinated by Wolfgang U. Dressler in behalf of the Austrian Academy of Sciences

Filler + Infinitive and Pre- and Protomorphology Demarcation in a French Acquisition Corpus

This paper presents a case study on the acquisition of grammatical morphemes via fillers, i.e., underspecified place holders, with particular focus on early structures made up of a filler followed by an infinitive. The path leading from fillers to French semi-auxiliaries and subject clitics is analyzed within the framework of Natural Morphology and constructivism which assumes that grammatical modules are not innate but are constructed by children. The evolution of fillers in the corpus studied is described as a grammaticization process of form and meaning through successive linguistic dissociations. Emphasis is put on the functional polyvalence of fillers and on their relation to the main phases in the construction of gramma

First tentative conclusions on the early development of verb morphology

In these conclusions we can deal only with some of the tentative comparative results of the workshop papers on the early development of verb morphology. The main focus is on criteria of how the child detects morphology and how this emerging morphological competence develops in its earliest phases. In view of the purpose and tentative character of these conclusions, all references will be limited to the papers of the workshop and to earlier studies by workshop participants within the "Crosslinguistic Project on Pre- and Protomorphology in Language Acquisition". Much more will be given in the projected final publication

On the Typology of Inflection Class Systems

Inflectional classes are a property of the ideal inflecting-fusional language type. Thus strongly inflecting languages have the most complex vertical and horizontal stratification of hierarchical tree structures. Weakly inflecting languages which also approach the ideal isolating type or languages which also approach the agglutinating type have much shallower structures. Such properties follow from principles of Natural Morphology and from the distinction of the descendent hierarchy of macroclasses, classes, subclasses, subsubclasses etc. and homogeneous microclasses. The main languages of illustration are Latin, Lithuanian, Russian, German, French, Finnish, Hungarian and Turkis

Eight months of continuous positive airway pressure (CPAP) decrease tumor necrosis factor alpha (TNFA) in men with obstructive sleep apnea syndrome

Objectives: The aim of this study was to assess serum tumor necrosis factor alpha (TNFA) concentrations 8months of continuous positive airway pressure (CPAP) therapy. Design: This study used prospective, observational clinical trial. Patients: Sixty-six patients with newly diagnosed sleep apnea syndrome (12 women, 54 men), age 52.3 ± 9.8 (mean ± SD) with a body mass index of 29.7 ± 4.4 and an apnea-hypopnea index of 39.7 ± 26.8, were studied. Intervention: CPAP was administered for a mean of 7.8 ± 1.3months. Measurements and results: TNFA concentrations using an ultrasensitive ELISA assay at baseline and follow-up. TNFA decreased in men with high (5.2 ± 1.7h/night, −0.46 ± 1.1ng/l, p = 0.001) and with low (2.5 ± 1.0h/night −0.63 ± 0.77ng/l, p = 0.001) adherence but not in women. Average number of hours of CPAP use correlated positively with delta TNFA (R 2 0.08, p = 0.04) Conclusion: Long-term CPAP positively affects TNFA even in men with poor adherence to CPA

Acquisition of verbs in Croatian, French and Austrian German - an outline of a comparative analysis

Research of child language acquisition, i. e. comparisons of acquisition in typologically different languages, play a significant role in shedding some light on universal linguistic features. The aim of our paper is to compare acquisition of verbal morphology in three languages belonging to different branches of IndoEuropean languages and to compare developing verbal systems in children as well as the order of emergence of verbal forms in each of them. Furthermore, the results on regularities occurring in all three languages have been discussed. The analysis of process of developing verbal system within each particular language is based on tense and mood. Provided error analysis gave us some further insights into the linguistically active role that child takes at certain stage of its linguistic development. The intention of this paper is to point to relevant aspects of developing linguistic system common to all three analysed languages, but at the same time drawing the attention to those language segments that need to be taken into consideration due to the limitations imposed by the language variations

Holographic imaging of an array of submicron light scatterers at low photon numbers

We experimentally test a recently proposed holographic method for imaging coherent light scatterers which are distributed over a 2-dimensional grid. In our setup the scatterers consist of a back-illuminated, opaque mask with submicron-sized holes. We study how the imaging fidelity depends on various parameters of the set-up. We observe that a few hundred scattered photons per hole already suffice to obtain a fidelity of 96% to correctly determine whether a hole is located at a given grid point. The holographic method demonstrated here has a high potential for applications with ultracold atoms in optical lattices.Comment: 8 pages, 9 figure

Quadriceps Strength in Patients With Isolated Cartilage Defects of the Knee : Results of Isokinetic Strength Measurements and Their Correlation With Clinical and Functional Results.

Background: Recent studies have found a significant deficit of maximum quadriceps strength after autologous chondrocyte implantation (ACI) of the knee. However, it is unclear whether muscular strength deficits in patients with cartilage damage exist prior to operative treatment. Purpose: To isokinetically test maximum quadriceps muscle strength and quantify the impact of possible strength deficits on functional and clinical test results. Study Design: Cross-sectional study; Level of evidence, 3. Methods: To identify clinically relevant muscular strength deficits, 24 patients (5 females, 19 males; mean age, 34.5 years; body mass index, 25.9 kg/m2) with isolated cartilage defects (mean onset, 5.05 years; SD, 7.8 years) in the knee joint underwent isokinetic strength measurements. Maximal quadriceps strength was recorded in 3 different testing modes: pure concentric contraction (flexors and extensors alternating work; con1), concentric-eccentric (only the extensors work concentrically and eccentrically; con2), and eccentric contraction in the alternating mode (ecc). Results were compared for functional performance (single-leg hop test), pain scales (visual analog scale [VAS], numeric rating scale [NRS]), self-reported questionnaires (International Knee Documentation Committee [IKDC], Knee Injury and Osteoarthritis Outcome Scale [KOOS]), and defect size (cm2). Results: Compared with the uninjured leg, significantly lower quadriceps strength was detected in the injured leg in all isokinetic working modes (con1 difference, 27.76 N·m [SD 17.47; P = .003]; con2 difference, 21.45 N·m [SD, 18.45; P =.025]; ecc difference, 29.48 N·m [SD, 21.51; P = .001]), with the largest deficits found for eccentric muscle performance. Moderate negative correlations were observed for the subjective pain scales NRS and VAS. The results of the IKDC and KOOS questionnaires showed low, nonsignificant correlations with findings in the isokinetic measurement. Moreover, defect sizes (mean, 3.13 cm2) were of no importance regarding the prediction of the strength deficit. The quadriceps strength deficit between the injured and the uninjured leg was best predicted by the results of the single-leg hop test. Conclusion: Patients with isolated cartilage defects of the knee joint have significant deficits in quadriceps muscle strength of the injured leg compared with the uninjured leg. The single-leg hop test may be used to predict quadriceps strength deficits. Future research should address whether preoperative strength training in patients with cartilage defects of the knee could be effective and should be taken into consideration in addition to surgical treatment. Keywords muscle strength, isokinetic, cartilage defect, cartilage repair, knee joint, rehabilitatio