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M Ott

Publications and source records attributed to M Ott.

At least 19 recordsLinked to original sources
PubMed2006

Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

The diagnosis of malignant lymphoma is a recognized difficult area in histopathology. Therefore, detection of clonality in a suspected lymphoproliferation is a valuable diagnostic criterion. We have developed primer sets for the detection of rearrangements in the B- and T-cell receptor genes as reliable tools for clonality assessment in lymphoproliferations suspected for lymphoma. In this issue of Leukemia, the participants of the BIOMED-2 Concerted Action CT98-3936 report on the validation of the newly developed clonality assays in various disease entities. Clonality was detected in 99% of all B-cell malignancies and in 94% of all T-cell malignancies, whereas the great majority of reactive lesions showed polyclonality. The combined BIOMED-2 results are summarized in a guideline, which can now be implemented in routine lymphoma diagnostics. The use of this standardized approach in patients with a suspect lymphoproliferation will result in improved diagnosis of malignant lymphoma.

False Negative Reactions↗
PubMed2006

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Chromosomes, Human, Pair 11↗
PubMed2006

Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.

Gene Amplification↗
PubMed2005

Inhibition of P-glycoprotein function by several antidepressants may not contribute to clinical efficacy.

INTRODUCTION: In many depressive patients the negative feedback mechanism of the HPA (hypothalamic-pituitary-adrenocortical) axis is impaired. It has been suggested that antidepressants inhibit membrane glucocorticoid transporters like P-Glycoprotein (Pgp) and hence enhance the intracellular glucocorticoid concentration, leading to an increased glucocorticoid-receptor mediated gene transcription and therefore to normalization of the function of the HPA axis. The aim of this study is to investigate inhibition of Pgp by several different antidepressants. METHODS: We characterized the inhibitory potencies of the antidepressants in two in vitro assays by using calcein-AM as Pgp substrate. The two different cell-systems expressing Pgp were: 1. PBCEC (porcine brain capillary endothelial cells) as model for the blood-brain-barrier, and 2. A human lymphocytic leukaemia cell line CEM and the multi-drug-resistant (MDR) cell line VLB-100, expressing Pgp as model for the human protein. RESULTS: All of the antidepressants tested inhibit the transport of calcein-AM by Pgp in the micromolecular range. DISCUSSION: Because this inhibition is only seen at concentrations above therapeutically relevant plasma levels, their effect my not play a role for the mechanism of action of the antidepressants tested.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Accommodation behaviour during prey capture in the Vietnamese leaf turtle ( Geoemyda spengleri).

Vietnamese leaf turtles ( Geoemyda spengleri) were tested for their ability to focus on prey objects at various distances. Accommodation was continuously measured by infrared photoretinoscopy. All animals investigated during this study showed a surprisingly high precision of accommodation over a range of over 30 D. Measured accommodation matched the target distance accurately for distances between 3 and 17 cm. The turtles switched between independent and coupled accommodation in the two eyes. Independent accommodation was observed when the turtles inspected their environment visually without a defined object of interest. Coupled accommodation was only observed during binocular prey fixation. When a turtle aimed at a target, the symmetrical focus of both eyes persisted even if vision was totally blocked in one eye or altered by ophthalmic lenses. This suggests that the eyes were linked by internal neuronal mechanisms. The pupil of the eye responded clearly to changes in ambient light intensity. A strong decrease in pupil size was also observed when the eye was focused on a close target. In this case, the constriction of the pupil probably aids in the deformation of the eye lens during near-accommodation.

Accommodation, Ocular↗
PubMed2003

Variations in the off-axis refractive state in the eye of the Vietnamese leaf turtle (Geoemyda spengleri).

Lower-field myopia has been described for various vertebrates as an adaptation that permits the animal to keep the ground in focus during foraging, and, at the same time, to look out for distant objects, such as predators, in the upper visual field. Off-axis measurements with infrared photoretinoscopy in the eye of Geoemyda spengleri revealed a constant refractive state in the horizontal plane of the visual field but variable refraction in the vertical plane. In the three turtles investigated, the refractions increased continuously from the ventral to the dorsal visual field over a range of 35, 40 and 56 D, respectively. While this finding confirms the presence of an adaptive change of the refractive state equivalent to lower field myopia, subsequent measurements with a rotated retinoscope showed that at least part of the variation in the ventral field was attributed to astigmatism. The reason for this astigmatism is unknown. Anatomical investigation of the retina revealed that the constant refractive values in the horizontal plane corresponded to a stripe of increased ganglion cell density. A maximum density of 4,200 ganglion cells mm(-2) was counted in the centre of this visual streak.

Animals↗
PubMed2003

Three-dimensional vestibular eye and head reflexes of the chameleon: characteristics of gain and phase and effects of eye position on orientation of ocular rotation axes during stimulation in yaw direction.

We investigated gaze-stabilizing reflexes in the chameleon using the three-dimensional search-coil technique. Animals were rotated sinusoidally around an earth-vertical axis under head-fixed and head-free conditions, in the dark and in the light. Gain, phase and the influence of eye position on vestibulo-ocular reflex rotation axes were studied. During head-restrained stimulation in the dark, vestibulo-ocular reflex gaze gains were low (0.1-0.3) and phase lead decreased with increasing frequencies (from 100 degrees at 0.04 Hz to < 30 degrees at 1 Hz). Gaze gains were larger during stimulation in the light (0.1-0.8) with a smaller phase lead (< 30 degrees) and were close to unity during the head-free conditions (around 0.6 in the dark, around 0.8 in the light) with small phase leads. These results confirm earlier findings that chameleons have a low vestibulo-ocular reflex gain during head-fixed conditions and stimulation in the dark and higher gains during head-free stimulation in the light. Vestibulo-ocular reflex eye rotation axes were roughly aligned with the head's rotation axis and did not systematically tilt when the animals were looking eccentrically, up- or downward (as predicted by Listing's Law). Therefore, vestibulo-ocular reflex responses in the chameleon follow a strategy, which optimally stabilizes the entire retinal images, a result previously found in non-human primates.

Adaptation, Physiological↗
PubMed2003

[Liver replacement therapy. Reliable indications in acute liver failure].

Extracorporeal liver support devices aim at improving the therapeutical options for liver failure. Numerous artificial and bioartificial devices have been tested to reduce the high mortality of this dynamic disease. In particular, the detoxification function of the liver should be upheld, by means of a number of different procedures, either until liver function is restored or until transplantation. Both purely artificial, machine-based procedures including different forms of dialysis and hemoadsorption as well as bioartificial procedures based on hepatocytes are being tested, as are different types of extracorporeal liver perfusion. This paper provides an overview of the different methods and devices and their clinical evidence in order to give a recommendation for the handling of the expensive devices. There is no current indication for the application of liver support devices outside of clinical studies at specialised centres.

Exchange Transfusion, Whole Blood↗
PubMed2002

Can contrast enhanced MRI predict the response of Graves' ophthalmopathy to orbital radiotherapy?

The purpose of this study was to try to determine by means of contrast-enhanced MRI, a subset of patients with Graves' ophthalmopathy who will not respond to orbital radiotherapy. 54 patients with Graves' ophthalmopathy were treated with orbital radiotherapy (10 x 2 Gy) and symptom relief was recorded. MRI examinations prior to radiotherapy were retrospectively evaluated for enlargement, contrast enhancement and fibrotic changes in extraocular muscles and surrounding soft tissue. Imaging data were correlated with clinical features and response. Symptom relief was observed in 61% of patients but this could not be predicted by any of the MRI signs investigated. However, there is a trend for a better treatment reponse in patients who show contrast enhancement of extraocular muscles prior to orbital radiotherapy (p=0.08). MRI could not adequately predict the efficacy of orbital radiotherapy in this group of patients. Clinical assessment of disease activity is still the most reliable method.

Adolescent↗
PubMed2001

A semi-automated system for analysis and storage of SNPs.

The discovery of single nucleotide polymorphisms ( SNPs) is currently pursued with a tremendous effort. SNPs represent a rich source for molecular markers, since estimations predict six to seven million of these DNA variations in the human genome. A subset of these genetic variants is thought to have a pervasive impact on modern medicine, be it for the elucidation of differential pharmacological response or for the facilitated identification of genes involved in monogenetic and complex human diseases. Here we describe the overall process that leads to the set up of a SNP database. We describe a high-throughput sequencing assay for SNP discovery, automation of the dataflow from the DNA sequencer to the SNP analysis, and the tools to facilitate it. At the end of the process, a web-accessible interface collects the SNP information, which is processed in order to be written into the SNP database and to be available for end users who would like to select appropriate SNPs for their special screening needs.

Automation↗
PubMed2001

Chameleons have independent eye movements but synchronise both eyes during saccadic prey tracking.

The movements of both eyes and the head were recorded with search coils in unrestrained, freely moving chameleons. As a main result I found that the generation of saccades in the left and the right eye was either independent from each other or was highly correlated according to the behavioural situation. When no prey item was fixated, disconjugate saccades were observed which was in accordance with earlier observations in chameleons. During prey tracking the chameleons switched to a different oculomotor behaviour and pursued the moving prey with synchronous saccades. At higher target velocities, the tracking movement of the head was also saccadic and was synchronised with the two eyes. Binocular coupling affected only the timing of the saccades but not the metrics: the amplitudes of the synchronous saccades were usually different in the two eyes. These observations suggest the existence of two independent premotor neuronal circuits for left and right eye saccadic motor control in the chameleon. Binocular coupling in prey-tracking chameleons is probably achieved by neuronal coupling of these premotor circuits during eye-head coordination. The ability to switch between synchronous and uncoupled saccadic eye movements has not been described for any other vertebrate. This unique ability of the chameleon may help to understand the organisation of the oculomotor system of other vertebrates since evidence for separate left eye and right eye saccade generation and position control has recently also been reported in primates.

Animals↗
PubMed2001

HIV-1 protein Tat reduces the glutamate-induced intracellular Ca2+ increase in cultured cortical astrocytes.

The trans-activator protein Tat of the human immunodeficiency virus type 1 (HIV-1) is regarded as an injurious molecule in the pathogenesis of HIV-1 associated encephalopathy (HIVE). We investigated the effects of Tat on neuroligand-induced intracellular Ca2+ increase in cultured astroglial cells. Rat cortical astrocytes, human glioblastoma cells and glial restricted precursor cells, from a human embryonic teratocarcinoma cell line, were incubated with recombinant Tat (100 ng/mL for 60 min) which induced a significant reduction of glutamate or ATP-induced intracellular Ca2+ increase ("glutamate response", "ATP response"). The reduction of the glutamate response was also observed following cell incubation with cell extracts of HeLa-T4+ cells transiently transfected with an expression plasmid coding for Tat. However, inactivation of the transcriptional trans-activity of Tat, by using a mutant form of Tat, as well as inhibition of de novo protein synthesis by cycloheximide abolished the effect on the glutamate response. This suggests that Tat acts upon induction of a so far unknown cellular gene whose gene product causes the reduction of glutamate responses. As the effect of Tat resembles the effect of TNFalpha on glutamate responses [Köller et al. (2001) Brain Res., 893, 237-243] which is locally released within the brains of HIVE patients, we also tested for synergistic effects of Tat and TNFalpha on the glutamate response. Low concentrations of Tat in combination with subthreshold concentrations of TNFalpha also elicited a marked reduction of astroglial glutamate responses. Our data suggest that Tat and TNFalpha, both by itself and synergistically, induce astroglial dysfunction.

AIDS Dementia Complex↗
PubMed2001

[Current status of cell-based therapies in liver diseases].

Major strides have been made during the past 10 years in the fields of liver cell transplantation and liver-directed gene therapy. Pre-clinical studies in animals have shown that primary hepatocytes transplanted into the liver as well as intravenously transfused bone marrow stem cells can generate new liver tissue. Such cell transplantation studies have contributed to our understanding of organogenesis and hepatocyte biology. Furthermore, transplantation of xenogenic hepatocytes has led to the development of new small animal models for studying viral hepatitis. In the clinical setting, liver cell transplantation offers a wide range of potential therapeutic applications, especially in metabolic diseases. In particular, the case of a patient with Crigler-Najjar Syndrome Type I clearly demonstrated the long-term viability of transplanted hepatocytes with stable metabolic function. Further studies are warranted to assess the full potential of cell- based therapies and their clinical application.

Animals↗