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Biomedical subjects

M Gotthardt

Publications and source records attributed to M Gotthardt.

23 records · Page 2Linked to original sources
PubMed1998

Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants.

The multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) has been postulated to participate in a number of diverse physiological and pathological processes ranging from the homeostasis of plasma lipoproteins, atherosclerosis, and fibrinolysis to neuronal regeneration and survival. It has not been possible to demonstrate in vivo the physiological significance of LRP for each of these complex processes by a conventional gene knockout approach because LRP is essential for embryonic development. Here we have used the Cre/loxP recombination system to achieve inducible, tissue-specific and quantitative disruption of the LRP gene in adult mice. Inactivation of LRP in the livers of LDL receptor-deficient mice resulted in the accumulation of cholesterol-rich remnant lipoproteins in the circulation. In normal animals, this caused a compensatory upregulation of the LDL receptor in the liver. Conditional gene targeting has thus allowed us to isolate a specific physiological function of LRP for in vivo analysis and has provided unequivocal evidence for another LDL receptor-independent cholesterol clearance pathway in liver.

Animals↗
PubMed1996

Sustained somatic gene inactivation by viral transfer of Cre recombinase.

Transgenic and knockout mice have proven invaluable tools for analyzing physiologically relavant functions of numerous genes. In some cases, however, pleiotropic effects that result from a variable requirement for a particular gene in different tissues, cell types, or stages of embryonic development may complicate the analysis due to a complex phenotype or embryonic lethality. The loxP/Cre-mediated recombination system, which allows tissue-specific gene targeting in the mouse, can be used to overcome these problems. A limitation of current methods is that a mouse carrying a loxP-tagged gene must be crossed with a transgenic mouse expressing the Cre recombinase in an appropriate tissue to obtain the desired gene rearrangement. We have used recombinant adenovirus carrying the Cre recombinase to induce virtually quantitative somatic cell gene disruption in the liver. The targeted gene was the multifunctional low-density lipoprotein receptor-related protein (LRP), a cell surface receptor for alpha 2-macroglobulin and other ligands. Transient expression of Cre following adenoviral infection produced the predicted gene rearrangement, functionally inactivating LRP in the liver. Rearrangement occurred within 6 days after infection and remained stable for at least 28 days. The results demonstrate the suitability of adenoviral Cre gene transfer to induce long-term, quantitative, and temporally controlled gene disruption in the mouse.

Adenoviridae↗
PubMed1996

"Ovarian asthma"-- act or fancy?

Hormonal interactions have been suspected of worsening airways dysfunction in a subgroup of female asthmatics. Despite reports of fatal and near-fatal asthma attacks associated with menstruation, there is little consensus about the impact of this biologic function on the clinical expression of asthma. The authors present a young asthmatic female whose episodic and potentially fatal worsening of asthma typically occurred within the days prior to her menses in the absence of other trigger factors.

Adult↗
PubMedDate not supplied

[Imaging of blocks in the spine with bone scintigraphy (SPECT)].

INTRODUCTION: One of the most important tasks of manual therapists is the treatment of hypomobile intervertebral joints. Such conditions of the spine are treated with various manipulations or mobilisation. The pathophysiological basis of hypomobility is still under discussion. Objective criteria for the diagnosis of impaired spinal mobility are not available. Nor is any substrate detectable by X-ray, computed tomography or NMR. AIM: To find evidence of a biomechanical alteration of hypomobile intervertebral joints with the aid of SPECT (Single Photon Emission Computed Tomography). STUDY DESIGN: 13 outpatients with back pain but otherwise healthy attending the Orthopaedic University Hospital in Marburg were examined by manual medical means, and were found to have hypomobility of an intervertebral joint. In addition, the spines of these patients were examined with SPECT (bone scanning). RESULTS: Comparison of the results of physical examination and bone scanning revealed that in 75% of all the cases the location (spinal segment) of the hypomobility identified by each of the two methods was identical. In 83%, they were in agreement on which of the sides (facet joint) was affected.

Adolescent↗