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Biomedical subjects

Michael H Weber

Publications and source records attributed to Michael H Weber.

5 recordsLinked to original sources
PubMed2005

Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology.

Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 microm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological "gold standard" The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure.

Animals↗
PubMed2003

Bacterial cold shock responses.

As a measure for molecular motion, temperature is one of the most important environmental factors for life as it directly influences structural and hence functional properties of cellular components. After a sudden increase in ambient temperature, which is termed heat shock, bacteria respond by expressing a specific set of genes whose protein products are designed to mainly cope with heat-induced alterations of protein conformation. This heat shock response comprises the expression of protein chaperones and proteases, and is under central control of an alternative sigma factor (sigma 32) which acts as a master regulator that specifically directs RNA polymerase to transcribe from the heat shock promotors. In a similar manner, bacteria express a well-defined set of proteins after a rapid decrease in temperature, which is termed cold shock. This protein set, however, is different from that expressed under heat shock conditions and predominantly comprises proteins such as helicases, nucleases, and ribosome-associated components that directly or indirectly interact with the biological information molecules DNA and RNA. Interestingly, in contrast to the heat shock response, to date no cold-specific sigma factor has been identified. Rather, it appears that the cold shock response is organized as a complex stimulon in which post-transcriptional events play an important role. In this review, we present a summary of research results that have been acquired in recent years by examinations of bacterial cold shock responses. Important processes such as cold signal perception, membrane adaptation, and the modification of the translation apparatus are discussed together with many other cold-relevant aspects of bacterial physiology and first attempts are made to dissect the cold shock stimulon into less complex regulatory subunits. Special emphasis is placed on findings concerning the nucleic acid-binding cold shock proteins which play a fundamental role not only during cold shock adaptation but also under optimal growth conditions.

Adaptation, Physiological↗
PubMed2002

Normal murine bone morphometry: a comparison of magnetic resonance microscopy with micro X-ray and histology.

OBJECTIVE: The authors have devised a means to assess subtle changes in the structure of bone using magnetic resonance (MR) microscopy. MR microscopy was compared with micro X-ray and histology to analyze the structure of normal bone. DESIGN: Femurs of C57Bl/6 mice were examined ex vivo using differently orientated slices and pulse sequences on both a 9.4 and 11.7 T MR scanner, followed by micro X-ray and histology. A thresholding analysis technique was applied to MR images, to generate contour lines delineating the boundaries between bone and marrow. RESULTS: By MR microscopy, optimal correlation with histological "gold standards" was obtained using a longitudinal sectional versus a cross-sectional slice profile, a short echo time gradient-echo sequence versus a long echo time spin-echo sequence, and a higher field strength, 11.7 T versus 9.4 T. Gradient-echo images at 11.7 T were acquired with a maximum in-plane resolution of 35 microm. CONCLUSION: Our results demonstrate that the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases on moving from the epiphyseal growth plate to the diaphysis. These changes observed with MR microscopy correlate with the histological data, but did not correlate with micro X-ray data, which showed no trends. Our quantitative evaluation using MR microscopy was found to be an effective means to visualize the normal variation in bone microanatomy compared with a histological "gold standard", and was a superior means of quantification in comparison with micro X-ray.

Animals↗
PubMed2002

The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model.

Bone metastases are generally associated with bone destruction which occurs in response to factors secreted by metastatic cells. Some of these factors secreted by the metastatic cells activate osteoclats while others are proteases that degrade bone collagen. To determine if Neovastat (AE-941), a naturally occurring multi-functional inhibitor of angiogenesis, is able to regulate properties that are thought to have relevance to their propensity to form bone metastases in vivo, we used the human breast cancer MDA-MB-231 cell line which can metastasize to bone. We showed that Neovastat prevented the degradation of osteoid-like radiolabeled extracellular matrices which was induced by incubation of human SaOS-2 osteoblast-like cells with MDA-MB-231 cells. Moreover, Neovastat was demonstrated to inhibit the gelatinolytic activity of matrix metalloproteinase (MMP)-9 expressed by MDA-MB-231 cells. The potential of Neovastat to retard the spread, growth, and osteolysis of MDA-MB-231 cells was then estimated in vivo. Histomorphometric analysis of the vertebral bodies indicated that MDA-MB-231 cells inoculated in nude mice (intracardiac) successfully generate osteolytic metastases with an 83% reduction of the volume of medullary bone (p< or =0.01). However, when tumor-bearing animals were treated orally with Neovastat, there was only a 19% decrease in medullary bone thus indicating that Neovastat can prevent bone metastasis in this model. Consistent with histological results, radiographic analysis indicated that Neovastat decreased the number of osteolytic lesions by 33% (p< or =0.3). Moreover, a decrease in the tumor volume in bone was observed in Neovastat-treated animals. These results indicate that Neovastat may be useful in preventing bone metastasis in cancer patients.

Angiogenesis Inhibitors↗