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Biomedical subjects

Michael Baum

Publications and source records attributed to Michael Baum.

At least 37 records · Page 2Linked to original sources

Characterization of an Escherichia coli elaC deletion mutant.

The elaC gene of Escherichia coli encodes a binuclear zinc phosphodiesterase (ZiPD). ZiPD homologs from various species act as3' tRNA processing endoribonucleases, and although the homologous gene in Bacillus subtilis is essential for viability [EMBO J. 22(2003) 4534], the physiological function of E. coli ZiPD has remained enigmatic. In order to investigate the function of E. coli ZiPDwe generated and characterized an E. coli elaC deletion mutant. Surprisingly, the E. coli elaC deletion mutant was viable and had wild-type like growth properties. Microarray-based transcriptional analysis indicated expression of the E. coli elaC gene at basal levels during aerobic growth. The elaC gene deletion had no effect on the expression of genes coding for RNases or amino-acyl tRNA synthetases or any other gene among a total of > 1300 genes probed. 2D-PAGE analysis showed that the elaC mutation, like-wise, had no effect on the proteome. These results strengthen doubts about the involvement of E. coli ZiPD in tRNA maturation and suggest functional diversity within the ZiPD/ElaC1 protein family. In addition to these unexpected features of the E. coli elaC deletion mutant, a sequence comparison of ZiPD (ElaC1) proteins revealed specific regions for either enterobacterial or mammalian ZiPD (ElaC1) proteins.

Amino Acid Sequence↗

Does the act of surgery provoke activation of "latent" metastases in early breast cancer?

This paper is written in support of the challenging article by Retsky and colleagues in this issue of Breast Cancer Research, and develops on the idea that the act of surgery can provoke the outgrowth of dormant micrometastases, which often leads to the failure of screening to deliver its promise. The therapeutic consequence of this idea involves the use of antiangiogenic drugs before surgery.

Breast Neoplasms↗

Functional maps of metastases from breast cancers: proof of the principle that multidimensional scaling can summarize disease progression.

The mathematic technique of multidimensional scaling can create "functional maps" of metastases from breast cancer such that positions of organs in these maps are proportional to the probability of metastases. Areas that are likely to share disease are close together in a functional map, even though they may be physically distant, and vice versa. Two functional maps of breast cancers-one of local metastases to axillary levels I to III and another of distant metastases-are statistically significant and clinically meaningful. The maps accurately reflect the clinical data ( r > 0.97, p < 0.01), and so the progression of disease is revealed in simple visual summaries. As an analogy, the metastatic sites are like buoys on a fluid surface, and cancer spreads from a primary tumor like waves emanating from a point of impact on that surface. Metastases are predicted when the waves swamp the buoys. Because breast cancers do not always spread to the next nearest site, these functional maps do not resemble anatomic maps. The maps are a view of the body as "seen" by the tumor. Several well known clinical features are seen in these maps: most local metastases are to axillary level I; upper-inner primaries spread equally to levels II and III; in-transit metastases in the lymph and blood vessels do not follow the pattern of other distant metastases. Future functional maps can expand these summary diagrams to include biologic parameters (gene-expression profiles or endocrine response) and give valuable insights into patterns of recurrence in different populations.

Adult↗

Intraoperative radiotherapy for breast cancer.

Postoperative radiotherapy, which forms part of breast-conserving therapy, may not need to encompass the whole breast. Apart from the consumption of huge resources and patients' time, postoperative radiotherapy deters many women from receiving the benefits of breast-conserving surgery, forcing them to choose a mastectomy instead. If radiotherapy could be given in the operating theatre immediately after surgery, many of these disadvantages could be overcome. One striking fact about local recurrence after breast-conserving surgery is that most occurs in the area of breast immediately next to the primary tumour; this is despite the finding that two-thirds of mastectomy samples have microscopic tumours distributed throughout the breast, even when radiotherapy is omitted. Thus, only the area adjacent to the tumour may need treatment with radiotherapy. On the basis of this premise, clinical scientists have used new technology to administer radiotherapy to the area at greatest risk of local recurrence, with the aim of completing the whole local treatment in one sitting. In this review, we have elaborated on the rationale and different methods of delivery of intraoperative radiotherapy. If this approach is validated by the results of current randomised trials, it could save time, money, and breasts.

Breast Neoplasms↗

Fluorescent sample labeling for DNA microarray analyses.

Three fluorophor-labeling methods for gene expression profiling on deoxyribonucleic acid (DNA) microarrays are described. All three techniques start from total ribonucleic acid (RNA) samples. Two procedures are based on first-strand complementary DNA synthesis by reverse transcription. Label is introduced either by direct incorporation of fluorescently labeled nucleotides or indirectly by incorporation of aminoally-dUTP and subsequent coupling of fluorescent dyes. The third method is based on an amplification of antisense RNA by in vitro transcription subsequent to first- and second-strand complementary DNA synthesis. While the first two methods are applied mainly in analyses on microarrays made from spotted polymerase chain reaction products or long oligonucleotides, the last procedure is mostly used for experiments on in situ synthesized oligonucleotide arrays.

DNA, Complementary↗

Validation of a novel, fully integrated and flexible microarray benchtop facility for gene expression profiling.

Here we describe a novel microarray platform that integrates all functions needed to perform any array-based experiment in a compact instrument on the researcher's laboratory benchtop. Oligonucle otide probes are synthesized in situ via a light- activated process within the channels of a three-dimensional microfluidic reaction carrier. Arrays can be designed and produced within hours according to the user's requirements. They are processed in a fully automatic workflow. We have characterized this new platform with regard to dynamic range, discrimination power, reproducibility and accuracy of biological results. The instrument detects sample RNAs present at a frequency of 1:100 000. Detection is quantitative over more than two orders of magnitude. Experiments on four identical arrays with 6398 features each revealed a mean coefficient of variation (CV) value of 0.09 for the 6398 unprocessed raw intensities indicating high reproducibility. In a more elaborate experiment targeting 1125 yeast genes from an unbiased selection, a mean CV of 0.11 on the fold change level was found. Analyzing the transcriptional response of yeast to osmotic shock, we found that biological data acquired on our platform are in good agreement with data from Affymetrix GeneChips, quantitative real-time PCR and--albeit somewhat less clearly--to data from spotted cDNA arrays obtained from the literature.

Automation↗

The current status of aromatase inhibitors in the management of breast cancer.

The third generation of specific AIs have made a very exciting contribution to the management of hormone responsive breast cancer. We can now state with confidence that their role in advanced breast cancer has overtaken that of tamoxifen, which should be relegated to a second-line treatment. Indeed, as a recent publication confirmed that first-line anastrozole followed by tamoxifen is an effective treatment sequence, this sequence may be considered the best choice for treating patients with hormone receptor-positive ABC. As far as the primary disease is concerned, the ATAC data certainly suggest that there is an alternative to tamoxifen in selected postmenopausal women with hormone receptor-positive disease. With more mature follow-up the study might even show that after a passage of nearly 20 years tamoxifen has lost its lead position in the adjuvant stakes as well.

Anastrozole↗