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Biomedical subjects

Michael Baum

Publications and source records attributed to Michael Baum.

At least 19 recordsLinked to original sources
PubMed2025

On the origin of the late-flowering ppd-H1 allele in barley.

To breed for climate resilient crops, an understanding of the genetic and environmental factors influencing adaptation is critical. Barley provides a model species to study adaptation to climate change. Here we present a detailed analysis of genetic variation at a major photoperiod response locus and relate this to the domestication history and dispersal of barley. The PPD-H1 locus (a PSEUDO-RESPONSE REGULATOR 7) promotes flowering under long-day conditions, and a natural mutation at this locus resulted in a recessive, late-flowering ppd-H1 allele. This mutation proved beneficial in high-latitude environments such as Northern Europe, where it allows extended vegetative growth during long spring days. We infer the origin of the mutated late-flowering ppd-H1 allele by re-sequencing a large geo-referenced collection of 942 Hordeum spontaneum, 5 Hordeum agriocrithon and 1110 domesticated (Hordeum vulgare) barleys. We demonstrate that the late-flowering phenotype originated from Desert-type wild barley in the Southern Levant and present evidence suggesting a post-domestication origin of the mutated ppd-H1 allele.

Hordeum↗
PubMed2005

Does surgery unfavourably perturb the "natural history" of early breast cancer by accelerating the appearance of distant metastases?

This historical perspective on breast cancer tells us how and why certain therapeutic eras have reached ascendancy and then declined. Therapeutic revolutions occur after a crisis develops when there is a general recognition that clinical interventions are not producing positive results predicted by the prevailing paradigm. The attitude of pre-modern surgeons was influenced by the very real possibility of doing more harm than good by operating upon women with breast cancer. Up until Halsted, the general consensus was clearly that, unless forced by the circumstances, surgical resection should be avoided for disease much more advanced than very early stage tumours (the cacoethesis of Celsus). Twentieth century progress in antisepsis, anaesthesia, and surgery changed this point of view. The first three quarters of that century saw more and more aggressive operations performed while the last quarter century reversed this trend, with reduction of the size of breast cancer operations based largely on the teachings of Fisher. A new crisis is upon us now in that trials of early detection have resulted in unexpected disadvantages to certain subgroups and there is previously unreported structure in early hazard of relapse, clinical data that suggests the act of surgery might accelerate the appearance of distant metastases. The explanation we propose that agrees with these results, as well as physicians of antiquity, is that surgery can induce angiogenesis and proliferation of distant dormant micrometastases, especially in young patients with positive nodes.

Breast Neoplasms↗
PubMed2005

A survey of breast cancer awareness and knowledge in a Western population: lots of light but little illumination.

There are conflicting data on breast cancer awareness and knowledge in specific population groups. We assessed awareness and knowledge of breast cancer in the general Irish population to identify sources of information on breast cancer and determine factors associated with knowledge and awareness of the disease. Participants (n=2355, 53% female) completed a multi-part questionnaire. Most (81%) had seen or heard something about breast cancer in the recent past and knowledge of symptoms and treatment was good overall. However, 66% of females overestimated their risk of developing disease, 88% underestimated the age at which it was most likely to develop and 56% underestimated 5-year survival. Knowledge of incidence and survival was higher in males (Odds Ratio (OR) 1.3, 95% Confidence Interval (CI); 1.1-1.5), participants with higher education (1.5; 1.2-1.7) and those who received information from television (1.3; 1.1-1.5). Ignorance regarding incidence, outcome and risk makes it unlikely that the general public or at risk females could currently make informed decisions on a range of breast cancer issues.

Adult↗
PubMed2005

TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation.

A revolution is challenging the dogma that local treatment for all patients with breast cancer treated with breast conservation therapy must include postoperative radiotherapy delivered to the whole breast. Such prolonged postoperative radiotherapy is a burden to patients and hospitals and forces many women to chose mastectomy instead. Furthermore, for patients receiving chemotherapy, the start of conventional radiotherapy may be delayed so long as to increase the risk of local relapse. These problems might be eliminated if effective radiotherapy could be given as a single treatment intraoperatively, immediately after the surgery. Local recurrence after breast-conserving surgery usually occurs in the portion of the breast in the immediate proximity of the tumor, even when radiotherapy is omitted. Therefore, it should usually be possible to restrict radiotherapy to only the area adjacent to the tumor in selected women. Based on this premise, we have devised a new technique of partial breast irradiation, with the intention of completing all local treatment in a single session. In this article, we elaborate on the rationale and on the different methods of delivering intraoperative radiotherapy. If this approach is validated in ongoing randomized trials, it could save time, money, and breasts.

Breast Neoplasms↗
PubMed2004

Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells.

Alternative splicing provides a versatile mechanism of gene regulation, which is often subverted in disease. We have used customized oligonucleotide microarrays to interrogate simultaneously the levels of expression of splicing factors and the patterns of alternative splicing of genes involved in tumor progression. Analysis of RNAs isolated from cell lines derived from Hodgkin lymphoma tumors indicate that the relative abundance of alternatively spliced isoforms correlates with transformation and tumor grade. Changes in expression of regulators were also detected, and a subset sample was confirmed at the protein level. Ectopic expression of neuron-specific splicing regulatory proteins of the Nova family was observed in some cell lines and tumor samples, correlating with expression of a neuron-specific mRNA isoform of JNK2 kinase. This microarray design can help assess the role of alternative splicing in a variety of biological and medical problems and potentially serve as a diagnostic tool.

Alternative Splicing↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗