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Biomedical subjects

Michael Field

Publications and source records attributed to Michael Field.

8 recordsLinked to original sources
PubMed2006

T cell activation alters intestinal structure and function.

Treatment with anti-CD3 antibody (anti-CD3) causes transient diarrhea. In this issue of the JCI, Clayburgh et al. show that, in jejunum of mice injected with anti-CD3 or with TNF, fluid accumulation and changes in epithelial phenotype develop, the latter including an increase in the passive permeability to proteins, smaller solutes, and water and the endocytosis of the brush border Na+/H+ exchanger, thereby inhibiting Na+ absorption (a second cytokine, LIGHT, has the former effect, but not the latter) (see the related article beginning on page 2682). These phenotypic changes, by themselves, do not, however, explain increased fluid secretion. Since active anion secretion is not stimulated (in fact it is inhibited), a non-epithelial cell-mediated driving force must be present--most likely an increase in interstitial pressure due to an effect of TNF on capillary permeability, smooth muscle contractility, or both.

Animals↗
PubMed2004

Frequency of the ATM IVS10-6T-->G variant in Australian multiple-case breast cancer families.

BACKGROUND: Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia-telangiectasia mutated (ATM) gene, IVS10-6T-->G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. METHODS: We determined the frequency of ATM IVS10-6T-->G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. RESULTS: Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T-->G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. CONCLUSION: These findings indicate that the ATM IVS10-6T-->G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T-->G is not warranted in mutation screening of affected individuals from high-risk families.

Adult↗
PubMed2003

Phase resetting effects for robust cycles between chaotic sets.

In the presence of symmetries or invariant subspaces, attractors in dynamical systems can become very complicated, owing to the interaction with the invariant subspaces. This gives rise to a number of new phenomena, including that of robust attractors showing chaotic itinerancy. At the simplest level this is an attracting heteroclinic cycle between equilibria, but cycles between more general invariant sets are also possible. In this paper we introduce and discuss an instructive example of an ordinary differential equation where one can observe and analyze robust cycling behavior. By design, we can show that there is a robust cycle between invariant sets that may be chaotic saddles (whose internal dynamics correspond to a Rössler system), and/or saddle equilibria. For this model, we distinguish between cycling that includes phase resetting connections (where there is only one connecting trajectory) and more general non(phase) resetting cases, where there may be an infinite number (even a continuum) of connections. In the nonresetting case there is a question of connection selection: which connections are observed for typical attracted trajectories? We discuss the instability of this cycling to resonances of Lyapunov exponents and relate this to a conjecture that phase resetting cycles typically lead to stable periodic orbits at instability, whereas more general cases may give rise to "stuck on" cycling. Finally, we discuss how the presence of positive Lyapunov exponents of the chaotic saddle mean that we need to be very careful in interpreting numerical simulations where the return times become long; this can critically influence the simulation of phase resetting and connection selection.

Journal Article↗
PubMed2002

Chromosome 13q neocentromeres: molecular cytogenetic characterization of three additional cases and clinical spectrum.

We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions.

Abnormalities, Multiple↗