Biomedical subjects
Publications and source records attributed to Thomas J Anderson.
Reaction of two equiv of 1-adamantylzinc bromide with (dippm)NiBr2 (dippm = bis(di-isopropylphosphino)methane) led to a dinuclear metal complex containing a unique linear bridging hydride ligand. The hydride was characterized by neutron diffraction methods, which confirmed a linear bonding mode. Preliminary reactivity studies of this unusual dimer are reported.
Addition of terpyridine to (TMEDA)Ni(CH3)2 results in the high-yield formation of (terpyridyl)NiMe (3). This NiI organometallic complex was found to be capable of transferring its methyl group to iodocyclohexane to produce methylcyclohexane in high yield. Compound 3 can also serve as an initiator for the catalytic cross-coupling of alkyl electrophiles performed under Negishi-like conditions.
Droplet-based programmable processors promise to offer solutions to a wide range of applications in which chemical and biological analysis and/or small-scale synthesis are required, suggesting they will become the microfluidic equivalents of microprocessors by offering off-the-shelf solutions for almost any fluid based analysis or small scale synthesis problem. A general purpose droplet processor should be able to manipulate droplets of different compositions (including those that are electrically conductive or insulating and those of polar or non-polar nature), to control reagent titrations accurately, and to remain free of contamination and carry over on its reaction surfaces. In this article we discuss the application of dielectrophoresis to droplet based processors and demonstrate that it can provide the means for accurately titrating, moving and mixing polar or non-polar droplets whether they are electrically conductive or not. DEP does not require contact with control surfaces and several strategies for minimizing surface contact are presented. As an example of a DEP actuated general purpose droplet processor, we show an embodiment based on a scaleable CMOS architecture that uses DEP manipulation on a 32 x 32 electrode array having built-in control and switching circuitry. Lastly, we demonstrate the concept of a general-purpose programming environment that facilitates droplet software development for any type of droplet processor.
The objective of this study was to determine the influence of annual mammography on pathology features of breast cancers in an invited population. We conducted a randomized trial of 53,890 invited and 106,971 control United Kingdom women who were recruited only from those aged 40 years, with central review of cancer histology. We compare the invasive cancer distribution for the categories of size, histological type, grade, and node status in subgroups of the invited population with that of controls. Among 1287 cancers identified in the total population through the end of December 1999, there are major differences among prevalence, incidence, interval, and lapsed-attender and nonattender subgroups for the distribution of cancer numbers in categories of chosen qualitative histological features. These reflect the biases known to affect a population exposed to screening. Comparing cancers from the unbiased group of the invited population with controls shows significant differences in distributions for size, grade, and node status but not histological type. Multivariate logistic regression shows significant reduction (odds ratio, 0.73; P = 0.043) in node-positive status for the unbiased group. We conclude that annual mammography from age 40 years significantly reduces size and positive-node status of invasive cancers in the invited population. The potential for phenotypic drift of grade emphasizes the relevance of screen detection of all grades at sizes smaller than 10 mm.
Apc (adenomatous polyposis coli) encodes a tumour suppressor gene that is mutated in the majority of colorectal cancers. Recent evidence has also implicated Apc mutations in the aetiology of breast tumours. Apc is a component of the canonical Wnt signal transduction pathway, of which one target is Tcf-1. In the mouse, mutations of both Apc and Tcf-1 have been implicated in mammary tumorigenesis. We have conditionally inactivated Apc in both the presence and absence of Tcf-1 to examine the function of these genes in both normal and neoplastic development. Mice harbouring mammary-specific mutations in Apc show markedly delayed development of the mammary ductal network. During lactation, the mice develop multiple metaplastic growths which, surprisingly, do not spontaneously progress to neoplasia up to a year following their induction. However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma.
PURPOSE: The morphologic and molecular phenotype of breast cancers may help identify patients who are likely to carry germline mutations in BRCA1 and BRCA2. This study evaluates the immunohistochemical profiles of tumors arising in patients with mutations in these genes. MATERIALS AND METHODS: Samples of breast cancers obtained from the International Breast Cancer Linkage Consortium were characterized morphologically and immunohistochemically using antibodies to estrogen receptor, progesterone receptor, HER-2 (c-erbB-2 oncogene), and p53 protein. RESULTS: Breast cancers in patients with BRCA1 germline mutations are more often negative for estrogen receptor, progesterone receptor, and HER-2, and are more likely to be positive for p53 protein compared with controls. In contrast, BRCA2 tumors do not show a significant difference in the expression of any of these proteins compared with controls. CONCLUSION: BRCA1 has a distinctive morphology and immunohistochemical phenotype. The combined morphologic and immunohistochemical data can be used to predict the risk of a young patient harboring a germline mutation in BRCA1. The BRCA2 phenotype is currently not well defined.
Three pathologists reviewed slides and reports of cancers arising in both the study and control populations of the U.K. trial of annual mammography screening from age 40 years. A total of 875 cases were scored independently as noninvasive, microinvasive, or invasive cancer, with the last also evaluated for histology grade, type, and lymphatic vascular invasion. Of these, 870 (99.2%) were confirmed malignant, 1 case had cytology only, and 5 were judged by all reviewers as benign. Reviewer complete concordance for the three classes of malignancy was achieved in 826 (95%) and majority agreement in 31 (3.6%) of 870 with complete data. All three readers recorded grade in 736 cancers, giving a kappa statistic of 0.69, 0.52, and 0.66 for grades I, II, and III, respectively, and 0.61 overall. Agreement that the cancer was special type or not was obtained in 671 (89.0%) with complete concordance in the nature of the type in 504 and majority view in 167; another 58 (7.7%) were characterised as "part special" pattern, with type disagreement in 23 (3%). The kappa statistic for single type subcategories in those cancers was substantial, at 0.68 overall. This improved to 0.76 for the last 230 invasive cancers after the pathologists agreed more explicit criteria for type discrimination. There was almost perfect agreement between original and review diagnosis of breast malignancy for both noninvasive/microinvasive and invasive cancer (kappa 0.84 and 0.91, respectively), justifying confidence in the diagnosis of breast cancer by U.K. pathologists. The specialists agreed substantially on qualitative histology features of type and grade of cancers, and improved further for typing by defining criteria. These consensus data, along with invasive size and node status, are reliable for use as surrogate measures of outcome, and to enhance interpretation of effect, when the trial case population sources are disclosed.