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Search Results: 1 - 10 of 162012 matches for " Michael T Lewis "
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Homeobox genes in mammary gland development and neoplasia
Michael T Lewis
Breast Cancer Research , 2000, DOI: 10.1186/bcr49
Abstract: The mammary gland is a remarkable organ with respect to its development and functional differentiation. It is also remarkable with respect to the consequences on mammalian life should development become abnormal, leading either to lactational failure or, most importantly, mammary cancer.Unlike most mammalian organs, which develop primarily embryonically with a more or less linear progression toward functional maturity, development of the mammary gland is primarily postpubertal and may be divided into both a linear and a cyclical phase (Fig. 1) (see [1,2,3] for detailed reviews). These phases can be characterized further as a series of highly orchestrated transitions, or switches, in which critical developmental decisions are made concerning cell differentiation, pattern formation and cell function. While mutations have been identified that block or delay most of these transitions (primarily in signal transduction networks), the higher order genetic determinants of cell identity that dictate cell type specific responses are largely unknown.Among other candidates, one superfamily of genes presents itself as capable of regulating developmental decisions during these transitions: the homeobox genes. As a general principle, homeobox genes encode transcription factors that play key roles in the determination and maintenance of cell fate and cell identity [4,5,6,7]. Homeobox genes share a common nucleotide sequence motif (the homeobox) encoding the roughly 61 amino acid homeodomain. The homeodomain, in turn, is a helix-turn-helix DNA binding domain of the functional transcription factor. Evolutionary relationships and family classifications are determined based upon the degree of identity and similarity among homeodomains followed by comparative analyses of amino acid sequences both amino-terminal and carboxyl-terminal to the homeodomain [8,9,10]. These terminal sequences vary considerably from protein to protein and, indeed, may demonstrate no evidence of evolutionary or
The more things change ... the more things change: developmental plasticity of tumor-initiating mammary epithelial cells
Michael T Lewis
Breast Cancer Research , 2010, DOI: 10.1186/bcr2459
Abstract: Change - the one thing you can count on ...A recent paper by Meyer and colleagues reminds us of this statement, and suggests we may have forgotten something in our rush to exploit the first set of breast cancer stem cell markers identified [1]. Namely, a full analysis of the developmental and tumor-initiating potential of the CD44pos; CD24pos breast cancer cell.In 2003, two cell surface markers - CD44high and CD24low/- - were associated with breast cancer stem cells [2]. In xenograft transplantation studies, this cell population regenerated tumors at high frequency whereas other cell populations were depleted for this function. Subsequent work in breast cancer cell lines showed that CD44high; CD24low/- cells were present in culture, and were also tumorigenic upon transplantation, with CD24 positivity being associated with decreased invasiveness (for example [3,4]). Naturally, this work set off a flurry of activity to characterize the CD44high; CD24low/- population molecularly relative to other populations present in tumors [5-8], and to evaluate their response to treatment (for example [9,10]).In the wake of this flurry of activity, it appears we may have forgotten something - to determine the full developmental and tumor-initiating potential of the CD44pos; CD24pos cell. The recent paper by Meyer and colleagues confirms that CD44pos; CD24low/- cells in a number of cell lines can give rise to CD44pos; CD24pos cells, and can yield total populations characteristic of the parental line [1]. This finding is not surprising, and in fact is as expected for a cancer stem cell. Using flow cytometry and single cell culture, however, these authors went on to show that the converse can also occur - CD44pos; CD24poscells can give rise to their CD44pos; CD24low/- counterparts, and are subsequently also capable of initiating tumors as xenografts with high efficiency. Further, their paper shows that the developmental potential for either CD44pos cell population to regenerate the ot
Emission-Line Diagnostics of the Central Engines of Weak-Line Radio Galaxies
Karen T. Lewis,Michael Eracleous,Rita M. Sambruna
Physics , 2003, DOI: 10.1086/376445
Abstract: A handful of well-studied Weak-Line Radio Galaxies (WLRGs) have been traditionally classified as Low Ionization Nuclear Emission-line Regions (LINERs), suggesting that these two groups of AGNs might be related. In this paper, we present new optical emission-line measurements for twenty Weak-Line Radio Galaxies which we supplement with measurements for an additional four from the literature. Classifying these objects by their emission-line ratios, we find that 50% of the objects are robustly classified as LINERs while an additional 25% are likely to be LINERs. Photoionization calculations show that the Spectral Energy Distribution of the well-studied WLRG 3C 270 (NGC 4261) is able to produce the observed emission-line ratios, but only if the UV emission seen by the narrow emission-line gas is significantly higher than that observed, implying A_V = 2.5-4.2 magnitudes along our line of sight to the nucleus. From the photoionization calculations, we find that the emission-line gas must have an ionization parameter between 10^-3.5 and 10^-4.0 and a wide range in hydrogen density (10^2-10^6 cm^-3) to reproduce the measured emission-line ratios, similar to the properties inferred for the emission-line gas in LINERs. Thus, we find that properties of the emission-line gas as well as the underlying excitation mechanism are indeed similar in LINERs and WLRGs. By extension, the central engines of accretion-powered LINERs and WLRGs, which do host an accreting black hole, may be qualitatively similar.
Long-Term Profile Variability in Active Galactic Nuclei with Double-Peaked Balmer Emission Lines
Karen T. Lewis,Michael Eracleous,Thaisa Storchi-Bergmann
Physics , 2010, DOI: 10.1088/0067-0049/187/2/416
Abstract: An increasing number of Active Galactic Nuclei (AGNs) exhibit broad, double-peaked Balmer emission lines,which represent some of the best evidence for the existence of relatively large-scale accretion disks in AGNs. A set of 20 double-peaked emitters have been monitored for nearly a decade in order to observe long-term variations in the profiles of the double-peaked Balmer lines. Variations generally occur on timescales of years, and are attributed to physical changes in the accretion disk. Here we characterize the variability of a subset of seven double-peaked emitters in a model independent way. We find that variability is caused primarily by the presence of one or more discrete "lumps" of excess emission; over a timescale of a year (and sometimes less) these lumps change in amplitude and shape, but the projected velocity of these lumps changes over much longer timescales (several years). We also find that all of the objects exhibit red peaks that are stronger than the blue peak at some epochs and/or blueshifts in the overall profile, contrary to the expectations for a simple, circular accretion disk model, thus emphasizing the need for asymmetries in the accretion disk. Comparisons with two simple models, an elliptical accretion disk and a circular disk with a spiral arm, are unable to reproduce all aspects of the observed variability, although both account for some of the observed behaviors. Three of the seven objects have robust estimates of the black hole masses. For these objects the observed variability timescale is consistent with the expected precession timescale for a spiral arm, but incompatible with that of an elliptical accretion disk. We suggest that with the simple modification of allowing the spiral arm to be fragmented, many of the observed variability patterns could be reproduced.
Emission Line Diagnostics of Accretion Flows in Weak-Line Radio Galaxies
Karen T. Lewis,Michael Eracleous,Rita M. Sambruna
Physics , 2001,
Abstract: In recent surveys of Radio-loud AGN, a new sub-class of objects, known as Weak-Line Radio Galaxies (WLRGs) has emerged. These radio galaxies have only weak, low-ionization optical emission lines. In the X-ray band, these objects are much fainter and have flatter spectra than broad-line and narrow-line radio galaxies. In these respects, WLRGs are reminiscent of Low Ionization Nuclear Emission Regions (LINERs). We have begun a multi-wavelength study of WLRGs to better understand their possible connection to LINERs and the structure of the accretion flow in both these systems. Here, we present new optical spectra of a sample of WLRGs. We find that 81% of the objects have optical emission-line properties that are similar to LINERs, indicating that these two classes of AGN may be related. Future high resolution X-ray observations of WLRGs will be critical in determining the true nature of the accretion flow in these objects.
Antiglucocorticoid Treatment in Depression
Michael Lewis
University of Toronto Medical Journal , 1999, DOI: 10.5015/utmj.v77i1.1128
Abstract:
Complement Factor C7 Contributes to Lung Immunopathology Caused by Mycobacterium tuberculosis
Kerry J. Welsh,Cole T. Lewis,Sydney Boyd,Michael C. Braun,Jeffrey K. Actor
Clinical and Developmental Immunology , 2012, DOI: 10.1155/2012/429675
Abstract: Mycobacterium tuberculosis (MTB) remains a significant global health burden despite the availability of antimicrobial chemotherapy. Increasing evidence indicates a critical role of the complement system in the development of host protection against the bacillus, but few studies have specifically explored the function of the terminal complement factors. Mice deficient in complement C7 and wild-type C57BL/6 mice were aerosol challenged with MTB Erdman and assessed for bacterial burden, histopathology, and lung cytokine responses at days 30 and 60 post-infection. Macrophages isolated from C7 −/− and wild-type mice were evaluated for MTB proliferation and cytokine production. C7 −/− mice had significantly less liver colony forming units (CFUs) at day 30; no differences were noted in lung CFUs. The C7 deficient mice had markedly reduced lung occlusion with significantly increased total lymphocytes, decreased macrophages, and increased numbers of CD4
Suprascapular Nerve: Is It Important in Cuff Pathology?
Lewis L. Shi,Michael T. Freehill,Paul Yannopoulos,Jon J. P. Warner
Advances in Orthopedics , 2012, DOI: 10.1155/2012/516985
Abstract: Suprascapular nerve and rotator cuff function are intimately connected. The incidence of suprascapular neuropathy has been increasing due to improved understanding of the disease entity and detection methods. The nerve dysfunction often results from a traction injury or compression, and a common cause is increased tension on the nerve from retracted rotator cuff tears. Suprascapular neuropathy should be considered as a diagnosis if patients exhibit posterosuperior shoulder pain, atrophy or weakness of supraspinatus and infraspinatus without rotator cuff tear, or massive rotator cuff with retraction. Magnetic resonance imaging and electromyography studies are indicated to evaluate the rotator cuff and function of the nerve. Fluoroscopically guided injections to the suprascapular notch can also be considered as a diagnostic option. Nonoperative treatment of suprascapular neuropathy can be successful, but in the recent decade there is increasing evidence espousing the success of surgical treatment, in particular arthroscopic suprascapular nerve decompression. There is often reliable improvement in shoulder pain, but muscle atrophy recovery is less predictable. More clinical data are needed to determine the role of rotator cuff repair and nerve decompression in the same setting.
The uptake and effect of a mailed multi-modal colon cancer screening intervention: A pilot controlled trial
Carmen L Lewis, Alison T Brenner, Jennifer M Griffith, Michael P Pignone
Implementation Science , 2008, DOI: 10.1186/1748-5908-3-32
Abstract: We conducted a controlled trial comparing the proportion of intervention patients who received colon cancer screening with wait list controls at one practice site. The intervention was a mailed package that included a letter from their primary care physician, a colon cancer screening decision aid, and instructions for obtaining each screening test without an office visit so that patients could access screening tests directly. Major outcomes were screening test completion and cost per additional patient screened.In the intervention group, 15% (20/137) were screened versus 4% (4/100) in the control group (difference 11%; (95%; CI 3%;18% p = 0.01). The cost per additional patient screened was estimated to be $94.A multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing patients direct access to schedule screening tests, increased colon cancer screening test completion in a subset of patients within a single academic practice. Although the uptake of the decision aid was low, the cost was also modest, suggesting that this method could be a viable approach to colon cancer screening.Colon cancer is the second leading cause of cancer-related deaths in the United States, and the third most commonly diagnosed cancer, with over 149,000 new diagnoses and 55,000 deaths expected in 2006 [1]. Colon cancer screening is effective in decreasing colon cancer incidence and mortality [2-4], and there are several recommended screening tests available to patients [5]. Despite its effectiveness, colon cancer screening is underutilized in the United States. Recent data on self-reported screening status from the Behavioral Risk Factor Surveillance System survey shows that only 57% of people in the United States are up to date with recommended screening [6].Barriers at multiple levels of the healthcare system (physician, patient, and system levels) contribute to the underutilization of colon cancer screening,
Suprascapular Nerve: Is It Important in Cuff Pathology?
Lewis L. Shi,Michael T. Freehill,Paul Yannopoulos,Jon J. P. Warner
Advances in Orthopedics , 2012, DOI: 10.1155/2012/516985
Abstract: Suprascapular nerve and rotator cuff function are intimately connected. The incidence of suprascapular neuropathy has been increasing due to improved understanding of the disease entity and detection methods. The nerve dysfunction often results from a traction injury or compression, and a common cause is increased tension on the nerve from retracted rotator cuff tears. Suprascapular neuropathy should be considered as a diagnosis if patients exhibit posterosuperior shoulder pain, atrophy or weakness of supraspinatus and infraspinatus without rotator cuff tear, or massive rotator cuff with retraction. Magnetic resonance imaging and electromyography studies are indicated to evaluate the rotator cuff and function of the nerve. Fluoroscopically guided injections to the suprascapular notch can also be considered as a diagnostic option. Nonoperative treatment of suprascapular neuropathy can be successful, but in the recent decade there is increasing evidence espousing the success of surgical treatment, in particular arthroscopic suprascapular nerve decompression. There is often reliable improvement in shoulder pain, but muscle atrophy recovery is less predictable. More clinical data are needed to determine the role of rotator cuff repair and nerve decompression in the same setting. 1. Introduction The suprascapular nerve provides sensory innervation to the posterosuperior aspect of the shoulder and motor innervation to supraspinatus and infraspinatus muscles. Dysfunction of the suprascapular nerve is intimately associated with rotator cuff pathology; nerve dysfunction can lead to cuff disease and vice versa. Suprascapular neuropathy is typically due to compression or traction of the nerve, and this can result in a spectrum of clinical symptoms, including pain in the posterosuperior aspects of the shoulder and weakness in forward flexion and external rotation. The various presentations of suprascapular neuropathy can make its diagnosis a challenge. Historically, suprascapular neuropathy has been viewed as a diagnosis of exclusion, but with recent advances, there is better understanding of both the etiology and treatment options, particularly relating to rotator cuff pathology. 2. Etiology of Suprascapular Neuropathy The suprascapular nerve arises from the upper trunk of the brachial plexus. It travels posterior to the clavicle and enters the suprascapular notch by passing beneath the transverse scapular ligament. The motor branches innervate the supraspinatus, and the nerve continues past the spinoglenoid notch and innervates the infraspinatus (Figure 1).
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