tbuckley/cabot-search huggingface dataset:
Assessing the spatial extent of breast tumor intrinsic optical contrast using ultrasound and diffuse optical spectroscopic imaging.
Authors: J Liu, AE Cerussi, A Li, W Tanamai, R Kwong, D Hsiang, BJ Tromberg
Journal: Cancer Research (2009)

Abstract Abstract #806 Background: Near infrared (NIR) light is sensitive to several important tissue components and has been used to detect, characterize, and monitor breast tumor functions. However, little is known about the relationship between anatomic and functional contrast derived from intrinsic optical signals. Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive, bedside functional imaging technique that quantifies the concentrations and molecular states of tissue hemoglobin, water, and lipids. Pilot studies have shown that DOSI may be a useful tool for breast lesion detection/characterization and therapeutic monitoring.&amp;#x2028; Materials and Methods: DOSI data were compared with theoretical computer simulations to estimate the nature and extent of optical contrast with respect to standard ultrasound imaging. DOSI reflectance measurements were obtained from 10 breast tumor patients, with both malignant (N=5) and benign (N=5) lesions. Patient average ages: 35+/-7.8 years vs. 44.3+/-14.7 years, lesion depth 10.9+/-5.5 mm vs. 15.8+/-5.3 mm, and maximum size 13.0+/-6.0 mm vs. 14.8+/-4.9 mm for benign and malignant, respectively. Two trial tumor models were simulated to model actual tumor optical properties (hemoglobin): (a) a discrete target constrained to ultrasound dimensions, and (b) a distributed target that spatially extended beyond ultrasound dimensions.&amp;#x2028; Results: High optical contrast (i.e., the ratio target to background) was observed for both benign (1.53+/-0.17) and malignant (2.06+/-0.4) lesions, even for this younger population. While the discrete target model could not match experiment and simulation, a distributed model provided excellent agreement. The spatial extent of optical properties in breast tumor was significantly greater than anatomical dimensions reported by ultrasound imaging. The extent of the distribution was greater in the malignant lesions than in the benign ones. Further simulations also suggested that invasive breast tumors in this population with anatomical size 10 mm may still be detectable at depth 30 mm using DOSI in reflectance.&amp;#x2028; Discussion: The spatial extension of tumor optical contrast complicates co-registration of optical functional images with anatomic images. The true optical contrast is significantly higher in breast cancer tumors, likely 4-5x than the hemoglobin levels in normal tissues. Breast tumor optical contrast is more realistically modeled as a spatially distributed target, which facilities a fast 3D imaging scheme in reflectance geometry. Results from these topographic reconstructions will be discussed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 806.
Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells
Authors: Azzam A. Maghazachi
Journal: Pharmacological Reviews (2005)

Human natural killer (NK) cells are important cells of the innate immune system. These cells perform two prominent functions: the first is recognizing and destroying virally infected cells and transformed cells; the second is secreting various cytokines that shape up the innate and adaptive immune re-sponses. For these cells to perform these activities, they express different sets of receptors. The receptors used by NK cells to extravasate into sites of injury belong to the seven transmembrane (7TM) family of receptors, which characteristically bind heterotrimeric G proteins. These receptors allow NK cells to sense the chemotactic gradients and activate second messengers, which aid NK cells in polarizing and migrating toward the sites of injured tissues. In addition, these receptors determine how and why human resting NK cells are mainly found in the bloodstream, whereas activated NK cells extravasate into inflammatory sites. Receptors for chemokines and lysophospholipids belong to the 7TM family. On the other hand, NK cells recognize invading or transformed cells through another set of receptors that belong to the single transmembrane-spanning domain family. These receptors are either inhibitory or activating. Inhibitory receptors contain the immune receptor tyrosine-based inhibitory motif, and activating receptors belong to either those that associate with adaptor molecules containing the immune receptor tyrosine-based activating motif (ITAM) or those that associate with adaptor molecules containing motifs other than ITAM. This article will describe the nature of these receptors and examine the intracellular signaling pathways induced in NK cells after ligating both types of receptors. These pathways are crucial for NK cell biology, development, and functions.
Vascular Injury Causes Neointimal Formation in Angiotensin II Type 1a Receptor Knockout Mice
Authors: Koichiro Harada, Issei Komuro, Takeshi Sugaya, Kazuo Murakami, Yoshio Yazaki
Journal: Circulation Research (1999)

Abstract —Many studies using small-animal models suggest that angiotensin II (Ang II) plays an important role in neointimal formation after vascular injury. In the present study, we examined whether Ang II type 1 receptor (AT 1 )-mediated Ang II signaling is indispensable for the development of injury-induced neointimal formation using AT 1a knockout (KO) mice. Reverse transcriptase–polymerase chain reaction analysis revealed that AT 1 mRNA was not detectable in both uninjured and injured carotid arteries of KO mice, whereas the AT 1 gene was expressed in uninjured carotid arteries of wild-type (WT) mice. At 14 days after injury, AT 1 mRNA levels were increased by 1.5-fold in injured arteries of WT mice. Although AT 2 mRNA was not detectable in uninjured arteries, expression of AT 2 gene was induced in both animal groups at 2 weeks after injury. Vascular injury induced neointimal formation in KO mice as well as in WT mice. There were no significant differences between WT and KO mice in the extent of histological findings such as increased cross-sectional areas of the neointima and the media, the number of proliferating smooth muscle cells, and the amount of collagen and fibronectin. Treatment with subpressor doses of Ang II after injury enhanced the growth of neointima in WT mice but not in KO mice. Moreover, treatment with the selective AT 1 antagonist CV-11974 before injury significantly decreased the formation of neointima in only WT mice, whereas treatment with the selective AT 2 antagonist PD-123319 before injury had no effects in both animal groups. These results suggest that AT 1 -mediated Ang II signaling is not essential for the development of neointimal formation, although it may modify it.
Colocalization of the Tetraspanins, CO-029 and CD151, with Integrins in Human Pancreatic Adenocarcinoma: Impact on Cell Motility
Authors: Sabine Gesierich, Claudia Paret, Dagmar Hildebrand, Jürgen Weitz, Kaspar Zgraggen, Friedrich H. Schmitz-Winnenthal, Vaclav Horejsi, Osamu Yoshie, Dorothee Herlyn, Leonie K. Ashman, Margot Zöller
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor. We recently reported that after protein kinase C activation, colocalization of α6β4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. Experimental Design: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. Results: The majority of pancreatic and colorectal tumors expressed the α2, α3, α6, β1, and β4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of α6β4 and CO-029 was restricted to tumor cells, whereas α1, α2, α3, α6, β1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and β1 expression was observed at comparably high levels in healthy pancreatic tissue. α3β1 frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas α6β4 colocalized and coimmunoprecipitated mostly with CD151 and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151 and CO-029 with β4 and was accompanied by internalization of the integrin-tetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. Conclusion: α6β4 is selectively up-regulated in pancreatic and colorectal cancer. The association of α6β4 with CD151 and CO-029 correlates with increased tumor cell motility.
Clinical check list for diagnosis of dementia.
Authors: M Hare
Journal: BMJ (1978)

A clinical check list for testing speech and parietal function as well as memory was used on 200 people admitted to a psychogeriatric assessment unit and repeated four to six weeks later, to see whether those with true dementias could be identified. The finding of errors in all three areas, particularly at the second test, accurately predicted cases with a poor outcome at six months follow-up. Amnesia alone was an unreliable indicator of dementia.
Reflections on Findings of the Cancer Outcomes Measurement Working Group: Moving to the Next Phase
Authors: Carolyn C. Gotay, Joseph Lipscomb, Claire F. Snyder
Journal: JNCI Journal of the National Cancer Institute (2005)

The Cancer Outcomes Measurement Working Group (COMWG) was a National Cancer Institute working group of 35 experts convened to examine the state of the science and identify future research priorities for outcomes assessment in cancer. The COMWG focused on three outcomes (health-related quality of life [HRQOL]), patient needs and satisfaction, and economic burden) in four cancers (breast, colorectal, lung, and prostate) across the continuum of care (prevention and screening, treatment, survivorship, and end of life). The majority of the research to date has focused on HRQOL assessment, which has been shown to be feasible in a research context, using questionnaires that meet established criteria for reliability and validity. The quality and quantity of HRQOL research has increased markedly in recent years, and additional methodological developments--particularly the application of item response theory to improve precision, efficiency, and comparability in measurement--hold considerable promise. Research is needed to develop and test predictive models of HRQOL and to establish the added value of including HRQOL assessment in clinical trials.
Risk factors for death among tuberculosis cases: analysis of European surveillance data
Authors: N. Lefebvre, D. Falzon
Journal: European Respiratory Journal (2008)

The proportion of tuberculosis (TB) patients in the European Union (EU) who die remains high (8% overall). The aim of the present study was to quantify the risk of dying associated with demographic and clinical factors. Case-based data on 39,566 TB patients notified by 15 EU countries during 2002–2004 were analysed using logistic regression. It was observed that advancing age and resistance to isoniazid and rifampicin were the strongest determinants of death, while male sex, European origin, pulmonary site of disease and previous anti-TB treatment were weaker predictors. Risk varied between reporting countries, presumably reflecting differences in patient profiles, reporting practices and programme effectiveness. In conclusion, earlier suspicion, diagnosis and treatment may reduce deaths, particularly among the elderly. Special attention is needed to avert the development and transmission of multidrug-resistant tuberculosis.
A mathematical analysis of the myogenic hypothesis with special reference to autoregulation of renal blood flow.
Authors: A H Oien, K Aukland
Journal: Circulation Research (1983)

To test the hypothesis that autoregulation of renal blood flow could result from myogenic regulation of arterial/arteriolar wall tension, we have explored a model based on the assumptions that (1) each preglomerular vessel segment reacts to a change in transmural pressure by altering its internal radius until the initial change in wall tension is reduced by a gain factor, (2) postglomerular structural resistance remains unchanged, (3) extravascular tissue pressure equals intrarenal venous pressure, and (4) the renal vascular system can be represented by one unbranched tube. General equations were obtained for flow and segmental radii and pressure as functions of aortic pressure. With a gain factor of 1 and a glomerular capillary pressure of 50% of aortic pressure under control conditions, the model predictions agree well with experimental data in dogs. Increasing aortic pressure from about 60% of control level causes only slight increase of blood flow. A rise in tissue pressure up to 40% of aortic pressure causes only moderate reduction. Changes in vessel radii begin in proximal vessel segments and spread distally toward glomerulus at increasing changes in aortic and tissue pressures from their control levels. Glomerular capillary pressure is autoregulated in proportion to blood flow. The degree of autoregulation is only moderately dependent on the gain factor: A moderate impairment caused by reducing the gain factor from 1 to 0.7 may be compensated by locating the myogenically responsive wall layer a distance 0.2 times the internal radius from the vessel lumen. "Superautoregulation," i.e., a rise in flow at reduced aortic pressure, is not possible. An upper limit of autoregulation is obtained only with the additional assumption of a fall in contractile force at extreme shortening of the muscle fibers. No definitive biological proof has yet been provided for a segmental wall tension-regulating mechanism in the preglomerular vessels, and obviously its existence cannot be proved by a mathematical model. However, if such a mechanism does exist, it can explain most of the renal resistance changes at varying arterial and intrarenal pressures, as well as the observed autoregulation of terminal interlobular arterial pressure.
Author's response: BCG and infection with Mycobacterium tuberculosis
Authors: S. W. Michelsen, E. M. Agger, S. T. Hoff, B. Soborg, L. Carstensen, A. Koch, T. Lillebaek, H. C. F. Sorensen, J. Wohlfahrt, M. Melbye
Journal: Thorax (2014)

Thanks to Turner et al for commenting on our article. Turner et al challenge our finding that the Bacillus Calmette-Guerin vaccine (BCG) can prevent Mycobacterium tuberculosis infection (MTI), and propose an alternative explanation: that the absence of a positive interferon gamma release assay (IGRA) could be due to antigenic sin and does not necessarily demonstrate absence of infection.

A positive IGRA is the best available surrogate for MTI, but we are fully aware of its limitations. With the IGRA test, MTI is defined by a T-cell-induced interferon gamma response to M tuberculosis antigens …
Glomerular Disease Workshop
Authors: Catherine M. Meyers, Mark Geanacopoulos, Lawrence B. Holzman, David J. Salant
Journal: Journal of the American Society of Nephrology (2005)

Recent observations regarding intrinsic glomerular cell biology, particularly in the podocyte, have provided exciting new insights into potential pathogenic mechanisms of human glomerular disease. Although both immune and nonimmune mechanisms of glomerular injury have been studied previously, experimental models of disease and recent techniques that provide tools for molecular profiling show great promise for identifying glomerular disease biomarkers. Despite these recent advances, additional work in both basic and clinical studies of glomerular disease is needed to advance the field. Standardization of animal models of distinct forms of glomerular disease would likely facilitate the search for biomarkers. Several factors limit current efforts to implement clinical trials of glomerular disease. Identification of disease biomarkers, development of disease-specific end points, and organization of collaborative clinical groups are critical for ultimately designing and implementing appropriately powered trials of glomerular disease.
Lack of Association between Folate-Receptor Autoantibodies and Neural-Tube Defects
Authors: Anne M. Molloy, Edward V. Quadros, Jeffrey M. Sequeira, James F. Troendle, John M. Scott, Peadar N. Kirke, James L. Mills
Journal: New England Journal of Medicine (2009)

A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neural-tube defects.
The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial
Authors: Anthony G Marson, Asya M Al-Kharusi, Muna Alwaidh, Richard Appleton, Gus A Baker, David W Chadwick, Celia Cramp, Oliver C Cockerell, Paul N Cooper, Julie Doughty, Barbara Eaton, Carrol Gamble, Peter J Goulding, Stephen JL Howell, Adrian Hughes, Margaret Jackson, Ann Jacoby, Mark Kellett, Geoffrey R Lawson, John Paul Leach, Paola Nicolaides, Richard Roberts, Phil Shackley, Jing Shen, David F Smith, Philip EM Smith, Catrin Tudur Smith, Alessandra Vanoli, Paula R Williamson
Journal: The Lancet (2007)
Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis
Authors: Gerd R Burmester, Michael E Weinblatt, Iain B McInnes, Duncan Porter, Olga Barbarash, Mykola Vatutin, Istvan Szombati, Ehsanollah Esfandiari, Matthew A Sleeman, Christopher D Kane, Guy Cavet, Bing Wang, Alex Godwood, Fabio Magrini
Journal: Annals of the Rheumatic Diseases (2012)

Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA).Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12.55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10 mg, 30 mg, 50 mg, and 100 mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (-0.48 vs -0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed.Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA.
Low Levels of Hepatitis C Virus RNA in Serum, Plasma, and Peripheral Blood Mononuclear Cells of Injecting Drug Users During Long Antibody-Undetectable Periods Before Seroconversion
Authors: Marcel Beld, Maarten Penning, Marieke van Putten, Anneke van den Hoek, Marjolein Damen, Michèl R. Klein, Jaap Goudsmit
Journal: Blood (1999)
Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice
Authors: Thomas H. Leung, Lillian F. Zhang, Jing Wang, Shoucheng Ning, Susan J. Knox, Seung K. Kim
Journal: Journal of Clinical Investigation (2013)

Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.
Microvascular Resistance Is Not Influenced by Epicardial Coronary Artery Stenosis Severity
Authors: William F. Fearon, Wilbert Aarnoudse, Nico H.J. Pijls, Bernard De Bruyne, Leora B. Balsam, David T. Cooke, Robert C. Robbins, Peter J. Fitzgerald, Alan C. Yeung, Paul G. Yock
Journal: Circulation (2004)

The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements. In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis. After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.