tbuckley/cabot-search huggingface dataset:
Robert MacGregor (“Rab”) Milne
Authors: Alex Cargill
Journal: BMJ (2007)

Innovator in perinatal mental healthDiana Riley was a key figure in obstetric liaison psychiatry and perinatal mental health.She researched and published widely over 36 years, including works for health professionals and lay readers on postnatal depression and drug addiction in pregnancy.Diana instituted one of the first mother and baby mental health units in the country, at St John's Hospital, Stone, to care for mothers with postnatal depression without separating them from their babies-a revolutionary idea at the time.She established and supervised psychotherapy groups for mothers with postnatal depression in Buckinghamshire, and developed expertise in drug addiction in pregnancy while working and teaching at University College Hospital, London.She was also a prime mover in one of the earliest dedicated pre-senile dementia units in the country, leading a multidisciplinary team at St John's Hospital, Stone.Brought up in a deprived area of London, Diana was influenced by seeing people unable to afford proper medical treatment.Her conviction that one must add to the sum of human health and happiness informed her work and her relationships with family, friends, and the wider community.After qualifying and marrying, she was a locum in general practice during 1956-60, producing a child a year.She cared for the families of the Royal Air Force at RAF Halton
Akt Phosphorylates and Regulates Pdcd4 Tumor Suppressor Protein
Authors: Alexey Palamarchuk, Alexey Efanov, Vadim Maximov, Rami I. Aqeilan, Carlo M. Croce, Yuri Pekarsky
Journal: Cancer Research (2005)

Abstract Programmed cell death 4 (Pdcd4) is a tumor suppressor protein that interacts with eukaryotic initiation factor 4A and inhibits protein synthesis. Pdcd4 also suppresses the transactivation of activator protein-1 (AP-1)–responsive promoters by c-Jun. The Akt (protein kinase B) serine/threonine kinase is a key mediator of phosphoinositide 3-kinase pathway involved in the regulation of cell proliferation, survival, and growth. Because Pdcd4 has two putative Akt phosphorylation sites at Ser67 and Ser457, we investigated whether Akt phosphorylates and regulates Pdcd4. Our results show that Akt specifically phosphorylates Ser67 and Ser457 residues of Pdcd4 in vitro and in vivo. We further show that phosphorylation of Pdcd4 by Akt causes nuclear translocation of Pdcd4. Using luciferase assay, we show that phosphorylation of Pdcd4 by Akt also causes a significant decrease of the ability of Pdcd4 to interfere with the transactivation of AP-1–responsive promoter by c-Jun. (Cancer Res 2005; 65(24): 11282-6)
Abstract A3: miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer
Authors: Katarzyna Augoff, Brian McCue, Edward F. Plow, Khalid Sossey-Alaoui
Journal: Cancer Research (2012)

Abstract Background: microRNAs have been established as powerful regulators of gene expression in normal physiological as well as in pathological conditions, including cancer progression and metastasis. Recent studies have demonstrated a key role of miR-31 in the progression and metastasis of breast cancer. Downregulation of miR-31 enhances several steps of the invasion-metastasis cascade in breast cancer, i.e., local invasion, extravasation and survival in the circulation system, and metastatic colonization of distant sites. miR-31 exerts its metastasis-suppressor activity by targeting a cohort of pro-metastatic genes, including RhoA and WAVE3. The molecular mechanisms that lead to the loss of miR-31 and the activation of its pro-metastatic target genes during these specific steps of the invasion-metastasis cascade are however unknown. Results: In the present report, we identify promoter hypermethylation as one of the major mechanisms for silencing miR-31 in breast cancer, and in the triple-negative breast cancer (TNBC) cell lines of basal subtype, in particular. miR-31 maps to the intronic sequence of a novel long non-coding (lnc)RNA, LOC554202 and the regulation of its transcriptional activity is under control of LOC554202. Both miR-31 and the host gene LOC554202 are down-regulated in the TNBC cell lines of basal subtype and over-expressed in the luminal counterparts. Treatment of the TNBC cell lines with either a de-methylating agent alone or in combination with a de-acetylating agent resulted in a significant increase of both miR-31 and its host gene, suggesting an epigenetic mechanism for the silencing of these two genes by promoter hypermethylation. Finally, both methylation-specific PCR and sequencing of bisulfite-converted DNA demonstrated that the LOC554202 promoter-associated CpG island is heavily methylated in the TNBC cell lines and hypomethylated in the luminal subtypes. Conclusion: Loss of miR-31 expression in TNBC cell lines is attributed to hypermethylation of its promoter-associated CpG island. Together, our results provide the initial evidence for a mechanism by which miR-31, an important determinant of the invasion metastasis cascade, is regulated in breast cancer. Citation Format: Katarzyna Augoff, Brian McCue, Edward F. Plow, Khalid Sossey-Alaoui. miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A3.
Oxidized LDL Upregulates Angiotensin II Type 1 Receptor Expression in Cultured Human Coronary Artery Endothelial Cells
Authors: Dayuan Li, Tom Saldeen, Francesco Romeo, Jawahar L. Mehta
Journal: Circulation (2000)

We demonstrated earlier that angiotensin II (Ang II), by AT(1) receptor activation, upregulates oxidized LDL (ox-LDL) endothelial receptor LOX-1 gene expression and uptake of ox-LDL in human coronary artery endothelial cells (HCAECs). In this study, we investigated the regulation of Ang II receptors (AT1R and AT2R) by ox-LDL and the role of the redox-sensitive transcription factor NF-kappaB in this process.HCAECs were incubated with ox-LDL for 24 hours. Ox-LDL (10 to 40 microg protein/mL) upregulated AT1R but not AT2R, mRNA, or protein. Ox-LDL degraded IkappaBalpha in cytoplasm and activated transcription factor NF-kappaB (P65) in HCAEC nuclear extract. Treatment of cells with the antioxidant alpha-tocopherol (10 to 50 micromol/L) attenuated ox-LDL-mediated degradation of IkappaBalpha and activation of NF-kappaB (P65) and inhibited the upregulation of AT1R mRNA and protein. The role of NF-kappaB signal transduction was further examined by use of an NF-kappaB inhibitor, caffeic acid phenethyl ester (CAPE). Pretreatment of cells with CAPE inhibited ox-LDL-mediated degradation of IkappaBalpha and NF-kappaB activation and inhibited ox-LDL-induced upregulation of AT1R expression. Incubation of cells with both ox-LDL and Ang II increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone. alpha-Tocopherol as well as the specific AT1R blocker CV11974 (candesartan) attenuated the cell-injurious effects of ox-LDL.These observations suggest an important role of ox-LDL-mediated AT1R upregulation in cell injury. In this process, NF-kappaB activation seems to play a critical role in signal transduction. These findings provide a basis for the use of antioxidants and AT1R blockers in designing therapy of atherosclerosis.
Patient Perceptions of Quality of Life With Diabetes-Related Complications and Treatments
Authors: Elbert S. Huang, Sydney E.S. Brown, Bernard G. Ewigman, Edward C. Foley, David O. Meltzer
Journal: Diabetes Care (2007)

Understanding how individuals weigh the quality of life associated with complications and treatments is important in assessing the economic value of diabetes care and may provide insight into treatment adherence. We quantify patients' utilities (a measure of preference) for the full array of diabetes-related complications and treatments.We conducted interviews with a multiethnic sample of 701 adult patients living with diabetes who were attending Chicago area clinics. We elicited utilities (ratings on a 0-1 scale, where 0 represents death and 1 represents perfect health) for hypothetical health states by using time-tradeoff questions. We evaluated 9 complication states (e.g., diabetic retinopathy and blindness) and 10 treatment states (e.g., intensive glucose control vs. conventional glucose control and comprehensive diabetes care [i.e., intensive control of multiple risk factors]).End-stage complications had lower mean utilities than intermediate complications (e.g., blindness 0.38 [SD 0.35] vs. retinopathy 0.53 [0.36], P < 0.01), and end-stage complications had the lowest ratings among all health states. Intensive treatments had lower mean utilities than conventional treatments (e.g., intensive glucose control 0.67 [0.34] vs. conventional glucose control 0.76 [0.31], P < 0.01), and the lowest rated treatment state was comprehensive diabetes care (0.64 [0.34]). Patients rated comprehensive treatment states similarly to intermediate complication states.End-stage complications have the greatest perceived burden on quality of life; however, comprehensive diabetes treatments also have significant negative quality-of-life effects. Acknowledging these effects of diabetes care will be important for future economic evaluations of novel drug combination therapies and innovations in drug delivery.
Human Melanoma Metastases Express Functional CXCR4
Authors: Stefania Scala, Paola Giuliano, Paolo A. Ascierto, Caterina Ieranò, Renato Franco, Maria Napolitano, Alessandro Ottaiano, Maria L. Lombardi, Monica Luongo, Ester Simeone, Daniele Castiglia, Francesca Mauro, Ileana De Michele, Rosa Calemma, Gerardo Botti, Corrado Caracò, Gianfranco Nicoletti, Rocco A. Satriano, Giuseppe Castello
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (&amp;gt;90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 μmol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.
Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status in early breast cancer
Authors: R. Ponzone, F. Montemurro, F. Maggiorotto, C. Robba, D. Gregori, M.E. Jacomuzzi, F. Kubatzki, D. Marenco, A. Dominguez, N. Biglia, P. Sismondi
Journal: Annals of Oncology (2006)
A new way of targeting phototherapy to body sites where it is needed
Authors: R.S. Dawe
Journal: British Journal of Dermatology (2015)

Journal Article A new way of targeting phototherapy to body sites where it is needed Get access R.S. Dawe R.S. Dawe Photobiology Unit Department of Dermatology Ninewells Hospital and Medical School Dundee U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 3, 1 March 2015, Pages 563–564, https://doi.org/10.1111/bjd.13663 Published: 01 March 2015
Kupffer Cells Promote Hepatic Steatosis Via Interleukin-1β–Dependent Suppression of Peroxisome Proliferator-Activated Receptor α Activity
Authors: Rinke Stienstra, Fredy Saudale, Caroline Duval, Shohreh Keshtkar, Johanna E. M. Groener, Nico van Rooijen, Bart Staels, Sander Kersten, Michael Müller
Journal: Hepatology (2009)

Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1β were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1A (Cpt1α), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1β decreased expression of PPARα and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1β suppressed human and mouse PPARα promoter activity. Suppression of PPARα promoter activity was recapitulated by overexpression of nuclear factor κB (NF-κB) subunit p50 and p65, and was abolished upon deletion of putative NF-κB binding sites. Finally, IL-1β and NF-κB interfered with the ability of PPARα to activate gene transcription. Conclusion: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1β, which suppresses PPARα expression and activity. (Hepatology 2010.)
African Lessons on Climate Change Risks for Agriculture
Authors: Christoph Müller
Journal: Annual Review of Nutrition (2013)

Climate change impact assessments on agriculture are subject to large uncertainties, as demonstrated in the present review of recent studies for Africa. There are multiple reasons for differences in projections, including uncertainties in greenhouse gas emissions and patterns of climate change; assumptions on future management, aggregation, and spatial extent; and methodological differences. Still, all projections agree that climate change poses a significant risk to African agriculture. Most projections also see the possibility of increasing agricultural production under climate change, especially if suitable adaptation measures are assumed. Climate change is not the only projected pressure on African agriculture, which struggles to meet demand today and may need to feed an additional one billion individuals by 2050. Development strategies are urgently needed, but they will need to consider future climate change and its inherent uncertainties. Science needs to show how existing synergies between climate change adaptation and development can be exploited.
Genomic Alterations of Anaplastic Lymphoma Kinase May Sensitize Tumors to Anaplastic Lymphoma Kinase Inhibitors
Authors: Ultan McDermott, A. John Iafrate, Nathanael S. Gray, Toshi Shioda, Marie Classon, Shyamala Maheswaran, Wenjun Zhou, Hwan Geun Choi, Shannon L. Smith, Lori Dowell, Lindsey E. Ulkus, Georgiana Kuhlmann, Patricia Greninger, James G. Christensen, Daniel A. Haber, Jeffrey Settleman
Journal: Cancer Research (2008)

Abstract Selective kinase inhibitors have had a substantial impact on the field of medical oncology. Whereas these agents can elicit dramatic clinical responses in some settings, their activity is generally limited to a subset of treated patients whose tumor cells harbor a specific genetic lesion. We have established an automated platform for examining the sensitivity to various molecularly targeted inhibitors across a large panel of human tumor-derived cell lines to identify additional genotype-correlated responses that may be clinically relevant. Among the inhibitors tested in a panel of 602 cell lines derived from a variety of human cancers, we found that a selective inhibitor of the anaplastic lymphoma kinase (ALK) potently suppressed growth of a small subset of tumor cells. This subset included lines derived from anaplastic large cell lymphomas, non–small-cell lung cancers, and neuroblastomas. ALK is a receptor tyrosine kinase that was first identified as part of a protein fusion derived from a chromosomal translocation detected in the majority of anaplastic large cell lymphoma patients, and has recently been implicated as an oncogene in a small fraction of non–small-cell lung cancers and neuroblastomas. Significantly, sensitivity in these cell lines was well correlated with specific ALK genomic rearrangements, including chromosomal translocations and gene amplification. Moreover, in such cell lines, ALK kinase inhibition can lead to potent suppression of downstream survival signaling and an apoptotic response. These findings suggest that a subset of lung cancers, lymphomas, and neuroblastomas that harbor genomic ALK alterations may be clinically responsive to pharmacologic ALK inhibition. [Cancer Res 2008;68(9):3389–95]
The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: An analysis of 129 cases
Authors: David H. Buss, John J. Stuart, Gary E. Lipscomb
Journal: American Journal of Hematology (1985)

We have presented a retrospective study of 129 patients with platelet counts of 1,000 X 10(9)/L or more--72 with myeloproliferative disorders (MPD), and 57 with reactive thrombocytosis (RT)--in an effort to determine the incidence of thrombohemorrhagic complications. Thrombotic disorders occurred with approximately equal frequency in the two groups, being found in three patients (4%) with MPD and three (5%) with RT when the platelet count was over 1,000 X 10(9)/L and in 11% of the patients in each group when the platelet count was less than 1,000 X 10(9)/L. In contrast, bleeding manifestations were more common in MPD, where 36% of patients were affected on one or more occasions versus only 4% of those with RT. However, bleeding was generally not severe, with only six patients requiring transfusions, and three of these patients had been receiving aspirin or corticosteroids when they developed severe gastrointestinal bleeding.
SEROLOGIC STUDIES OF PROTEOLYTIC FRAGMENTS OF RABBIT AGGLUTINATING ANTIBODIES*
Authors: Hugh Fudenberg, William J. Mandy, Alfred Nisonoff
Journal: Journal of Clinical Investigation (1962)

The reaction of the bivalent rabbit antibody molecule with papain (1, 2) or pepsin (3) and a reducing agent results in the release of two univalent fragments. The evidence for univalence is provided by the capacity of the  of hydrolyzed antiprotein antibody to inhibit specifically the homologous precipitin reaction (2), and by direct measurements of the maximal number of moles of hapten that can be bound by a mole of active fragments after hydrolysis of antihapten antibody with papain (4, 5, 6). The present communication describes another property of the univalent fragments, namely, their capacity to combine with, but not agglutinate, red blood cells of the appropriate antigenic type. Whether unfragmented 7S incomplete antibodies are univalent is not known. This appears unlikely, at least in the case of incomplete antiRho, since it is difficult to understand how treatment of red cells with trypsin or other proteolytic enzymes could render them agglutinable by univalent antibody. The data presented here indicate that univalent  of antibody can react specifically with antigens of erythrocytes and that the reaction does not cause agglutination, even when the cells are first treated with one of several proteolytic enzymes. That the  combine with the erythrocytes is shown by the occurrence of agglutination on subsequent addition of an untreated antibody specific for the univalent fragments.
Role of Sensory Nerve Peptides Rather than Mast Cell Histamine in Paclitaxel Hypersensitivity
Authors: Yoshinori Itoh, Toshiaki Sendo, Toshio Hirakawa, Takeshi Goromaru, Shinya Takasaki, Hideaki Yahata, Hitoo Nakano, Ryozo Oishi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Paclitaxel is one of the most extensively used anticancer agents, however, its use is often limited by severe hypersensitivity reactions, including respiratory distress, bronchospasm, and hypotension, which can occur despite premedication with dexamethasone and histamine H1 and H2 antagonists. The present study was designed to determine the mechanisms of paclitaxel hypersensitivity. In rats, paclitaxel (15 mg/kg, intravenously) caused a marked increase in pulmonary vascular permeability and edema. PaO2 decreased, whereas PaCO2 increased, transiently after paclitaxel injection. The paclitaxel-induced pulmonary vascular hyperpermeability was blocked by dexamethasone but not by histamine H1 or H2 antagonists. Paclitaxel increased the vascular permeability in lungs of mast cell-deficient rats Ws/Ws(-/-) to almost the similar extent as that elicited in wild-type rats. On the other hand, the paclitaxel-induced pulmonary vascular hyperpermeability was reversed by sensory denervation with capsaicin or pretreatment with LY303870 and SR48968, NK1 and NK2 antagonists, respectively. Consistent with these findings, a marked elevation of sensory neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide was observed in rat bronchoalveolar lavage fluid after paclitaxel injection. These findings suggest that sensory nerves rather than mast cells are implicated in the etiology of paclitaxel hypersensitivity.