tbuckley/cabot-search huggingface dataset:
Abstract 4561: The antihistamine cyproheptadine induces cell apoptosis through inhibition of β-catenin signaling pathways in urothelial carcinoma
Authors: Hsiao-Yen Hsieh, Yuan-Hung Wang, Cheng-Huang Shen, Shiu-Yi Chen, Michael W. Chan, Cheng-Da Hsu
Journal: Cancer Research (2014)

Abstract Recent studies have revealed that the cyproheptadine is a novel therapeutic agent for the treatment of malignancy, such as myeloma, leukemia and HCC. However, its effect on urothelial carcinoma cell is still unknown. The aim of this study was to investigate the effect and underline mechanism of cyproheptadine on UC. We used cell viability assay to investigate the drug effect on two UC cell lines, TSGH8301 and BFTC905, and found the IC50 which was about 55 μM. After treatment of cyproheptadine, cell cycle and apoptosis status of the UC cells were determined by flow cytometry and indicated cell cycle arrest in G0/G1 phase and induction of apoptosis. We further investigated the mechanism of the drug effect using western blot analysis and found that cyproheptadine induced downregulation of cyclin-D1 and c-Myc expression through the inhibition of β-catenin signaling pathway in UC cells. More importantly, Inhibition of β-catenin signaling pathway was related to downregulation of CCRK protein in TSGH8301 cell line, but through activation of IDAX protein leading to inhibition of β-catenin signaling pathway in BFTC905 cell line. These novel results demonstrated that cyproheptadine suppressed the β-catenin signaling pathway and induced UC cell apoptosis. Citation Format: Hsiao-Yen Hsieh, Yuan-Hung Wang, Cheng-Huang Shen, Shiu-Yi Chen, Michael Wy Chan, Cheng-Da Hsu. The antihistamine cyproheptadine induces cell apoptosis through inhibition of β-catenin signaling pathways in urothelial carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4561. doi:10.1158/1538-7445.AM2014-4561
Can current methods of pathonormal inference tell us anything about modularity?
Authors: David W. Gow, Philip C. Rodkin
Journal: Behavioral and Brain Sciences (1999)

This commentary on Müller's target article is designed to help bridge the gap between method and theory in neurobiological approaches to language. We focus on pathonormal inference as reflective of broader conceptual issues concerning universality and modularity. Our commentary directs attention to how current methodological and analytic procedures are less than optimal and minimize possibilities for reaching theoretical consensus. We make suggestions about alternative analytic strategies that provide a direction for future scientific progress.
Large Cell Neuroendocrine Lung Cancer: The Strength of Large Databases and the Need for Prospective Trials
Authors: John M. Varlotto, Laura Nyshel Medford-Davis, Abram Recht, John C. Flickinger, Eric Schaefer, Dani S. Zander, Malcolm M. DeCamp
Journal: Journal of Thoracic Oncology (2011)
ORTHOTOPIC HEART TRANSPLANTATION &amp;amp; PSEUDORESTRICTIVE LV FILLING PATTERN: A STUDY OF TRANSMITRAL DOPPLER FLOW / TISSUE DOPPLER IMAGING AND COMPARATIVE INVASIVE HEMODYNAMICS IN PATIENTS WITH ORTHOTOPIC HEART TRANSPLANTATION
Authors: Ziad Taimeh, Hareeprasad Vongooru, Kelly McCants, Emma Birks, Mark Slaughter, Marcus Stoddard
Journal: Journal of the American College of Cardiology (2012)
Porphyria turcica due to hexachlorobenzene: a 20 to 30 year follow-up study on 204 patients
Authors: D.J. CRIPPS, H.A. PETERS, A. GOCMEN, I. DOGRAMICI
Journal: British Journal of Dermatology (1984)

During 1955-1961 in south-east Turkey, over 3000 patients developed porphyria due to ingestion of hexachlorobenzene, a fungicide added to wheat seedlings. Subsequently they developed pigmentation, hirsutism, weakness, porphyrinuria and bullae. The condition was called kara yara or 'black sore'. Many of the breast-fed children under the age of 1 year died from a disease known as pembe yara or 'pink sore'. In this follow-up study of 204 patients, 20-30 years later, there were 132 males and 72 females, average age 32.1 years (at time of examination), with an average age of onset of 10.2 years, and duration of 2.4 years. Neurological, dermatological, and orthopaedic abnormalities still persisted. Neurological symptoms included weakness (66%), paraesthesiae (54%), neuritis (63%), myotonia (49%), and occasional 'cogwheeling' (29%). Some individuals affected before puberty had small stature (44%), small hands (64%) and painless arthritis (67%). Severe residual scarring was common (85%), and pinched facies (42%), hirsutism (47%) and hyperpigmentation (71%) were also observed. Enlarged thyroids were observed in 37% (59% in females), which was above average of 5% in this area of Turkey. Porphyrin excretion, particularly uroporphyrin in the urine and stools, was still significantly increased in seventeen patients. Hexachlorobenzene levels as high as 2.8 p.p.m. were detected in human milk, and the average level (0.29 p.p.m. +/- s.d. 0.06) was 140 times the level allowed in cow's milk.
Is NHS patronage another sign of sleaze?
Authors: J Warden
Journal: BMJ (1994)

Long ago MPs were obliged to abandon Westminster from May till October because the River Thames smelt so foul. This week, as parliament was prorogued until the Queen's speech on 16 November, its members retreated thankfully not from the smell of the river but from the smell of sleaze. Sleaze has been the talk of British political life over the past few weeks. It is a conveniently imprecise term, conveying the smell rather than the substance of corruption over undisclosed payments to MPs and free hospitality in the Paris Ritz.

Typically of British scandals, it had more of comedy about it than of crisis - even though it brought the resignation of two junior ministers and …
Reinforced regiment of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomized trial
Authors: Françoise Degos, Véronique Daurat, Sylvie Chevret, Sophie Gayno, Anne Bastie, Ghassan Riachi, Isabelle Bartolomei-Portal, Karl Barange, Joseph Moussalli, Sylvie Naveau, François Bailly, Philippe Chaumet-Riffaud, Claude Chastang
Journal: Journal of Hepatology (1998)
Prevalence of asthma and hay fever in England and Wales.
Authors: D M Fleming, D L Crombie
Journal: BMJ (1987)

The results concerned with the prevalence of asthma and hay fever in the large surveys of morbidity in general practice in 1970-1 and 1981-2 were compared. In data standardised for age the prevalence of asthma in men increased from 11.6 to 20.5 people consulting per 1000 population (p less than 0.001) and in women from 8.8 to 15.9 per 1000 population (p less than 0.001). Similar increases were also evident in data analysed from the 19 practices contributing to both surveys. The prevalence of asthma increased in each age group examined. Increases of similar magnitude were reported for hay fever--the prevalence in men increased from 10.8 to 19.8 people consulting per 1000 population (p less than 0.001) and in women from 10.3 to 19.7 per 1000 population (p less than 0.001) and occurred in all age groups. The prevalence of acute bronchitis was reduced significantly in the age group 5-14 and increased among the elderly. The prevalence of chronic bronchitis was reduced substantially in 1981-2. The reported increased prevalence of both asthma and hay fever represented a real increase and was not accounted for by changes in diagnostic preference. Only in the age group 5-14 was there any likelihood that some of the increased prevalence of asthma might have resulted from a reduction in the prevalence of acute bronchitis.
Response to Letter Regarding Article, “Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement”
Authors: Dirk Sibbing, Werner Koch, Daniela Gebhard, Siegmund Braun, Julia Stegherr, Tanja Morath, Albert Schömig, Nicolas von Beckerath, Adnan Kastrati, Tibor Schuster
Journal: Circulation (2010)
Two-year follow up study of stress-related disorders among immigrants to Israel from the Chernobyl area.
Authors: J Cwikel, A Abdelgani, J R Goldsmith, M Quastel, I I Yevelson
Journal: Environmental Health Perspectives (1997)

We report on findings from a 2-year follow-up study of immigrants originating from exposed areas around the site of the 1986 Chernobyl accident matched with comparison subjects emigrating from other republics in the Confederation of Independent States. In the initial study of 708 immigrants, the samples were matched by age, gender, and year of immigration. We assessed two exposure groups--high and low--by estimating levels of ground cesium contamination from the International Atomic Energy Agency maps. We reinterviewed 520 immigrants from the first wave of data collection (a reinterview rate of 73%), 87 from high-exposure areas, 217 from low-exposure areas, and 216 comparison subjects. This study examined the prevalence of symptoms of posttraumatic stress disorders (PTSD), depression, somatization, anxiety, and physical effects (high blood pressure, acute symptoms, and chronic illness). The results obtained in the first wave conducted 8 years after the accident showed that psychological symptoms were significantly higher in exposed respondents than in the comparison group. During the second wave (10 years after the accident) we observed a decline in the prevalence of PTSD and related distress except for somatization, which remained at the same level. An association between exposure and high blood pressure was observed in the first wave of data, but was not still significant in the second wave of data collection. The proportion of those who reported three or more chronic health problems was 48.3% among the high-exposure group, 49.3% in the low-exposure group, and 30.6% in the comparison group (p = 0.0003). The most commonly reported problems were heart disease. problems with vision or hearing, migraine headaches, problems with the lymphatic system, and arthritis. Based on the results, it was concluded that the Chernobyl accident was a powerful stressor, having a strong impact on both mental and physical health. Since all respondents were engaged in the process of acculturation and accommodation to a new country after emigration, it is encouraging that this study shows that levels of psychological distress are waning as the new immigrants are absorbed into Israeli society. However, there still remains some independent effect on health associated with the experience of the Chernobyl accident.
Penicillin-induced haemolytic anaemia.
Authors: H. E. Amos, A. N. Bishop, M. J. Seaman, J. Trowell
Journal: BMJ (1968)

MIC OURA of, various joints, specially the knee joint, without the guineaworm being inside the joint cavity, and in these the larvae play no role.Fairley and Glen Liston (quoted by Manson Bahr 19664 failed to induce any local or general reaction by subcutaneous injection of guineaworm larvae.It is therefore likely that it is a toxin liberated by the adult worm that causes the arthritic lesion irrespective of its actual location.-Weare, etc.,
A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia
Authors: J E Lancet, F Ravandi, R M Ricklis, L D Cripe, H M Kantarjian, F J Giles, A F List, T Chen, R S Allen, J A Fox, G C Michelson, J E Karp
Journal: Leukemia (2011)

This study of vosaroxin evaluated dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), pharmacokinetics (PK), clinical activity and pharmacodynamics in relapsed/refractory leukemia. Dosing was weekly (days 1, 8 and 15) or twice weekly (days 1, 4, 8 and 11). Seventy-three treated patients had a median age of 65 years, 85% had acute myeloid leukemia and 78% had refractory disease. Weekly schedule: 42 patients received 18-90 mg/m(2); MTD was 72 mg/m(2). Twice-weekly schedule: 31 patients received 9-50 mg/m(2); MTD was 40 mg/m(2). DLT was stomatitis; primary non-hematologic toxicity was reversible gastrointestinal symptoms and febrile neutropenia. Thirty-day all-cause mortality was 11%. Five patients had complete or incomplete remissions; median duration was 3.1 months. A morphologic leukemia-free state (bone marrow blast reduction to <5%) occurred in 11 additional patients. Antileukemic activity was associated with total dose or weekly time above 1 μmol/l plasma vosaroxin concentration (P<0.05). Vosaroxin exposure was dose proportional over 9-90 mg/m(2). The average terminal half-life was ~25 h and clearance was non-renal. No induction or inhibition of vosaroxin metabolism was evident. Vosaroxin-induced DNA damage was detected as increased intracellular γH2AX. Vosaroxin had an acceptable safety profile, linear PK and encouraging clinical activity in relapsed/refractory leukemia.
Lipoprotein(a) Levels in Black and White Children and Adolescents With IDDM
Authors: Lynne L Levitsky, Angelo M Scanu, Samuel H. Gould
Journal: Diabetes Care (1991)

Objective To examine the relationship between levels of lipoprotein(a) [Lp(a)], diabetes, and glycemic control in white and black nondiabetic control and insulindependent diabetic (IDDM) children and adolescents, fasting blood analyses were conducted on a subject sample drawn from referral-based diabetes and endocrine clinics and a primary-care general pediatric clinic. Research Design and Methods Thirty-six white and 16 black children with IDDM who volunteered to participate in this study were compared with 30 white and 42 black nondiabetic control children. Results Lp(a) protein levels were significantly higher (P &amp;lt; 0.05) in both groups of black children compared with whites (black vs. white nondiabetic children 6.8 ± 0.95 vs. 3.1 ± 0.68 mg/dl and black vs. white diabetic children 7.5 ± 1.52 vs. 3.0 ± 0.64 mg/dl). Lp(a) protein levels directly correlated with the level of glycosylated hemoglobin (r = 0.46, P &amp;lt; 0.01) in white diabetic children but not in black diabetic children. Well-controlled white diabetic children (n = 12, glycosylated hemoglobin &amp;lt;10%) had a mean Lp(a) protein level of 1.4 ± 0.3 mg/dl compared with poorly controlled white diabetic children (n = 10, glycosylated hemoglobin &amp;gt;13%) whose mean Lp(a) protein level was 5.7 ± 1 . 7 mg/dl (P &amp;lt; 0.01). Conclusions We conclude that circulating levels of Lp(a) protein are increased in hyperglycemia. A genetically determined elevated level of Lp(a) is a risk factor for atherosclerotic disease in white and Asian adults. Elevated Lp(a) should be investigated as an independent risk factor for atherosclerotic disease in IDDM. It could prove to be an additional mechanism for the development of diabetic complications in selected populations.
Leukemic Stem Cells in Childhood High-Risk ALL/t(9;22) and t(4;11) Are Present in Primitive Lymphoid-Restricted CD34+CD19− Cells
Authors: Marc Hotfilder, Silja Röttgers, Annegret Rosemann, André Schrauder, Martin Schrappe, Rob Pieters, Heribert Jürgens, Jochen Harbott, Josef Vormoor
Journal: Cancer Research (2005)

Abstract Open questions in the pathogenesis of childhood acute lymphoblastic leukemia (ALL) are which hematopoietic cell is target of the malignant transformation and whether primitive stem cells contribute to the leukemic clone. Although good-prognosis ALL is thought to originate in a lymphoid progenitor, it is unclear if this applies to high-risk ALL. Therefore, immature CD34+CD19− bone marrow cells from 8 children with ALL/t(9;22) and 12 with ALL/t(4;11) were purified and analyzed by fluorescence in situ hybridization, reverse transcription-PCR (RT-PCR), and colony assays. Fifty-six percent (n = 8, SD 31%) and 68% (n = 12, SD 26%) of CD34+CD19− cells in ALL/t(9;22) and ALL/t(4;11), respectively, carried the translocation. In addition, 5 of 168 (3%) and 22 of 228 (10%) myeloerythroid colonies expressed BCR/ABL and MLL/AF4. RT-PCR results were confirmed by sequence analysis. Interestingly, in some patients with ALL/t(4;11), alternative splicing was seen in myeloid progenitors compared with the bulk leukemic population, suggesting that these myeloid colonies might be part of the leukemic cell clone. Fluorescence in situ hybridization analysis, however, shows that none of these myeloid colonies (0 of 41 RT-PCR-positive colonies) originated from a progenitor cell that carries the leukemia-specific translocation. Thus, leukemic, translocation-positive CD34+CD19− progenitor/stem cells that were copurified by cell sorting were able to survive in these colony assays for up to 28 days allowing amplification of the respective fusion transcripts by sensitive RT-PCR. In conclusion, we show that childhood high-risk ALL/t(9;22) and t(4;11) originate in a primitive CD34+CD19− progenitor/stem cell without a myeloerythroid developmental potential.
Hemorrhagic Proctosigmoiditis and Blastocystis hominis
Authors: Miguel Carrascosa
Journal: Annals of Internal Medicine (1996)

Letters15 November 1996Hemorrhagic Proctosigmoiditis and Blastocystis hominisMiguel Carrascosa, MD, Josefina Martinez, MD, and Jose L. Perez-Castrillon, MDMiguel Carrascosa, MDHospital of Laredo, Cantabria, Spain.Search for more papers by this author, Josefina Martinez, MDHospital of Laredo, Cantabria, Spain.Search for more papers by this author, and Jose L. Perez-Castrillon, MDHospital of Laredo, Cantabria, Spain.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-10-199611150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Yarze for his valuable comments. When we refer to Shiga-like toxins, we are thinking about the syndrome of hemorrhagic colitis linked to verotoxigenic strains of E. coli, most often serotype O157:H7. Because stool culture for these strains was not done and stools were not examined for free toxins, we could not definitively exclude enterohemorrhagic E. coli infection. We therefore reported that we believed our patient's case was caused by B. hominis. However, there are several reasons to consider the etiologic role of B. hominis. First, although cases of infection with E. coli O157:H7 have been ...References1. Su C, Brandt LJ. Escherichia coli O157:H7 infection in humans. Ann Intern Med. 1995; 123:698-714. Google Scholar2. Prats G, Frias C, Margall N, Llovet T, Gaztelurrutia L, Elcuaz R, et al. Colitis hemorragica por Escherichia coli verotoxigenica. Presentacion de 9 casos. Enferm Infecc Microbiol Clin. 1996; 14:7-15. Google Scholar3. Sack RB. Escherichia coli infections. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. Philadelphia: WB Saunders; 1992:589-96. Google Scholar4. Grendell JH, Ockner RK. Vascular diseases of the bowel. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. 4th ed. Philadelphia: WB Saunders; 1989:1903-32. Google Scholar Author, Article, and Disclosure InformationAuthors: Miguel Carrascosa, MD; Josefina Martinez, MD; Jose L. Perez-Castrillon, MDAffiliations: Hospital of Laredo, Cantabria, Spain. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHemorrhagic Colitis Due to Amoxicillin/Clavulanate and Nasal Decongestants? 15 November 1996Volume 125, Issue 10Page: 861KeywordsCecumColitisColonEscherichia coli infectionsHemorrhageIschemiaThrombosisToxinsUlcerative colitisUlcers ePublished: 15 August 2000 Issue Published: 15 November 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pool NHS and local authority spending to fund care for older people, says think tank
Authors: A. Cole
Journal: BMJ (2010)

The new commission into the funding of social care should consider merging NHS and local authority spending on care for elderly people to keep costs in check, says a report from the right of centre think tank Policy Exchange.

The report points out that the NHS is already responsible for a quarter of the estimated £16.17bn (€19.3bn; $25bn) of public spending on long term care and that its contribution is set to rise substantially as cuts take effect in local government.

“It would be naive to think that reducing spending on …
Stemming bone loss by suppressing apoptosis
Authors: Janet M. Hock
Journal: Journal of Clinical Investigation (1999)

It’s been over 100 years since the discovery of parathyroid hormone (PTH), yet the in vivo mechanisms of action of PTH at the cellular and molecular levels are still not well understood. Despite a wealth of in vitro studies, none predicted the anabolic effect of PTH on the skeleton. The anabolic effect of PTH was initially observed using parathyroid gland extract (PTE) in young rats and rabbits (1, 2). At the time, the models were thought to reproduce, in part, the pathologic processes of hyperparathyroidism, in which an early destructive phase was followed by an ebullient reparative phase of bone formation (1). After the successful synthesis of hPTH 1-34 in the early 1970s (3), its anabolic phenomenon was revisited, and small clinical trials suggested that PTH could be used as an anabolic therapy for osteoporosis (4, 5). The data were viewed with scepticism, because the literature at the time was dominated by the notion that PTH was a hormone controlling calcium homeostasis, in part by stimulating bone resorption. In vitro, embryonic bone organ culture studies confirmed the original in vivo studies with PTE, by showing that PTH initially stimulated resorption and had a delayed, stimulatory effect on the rate of matrix synthesis (6). These data supported the concept of “coupling” between resorption and formation, with PTH as a key stimulator of bone turnover (6). However, in vivo data from rats and humans showed that PTH stimulated bone formation de novo, without a prior episode of resorption (7, 8).
Relationships between toxicopathic hepatic lesions and exposure to chemical contaminants in English sole (Pleuronectes vetulus), starry flounder (Platichthys stellatus), and white croaker (Genyonemus lineatus) from selected marine sites on the Pacific Coast, USA.
Authors: M S Myers, C M Stehr, O P Olson, L L Johnson, B B McCain, S L Chan, U Varanasi
Journal: Environmental Health Perspectives (1994)

Relationships between hepatic lesions and chemical contaminant concentrations in sediments, stomach contents, liver tissue, and bile were statistically evaluated in three species of bottomfish, English sole (Pleuronectes vetulus), starry flounder (Platichthys stellatus), and white croaker (Genyonemus lineatus), captured from 27 urban and nonurban sites on the Pacific Coast from Alaska to southern California. Lesions detected were neoplasms, preneoplastic foci of cellular alteration, nonneoplastic proliferative lesions, unique or specific degenerative/necrotic lesions, nonspecific degenerative/necrotic lesions, and hydropic vacuolation of biliary epithelial cells and hepatocytes. In general, lesion prevalences were significantly higher in all three species captured at chemically contaminated urban sites, and certain lesions had significantly higher relative risks of occurrence at urban sites in Puget Sound, San Francisco Bay, the vicinity of Los Angeles, and San Diego Bay. Concentrations of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, DDT and its derivatives, and chlordanes and dieldrin in sediment, stomach contents, liver, and fluorescent aromatic compounds in bile were significant risk factors for the occurrence of neoplastic, preneoplastic, nonneoplastic proliferative, and specific degenerative/necrotic lesions, as well as hydropic vacuolation. Fish age also had a significant influence on occurrence of several hepatic lesions, but gender was rarely a significant risk factor. These relationships provide strong evidence for the involvement of environmental contaminants in the etiology of hepatic lesions in several marine bottomfish species and clearly indicate the utility of these lesions as biomarkers of contaminant-induced effects in wild fish.