tbuckley/cabot-search huggingface dataset:
Abstract A22: Temozolomide upregulates B7-H1 in glioma cells and promotes immunoressistance against T cells
Authors: Dwain K. Irvin, Shinya Miyamoto, Keith Black, Altanchimeg Rentsendorj
Journal: Clinical Cancer Research (2010)

Abstract Temozolomide is widely used as the first-line chemotherapeutic agent for malignant glioma. However, it can prolong the median survival and progression-free survival in glioblastoma patients by only a few months. Recently, it has been demonstrated that multiple human tumors express B7-H1 and B7-H4, immune inhibitory transmembrane glycoproteins, including glioblastoma. It has been suggested that tumor cells utilize these proteins as a potential mechanism of immunoressistance. Therefore, we sought to determine if glioma cells up-regulate B7-H1 and B7-H4 and promotes immunoressistance in glioma cells. We show by fluorescent activated cells sorting that T98G, human glioblastoma cell line, GBM157, GBM177, primary human glioblastoma cells, and GL26, murine glioma cell line, express both B7-H1 and B7-H4. We also demonstrate that both B7-H1 and B7-H4 were significantly up-regulated in surviving T98G, GBM157, and GL26 cells after 3-day temozolomide exposure. The standardized fluorescence index of B7-H1 protein after temozolomide (1000 mM) exposure significantly increased from 1.54 to 3.07 (p =0.0021) and that of B7-H4 significantly increased from 1.99 to 3.17 (p =0.0043) in surviving T98G cells. Real-time quantitative PCR also showed significant up-regulation in B7-H1 gene expression by 4.6 times (p &amp;lt; 0.0001) and in B7-H4 gene expression by 2.0 times (p = 0.0398) after 3-day temozolomide (1000mM) exposure in surviving T98G cells. In order to determine if up-regulation of B7-H1 promoted immunoressistance we co-culture surviving temozolamide exposed glioma cells with either CD4+ or CD8+ T-cells and determined secreted levels of IL-10 by enzyme-linked immunofluorescence assay and T-cell apoptosis, respectively. We show that CD4+ T-cells significantly up-regulate IL-10 secretion after co-culture with surviving temozolamide exposed glioma cells and that CD8+ T-cells apoptosis is also significantly increased as compared to control GL26 glioma cells. Taken together, these results suggest that up-regulation of B7-H1 and B7-H4 in glioma cells promotes glioma immunoressistance through the up-regulation of CD4+ T-cell IL-10 secretion and CD8+ T-cell apoptosis. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A22
The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia
Authors: Fortunato Morabito, Rosaria De Filippi, Luca Laurenti, Katja Zirlik, Anna Grazia Recchia, Massimo Gentile, Emanuela Morelli, Ernesto Vigna, Vincenzo Gigliotti, Rosa Calemma, Barbara Amoroso, Antonino Neri, Giovanna Cutrona, Manlio Ferrarini, Stefano Molica, Giovanni Del Poeta, Claudio Tripodo, Antonio Pinto
Journal: Blood (2011)
890 The molecular mechanisms of vitamin K2 as a promising chemopreventive drug in the management of hepatocellular carcinoma
Authors: M OTSUKA, Y KOIKE, N KATO, R SHAO, Y HOSHIDA, M MORIYAMA, T HIROYOSHI, T KAWAKAMI, H IJICHI, K TATEISHI
Journal: Hepatology (2003)

The inactivation of the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor p16INK4A may be caused by gene deletion, mutation or promoter hypermethylation. We have previously reported that p16INK4A in hepatocellular carcinoma (HCC) tissues and cell lines is inactivated predominantly by promoter hypermethylation rather than genomic aberrations. In the present experiments, we have studied the effects of the demethylating agent, 5-aza-2′-deoxycytidine (5-AZA/decitabine), on the expression of aberrant p16INK4A RNA transcripts and the CDK–retinoblastoma gene pathway in HCC cell lines with p16INK4A promoter hypermethylation. The expression of aberrant p16INK4A RNA transcripts was down-regulated and p16INK4A protein was strongly re-expressed in the HCC cell lines, SNU 354, 398, 423 and 475 after 5-AZA/decitabine treatment for 5 days. The re-expressed p16INK4A was functional, because it bound to and inhibited CDK4 kinase activity, and increased the concentrations of the hypophosphorylated form of retinoblastoma protein (pRB) in cells with a wild type RB gene. Moreover, treatment with the demethylating agent led not only to G1 cell cycle arrest, but also to the increased expression of the senescence-associated marker β-galactosidase. This up-regulation of p16INK4A mRNA and protein correlated with demethylation of the p16INK4A promoter, and with the down-regulation or disappearance of aberrant p16INK4A transcripts. These results suggest that the aberrant p16INK4A RNA transcript can be transcribed from the methylated p16INK4A gene, and endogenous reactivation of functional p16INK4A mRNA by a demethylating agent can restore the pRB pathway in HCC, and foster the terminal differentiation of the malignant cells. Therefore, demethylating agents, such as 5-AZA/decitabine, may have potential in the treatment of HCC.
Ectopic production of methionine enkephalin and beta-endorphin.
Authors: S I Cohen
Journal: BMJ (1980)

blown into his face.After he replaced the original Gramoxone container with a new plastic container he had no further symptoms.His chest x-radio- graph during these episoaes of fever was not significantly altered.As in the case reported by Drs George and Hedworth-Whitty, it was not possible to investigate this further as my patient was not seen soon after exposure; but his story strongly suggests that inhalation of paraquat was responsible for his symptoms.
Clostridial Myositis After Parenteral Injections
Authors: Ronald B. Berggren, Thomas D. Batterton, Gilbert McArdle, William H. Erb
Journal: JAMA (1964)

Clostridial myositis following parenteral administration of medication is a serious complication with a high mortality. In most cases, the true nature of the disease is not suspected early, and adequate therapy is delayed. Organisms may be introduced with a needle from overlying skin that has not been adequately prepared. Medication, needle, syringe, personnel, or other fomites might harbor organisms and contaminate the procedure. Trauma from injection can set up a<i>locus minoris resistentiae</i>where circulating anaerobic organisms may colonize. Confirmation of diagnosis by needle aspiration of the area is encouraged. Thirteen cases have been previously published in the American literature; five additional cases are reported here.
750-6 B-mode Ultrasound Assessment of the Treatment Effect of Pravastatin on the Progression of Carotid and Femoral Intima-Media Thickness in a Population Selected on Coronary Disease
Authors: Eric de Groot, Alexander Montauban van Swijndregt, Rob G. Ackerstaff, Aeilko Zwinderman, Ton F.W. van der Steen, Gene Bond, Klaas Bom, Albert VG. Bruschke, Kong I. Lie
Journal: Journal of the American College of Cardiology (1995)
Attitudes, training and smoking profile of European Respiratory Society members
Authors: Z. Kabir, B. Ward, L. Clancy
Journal: European Respiratory Journal (2011)

To the Editors:

Patients regard healthcare professionals, particularly physicians, as role models for leading a healthy lifestyle. Healthcare professionals’ own behaviour and attitudes concerning healthy lifestyles have an influence on counselling of patients. A recent survey in the USA reported ∼6% tobacco use among healthcare professionals [1], while 41% of Chinese male medical doctors smoke [2]. Tobacco dependence treatment (TDT) efforts generally focus on physicians, but evidence suggests that physicians are inadequately trained to help smokers quit [3, 4]. For a successful TDT programme, appropriately trained healthcare professionals are essential. The need and quality of training for TDT currently available for healthcare professionals across Europe is unknown.

The European Respiratory Society (ERS) is the leading professional organisation in its field in Europe (www.ersnet.org). ERS is broad-based, with ∼10,000 members from 100 different countries working in the field of respiratory health. We undertook this telephone survey on smoking profiles of ERS members in Europe from November 2009 to January 2010, using a standardised questionnaire designed with the leadership of the Tobacco Control Committee of the ERS.

Three main outcome measures were examined among ERS members: 1) percentages of current and ever-smokers (smoked >100 cigarettes in their lifetime); 2) second-hand smoke (SHS) exposure; and 3) attitudes and training of the ERS members regarding TDT.

The estimated sample size was derived from 25 European countries across five different geographic regions proportionally representative of the ERS membership (Western Europe, the Mediterranean region, Scandinavia, Central and Eastern Europe, and the Baltic region), as shown in table 1. An estimated sample size of 722 subjects was based on an expected response rate of 50%, with 95% confidence and a 5% margin of error. Respondents were recruited randomly using a list of ERS members provided by the ERS. Consent …
Rat Prolactinoma Cell Growth Regulation by Epidermal Growth Factor Receptor Ligands
Authors: George Vlotides, Emily Siegel, Ines Donangelo, Shiri Gutman, Song-Guang Ren, Shlomo Melmed
Journal: Cancer Research (2008)

Abstract Epidermal growth factor (EGF) regulates pituitary development, hormone synthesis, and cell proliferation. Although ErbB receptor family members are expressed in pituitary tumors, the effects of EGF signaling on pituitary tumors are not known. Immunoprecipitation and Western blot confirmed EGF receptor (EGFR) and p185c-neu protein expression in GH3 lacto-somatotroph but not in adrenocorticotropic hormone–secreting AtT20 pituitary tumor cells. EGF (5 nmol/L) selectively enhanced baseline (∼4-fold) and serum-induced (&amp;gt;6-fold) prolactin (PRL) mRNA levels, whereas gefitinib, an EGFR antagonist, suppressed serum-induced cell proliferation and Pttg1 expression, blocked PRL gene expression, and reversed EGF-mediated somatotroph-lactotroph phenotype switching. Downstream EGFR signaling by ERK, but not phosphoinositide-3-kinase or protein kinase C, mediated the gefitinib response. Tumors in athymic mice implanted s.c. with GH3 cells resulted in weight gain accompanied by increased serum PRL, growth hormone, and insulin growth factor 1. Gefitinib decreased tumor volumes and peripheral hormone levels by ∼30% and restored normal mouse body weight patterns. Mice treated with gefitinib exhibited decreased tumor tissue ERK1/2 phosphorylation and down-regulated tumor PRL and Pttg1 mRNA abundance. These results show that EGFR inhibition controls tumor growth and PRL secretion in experimental lacto-somatotroph tumors. EGFR inhibitors could therefore be useful for the control of PRL secretion and tumor load in prolactinomas resistant to dopaminergic treatment, or for those prolactinomas undergoing rare malignant transformation. [Cancer Res 2008;68(15):6377–86]
Computing the Length of Survival in Long-Term Disease
Authors: Baruch Modan
Journal: JAMA (1965)

Any evaluation of survival data is subject to numerous pitfalls. A comparison of two groups of patients with polycythemia vera, one group treated by<sup>32</sup>p and the second receiving treatment other than radiation, demonstrated that several incidental factors, mainly the lapse of time between the diagnosis and the onset of treatment, influenced the pattern of survival in a number of series of cases reported in the literature. This lead to the erroneous conclusion that the length of survival for patients treated with<sup>32</sup>p is considerably greater than of those not so treated. After an adjustment for these factors was made, the pattern of survival of the two groups became similar. These findings serve to stress the possible bias in interpreting survival data of retrospective case-control studies, unless the same base line is used for the two groups under consideration.
Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH2) in children with GH insufficiency and idiopathic short stature
Authors: Anatoly N. Tuilpakov, Aleksander A. Bulatov, Valentine A. Peterkova, Galine P. Elizarova, Natalya N. Volevodz, Cyril Y. Bowers
Journal: Metabolism (1995)
The Balance of Power: The Law of Yin and Yang in Smooth Muscle Cell Fate
Authors: Masanori Aikawa
Journal: Circulation Research (2007)

O nce upon a time in China, the Han philosophers intro- duced a syncretic intellectual framework to unite various thoughts using a new theory: the law of Yin and Yang.The basic concept of the theory is that the balance of two opposite principles regulates the universe and thus all phenomena, including human health.Yin represents the moon, cold, darkness, night, black, and quiescence, whereas Yang is sun, heat, brightness, day, white, and activity.Notably, the concept underscores the interplay of two opposite forces, but not conflicts between the two.In other words, they are not simply black and white, rather, two principles interrelating, complementing and harmonizing each other.Ancient philosophers already knew that health is life in balance, but underlying mechanisms are complex.More than a millennium later, we are still attempting to answer the same questions.An exciting and provocative study by Santiago et al, published in this issue of Circulation Research, used comprehensive in vitro and in vivo approaches to demonstrate that Yin Yang 1 (YY1), a ubiquitous and dual-functional GLI-Kru ¨ppel zinc finger transcription factor, suppresses smooth muscle cell (SMC) growth. 1 The authors suggest YY1 may serve as a therapeutic tool, combating neointima formation following vascular injury.Despite a relatively new face in vascular biology, investigators in other fields of medical sciences, particularly cancer biology, have extensively studied this mysterious molecule since its initial characterizations in the late 1980s to early 1990s. 2 YY1 was originally discovered as a transcriptional regulator that interacts with E1A gene products, oncoproteins that activate the adenoassociated virus (AAV) P5 promoter.When E1A is present, YY1 induces transcription; its absence converts YY1 into a repressor.The YY1 gene encodes a 414 amino-acid protein with an estimated weight of 44kD.Alternative splicing generates at least eight isoforms with unknown functional differences.YY1 also contributes to various normal biological processes, including development, differentiation, and
Non-Anticoagulant Uses of Heparin
Authors: David A. Lane, Lewis Adams
Journal: New England Journal of Medicine (1993)

The clinical use of heparin as an anticoagulant and antithrombotic agent is established practice in prophylaxis against postoperative deep-vein thrombosis, in the initial treatment of overt deep-vein thrombosis, and in the prevention of thrombosis during extracorporeal circulation1. With its anticoagulant and antithrombotic action, heparin primarily binds to and accelerates the plasma inhibitor antithrombin III, and it has essential interactions with various coagulation proteinases. Furthermore, its interaction with other inhibitory proteins, such as heparin cofactor II and tissue-factor-pathway inhibitor, promotes additional proteinase inhibitory reactions24.Heparin is a highly sulfated, unbranched glycosaminoglycan present in the mast cells of most . . .
The ORMDL3 Locus And Asthma In Four Populations Of African Ancestry
Authors: R.A. Mathias, N. Rafaels, V. Mantese, T. Murray, C. Vergara, L. Gao, M. Araujo, L. Caraballo, J.M. Knight-Madden, G. Dunston
Journal: Journal of Allergy and Clinical Immunology (2011)
Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan
Authors: Takashi Tokunaga, Kazuyuki Shimada, Kazuhito Yamamoto, Dai Chihara, Takuji Ichihashi, Rika Oshima, Mitsune Tanimoto, Toshihiro Iwasaki, Atsushi Isoda, Akira Sakai, Hikaru Kobayashi, Kunio Kitamura, Kosei Matsue, Masafumi Taniwaki, Sadahiro Tamashima, Yoshio Saburi, Taro Masunari, Tomoki Naoe, Shigeo Nakamura, Tomohiro Kinoshita
Journal: Blood (2012)
Expression of CD23 antigen and its ligands in children with intrinsic and extrinsic asthma
Authors: N. Aberle, A. Gagro, S. Rabatić, Ž. Reiner‐Banovac, D. Dekaris
Journal: Allergy (1997)

The role of the low‐affinity IgE receptor CD23 in immune reactions has been further emphasized by recent discoveries of novel surface ligands for CD23: CD21, CD11b, and CD11c. We previously observed the difference between the expression of CD23 and CD21 antigens in children suffering from extrinsic asthma when compared to healthy controls. In the present study, we investigated the expression of CD23 and its ligand CD21 on CD20 + B cells in 44 asthmatic children (23 allergic and 21 nonallergic) using three‐color immunofluorescence analysis. In addition, the expression of two other ligands for CD23, CD11b, and CD11c, on T cells (CD3 + ), a subpopulation of T cells (CD4 + and CD8 + ), natural killer cells (CD56 + ), and monocytes (CD14 + ) was tested by two‐color immunofluorescence analysis in 12 allergic and 14 nonallergic children. We found that children with extrinsic asthma had higher levels of CD23 + B cells than those with intrinsic asthma. No difference was observed in the percentage of either CD23 + CD21 + or CD23 ‐ CD21 + B cells. The CD11b antigen was expressed on each tested population, but only on CD4 + T cells was CD11b significantly increased in children with extrinsic asthma. CD11c was expressed mainly on monocytes, and no difference was observed between tested groups. The increased percentage of CD11b antigen on CD4 + T cells and the increased percentage of CD23 antigen on B cells in children with extrinsic asthma provide further evidence of the immunologic differences between intrinsic and extrinsic asthma.
Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation
Authors: Yukiko Nakano, Shumpei Niida, Keigo Dote, Sou Takenaka, Hidekazu Hirao, Fumiharu Miura, Mari Ishida, Tetsuji Shingu, Taijiro Sueda, Masao Yoshizumi, Kazuaki Chayama
Journal: Journal of the American College of Cardiology (2004)
Over-the-Counter Cold Remedies-Reply
Authors: William Feldman
Journal: JAMA (1993)

<h3>In Reply.</h3> —We appreciate the thoughtful and careful review of our study recently reported in<i>JAMA</i>. Drs Luks and Anderson raised several important points but highlight the importance of clinical significance in the evaluation of over-the-counter cold medications. The purpose of our review was to provide a quantitative evaluation of the studies using over-the-counter cold medications. Clinical significance was one part of the evaluation (Table 1, item 11). We should clarify that this was evaluated with each of the articles we reviewed. We specifically paid attention to the practical importance of a difference in clinical outcomes. If the difference between treatment and placebo was statistically significant, we asked whether it was clinically significant as well. Conversely, if the difference was not statistically significant, we asked whether the trial was large enough to show a clinically important difference if it had occurred (ie, a β error). We agree that none of
Studies in Adoption: Requests for Psychiatric Treatment
Authors: HENRY H. WORK, HANS ANDERSON
Journal: American Journal of Psychiatry (1971)

It has been observed that parents of adopted children frequently seek psychiatric treatment for them. The authors conducted a study of the children at the U.C.L.A. Neuropsychiatric Institute and confirmed this finding. They believe that certain patterns of child rearing among adoptive parents contribute to their adopted children's difficulties.
REDUCTION OF ARRHYTHMIAS BY A PROTOCOL FOR TREATMENT OF CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA
Authors: Fernando Wangüemert Pérez, Pablo Ruiz Hernandez, Paola Berne, Carmelo Pérez, Oscar Campuzano, Josep Brugada
Journal: Journal of the American College of Cardiology (2013)
Does the Aspartic Acid to Asparagine Substitution at Position 76 in the Pancreas Duodenum Homeobox Gene (<i>PDX1</i>) Cause Late-Onset Type 2 Diabetes?
Authors: Steven C. Elbein, Mohammad A. Karim
Journal: Diabetes Care (2004)

OBJECTIVE—Considerable data support an inherited defect in insulin secretion as one component of type 2 diabetes. Coding variants of the pancreas duodenum homeobox gene (PDX1) were proposed to predispose late-onset type 2 diabetes and to decrease transactivation in vitro. We tested the hypothesis that the Asp76Asn (D76N) variant that was identified in several populations predisposed type 2 diabetes and reduced insulin secretion. RESEARCH DESIGN AND METHODS—We performed a case-control study in 191 control subjects and 190 individuals with type 2 diabetes, all of European descent, then characterized the D76N variant in 704 members of 68 families. We compared the phenotypic characteristics of those with and without the variant by diagnostic status and determined the insulin secretory response to intravenous glucose and tolbutamide among nondiabetic family members. RESULTS—D76N was not associated with type 2 diabetes, either in our population or when all reported studies in Caucasians were combined. D76N did not segregate with diabetes among the families examined. Among D76N carriers, nondiabetic individuals had a lower waist-to-hip ratio and a trend to lower BMI than their diabetic counterparts. Diabetic carriers of D76N were significantly leaner by BMI (P = 0.012) and tended to be younger than diabetic individuals with the D/D genotype. However, insulin secretion in response to oral and intravenous glucose challenge and to intravenous tolbutamide was not reduced in D76N carriers. CONCLUSIONS—The D76N variant of PDX1 does not significantly alter insulin secretion or act as a high-risk susceptibility allele for late-onset type 2 diabetes as proposed previously, although we cannot exclude a minor role in increasing risk of diabetes.
Surgical Significance of Angiographic Patterns in Coronary Arterial Disease
Authors: EDWARD B. DIETHRICH, JOHN E. LIDDICOAT, SAMUEL A. KINARD, H. EDWARD GARRETT, JOHN M. LEWIS, MICHAEL E. DEBAKEY
Journal: Circulation (1967)

A review of 313 selective cine coronary arteriograms performed in patients with angina pectoris is presented. Classification of coronary arterial disease by location and severity of stenosis has established certain patterns of disease. Significant disease (greater than 75% stenosis of at least one major vessel) occurred in 270 of 313 (89%) patients. Significant single-vessel disease occurred in only 58 of 270 (23%) patients, while the occurrence of significant multiple-vessel disease was: double, 110 of 270 (40%) patients; triple, 78 of 270 (29%) patients; and quadruple, 24 of 270 (9%) patients. The distribution in 191 arterial occlusions was: right coronary, 101 of 191 (53%); anterior descending, 64 of 191 (33%); and circumflex, 26 of 191 (14%). Anterior and anterior-lateral myocardial ischemia occurred in 80 of 270 (29%) patients, isolated posterior myocardial ischemia in 46 of 270 (18%) patients, and equal anterior and posterior ischemia in 144 of 270 (53%) cases. The angiographic studies were correlated with clinical history and electrocardiographic findings. The frequency of severe posterior myocardial ischemia, either alone or in conjunction with severe anterior ischemia, indicates the need for selective posterior or total myocardial ischemia, either alone or in conjunction of patients are to benefit from myocardial revascularization.