tbuckley/cabot-search huggingface dataset:
Abstract 4560: Anti-tumor activity of a fully human anti-CD27 monoclonal antibody in a transgenic mouse model
Authors: Lawrence J. Thomas, Li-Zhen He, Eric M. Forsberg, Laura Vitale, James M. Boyer, Kristen L. Jones, Jeffrey Weidlick, Martin J. Glennie, Tibor Keler, Henry C. Marsh
Journal: Cancer Research (2011)

Abstract The costimulatory molecule CD27 is a member of the TNF receptor superfamily, and is constitutively expressed on the majority of mature T cells, memory B cells, and a portion of NK cells. The interaction of CD27 with its ligand CD70 plays an important role in the activation, proliferation, survival, and maturation of effector capacity and memory in T cells; in clonal B cell expansion and germinal center formation; and in NK cell cytolytic activity. Previous published work demonstrated that agonistic anti-mouse CD27 mAbs, given without a DC maturation signal, have potent anti-tumor activity through boosting of T cell immunity. To explore the therapeutic potential of this target, a panel of fully human antibodies recognizing human CD27 was generated using human Ig transgenic mice immunized with recombinant CD27. These anti-CD27 mAbs showed specific and high affinity binding to recombinant CD27 and CD27-expressing lymphoma cells. Human CD27-transgenic (hCD27-Tg) mice were generated to evaluate the anti-CD27 mAbs in vivo. The CD27-Tg mouse line was back-crossed onto a Balb/c background in order to assess anti-tumor activity using the BCL1 B-lymphoma line. Approximately 107 BCL1 cells were delivered i.v. to backcrossed animals on day 0. Doses of 150 to 600 ug of our lead anti-CD27 mAb (clone 1F5) were delivered to mice i.p. on days 3, 5, 7, 9 and 11. In multiple experiments, tumor growth in mice treated with the anti-CD27 mAb 1F5 was substantially delayed compared to that of control-treated mice. Further, many anti-CD27 treated animals did not show evidence of tumor growth several weeks past the point where all control animals had been euthanized. These data confirm that anti-human CD27 mAbs can mediate similar anti-tumor effects as the anti-mouse CD27 agonist antibodies. The 1F5 antibody was also demonstrated to cross-react with CD27 from cynomolgus monkeys, and in a small pilot study was well tolerated and without evidence of significant lymphocyte activation. Taken together the data support the therapeutic potential of this anti-CD27 mAb to enhance immune responses in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4560. doi:10.1158/1538-7445.AM2011-4560
Response to Letter Regarding Article, “Heart Failure With Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes”
Authors: Anupam Basuray, Benjamin French, Bonnie Ky, Esther Vorovich, Caroline Olt, Nancy Sweitzer, Thomas Cappola, James C. Fang
Journal: Circulation (2015)

We thank Drs Psaty, Shah, and Gottdiener for their interest in our article.They expressed concern with our study methodology and, more specifically, our patient population.The Penn Heart Failure Study cohort was composed of patients who had heart failure for an average of 6 years before recruitment at 1 of 3 tertiary care centers. 1 As the authors note, this delay in study enrollment selects for patients who survived early disease, but are sufficiently ill to require referral to a tertiary care center.This may introduce bias in the estimation of prognosis, and precludes analysis of early risk factors.Finally, the authors question the external validity of the results outside of tertiary care centers and emphasize the need of an inception cohort.We agree with Psaty and colleagues that an inception cohort would provide a less biased understanding of the natural history of heart failure in its various forms.However, this superior design has to be balanced against practical considerations in obtaining such a cohort.Identifying the initial onset of disease is challenging in heart failure because many patients have asymptomatic pathology (Stage B) for a period of time before the onset of symptoms, and there is further delay until a diagnosis is actually made. 2 We welcome the efforts of large community-based cohorts to characterize early heart failure phenotypes, including preclinical heart failure and newly diagnosed heart failure.As stated in our discussion, we concur that findings may be generalizable to referral centers but should not be extrapolated to the general population because of the referral nature of the cohort.The primary purpose of our article was to introduce heart failure with recovered left ventricular ejection fraction as an emergent clinical entity in the era of modern heart failure therapies. 1,3This group appears to have recovery of ventricular function to the normal range, but nevertheless continues to experience heart failure morbidity.Further work is required to understand this new heart failure phenotype in a variety of clinical contexts, including work using the inception cohort design.
Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field
Authors: Tong-Chun Wen, Junya Tanaka, Hui Peng, Junzo Desaki, Seiji Matsuda, Nobuji Maeda, Hiroko Fujita, Kohji Sato, Masahiro Sakanaka
Journal: The Journal of Experimental Medicine (1998)

In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mechanism(s) underlying the neurotrophic action of IL-3 has not been elucidated, although an erythroleukemic cell line is known to enter apoptosis after IL-3 starvation possibly due to a rapid decrease in Bcl-2 expression. This in vivo study focused on whether IL-3 rescued noncholinergic hippocampal neurons from lethal ischemic damage by modulating the expression of Bcl-xL, a Bcl-2 family protein produced in the mature brain. 7-d IL-3 infusion into the lateral ventricle of gerbils with transient forebrain ischemia prevented significantly hippocampal CA1 neuron death and ischemia-induced learning disability. TUNEL (terminal deoxynucleotidyltransferase–mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling) staining revealed that IL-3 infusion caused a significant reduction in the number of CA1 neurons exhibiting DNA fragmentation 7 d after ischemia. The neuroprotective action of IL-3 appeared to be mediated by a postischemic transient upregulation of the IL-3R α subunit in the hippocampal CA1 field where IL-3Rα was barely detectable under normal conditions. In situ hybridization histochemistry and immunoblot analysis demonstrated that Bcl-xL mRNA expression, even though upregulated transiently in CA1 pyramidal neurons after ischemia, did not lead to the production of Bcl-xL protein in ischemic gerbils infused with vehicle. However, IL-3 infusion prevented the decrease in Bcl-xL protein expression in the CA1 field of ischemic gerbils. Subsequent in vitro experiments showed that IL-3 induced the expression of Bcl-xL mRNA and protein in cultured neurons with IL-3Rα and attenuated neuronal damage caused by a free radical–producing agent FeSO4. These findings suggest that IL-3 prevents delayed neuronal death in the hippocampal CA1 field through a receptor-mediated expression of Bcl-xL protein, which is known to facilitate neuron survival. Since IL-3Rα in the hippocampal CA1 region, even though upregulated in response to ischemic insult, is much less intensely expressed than that in the CA3 region tolerant to ischemia, the paucity of IL-3R interacting with the ligand may account for the vulnerability of CA1 neurons to ischemia.
Abstract 4908: Detection of bladder tumor by quantitative methylation specific real time PCR from urine sediment DNA
Authors: Woonbok Chung, Jolanta Bondaruk, Daniel D. Kim, Bogdan Czerniak, Jean-Pierre J. Issa
Journal: Cancer Research (2010)

Abstract Bladder cancer is the fifth most frequent human cancer and causes approximately 3% of all cancer-related deaths. DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone new cancer-related genes as well as a marker of the disease activity. Recently, we developed a high throughput genome wide methylation assay, Methylated CpG Island Amplification Microarray (MCAM). Using MCAM, we investigated methylation changes in about 8,000 genes in bladder tumors. Through this screening method and validation by bisulfite pyrosequencing, we have developed novel biomarkers for diagnosis and prognosis of bladder tumor. We characterized a group of genes that was found to be methylated in 80-90% of the tested bladder tumor samples. These candidate genes (DBC1, MYO3A, SOX11, SLC16A12, NPTX2, NKX6-2, A2BP1, PENK and CA10) were used to screen for bladder cancer in urine samples by quantitative methylation specific real time PCR, thus representing a non-invasive method for early detection. Based on these data, we established a panel of 6 biomarkers (MYO3A, SOX11, NKX6-2, PENK, CA10 and quantity of DNA in test urine) that can be used for bladder tumor screening in urine samples. The method showed 89.1 % sensitivity and 91.4 % specificity for detection of bladder tumor urines (n=128) compared to normal control urine (n=105) by 3 or more than 3 positive out of 6 biomarkers. Analyzing by stage of bladder tumors, 5 out of 5 (100 %) in Tis, 21 out of 29 (72 %) in Ta, 18 out of 19 (95 %) in T1, 57 out of 60 (95 %) in T2, 6 out of 6 (100 %) in T3 and 2 out of 2 (100 %) in T4 showed 3 or more than 3 positive out of 6 biomarkers. Thus, 83% of Tis-Ta-T1 stages and 95.6 % of T2-T3-T4 stages were detected in analyzed bladder tumor urines. This DNA methylation biomarkers panel will help the early detection and monitoring of bladder tumor patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4908.
11 OPERA-1 TRIAL: INTERIM ANALYSIS OF SAFETY AND ANTIVIRAL ACTIVITY OF TMC435 IN TREATMENT-NAIVE GENOTYPE 1 HCV PATIENTS
Authors: M. Manns, H. Reesink, C. Moreno, T. Berg, Y. Benhamou, Y. Horsmans, G. Dusheiko, R. Flisiak, P. Meyvisch, O. Lenz, V. Sekar, G. van't Klooster, K. Simmen, R. Verloes
Journal: Journal of Hepatology (2009)
CAN THE STATE SUPPRESS GENITO-URINARY DISEASES?
Authors: FERD. C. VALENTINE
Journal: JAMA (1900)

It is but meet that I preface this effort with my thanks to your chairman, for the compliment given me in his invitation to prepare a paper for this meeting. Never having made a special study of state medicine, I can not offer more than the outcome of practical experience, observation and thought on the devastations caused by the diseases which are the subject of my investigations. Over twenty years ago I strenuously advocated the registration and systematic examination of the unfortunates believed to be the principal disseminators of genito-urinary diseases. Subsequent study, however, and personal observation since then, especially in Europe, have shown me that the control of public prostitution, even if ideally carried out, can be but a small factor in the prevention of genito-urinary diseases. Ideal compliance with the law is indeed impossible, as the following considerations show. Five years ago there were 20,000 registered prostitutes in
The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver
Authors: Juan J Dı́az-Gil, Pedro L Majano, Manuel López-Cabrera, Vicente Sánchez-López, Carmen Rúa, Celia Machı́n, Carolina Trilla, Rafael Garcı́a-Cañero, Ricardo Moreno-Otero
Journal: Journal of Hepatology (2003)
From Asylum to Community: Mental Health Policy in Modern America
Authors: Carl C. Bell
Journal: JAMA (1991)

This book represents another effort at chronicling the process of deinstitutionalization that began after World War II. Unlike<i>Out of Bedlam</i>by Ann Braden Johnson (Basic Books, 1990), the text is neither cynical nor angry but, rather, matter-of-factly explains the role organized psychiatry and politics played in the process of moving patients from the asylum to the community. It is a well-documented historical perspective, drawing on organized psychiatric documents and governmental reports to describe what happened, rather than focusing on the external forces that shaped deinstitutionalization, as was done quite well in<i>Madness in the Streets</i>by Rael Jean Isaac and Virginia C. Armat (Free Press, 1990). The book begins with the cogent observation that the Second World War taught psychiatry that environmental stressors could precipitate mental illness, and, by using psychotherapy along with environmental changes, neurotic and more extreme symptoms could be arrested. As a result, psychodynamic psychiatrists became
Antiplatelet antibodies in childhood idiopathic thrombocytopenic purpura
Authors: Şlinasi Özsoylu, Adnan Karabent, Gülersu Irken, Murat Tuncer
Journal: American Journal of Hematology (1991)

Antiplatelet antibodies were shown by the Handin and Stossel method in the sera of all 103 patients with acute idiopathic thrombocytopenic purpura (ITP) and in 100 cases following recovery from it. These antibodies were also shown in the sera of all 46 patients with chronic ITP and 32 cases after recovery. The decrease in level of antiplatelet antibodies was significant in all these children following recovery (P less than 0.001 for acute ITP, P less than 0.05 for chronic ITP). Antiplatelet antibodies could be determined in 67 acute and 21 chronic ITP cases in thrombocytopenic phase and following recovery, which showed very significant decreases in levels in each case in a later period. Antiplatelet antibody levels corresponding to the thrombocytopenic phase and recovery in acute and chronic ITP were significantly higher than normal and thrombocytopenic control values (P less than 0.001 for each).
STUDIES ON MESCALINE VIII: PSYCHODYNAMIC OBSERVATIONS
Authors: HERMAN C. B. DENBER
Journal: American Journal of Psychiatry (1958)

Psychodynamic observations made during the mescaline-induced state in 124 patients are reviewed. Mescaline produces a "state of being" in which the clinical spectrum can range from sleep to rage and from normalcy to thoroughly disorganized mental states. Anxiety is considered the background upon which the mescaline experience evolves. One may consider the mescaline-induced state under three headings: 1. Hostility-aggression, 2. Sexuality, and 3. The transference. Various recurring symbolic gestures were noted, and many were frequently of a sexual nature. The primary role of anxiety is reviewed and some theoretical concepts presented. Much further work remains to be done.
DERMATITIS VENENATA FROM THE LACQUER ON THE BOXES OF MAH JONGG SETS
Authors: ERWIN P. ZEISLER
Journal: JAMA (1924)

The increasing popularity of mah jongg has brought to my attention a number of cases of dermatitis of the hands and face in which I have suspected that the irritating agent was the Japanese lacquer with which the mah jongg sets are varnished. In the subjoined case this was definitely proved to be the etiologic factor. <h3>REPORT OF CASE</h3> A man, aged 38, who had been under my care for several years with a mild ichthyosis and at various times had had an eczematoid ringworm of the feet, presented himself, Dec. 24, 1923, with a vesicular dermatitis of the right forearm. The diagnosis I made at this time was a plant dermatitis, as inquiry elicited the fact that he had ferns and other plants in his apartment. Under soothing local applications (calamine lotion) the eruption subsided in a few days. On the morning of December 30, I was called to
Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial
Authors: John M.S. Bartlett, Cassandra L. Brookes, Tammy Robson, Cornelis J.H. van de Velde, Lucinda J. Billingham, Fiona M. Campbell, Margaret Grant, Annette Hasenburg, Elysée T.M. Hille, Charlene Kay, Dirk G. Kieback, Hein Putter, Christos Markopoulos, Elma Meershoek-Klein Kranenbarg, Elizabeth A. Mallon, Luc Dirix, Caroline Seynaeve, Daniel Rea
Journal: Journal of Clinical Oncology (2011)

The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen.
A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use
Authors: Mei-Ling Blank, Lianne Parkin, Charlotte Paul, Peter Herbison
Journal: Kidney International (2014)

The magnitude of the suspected increase in risk of acute interstitial nephritis among proton pump inhibitor users is uncertain. Here, we conducted a nested case-control study using routinely collected national health and drug dispensing data in New Zealand to estimate the relative and absolute risks of acute interstitial nephritis resulting in hospitalization or death in users of proton pump inhibitors. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of proton pump inhibitor use between 2005 and 2009. Cases had a first diagnosis after cohort entry of acute interstitial nephritis confirmed by hospital discharge letter or death record, and renal histology (definite, 46 patients), or discharge letter or death record only (probable, 26 patients). Ten controls, matched by birth year and sex, were randomly selected for each case. In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (95% confidence interval) for current versus past use of proton pump inhibitors was 5.16 (2.21–12.05). The estimate was similar when all cases (definite and probable) and their corresponding controls were analyzed, and when potential confounders were added to the models. The crude incidence rates and confidence intervals per 100,000 person-years were 11.98 (9.11–15.47) and 1.68 (0.91–2.86) for current and past use, respectively. Thus, current use of a proton pump inhibitor was associated with a significantly increased risk of acute interstitial nephritis, relative to past use.
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates
Authors: Christian C. Yost, Mark J. Cody, Estelle S. Harris, Nathan L. Thornton, Alison M. McInturff, Mark L. Martinez, Nancy B. Chandler, Christopher K. Rodesch, Kurt H. Albertine, Cathy A. Petti, Andrew S. Weyrich, Guy A. Zimmerman
Journal: Blood (2009)
Carotid Artery Disease in NIDDM Diabetes
Authors: Anthony Chan, Kirk W Beach, Donald C Martin, D Eugene Strandness
Journal: Diabetes Care (1983)

A prospective study of 135 controls, 286 non-insulin-dependent diabetic patients, and 31 subjects with an elevated fasting plasma glucose was performed to assess the prevalence of high-grade carotid artery stenosis. The carotid artery evaluation was performed using an ultrasonic duplex scanner. When those patients with an elevated fasting plasma glucose and non-insulin-dependent diabetes were considered together, the prevalence was 8.2% as compared with 0.7% for the controls (P = 0.0007). Those risk factors found to be significantly related to the higher prevalence of carotid disease in the combined groups of patients included age, ratio of systolic blood pressure to diastolic blood pressure, plasma cholesterol, and cigarette smoking. These findings may be an explanation for the greater incidence of stroke in patients with diabetes mellitus.
Fatal Case of Encephalitis After Phenolphthalein Ingestion
Authors: A. C. Kendall
Journal: BMJ (1954)

TALC PNEUMOCONIOSIS BRISHr 1461 tions revealed no abnormality in the levels of his total and differential white count.His serum alkaline phosphatase, serum proteins, albumin/globulin ratio, serum calcium, P.C.V., and E.S.R. were within normal limits.His maxi- mum breathing capacity was 62.
Serum Alcohol Dehydrogenase, an Indicator of Intrahepatic Cholestasis
Authors: Esteban Mezey, Gilbert R. Cherrick, Peter R. Holt
Journal: New England Journal of Medicine (1968)

The activity of alcohol dehydrogenase, an enzyme present principally in liver tissue, was repetitively determined in the serums of 266 patients with hepatic and nonhepatic diseases. The enzyme was present only in patients with liver-cell necrosis. The level of serum activity reflected the extent of parenchymal necrosis, and in acute hepatitis the enzyme was present for as long as three weeks after onset of jaundice. Disappearance from the serum correlated with relief of intrahepatic cholestasis. In patients with hepatocellular necrosis and prolonged cholestasis persistent serum alcohol dehydrogenase activity was present while serum glutamic oxalacetic transaminase values fell close to normal. Only three of 40 patients with jaundice secondary to extrahepatic biliary obstruction had serum alcohol dehydrogenase elevation. These results indicate that serum activity is a specific reflection of hepatocellular necrosis, a good index of intrahepatic cholestasis and of value in the differential diagnosis of intrahepatic cholestasis and extrahepatic biliary obstruction.