tbuckley/cabot-search huggingface dataset:
Inhibition of Histone Deacetylation Does Not Block Resilencing of p16 after 5-Aza-2′-Deoxycytidine Treatment
Authors: Gerda Egger, Ana M. Aparicio, Sonia G. Escobar, Peter A. Jones
Journal: Cancer Research (2007)

Abstract Epigenetic drugs are in use in clinical trials of various human cancers and are potent at reactivating genes silenced by DNA methylation and chromatin modifications. We report here the analysis of a set of normal fibroblast and cancer cell lines after combination treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) and the histone deacetylase inhibitor 4-phenylbutyric acid (PBA). Low doses of the drug combination caused cell cycle arrest, whereas high doses induced apoptosis in T24 bladder carcinoma cells. Both p16 (CDKN2A/INK4) and p21 (CIP1/SDI1/WAF1) expression were induced to similar levels in normal and cancer cells in a dose-dependent fashion after combination treatments. We detected a distinct increase of histone H3 acetylation at lysine 9/14 near the transcription start sites, in both LD419 normal fibroblasts and T24 bladder carcinoma cells, whereas the acetylation changes in the p21 locus were less apparent. Interestingly, the levels of trimethylation of histone H3 on lysine 9, which usually marks inactive chromatin regions and was associated with the p16 promoter in silenced T24 cells, did not change after drug treatments. Furthermore, we provide evidence that the remethylation of the p16 promoter CpG island in T24 cells after 5-aza-CdR treatment cannot be halted by subsequent continuous PBA treatment. The p16 gene is resilenced with kinetics similar to 5-aza-CdR only–treated cells, which is also marked by a localized loss of histone acetylation at the transcription start site. Altogether, our data provide new insights into the mechanism of epigenetic drugs and have important implications for epigenetic therapy. [Cancer Res 2007;67(1):346–53]
Forearm blood flow responses to a nitric oxide synthase inhibitor in patients with treated essential hypertension
Authors: A. Calver, J. Collier, P. Vallance
Journal: Cardiovascular Research (1994)

Journal Article Forearm blood flow responses to a nitric oxide synthase inhibitor in patients with treated essential hypertension Get access Alison Calver, Alison Calver Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom: A Calver, J Collier, P Vallance. Correspondence to Dr Calver. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joe Collier, Joe Collier Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom: A Calver, J Collier, P Vallance. Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick Vallance Patrick Vallance Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom: A Calver, J Collier, P Vallance. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 11, November 1994, Pages 1720–1725, https://doi.org/10.1093/cvr/28.11.1720 Published: 01 November 1994 Article history Received: 05 April 1994 Accepted: 16 August 1994 Published: 01 November 1994
Counterpoint: Do People With Diabetes Benefit From Coronary Calcium Scans?
Authors: Robert Detrano
Journal: Diabetes Care (2003)

Admission of ignorance is the first step toward knowledge . —Benjamin Disraeli

Cardiovascular disease is responsible for most death and disability associated with diabetes. Those with diabetes suffer two to four times more myocardial infarctions, strokes, and sudden deaths than those without this condition (1–3). The medical community has recognized the increased vulnerability of these patients by assigning diabetes “coronary heart disease equivalent” status in its prevention guidelines (4). Since coronary syndromes tend to be clinically atypical and difficult to diagnose in diabetes, noninvasive approaches in asymptomatic or mildly symptomatic subjects have been proposed for screening and diagnosis (5,6).

Pathologic studies have demonstrated a strong correlation between the presence of coronary calcium and the amount of atheromatous plaque (7). Since sensitive and noninvasive radiographic techniques are capable of detecting and quantitating calcium, calcium screening is an obvious candidate for screening for subclinical atherosclerosis. Morrison (8) has defined the purpose of screening for chronic diseases. “Screening for disease control can be defined as the examination of asymptomatic people in order to classify them as likely or not likely to have the disease that is the object of screening […]. The goal of screening is to reduce morbidity and mortality from disease among the people screened by early treatment of the cases discovered.”

If one accepts this definition, one can then surmise that three distinct …
Opsonic Activity of Human Ascitic Fluid: A Potentially Important Protective Mechanism Against Spontaneous Bacterial Peritonitis
Authors: Bruce A. Runyon, Richard L. Morrissey, John C. Hoefs, Frederic A. Wyle
Journal: Hepatology (1985)

The opsonic activity of 60 ascitic fluids from 47 patients was measured using a standard opsonophagocytic assay. Curve analysis of the opsonic activity compared to the ascitic fluid concentration of total protein, total hemolytic complement, C3 and C4 yielded correlation coefficients of 0.84 (p less than 0.001), 0.84 (p less than 0.001), 0.94 (p less than 0.001) and 0.92 (p less than 0.001), respectively. There appeared to be a threshold of concentration for each protein below which there was no killing of bacteria. Cirrhotic ascites had significantly (all p less than 0.001) lower concentrations of total protein and complement and less opsonic activity than noncirrhotic ascites (including malignant, cardiac and miscellaneous types). Perhaps it is the dilution of crucial antimicrobial proteins below a threshold which predisposes to spontaneous bacterial peritonitis.
Frequency of Drug-Resistant Mycobacteria
Authors: Charles Z. Lebowitz
Journal: JAMA (1985)

<h3>To the Editor.—</h3> A recent study of epidemic drug-resistant tuberculosis among the homeless<sup>1</sup>helps to correct any misunderstanding that this phenomenon in the United States is exclusively an ethnic and racial one. In the past, its occurrence among ethnic-racial groups has received prominent attention, as for example among Mexican-Americans in southern Texas, among Vietnamese and other Asian immigrants in the state of Washington and in Canada, and among newly admitted Haitian immigrants in Florida. By contrast, at various times other studies have attributed a prominent influence to local circumstances and to certain nonethnic characteristics of populations in which drug-resistant tuberculosis has been identified. In Hawaii, for example,<sup>2</sup>between 1977 and 1981, with a high tuberculosis rate and strict immigration health policies, only 4.7% of tuberculous isolates were reported to be primary drug-resistant and 5.3% secondarily resistant, despite a heavy Oriental immigration. Variable frequencies of such drug resistance have
Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non–Small Cell Lung Cancer Patients (SAKK 19/05 trial)
Authors: Anca Franzini, Florent Baty, Ina I. Macovei, Oliver Dürr, Cornelia Droege, Daniel Betticher, Bogdan D. Grigoriu, Dirk Klingbiel, Francesco Zappa, Martin H. Brutsche
Journal: Clinical Cancer Research (2015)

We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non-small cell lung cancer (NSCLC) patients.Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome.Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001).We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response.
Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice
Authors: Giuseppina Caligiuri, Antonino Nicoletti, Bruno Poirier, Göran K. Hansson
Journal: Journal of Clinical Investigation (2002)

Atherosclerosis is characterized by vascular inflammation and associated with systemic and local immune responses to oxidized LDL (oxLDL) and other antigens. Since immunization with oxLDL reduces atherosclerosis, we hypothesized that the disease might be associated with development of protective immunity. Here we show that spleen-associated immune activity protects against atherosclerosis. Splenectomy dramatically aggravated atherosclerosis in hypercholesterolemic apoE knockout (apoE°) mice. Transfer of spleen cells from atherosclerotic apoE° mice significantly reduced disease development in young apoE° mice. To identify the protective subset, donor spleen cells were divided into B and T cells by immunomagnetic separation before transfer. Protection was conferred by B cells, which reduced disease in splenectomized apoE° mice to one-fourth of that in splenectomized apoE° controls. Protection could also be demonstrated in intact, nonsplenectomized mice and was associated with an increase in antibody titers to oxLDL. Fewer CD4+ T cells were found in lesions of protected mice, suggesting a role for T-B cell cooperation. These results demonstrate that B cell–associated protective immunity develops during atherosclerosis and reduces disease progression.
INFECTIOUS PAPILLOMATOSIS OF RABBITS
Authors: Richard E. Shope, E. Weston Hurst
Journal: The Journal of Experimental Medicine (1933)

A papilloma has been observed in wild cottontail rabbits and has been found to be transmissible to both wild and domestic rabbits. The clinical and pathological pictures of the condition have been described. It has been found that the causative agent is readily filtrable through Berkefeld but not regularly through Seitz filters, that it stores well in glycerol, that it is still active after heating to 67°C. for 30 minutes, but not after heating to 70°C., and that it exhibits a marked tropism for cutaneous epithelium. The activities and properties of the papilloma-producing agent warrant its classification as a filtrable virus. Rabbits carrying experimentally produced papillomata are partially or completely immune to reinfection and, furthermore, their sera partially or completely neutralize the causative virus. The disease is transmissible in series through wild rabbits and virus of wild rabbit origin is readily transmissible to domestic rabbits, producing in this species papillomata identical in appearance with those found in wild rabbits. However, the condition is not transmissible in series through domestic rabbits. The possible significance of this observation has been discussed. The virus of infectious papillomatosis is not related immunologically to either the virus of infectious fibroma or to that of infectious myxoma of rabbits.
Testicular Xenografts: A Novel Approach to Study Cytotoxic Damage in Juvenile Primate Testis
Authors: Kirsi Jahnukainen, Jens Ehmcke, Stefan Schlatt
Journal: Cancer Research (2006)

Abstract The underlying primary damage to the testis caused by chemotherapeutic regimens during childhood is largely unknown. Xenografting of monkey testes was successfully applied in maturation of juvenile testis to the point of complete spermatogenesis. This allows us to manipulate developing primate testis without direct treatment of patients. This new model is validated establishing the effects of cytotoxic treatment in the immature primate testis. Male castrated nude mice received eight s.c. grafts of juvenile monkey testicular tissue and, 28 weeks later, were injected with busulfan (38 mg/kg, i.p.) or vehicle. Graft numbers, size, and histology were examined. Grafts showed pubertal induction of spermatogenesis to the level of pachytene spermatocytes at point of busulfan treatment and further progressed to the level of round spermatids in control samples at 4 weeks. Busulfan treatment caused a statistically significant decrease in the number of seminiferous tubules containing germ cells. Type B spermatogonia and more advanced stages of spermatogenesis were depleted. A statistically significant decrease to pretreatment level was observed in the number of type A pale and centrally located spermatogonia. Busulfan did not affect type A dark spermatogonia. Occasionally, elongating spermatids were detected in busulfan-treated grafts. Observations show that busulfan selectively destroys differentiating spermatogonia whereas some of the spermatocytes present at the moment of cytotoxic insult are able to continue differentiation. Data indicate that xenografting of testicular monkey tissue is a valid approach to detect the busulfan-induced germ cell damage and serves as a powerful experimental tool to study cytotoxic effects in developing primate testis. (Cancer Res 2006; 66(7): 3813-8)
Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system
Authors: C L H Snozek, J A Katzmann, R A Kyle, A Dispenzieri, D R Larson, T M Therneau, L J Melton, S Kumar, P R Greipp, R J Clark, S V Rajkumar
Journal: Leukemia (2008)
ANALYSIS OF THE PROTEINS OF RAT SERUM BY STARCH ELECTROPHORESIS AND BY CATIONIC DETERGENT ANALYSIS
Authors: Ralph F. Jacox
Journal: The Journal of Experimental Medicine (1959)

A protein of unusual characteristics has been identified in normal rat sera by electrophoretic separation at pH 8.6, followed by precipitation of each fraction with a cationic detergent. This protein, which is closely identified with albumin after electrophoresis at pH 8.6, precipitates with cationic detergent at a low pH in contrast to albumin which precipitates with detergent only at a high pH. This protein has characteristics of a globulin and is designated as a "fast alpha fraction." This fraction and albumin are present in about equal amounts in sera of normal rats. A separation of the fast alpha fraction can be made by electrophoresis in an acetate buffer of pH 4.25 and by precipitation according to a modified Cohn, cold-alcohol technique. A protein of similar characteristics has not been found in either human or rabbit sera studied by the same method of electrophoresis and subsequent sub-fractionation with cationic detergent.
Major Players in Unique New Huddle With Goal of Developing Better Strategies for AIDS Research
Authors: Paul Cotton
Journal: JAMA (1993)

MEETINGS next month may tell how much talk of change in AIDS research will translate into action. A new open-mindedness has apparently blossomed since the presentation of disheartening reports at the Ninth International Conference on AIDS, held in Berlin, Germany, in June. Some of those reports deflated hopes for what were promising new drugs, others underscored doubts about what had bordered on dogma about the value of early intervention with antiretroviral drugs and combinations of those agents. Those who had crowed about how much has been learned are now acknowledging that most of the most basic questions remain unanswered. At the same time, there is renewed interest in trying to restore, or at least augment, the damaged immune system, even in patients during the latest stages of human immunodeficiency virus (HIV) disease, an area of research that has been overshadowed since the advent of nucleoside analogue antiretrovirals in the late
Pulsatile Administration of Low-Dose Gonadotropin-Releasing Hormone
Authors: David S. Miller, Robert R. Reid, Nancy S. Cetel, Robert W. Rebar, Samuel S. C. Yen
Journal: JAMA (1983)

We administered pulsatile low doses of gonadotropin-releasing hormone (GnRH) (1 to 5 micrograms) to patients whose anovulation was caused by relative and absolute deficiency of endogenous GnRH. Eight such patients, including one with previous pituitary stalk transection, were treated during a total of 23 cycles; pulses of GnRH were administered via a portable pump every 96 or 120 minutes. Activation of pituitary-ovarian function with orderly development of a single dominant follicle, a luteinizing hormone surge, and ovulation occurred in 20 of the 23 cycles. The other three cycles were anovulatory. All patients responded, and five (62%) of the eight conceived, for a total of seven pregnancies and four full-term deliveries of normal infants. This study demonstrates that small pulsatile doses of GnRH can activate cyclic pituitary-ovarian function in hypogonadotropin-acyclic women and induce ovulation resulting in pregnancy and live birth.
Large molecule fraction of plasma separated with polyethylene glycol in treatment of chronic relapsing thrombotic thrombocytopenic purpura
Authors: Masahiro Fujita, Kazuhiko Ito, Tetsuji Koyama, Kazuko Shino, Mihoko Norioka, Saburo Kashii, Hiroshi Kawamoto, Sumie Monden, Eizo Kakishita, Minoru Okuma
Journal: American Journal of Hematology (1995)

Abstract Plasma exchange and plasma infusion are effective in the treatment of patients with thrombotic thrombocytopenic purpura (TTP). It has been proposed that some component in normal plasma may be deficient in TTP patients. In this experiment normal plasma was fractionated and an effective fraction for the treatment of TTP was sought. Plasma was fractionated with 5% polyethylene glycol and a large molecule fraction was obtained which was composed mainly of proteins and lipoproteins with molecules larger than that of IgG. The fraction was dissolved in physiological saline and infused in two patients with chronic relapsing TTP who had been successfully treated periodically with plasma infusion. Peripheral platelet counts and serum LDH levels were measured, and the efficacy of the treatment was assessed. Infusion of the large molecule fraction elevated platelet counts and lowered the LDH level. However, the efficacy of the large molecule fraction was 25 to 50% that of plasma. Components in the fraction may have been inactivated partially during preparation. We propose that the large molecule fraction contains factors which are effective in some patients with TTP. © 1995 Wiley‐Liss, inc.
New hygiene law aims to reduce infections in German hospitals
Authors: N. Stafford
Journal: BMJ (2011)

Germany’s ruling coalition headed by Chancellor Angela Merkel is planning a new law that will require hospitals to improve overall hygiene standards, which some experts believe often fall below minimum requirements and lead each year to thousands of avoidable infections and deaths.

A draft bill is expected to be introduced by March in the Bundestag, the lower house of parliament, and approved by summer, said Jens Spahn, a Bundestag member who is a health expert within Chancellor Merkel’s Christian Democratic Union (CDU) party.

The ruling coalition and the federal Ministry of Health believe that some …
Idiopathic Esophageal Varices with Longitudinal Erosion
Authors: Y. Motoo, T. Okai, H. Ohta, O. Matsui, N. Sawabu
Journal: Endoscopy (1989)

A 60-year-old man with idiopathic esophageal varices is presented. Endoscopy and endoscopic ultrasonography clearly demonstrated a longitudinal erosion on one of two straight varices. There was no evidence of portal hypertension, and no abnormality in the superior vena cava system. Peritoneoscopy and liver biopsy were normal. These varices with longitudinal erosion represent unique endoscopic findings as compared with previously reported cases. There has been no variceal bleeding during a 6-year follow-up.
Small Cell Carcinoma of the Urinary Bladder
Authors: I. Trias, I. Trias, F. Algaba, F. Algaba, E. Condom, E. Condom, I. Espa&ntilde;ol, I. Espa&ntilde;ol, J. Segu&iacute;, J. Segu&iacute;, I. Orsola, I. Orsola, H. Villavicencio, H. Villavicencio, X. Garc&iacute;a del Muro, X. Garc&iacute;a del Muro
Journal: European Urology (2001)
Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients
Authors: Ataru Taniguchi, Mitsuo Fukushima, Masahiko Sakai, Kumpei Tokuyama, Itaru Nagata, Akiko Fukunaga, Hiroyuki Kishimoto, Kentaro Doi, Yukio Yamashita, Toshifumi Matsuura, Naomi Kitatani, Takahide Okumura, Shoichiro Nagasaka, Shigeo Nakaishi, Yoshikatsu Nakai
Journal: Metabolism (2001)
Aldosteronism in Hypertension
Authors: RICHARD F. SPARK
Journal: Annals of Internal Medicine (1968)

Hyperaldosteronism causes the hypertension and metabolic abnormalities characteristic of primary aldosteronism. Hyperaldosteronism does not cause the hypertension of patients with secondary aldosteronism but may be responsible for certain electrolyte abnormalities generally associated with aldosterone excess. In view of this, elimination of excess aldosterone either by adrenalectomy or as reported here by pharmacologic blockade with high dose (400 mg/day), long-term (3 to 5 weeks) spironolactone corrects both the hypertension and metabolic abnormalities of primary aldosteronism but only reverses the metabolic abnormalities and does not relieve the hypertension of secondary aldosteronism. Thus, preoperative treatment with high-dose, long-term spironolactone therapy accurately predicts the response that might be expected after adrenal surgery.