tbuckley/cabot-search huggingface dataset:
Abstract 1723: Thiazolinediones (TZDs) mediate proliferation and cell cycle kinetics in ovarian cancer cells in a PPARγ-dependent and -independent manner
Authors: Linah F. Al-Alem, Chase R. Southard, Michael W. Kilgore, Thomas E. Curry
Journal: Cancer Research (2010)

Abstract Ovarian cancer is the leading cause of death in women with gynecological malignancies and is often called the ‘silent killer’. Thus, new treatment targets are constantly being investigated. PPARγ (Peroxisome Proliferator Activated Receptor gamma) is a nuclear transcription factor that has been implicated in several diseases. However, little is known about PPARγ in ovarian cancer. Recently, PPARγ agonists such as the thiazolinediones (TZDs) have been studied for their potential use as a therapeutic treatment for cancer. In the present study, we investigated the effect of the four TZDs: Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio), on cell proliferation and PPARγ expression in an ovarian cancer cell line: Ovcar3. Treatment with 10 μM CGZ or TGZ for 24 hours decreased proliferation, whereas Rosi and Pio had no effect. We observed that this decrease in Ovcar3 cell proliferation is due to a higher fraction of cells in the G0/G1 stage of the cell cycle. In order to assess whether this was mediated by PPARγ, we investigated the effect of TGZ and CGZ on PPARγ mRNA, protein expression and activity. As Rosi and Pio had no effect on proliferation, only CGZ and TGZ were further investigated. CGZ and TGZ increased PPARγ mRNA expression in Ovcar3 cells (6.9 and 18.1 fold respectively). However, levels of PPARγ protein expression did not correlate with mRNA levels. Moreover, luciferase reporter assays showed that neither of the TZDs increased PPARγ activity. Ovcar3 cells were transfected with a PPARγ overexpression vector (WT) or a mutant dominant negative form of PPARγ (DN). Both CGZ and TGZ increased PPARγ activity when the receptor was over-expressed. Interestingly, the over-expression of WT in unstimulated cells caused an increase in reporter activity, indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. Cells exhibited no changes in proliferation when transfected with the WT or DN forms of PPARγ. Also, the effect on proliferation was not impacted when CGZ or TGZ were added to the WT or DN transfected cells. These findings demonstrate that PPARγ agonists, CGZ and TGZ, stimulate PPARγ expression. However, the decrease in cell proliferation and increased cell cycle arrest seems to be due to both PPARγ dependent and independent mechanisms. These data suggest that the non-PPAR targets of TZDs need to be further investigated. (Supported by NIH RO1 CA 95609-01, and NCRR-P20-RR15592). 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 1723.
Maternal serum dioxin levels and birth outcomes in women of Seveso, Italy.
Authors: Brenda Eskenazi, Paolo Mocarelli, Marcella Warner, Wan-Ying Chee, Pier Mario Gerthoux, Steven Samuels, Larry L Needham, Donald G Patterson
Journal: Environmental Health Perspectives (2003)

2,3,7,8-Tetrachlorodibenzo-(italic)para(/italic)-dioxin (TCDD), a ubiquitous environmental contaminant, is associated with increased fetal loss and reduced birth weight in animal studies. In 1976, an explosion at a trichlorophenol plant near Seveso, Italy, resulted in the highest TCDD exposure known in human residential populations. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of women who resided in the most contaminated areas, zones A and B. We examined the relation of pregnancy outcome in 510 women (888 total pregnancies) to maternal TCDD levels measured in serum collected shortly after the explosion. Ninety-seven pregnancies (10.9%) ended as spontaneous abortions (SABs). There was no association of log(subscript)10(/subscript) TCDD with SAB [adjusted odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.6-1.2], with birth weight (adjusted beta = -4 g; 95% CI, -68 to 60), or with births that were small for gestational age (SGA) (adjusted OR = 1.2; 95% CI, 0.8-1.8). However, associations with birth weight (adjusted beta = -92 g; 95% CI, -204 to 19) and with SGA (adjusted OR = 1.4; 95% CI, 0.6-2.9) were stronger for pregnancies within the first 8 years after exposure. TCDD was associated with a 1.0-1.3 day nonsignificant adjusted decrease in gestational age and a 20-50% nonsignificant increase in the odds of preterm delivery. It remains possible that the effects of TCDD on birth outcomes are yet to be observed, because the most heavily exposed women in Seveso were the youngest and the least likely to have yet had a pregnancy.
TCTAP A-028 Comparison of Platelet Aggregation Before &amp; After Loading Dose of Prasugrel and Clopidogrel in Percutaneous Coronary Intervention in Adult Pakistani Coronary Artery Disease Patients
Authors: Ahmad Shahbaz, Ahmad Nouman, Khawar Mehdi, Muhammad Azhar
Journal: Journal of the American College of Cardiology (2014)
Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding
Authors: A Ptasinska, S A Assi, D Mannari, S R James, D Williamson, J Dunne, M Hoogenkamp, M Wu, M Care, H McNeill, P Cauchy, M Cullen, R M Tooze, D G Tenen, B D Young, P N Cockerill, D R Westhead, O Heidenreich, C Bonifer
Journal: Leukemia (2012)

The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML.
Textbook of Diagnostic Imaging
Authors: Lynne S. Steinbach
Journal: JAMA (1989)

Editors Charles Putman and Carl Ravin have coordinated an excellent review of diagnostic imaging utilizing the talents of 193 contributors from many North American academic institutions. The authors are highly regarded authorities in their fields. Following a section on fundamentals of diagnostic imaging, the textbook is organized by an organ system approach that includes the central nervous, pulmonary, gastrointestinal, genitourinary, musculoskeletal, and cardiovascular systems. There is also a large section devoted to aspects of the female patient that includes obstetric, fetal, and gynecologic sonography as well as mammography. In general, the sections are well organized with introductory chapters covering radiological techniques for evaluation of each organ system, followed by specific disease categories. Exceptional chapters include "Risks of Medical Imaging," "Central Nervous System Infection," "Orbital Neoplasms," "Introduction to Chest Radiography," "Diseases of the Mediastinum," "Infectious Pneumonias," "The Liver and Spleen," "The Pancreas," and the entire section on the genitourinary system. There
The Hawksley random zero sphygmomanometer: Measuring instruments are never perfect
Authors: S. J Ellis, P J Ellis
Journal: BMJ (1993)

Results of different studies examining accuracy of Hawksley random zero sphygmomanometer compared with standard mercury sphygnomanometer.Three groups presented results as the mean differences between the two instruments; the two others reported the range ofdifference Systolic Diastolic pressure (mm Hg) pressure Study Measurement given (mm Hg) Phase IV Phase V No of subjects Evans and Prior-2 Mean difference -1-2 -22 906
Group II subfamily secretory phospholipase A<sub>2</sub> enzymes: expression in chronic rhinosinusitis with and without nasal polyps
Authors: Z. Liu, X. Lu, H. Wang, X. J. You, Q. X. Gao, Y. H. Cui
Journal: Allergy (2007)

Background: Group II subfamily secretory phospholipases A 2 (sPLA 2 s) are the enzymes that can play a major role in inflammation. However, the presence of group II subfamily sPLA 2 s in human sinonasal mucosa and their roles in chronic rhinosinusitis (CRS) are not well known. The purpose of this study was to investigate the expression of group II subfamily sPLA 2 s in human sinonasal mucosa from controls and CRS patients with and without nasal polyps (NPs) and the regulation of expression by proinflammatory cytokines. Methods: Surgical samples were investigated by means of reverse transcriptase polymerase chain reaction (RT‐PCR) for evaluation of group II subfamily sPLA 2 s mRNA expression, and the presence and location of group II subfamily sPLA 2 s‐positive cells were analyzed by means of immunohistochemistry. Furthermore, nasal explant culture and quantitative RT‐PCR techniques were used to investigate the effect of interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α on group II subfamily sPLA 2 s mRNA production in sinonasal mucosa. Results: Messenger RNA expression of sPLA 2 ‐IIA, ‐IID, and ‐IIE was significantly upregulated in tissues from CRS patients compared with control tissues. Among CRS patients, patients without NPs showed significantly stronger expression in sinonasal mucosa than patients with NPs of sPLA 2 ‐IIA mRNA, and weaker expression of sPLA 2 ‐IIE mRNA. Immunohistochemistry revealed enhanced protein expression of type II sPLA 2 s and specific type IIA sPLA 2 in epithelial cells and submucosal glands in samples from CRS patients. Stronger type IIA sPLA 2 protein expression was found in samples from CRS patients without NPs when compared with NPs. Nasal explant culture experiments demonstrated that mRNA expression of sPLA 2 ‐IIA, ‐IID, and ‐IIE was dramatically induced by IL‐1β and TNF‐α. Conclusions: The expression of some members of group II subfamily of sPLA 2 s is upregulated in CRS and it may result from IL‐1β and TNF‐α overexpression. Different individual group II subfamily sPLA 2 s may play different roles in the pathogenesis of CRS with and without NPs.
The Charcoal T3 Ratio
Authors: Lewis E. Braverman
Journal: JAMA (1967)

In recent years, many tests of thyroid function have been described using liothyronine (T<sub>3</sub>) I131 and a variety of adsorptive substances such as red blood cells (RBCs)<sup>1</sup>and resins.<sup>2-4</sup>More recently, Herbert et al<sup>5</sup>have utilized hemoglobin-coated charcoal as the adsorptive material and described a rapid, easily performed liothyronine I 131 uptake test. This test has been modified and simplified using liothyronine I 125, and evaluated in the sera of 238 subjects. <h3>Methods</h3> The majority of the patients were seen in the Endocrine Clinic and on the wards of the St. Elizabeth's Hospital. Thyroid status was evaluated by one or more of the following tests: protein-bound iodine (PBI), 24-hour sodium iodide I 131 uptake, and basal metabolic rate (BMR). Patients with nonthyroidal illness were euthyroid but had a wide variety of acute and chronic illness and were taking no medication known to affect thyroxine (T<sub>4</sub>
Breastfeeding and risk of breast cancer: a meta-analysis of published studies
Authors: M. O. Bernier
Journal: Human Reproduction Update (2000)

Evidence in favour of an association of breastfeeding with a breast cancer risk reduction remains limited and inconsistent. To evaluate the relation between breastfeeding and breast cancer, a meta-analysis based on a review of the literature was carried out, using as variables ever/never breastfeeding and duration of breastfeeding. Menopausal status at the time of diagnosis of breast cancer was considered to be a potential effect modifier. Only case-control studies could be included in the final analysis. A slight but significant decreased risk of breast cancer was observed in ever breastfeeding, compared with never breastfeeding parous women, using both the fixed and random-effect models. This decrease was more pronounced in non-menopausal women at the time of diagnosis of breast cancer and in long-term breastfeeding women. Hence, breastfeeding appeared to be a protective factor but was of small magnitude compared with other known risk factors for breast cancer. Whether this result should imply a modification in the attitude of both health care providers and women towards breastfeeding, which represents one of the few identified protective factors which is under the control of the mother, and is thus (theoretically) modifiable, remains questionable.
Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.
Authors: M Takara, I Komiya, Y Kinjo, T Tomoyose, S Yamashiro, H Akamine, M Masuda, N Takasu
Journal: Diabetes Care (2000)

We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population.We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis.The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects.An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.
Ouabain Pharmacokinetics in Dog and Man
Authors: RICHARD SELDEN, THOMAS W. SMITH, William Findley
Journal: Circulation (1972)

The pharmacokinetics of the relatively polar and rapidly acting cardiac glycoside ouabain (G-strophanthin) were studied in dogs and human subjects by the use of a newly devised radioimmunoassay technic. This method had high specificity and a sensitivity of less than 0.1 ng of ouabain per ml of plasma or urine. After administration of a single intravenous dose, the plasma ouabain concentration fell rapidly in both dogs and humans. After 7 hours, a phase of exponential decline was reached which had a half-life of 18 hours in dogs and 21 hours in normal human subjects. Repeated intravenous administration of ouabain to human subjects for 9 consecutive days resulted in the establishment of a plateau of plasma concentration and urinary excretion after 4-5 days, confirming plasma and urinary half-lives in the 19-24-hour range. The mean ratio of renal clearance of ouabain to that of creatinine was 0.81 in the human subjects. The plasma half-life of ouabain determined in these studies is in good agreement with previous observations of the half-life of dissipation of positive inotropy and of slowing of ventricular response to atrial fibrillation after ouabain administration.
Court Responses to Withholding or Withdrawing Artificial Nutrition and Fluids
Authors: John J. Paris
Journal: JAMA (1985)

Three state court decisions since 1983 that approved the withholding or withdrawal of artificial feeding are discussed. In Barber v. Superior Court, the California Court of Appeal dismissed a murder indictment against two physicians who, at the request of the family, had removed a comatose man's respirator and intravenous (IV) feeding lines. The ruling, based on a "proportionate-disproportionate" benefit standard, marked the first time an appellate court equated discontinuation of IV feeding with removal of a respirator. The Massachusetts Appeals Court, in In re Hier, used a "substituted judgement" standard to decide that an aged patient who had repeatedly pulled out her gastrostomy tube need not undergo surgery to reinsert it. The New Jersey Supreme Court, in In re Conroy, was the first state supreme court to rule that artificial feeding may be withheld from an incompetent patient if it is disproportionately burdensome.
Intravascular coagulation in acute liver failure in rats and its treatment with antithrombin III.
Authors: K Fujiwara, I Ogata, Y Ohta, K Hirata, Y Oka, S Yamada, Y Sato, N Masaki, H Oka
Journal: Gut (1988)

Liver damage was induced in rats by injection of dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). Fibrin clots were observed in the hepatic sinusoids at 12 hours and soluble fibrin monomer complexes were markedly detected at 24 hours only in the rats given DMN. When antithrombin III concentrate was infused at 12 hours there was a dose dependent improvement of the values of serum total bilirubin, SGPT, prothrombin time, peripheral platelet count, and plasma fibrinogen and coagulation factor VIIIC and of the histological degree of liver injury at 24 hours in the DMN group. The CCl4-group showed no such improvement. Intravascular coagulation may complicate the course of certain types of acute liver injury and contribute to its aggravation in rats. Under such circumstances, treatment with antithrombin III concentrate would be beneficial.
Abuse At Work Drains People, Money, And Medical Workplace Not Immune
Authors: Teri Randall
Journal: JAMA (1992)

ABUSE in the workplace can plague a staff's morale, productivity, and health. In some recent studies, employees across all professions have reported that they experience abuse at work as much or more often than they do at home, and that this abuse contributes to a host of medical problems. For the medical profession, workplace abuse is a double-edged sword. Not only must it treat the many stress-related illnesses caused by abuse, and intervene to prevent their recurrence, but it must also cope with abuse that happens between its own professionals. The medical workplace, despite its dedication to health and well-being, is not immune from abusive staff members and the toll they exact on the people they work with. A recent survey of medical students, in which a high proportion reported suffering psychopathological consequences from abuse during their training (<i>JAMA</i>. 1991;267:692-694, 738), and the temporary resignation of Stanford neurosurgeon Frances K.
Opioid Side Effects — Mechanism-Based Therapy
Authors: Charles Berde, Samuel Nurko
Journal: New England Journal of Medicine (2008)

Opioid analgesics generate numerous side effects that complicate their use in postoperative care,1 in the treatment of sickle cell vaso-occlusive episodes, and in the treatment of pain associated with advanced cancer and other life-shortening illnesses.2 These side effects include sedation, respiratory depression, impaired cognition, nausea and vomiting, loss of appetite, pruritus, urinary retention, impaired orthostatic tolerance, and (perhaps most commonly of all) ileus and constipation. The therapies that are typically used for opioid side effects are rarely evidence-based and are often ineffective.2 In this issue of the Journal, Thomas et al.3 describe the results of a multicenter trial of methylnaltrexone . . .
Why costs of consultations in general practice vary.
Authors: S E Twaddle, A M Porter, J G Howie, J F Forbes
Journal: BMJ (1990)

These findings indicate that the management ofpatients found to have a dyskaryotic smear does not protect completely against subsequent invasive cancer.Three of the five cases of invasive cancer were in women aged under 35.Over the past decade mortality and incidence rates for cancer of the cervix have increased in younger women, although the rates in those under 25 are still very low compared with those in older women.2'Robertson et al described 10 cases of invasive cancer of the cervix occurring in their study of 1781 women identified with a dyskaryotic smear over 20 years.12It was not clear, however, whether those cases represented a significant excess or the number to be expected on the basis of the background rate or, indeed, a deficit as no statistical criteria were applied.Our criteria for reversion to normal were more rigorous than those reported by some workers.We checked on the subsequent outcome of these patients after a further two years.Fifty five of the 157 patients classified as having reverted to normal (35%) had a record of a subsequent smear.In 53 out of these 55 women this smear was reported as negative after a mean of 17 months (range 1-47 months).Twenty one of these 53 patients had two or more negative smears subsequently.This suggests that when several adequate repeat smears remain negative over more than 18 months regression may be real rather than apparent.Almost two thirds of women, however, had no further smears, and there may have been a selection bias in the 35% who continued to have smears despite being discharged.The poor reliability of a single negative smear to suggest apparent regression is shown by the finding that 22% of these women (83/37 1) had a follow up smear showing dyskaryosis.When the negative smear was also inadequate this figure increased to 40% (22/55).Our study clearly indicates the importance of following up women with dyskaryotic smears and especially those with a smear showing moderate dyskaryosis or two smears showing mild dyskaryosis.We do not wish to make recommendations about the exact details of how this follow up should be conducted in the current state of knowledge.There is no experimental evidence that prognosis is improved by colposcopic compared with cytological surveillance.We endorse the inter- collegiate working party's proposal for a randomised controlled trial to examine costs and benefits of these two alternatives.
Pseudotumor Cerebri Secondary to Lithium Carbonate
Authors: Robert F. Saul
Journal: JAMA (1985)

Three patients were initially seen with headache, blurred vision, and papilledema while taking lithium carbonate for their respective bipolar affective disorder. A diagnosis of pseudotumor cerebri was made in each case when a thorough evaluation revealed only elevated intracranial pressure. Two of the patients had complete resolution of their symptoms and papilledema after discontinuing use of the drug. Increased intracranial pressure with papilledema persisted in the third patient when she failed to adjust psychiatrically, necessitating continuance of the lithium carbonate therapy. A history of lithium carbonate ingestion should be sought in patients with the syndrome of pseudotumor cerebri. All patients receiving this drug should have a regular funduscopic examination. (<i>JAMA</i>1985;253:2869-2870)