tbuckley/cabot-search huggingface dataset:
Bisphenol A and Its Analogues Activate Human Pregnane X Receptor
Authors: Yipeng Sui, Ni Ai, Se-Hyung Park, Jennifer Rios-Pilier, Jordan T. Perkins, William J. Welsh, Changcheng Zhou
Journal: Environmental Health Perspectives (2012)

Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. We investigated the mechanism by which BPA interacts with and activates PXR and examined selected BPA analogues to determine whether they bind to and activate PXR. Cell-based reporter assays, in silico ligand-PXR docking studies, and site-directed mutagenesis were combined to study the interaction between BPA and PXR. We also investigated the influence of BPA and its analogues on the regulation of PXR target genes in human LS180 cells. We found that BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity. We identified key residues within hPXR's ligand-binding pocket that constitute points of interaction with BPA. We also deduced the structural requirements of BPA analogues that activate hPXR. BPA and its analogues can also induce PXR target gene expression in human LS180 cells. The present study advances our understanding of the mechanism by which BPA interacts with and activates human PXR. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans.
Phase I Dose Escalation Study of the Anti–Insulin-Like Growth Factor-I Receptor Monoclonal Antibody CP-751,871 in Patients with Refractory Solid Tumors
Authors: Paul Haluska, Heather M. Shaw, Gretchen N. Batzel, Donghua Yin, Julian R. Molina, L. Rhoda Molife, Timothy A. Yap, M. Luisa Roberts, Amarnath Sharma, Antonio Gualberto, Alex A. Adjei, Johann S. de Bono
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871. Experimental Design: Using a rapid dose escalation design, patients with advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v. on day 1 of each 21-day cycle. Pharmacokinetic evaluation was done in all treatment cohorts during cycles 1 and 4. Results: Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated γ-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability. There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and ∼2-fold accumulation on repeated dosing in 21-day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels. Conclusions: CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At the maximal feasible dose of 20 mg/kg, there was a moderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.
Virulence of Entamoeba histolytica trophozoites. Effects of bacteria, microaerobic conditions, and metronidazole.
Authors: R Bracha, D Mirelman
Journal: The Journal of Experimental Medicine (1984)

The association of axenically grown trophozoites of Entamoeba histolytica strains HK-9 or HM-1:IMSS with various types of gram-negative bacteria for relatively short periods markedly increased their virulence, as evidenced by their ability to destroy monolayers of tissue-cultured cells. Interaction of trophozoites with bacteria that were heat inactivated, glutaraldehyde fixed, or disrupted by sonication, or bacteria treated with inhibitors of protein synthesis, did not augment amebic virulence. Lethally irradiated bacteria, however, retained their stimulative properties and trophozoites that ingested bacteria were protected from the toxic effects of added hydrogen peroxide. An increase in virulent properties of amebae was also found in experiments carried out under microaerobic conditions (5% O2, 10% CO2). The augmentation of amebic virulence due to association with bacteria was specifically blocked by metronidazole, but not by tetracycline or aminoglycosides, and the rate of metronidazole uptake in stimulated trophozoites was two to three times higher. The results obtained suggest that virulence of axenically grown E. histolytica trophozoites may depend to a considerable extent on the cell's reducing power. Both microaerobic conditions and the association with bacteria apparently stimulate the electron transport system of the ameba. Bacteria may function as broad range scavengers for oxidized molecules and metabolites through the contribution of enzymatic systems, components, or products.
TCT-210 Optimized Immediate Angiographic Result After Percutaneous Coronary Intervention for Chronic Total Occlusion Is Associated With Lower Restenosis Rates. A Single Centre Experience
Authors: Karl ISAAZ, Antoine GERBAY, Jérémy TERREAUX, Khalid TAMMAM, Hazem Khamis, Laure Richard, Alexis Cerisier, Michel Lamaud, Antoine Da Costa
Journal: Journal of the American College of Cardiology (2014)
Tumors of the Chest.
Authors: John H. Kennedy
Journal: JAMA (1963)

Dr. Kinsella's worthwhile monograph reflects a long personal experience with thoracic neoplasms, and the illustrative case material has been well chosen from an abundant clinical experience. The author has written in a pleasing, informal style of a subject he knows well. It is unfortunate that, considered as a prose piece, this work is in need of further editing, as this need tends to divert the reader from the subject matter. W. H. Auden wrote, "There is one evil that concerns literature which should never be passed over in silence but be continually publicly attacked, and that is corruption of the language...." The dust jacket alleges this monograph to be the "first and only atlas of chest tumors on the market today." This is somewhat misleading, as the<i>Fasicles of Tumor Pathology</i>published by the Armed Forces Institute of Pathology still constitute the most authoritative source material on thoracic neoplasms. Unfortunately,
The risk of childhood cancer from intrauterine and preconceptional exposure to ionizing radiation.
Authors: R Wakeford
Journal: Environmental Health Perspectives (1995)

The findings of studies investigating whether exposures to ionizing radiation before birth, either pre- or post-conception, increase the risk of childhood cancer have provoked much scientific controversy. An epidemiological association between the abdominal exposure of pregnant women to diagnostic X-rays and childhood cancer was first reported in the 1950s, while an association between the recorded dose of radiation received occupationally by fathers before the conception of their offspring and childhood leukemia was reported only recently in 1990. The scientific interpretation of these particular statistical associations is by no means straightforward, but the latest analyses of intrauterine irradiation and childhood cancer indicate that a causal inference is likely. Scientific committees have adopted risk coefficients for the intrauterine exposure of somatic tissues, which for childhood leukemia are comparable to those accepted for exposure in infancy, although questions remain about the level of risk of childhood solid tumors imparted by exposure to radiation in utero and shortly after birth. In contrast, the association between paternal preconceptional radiation dose and childhood leukemia has not been confirmed by studies using objectively determined doses. The original association has been found to be restricted to children born in one village, it does not extend to cancers other than leukemia, and it is markedly inconsistent with the established body of knowledge on radiation-induced hereditary disease. A causal interpretation of this association has effectively been abandoned by scientific authorities.
SOME NEW INSTRUMENTS.
Authors: FRANK ALLPORT
Journal: JAMA (1901)

An annoying feature of eye and ear work in a general hospital is the lack of concentration of instruments, drugs, appliances, etc., necessitating many delays incident to nurses or internes going from ward to ward in search of needed articles. I have endeavored to obviate this difficulty by designing an eye and ear case for hospital work which will contain practically all that is essential for ordinary service. The case is constructed of nickel-plated copper. It has a strong handle, making it easy of transportation from ward to ward. It has a cover for protecting it from dirt. The top compartment is divided into large spaces for holding bulky objects, such as head mirrors, insufflators, tuning forks, etc., and small places for holding solutions, ointments, cotton, etc. It has a large drawer also for holding bulky objects, and a small drawer for holding knives, scissors, forceps, etc. In my own
α-Adducin polymorphisms and renal sodium handling in essential hypertensive patients
Authors: Paolo Manunta, Daniele Cusi, Cristina Barlassina, Marco Righetti, Chiara Lanzani, Marco D’Amico, Laura Buzzi, Lorena Citterio, Paola Stella, Rodolfo Rivera, Giuseppe Bianchi
Journal: Kidney International (1998)
Progression of Early Carotid Atherosclerosis Is Only Temporarily Reduced After Antibiotic Treatment of <i>Chlamydia pneumoniae</i> Seropositivity
Authors: Dirk Sander, Kerstin Winbeck, Jürgen Klingelhöfer, Thorleif Etgen, Bastian Conrad
Journal: Circulation (2004)

Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and cardiovascular events. There are controversial results regarding the beneficial effects of antibiotic therapy on future cardiovascular end points.We determined the long-term effect of a 30-day roxithromycin therapy on intima-to-media thickness (IMT) progression of the common carotid artery in 272 consecutive Cp-positive and Cp-negative patients with ischemic stroke in a prospective, double-blind, randomized trial with a follow-up of 4 years. Cp IgG (> or =1:64) or IgA (> or =1:16) antibodies were initially found in 125 (46%) patients. During the 3 years before antibiotic therapy, Cp-positive patients showed an enhanced IMT progression even after adjustment for other cardiovascular risk factors (0.12 [0.11 to 0.14] versus 0.07 [0.05 to 0.09] mm/year; P<0.005). The 62 Cp-positive patients given roxithromycin showed a reduced IMT progression during the first 2 years compared with the Cp-positive patients without therapy (0.07 [0.045 to 0.095] versus 0.11 [0.088 to 0.132] mm/year; P<0.01). However, IMT progression increased again during the third and fourth year to similar values as before treatment. No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up.The only limited positive impact of antibiotic therapy on early atherosclerosis progression in Cp-positive patients observed in our study may explain the negative results of most antibiotic trials on clinical end points.
NOTES of a CASE of ACROMEGALY TREATED by OPERATION
Authors: R. Caton
Journal: BMJ (1893)

abnormal flexures; and it is probable-though I have not been able distinctly to observe this-that other bones undergo slight changes in form from abnormal stress in these cases.Bones do thus become modified in shape under ab- inormal pressure or traction, as shown by the ordinary lateral curvature of the spine, and no less markedly in that hardest of all bones, the lowerjaw, under the influence of contraction of cicatrices and the pressure of a prolapsing macroglossia <see Spec. 1228Camb.P. Mus.).The elongation of the ligaments ist of course, due to the same cause.Further, the specimen is clearly an exaggerated form of the ordinary flat foot in which the same joint (mid-tarsal) is pre- ternaturally extended, and the heel bone rendered horizontal.That is, in the main, due, as we know, to superincumbent weight.It is also, as in this case, attended with want of mus- cular balance, the extensors of the toes and the flexors of the ankle being preternaturally tense, and resisting return to the normal position.
Homer William Smith, ScD: His Scientific and Literary Achievements
Authors: John H. Talbott
Journal: JAMA (1965)

The jacket and subtitle suggest a biography, but the product is quite different from the current recounting of the life and letters of a medical scientist. Since Homer W. Smith did not fit the mold of a contemporary professor of physiology, the unusual presentation seems most appropriate.  I knew Smith more than casually as an instructor in physiology, as a father confessor in the interpretation of experimental observations in clinical investigation, and, finally, as a member of the National Research Council on Chemical Warfare during World War II. I had taken H.W.S. for a born and educated Manhattanite, which seems justified in analyzing his Bachrach portrait. But Smith was born in Cripple Creek, Colo, during the golden days of mining and showed an early interest in natural science and philosophy. In maturity he was highly successful in integrating a continuing perception of philosophy with the development of quantitative techniques for
Study of blood coagulation in gout patients
Authors: D. A. Lane, L. G. Darlington
Journal: Annals of the Rheumatic Diseases (1983)

p 91 60 patients have presented to our rheumatology department with gout: 51 men, mean age 55-2 years and mean age of onset 46-6 years and nine women, mean age 80 years and mean age of onset of 78-6 years.We studied the prevalence of hyperlipidaemia, hypertension, obesity, and cardiovascular disease in these two groups.Eighteen men but none of the women
Cognitive and Academic Consequences of Stem-Cell Transplantation in Children
Authors: Sean Phipps, Shesh N. Rai, Wing-Hang Leung, Shelly Lensing, Maggi Dunavant
Journal: Journal of Clinical Oncology (2008)

To describe cognitive and academic outcomes in survivors after pediatric stem-cell transplantation (SCT) through 5-years post-SCT.A battery of neurocognitive measures were administered before admission and at 1, 3, and 5 years post-SCT for 268 patients who underwent SCT; the study sample is comprised of 158 patients who survived and were evaluated at 1-year post-SCT. Random coefficient models were generated to depict change over time, and to test differences in slope and intercept for medical and demographic predictor variables.In the cohort as a whole, no significant changes were seen in global intelligence quotient and academic achievement. Despite the overall stability, some significant differences in slopes were found based on diagnosis, type of transplantation, use of total-body irradiation (TBI), and presence of graft-versus-host disease (GVHD). However, these differences were small, and of limited clinical significance. In comparison, differences as a function of socioeconomic status (SES) were much larger. SES was a significant determinant of all cognitive and academic outcomes, and the effect size generally dwarfed that of other significant predictor variables. Age, which had previously been identified as an important determinant of outcome, was not significantly predictive of outcome in this cohort.The procedure of SCT entails minimal risk of late cognitive and academic sequelae. Subgroups of patients are at relatively higher risk: patients undergoing unrelated donor transplantation, receiving TBI, and those who experience GVHD. However, these differences are small relative to differences in premorbid functioning, particularly those associated with SES.
Lesson of the week: Reye's syndrome and aspirin: lest we forget
Authors: M C McGovern
Journal: BMJ (2001)

Aspirin is an avoidable risk factor for Reye's syndrome: heightened vigilance can prevent an increasing incidence 

Reye's syndrome represents an abrupt, profound failure of mitochondria, the cause of which is uncertain. It is a biphasic illness, occurring mainly in childhood, which consists of an acute viral prodrome followed several days later by an acute encephalopathy associated with selective hepatic abnormality and metabolic decompensation. A consistent association has been shown between Reye's syndrome and the use of aspirin during the prodromal illness.1 Of the 56 children with Reye's syndrome treated at this centre between January 1979 and December 1986, 46 (82%) had been given aspirin. During the past 13 years just five cases have been seen—two occurred in February 1999, and in both cases the child had been given aspirin.

A boy aged 12.5 years had flu-like symptoms of mild fever, headache, and generalised aches for five days. He was given aspirin (300 mg every four hours for 24 hours) after which his symptoms seemed to resolve. However, 12 hours later he began vomiting, and this continued almost hourly for 24 hours, at which time his parents sought medical help.

There was no relevant medical history. The boy was admitted to hospital and managed with intravenous fluids. Twelve hours later he became agitated and uncontrollable; no lateralising neurological features were present and fundoscopy findings were normal. No abnormalities were noted in cerebrospinal fluid or on urine toxicology screening or on a computed tomogram of the brain. The boy's liver transaminase activities and blood ammonia …
Bipartisan approach to improve health of Aboriginal people may prove difficult
Authors: Stephen Pincock
Journal: BMJ (2008)

<h3>Objective</h3> The use of specialist retrieval teams to transport critically ill children is associated with reduced risk-adjusted mortality and morbidity; however, there is a paucity of data to guide decision-making related to retrieval team activation. We aimed to assess the accuracy of a novel triage tool designed to identify critically ill children at the time of referral for interhospital transport. <h3>Design</h3> Prospective observational study. <h3>Setting</h3> Regional paediatric retrieval and transport services. <h3>Patients</h3> Data were collected for 1815 children referred consecutively for interhospital transport from 87 hospitals in Queensland and northern New South Wales. <h3>Intervention</h3> Implementation of the Queensland Paediatric Transport Triage Tool. <h3>Main outcome measures</h3> Accuracy was assessed by calculating the sensitivity, specificity and negative predictive value for predicting transport by a retrieval team, or admission to intensive care following transport. <h3>Results</h3> A total of 574 (32%) children were transported with a retrieval team. Prediction of retrieval (95% CIs): sensitivity 96.9% (95% CI 95.1% to 98.1%), specificity 91.4% (95% CI 89.7% to 92.9%), negative predictive value 98.4% (95% CI 97.5% to 99.1%). There were 412 (23%) children admitted to intensive care following transport. Prediction of intensive care admission: sensitivity 96.8% (95% CI 94.7% to 98.3%), specificity 81.2% (95% CI 79.0% to 83.2%), negative predictive value 98.9% (95% CI 98.1% to 99.4%). <h3>Conclusions</h3> The triage tool predicted the need for retrieval or intensive care admission with high sensitivity and specificity. The high negative predictive value indicates that, in our setting, children categorised as acutely ill rather than critically ill are generally suitable for interhospital transport without a retrieval team.
Nonalcoholic Fatty Liver Disease
Authors: Paul Angulo
Journal: New England Journal of Medicine (2002)

Alcohol abuse is the most common cause of fatty liver disease, but it is now apparent that fat deposition in the liver, and its consequences, may occur without alcohol abuse. The principal risk factors are obesity, non-insulin-dependent diabetes mellitus, and hyperlipidemia. The disorder has a wide clinical spectrum, ranging from asymptomatic steatosis to steatohepatitis, fibrosis, and cirrhosis. This article provides a broad overview of this increasingly recognized liver disease.
Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: Identification and characterization by radioimmunoassay and immunoblotting
Authors: Michael Manns, Guido Gerken, Apostolos Kyriatsoulis, Christian Trautwein, Konrad Reske, Karl-Hermann Meyer Zum Büschenfelde
Journal: Hepatology (1987)

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radioimmunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti-p 62 and anti-p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug-induced pseudolupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluorescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin- and chymotrypsin-sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm3 and p 48 at 1.30 gm per cm3. Thus, radioimmunoassays have been developed that specifically detect two distinct primary biliary cirrhosis-specific subtypes of antimitochondrial antibodies: anti-p 62 and anti-p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)
The Anginal Syndrome With Normal Coronary Arteries
Authors: Anthony N. DeMaria, Garrett Lee, Ezra A. Amsterdam, Reginald Low, Dean T. Mason
Journal: JAMA (1980)

THE INCREASING application of coronary angiography to the evaluation of patients with angina pectoris has led to the identification of a group of patients who experience anginal-type chest pain despite the presence of normal coronary artery anatomy by arteriography. Indeed, such patients may constitute up to 20% of those who have undergone elective coronary arteriography for suspected coronary artery disease.<sup>1</sup>Although initially believed to be primarily an affliction of women, the syndrome has been detected with increasing frequency in men and in some studies has been found to be equally prevalent in both sexes. Despite the presence of normal coronary arteries, persons with this syndrome may have major functional impairment. They may often require hospitalization for chest pain evaluation and management and may even present a condition of unstable angina. Recently, coronary artery spasm has been demonstrated to be responsible for many chest pain syndromes, including variant angina pectoris,