tbuckley/cabot-search huggingface dataset:
Current Assessment of the Effects of Environmental Chemicals on the Mammary Gland in Guideline Rodent Studies by the U.S. Environmental Protection Agency (U.S. EPA), Organisation for Economic Co-operation and Development (OECD), and National Toxicology Program (NTP)
Authors: Susan L. Makris
Journal: Environmental Health Perspectives (2010)

Evaluation of the structural and/or functional integrity of the mammary gland (MG) across life stages is integral to the assessment of developmental, reproductive, and carcinogenic risk for environmental chemicals.In this commentary I characterize MG assessment recommended in U.S. Environmental Protection Agency, Organisation for Economic Co-operation and Development, and National Toxicology Program guideline toxicology study protocols and identify any information gaps for the evaluation of MG development, structure, and function.Several data gaps, issues, and challenges were identified. Current guidelines that include a lactation phase do not provide specific recommendations to record observations on maternal or offspring lactation or nursing behavior. In guideline studies, the assessment of MG toxicity often relies upon indirect, nonspecific, or surrogate end points, and information that could be useful in the interpretation of these data (e.g., mode of action or toxicokinetics) is often unavailable. Most guideline studies designed to assess general organ toxicity do not expose test animals during sensitive stages of MG development; histopathological evaluation of the developing MG is not routinely conducted; and evaluation of MG tissue for both sexes is inconsistently recommended.I propose the following general recommendations to enhance MG assessment in guideline toxicology studies: a) inclusion of more specific criteria for the evaluation of MG end points in guideline language, b) inclusion of histopathological evaluation of MG development (using whole-mount techniques) in existing or new guideline protocols that include offspring with perinatal and/or pubertal treatment, c) incorporation of perinatal exposures into rodent subchronic and carcinogenicity assays, and d) expansion of the histopathological evaluation of male MG tissue.
Multiple Myeloma Cell Killing by Depletion of the MET Receptor Tyrosine Kinase
Authors: Christine M. Stellrecht, Cornel J. Phillip, Fabiola Cervantes-Gomez, Varsha Gandhi
Journal: Cancer Research (2007)

Abstract Multiple myeloma (MM) is an invariably fatal plasma cell malignancy, primarily due to the therapeutic resistance which ultimately arises. Much of the resistance results from the expression of various survival factors. Despite this, the ribonucleoside analogue, 8-chloro-adenosine (8-Cl-Ado), is cytotoxic to a number of MM cell lines. Previously, we established that the analogue incorporates into the RNA and inhibits mRNA synthesis. Because 8-Cl-Ado is able to overcome survival signals present in MM cells and inhibits mRNA synthesis, it is likely that the drug induces cytotoxicity by depleting the expression of critical MM survival genes. We investigated this question using gene array analysis, real-time reverse transcription-PCR, and immunoblot analysis on 8-Cl-Ado–treated MM.1S cells and found that the mRNA and protein levels of the receptor tyrosine kinase MET decrease prior to apoptosis. To determine MET's role in 8-Cl-Ado cytotoxicity, we generated MM.1S clones stably expressing a MET ribozyme. None of the clones expressed &amp;lt;25% of the basal levels of MET mRNA, suggesting that a threshold level of MET is necessary for their survival. Additionally, the ribozyme knockdown lines were more sensitive to the cytotoxic actions of 8-Cl-Ado as caspase-3 activation and the induction of poly-ADP-ribose polymerase (PARP) cleavage were more pronounced and evident 12 h earlier than in the parental cells. We further established MET's role in MM cell survival by demonstrating that a retroviral MET RNA interference construct induces PARP cleavage in MM.1S cells. These results show that MET provides a survival mechanism for MM cells. 8-Cl-Ado overcomes MM cell survival by a mechanism that involves the depletion of MET. [Cancer Res 2007;67(20):9913–20]
TWO CASES IN WHICH DEATH FOLLOWED INSUFFLATION OF THE FALLOPIAN TUBES
Authors: G. L. Moench
Journal: JAMA (1927)

At the New York Post-Graduate Medical School and Hospital in Dr. H. D. Furniss' service we had up to May, 1927, insufflated the fallopian tubes of considerably more than 200 women without any fatality or even untoward results of any nature. Nevertheless, accidents with the insufflation test of the fallopian tubes are now and again reported in the literature,<sup>1</sup>and the two cases reported here, from the office of the chief medical examiner of New York City, give the necropsy results in two women who died directly following such insufflation. In both instances I was assured by the physician to whom this unfortunate accident occurred that he had insufflated numerous patients before, had previously never seen any untoward results, and had carried out the procedure in this fatally ending case in exactly the same manner as always. A pressure of 220 mm. of mercury was not exceeded in either case.
Altered thrombus formation in von Willebrand factor–deficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa
Authors: Isabelle Marx, Olivier D. Christophe, Peter J. Lenting, Alain Rupin, Marie-Odile Vallez, Tony J. Verbeuren, Cécile V. Denis
Journal: Blood (2008)
GE-04 * COMPREHENSIVE GENOMIC PROFILING (CGP) OF PEDIATRIC GLIOMAS REVEALS A HIGH FREQUENCY OF CLINICALLY RELEVANT GENOMIC ALTERATIONS (CRGA) ASSOCIATED WITH BENEFIT FROM TARGETED THERAPY
Authors: Z. R. Chalmers, S. M. Ali, G. M. Frampton, J. Chmielecki, N. A. Palma, J. A. Elvin, A. Johnson, R. Yelensky, J. S. Ross, P. J. Stephens, V. A. Miller, A. J. Waanders, J. Crawford
Journal: Neuro-Oncology (2015)

BACKGROUND: Primary CNS tumors, which include both low-grade and high-grade gliomas, are the most common pediatric solid malignancies. We queried whether CGP could uncover a significant frequency of CRGA that could inform treatment decisions and improve clinical outcome for these aggressive tumors. METHODS: DNA was extracted from 75 pediatric glioma formalin-fixed paraffin-embedded clinical specimens. Hybridization captured libraries of 236 (FoundationOne, n = 43) or 405 (FoundationOne Heme, n = 32) genes, plus select introns frequently rearranged in cancer were sequenced to high (>500x), uniform coverage. All classes of genomic alterations including base substitutions, small insertions and deletions, rearrangements, and copy number alterations, were evaluated and reported. CRGA were defined as GA associated with FDA approved therapies or targeted therapies in mechanism-driven clinical trials. RESULTS: The median age of the patients was 9 years (range 0 to 18 years). There were 41 male (57%) and 34 female (43%) patients. The study included glioblastomas (n = 30, 42%), astrocytomas not otherwise specified (NOS) (n = 17, 24%), gliomas NOS (n = 10, 14%), pilocytic astrocytomas and anaplastic astrocytomas (9 each, 13%). 89% of cases harbored at least one CRGA. Pediatric gliomas frequently harbored short variants or copy number alterations in TP53 (39%); BRAF (15%) for which 82% were the V600E base substitution; CDKN2A/B (15%), NF1 (14%), PIK3CA (14%), ATRX (13%) and EGFR (11%). Ten cases (14%) harbored a BRAF fusion, including 44% of pilocytic astrocytomas. BRAF fusions included the known KIAA1549-BRAF and the novel CCDC6-BRAF and BCAS1-BRAF. ATG7-RAF1, ALK-PPCB1 and QK1-RAF1 rearrangements were also identified. Outcomes from cases where targeted therapy was utilized will be presented. CONCLUSIONS: CRGA are frequently identified in pediatric glial tumors of both low-grade and high-grade histology and can be identified by CGP in the course of clinical care. CGP has the potential to identify opportunities for targeted therapies or enrollment in clinical trials for these patients.
Second-Generation Antipsychotic Drugs in Anorexia Nervosa: A Meta-Analysis of Randomized Controlled Trials
Authors: Markus Dold, Martin Aigner, Megan Klabunde, Janet Treasure, Siegfried Kasper
Journal: Psychotherapy and Psychosomatics (2015)

Background: Second-generation antipsychotic drugs (SGAs) are increasingly administered to achieve weight gain in anorexia nervosa. In this meta-analysis, we aimed to determine if any evidence for this treatment option can be derived from randomized controlled trials (RCTs). Methods: Based on the 'World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders', a systematic update literature search was applied to identify all RCTs investigating the efficacy, acceptability, and tolerability of SGAs in anorexia nervosa in comparison to placebo/no treatment. The primary outcome was weight gain measured by mean change in body mass index (BMI). Secondary outcomes were mean changes in Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) total score and Eating Disorders Inventory (EDI) total score and premature discontinuation of treatment. Employing a random-effects model standardized mean differences based on Hedges's g and Mantel-Haenszel risk ratios were calculated. Results: Seven RCTs (n = 201) investigating olanzapine (N = 4), quetiapine (N = 2), and risperidone (N = 1) were included. We found no statistically significant between-group differences for mean BMI change when pooling the SGAs (N = 7, n = 161; Hedges's g = 0.13, 95% CI: -0.17 to 0.43; p = 0.4) and when examining the individual drugs. Furthermore, the SGAs failed to differentiate statistically significantly from placebo/no treatment for all secondary outcomes. Conclusions: Based on the current evidence, pharmacological treatment of anorexia nervosa with SGAs cannot be generally recommended although some individuals or subgroups of patients might benefit from an antipsychotic medication. Further research is required to identify which patients will likely benefit from such a treatment option. © 2015 S. Karger AG, Basel.
Eosinophilia In Atopic Disease
Authors: Francis C. Lowell
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The two points raised by Dr. Naterman should perhaps have received more attention than they did in the article referred to. It has always been assumed, as Dr. Naterman states, that infection is the common offender in severe asthmatic relapse with purulent sputum, with or without slight fever. The sedimentation rate is rarely measured under such circumstances, but we have made many such measurements and have often observed elevations not only in the colder months but also in patients having what seemed to be polleninduced relapses occurring in the appropriate season. Attempts to isolate a bacterial pathogen in the sputum of these and many other instances of asthmatic relapse were so unsuccessful that we concluded that either infection was absent or that a virus infection was present. The suppression of manifestations of infection by steroids is well recognized, and we were naturally concerned that this explained the
AAI-guided anaesthesia is associated with lower incidence of 24-h MMSE &lt; 25 and may impact the IL-6 response
Authors: Pether K. Jildenstål, Jan L. Hallén, Narinder Rawal, Lars Berggren, Jan G. Jakobsson
Journal: International Journal of Surgery (2014)

Trauma stress and neuro-inflammation caused by surgery/anaesthesia releases cytokines. This study analysed impact of Auditory Evoked Potential Index (AAI) depth-of-anaesthesia titration on the early plasma IL-6 release after eye surgery under general anaesthesia.This is a subgroup analysis of a prospective randomized study on the effect of auditory evoked potential guided anaesthesia for eye surgery. Plasma IL-6 levels taken before, 5 and 24 h after end of surgery from 450 patients undergoing elective ophthalmic surgery under desflurane anaesthesia were analysed. Minimal mental state examination (MMSE) was also tested at 24-h.IL- 6 increased significantly at both 5 and further at 24 h after surgery (3.2, 4.5 and 5.1 base-line, 5 and 24-h respectively), the IL-6 increase showed different patterns between the 2 groups; IL-6 was significantly increased in the control group of patients between preoperative baseline and 24 h after surgery (p = 0.008) also between 5 h and 24 h, (p = 0.006) after surgery while the AAI-group had only minor non-significant changes. The 18 patients that showed a 24-h MMSE score less than 25 had a significant higher 24-h IL-6 compared to the 390 patients with a MMSE score > 24 (p = 0.002).The IL-6 increase after surgery was less pronounced in patients where anaesthesia was titrated by AAI compared to anaesthesia adjusted on clinical signs only. IL-6 were also found to be higher in patients with a MMSE < 25 at 24-h. Further studies are warranted evaluating the role of depth of anaesthesia monitoring on the risk for early cognitive impairment and neuro-inflammation.Clinicaltrials.gov identifier: NA/study were conducted between January 2005-April 2008.
Low back pain. Serial epidural injections effective.
Authors: K Bush
Journal: BMJ (1993)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Low back pain. Serial epidural injections effective. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Sir Paul Chambers's Inquiry
Authors: R. G. Bullock
Journal: BMJ (1972)

bone changes also remains uncertain, but an alternative to the enzyme induction hypothesis deserves consideration in view of the report of Ragab et al.6 that the folate antagonist, methotrexate, can produce osteoporosis with some features similar to those produced by anticonvulsants.(Dent, personal communication).Could not the bone disease in epileptic patients also be related to the effects of anticonvulsant drugs on folate metabolism?Certainly there is a great deal of clinical overlap between the folate and metabolic bone changes in epileptic patients, as the similar correlations with urinary glucaric acid excretion would suggest, and as would be expected if both are doserelated complications.-Iam, etc.,
Gene therapy in the cardiovascular system: an update
Authors: P Sinnaeve
Journal: Cardiovascular Research (1999)

This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdles are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important questions regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.
Teaching Medical Ethics
Authors: Howard Brody
Journal: JAMA (1974)

While the mechanics and the immediate goals of setting up programs for teaching medical ethics to medical students are reasonably well established, there are a number of important conceptual issues that have so far received insufficient attention in the literature. These include writing behavioral objectives and formal evaluations for an ethics program; deciding on the proper placement of ethics in the student's academic career; defining a health care team ethic to replace a strictly individual ethic; maintaining a critical tension between the individual and the bioethical dimensions; and preparing for ethical issues of the future. These issues are raised here not to provide answers, but rather to stimulate increased discussion and intellectual interchange in the medical-educational community. (<i>JAMA</i>229:177-179, 1974)
Abstract 1922: Do stress response genes play a role in maintaining MDSC survival and suppression
Authors: Daniel W. Beury, Phillip Fitzgerald, Minu K. Srivastava, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2010)

Abstract Myeloid- derived suppressor cells (MDSC) contribute to immune suppression in tumor bearing individuals. Their suppression and survival are increased by inflammation. MDSC production of toxic radicals is the primary mechanism of suppression but the toxic mediators do not affect the MDSC themselves. We are investigating stress response genes that may maintain MDSC survival and facilitate suppression. BALB/c mice were injected with BALB/c derived mammary carcinoma 4T1 or 4T1 constitutively expressing the pro-inflammatory cytokine IL-1β (4T1/IL-1β). Primary tumors were surgically removed after 25 days. At 35 days, spleens were harvested and assayed for the percentage of Gr1+ CD11b+ MDSC. Surgical removal of 4T1 results in a regression of the MDSC population, however MDSC do not regress in mice bearing 4T1/IL-1β tumors, confirming that inflammation increases MDSC survival. Western blots and confocal microscopy of MDSC induced by 4T1 and 4T1/IL-1β tumors localize Nrf2 in the nucleus, demonstrating that Nrf2 is activated in MDSC. In flow cytometry assays, MDSC induced by 4T1/IL-1β have higher expression of one chain of the cystine transporter, xCT, compared to 4T1 induced MDSC. 4T1/IL-1β induced MDSC also expressed more reactive oxygen species (ROS) compared to 4T1 MDSC. The increased expression of ROS and xCT in 4T1/IL-1β induced MDSC represent mechanisms for the increased suppression of CD4+ and CD8+ T cells compared to 4T1 induced MDSC. Catalase, a protein transcriptionally regulated by Nrf2, when added to a T cell activation assay eliminates MDSC suppressive activity. Addition of catalase to T cells co-cultured with MDSC and peptide causes a synergistic effect, activating T cells to a greater level than peptide alone. Collectively these data suggest that stress genes may play a role in maintaining MDSC survival and suppressive activity. 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 1922.
SOLID FIBROID OF OVARY OBSTRUCTING DELIVERY
Authors: J. Stewart
Journal: BMJ (1908)

Doran received a false report of the patient's death, but on February 12th, 1908, a patient came to see him at the hospital.She complained of dyspepsia, due, it appeared, to excessive tea-drinking, but she added that she had gone on wonderfully well since her operation.Then, on looking into his notebook, Mr. Doran found she was Case ii, and there was a report of her death.On further inquiry it transpired that the report referred to some other patient with a similar name and complaint,
The Human Lung
Authors: Jerome R. Head
Journal: JAMA (1961)

Many works have been published on the human lung, but since the time of William Snow Miller no one has presented as detailed and comprehensive a study of the microscopic anatomy of this structure. We find in this book, moreover, not only the results of an extensive individual investigation of the gross and microscopic anatomy of the lung, but also an attempt to correlate such anatomical facts with both physiologic and pathologic states in the pulmonary systems. In recent years the lungs have received more attention and have become more important clinically than ever before. This has been due not only to the marked increase in the incidence of and mortality from carcinoma of the lung, but also to the rising incidence and morbidity associated with pulmonary emphysema, pulmonary fibrosis, far advanced pulmonary tuberculosis, and pulmonary insufficiency secondary to cardiac disease. If we are to understand these pathologic processes and
Death following Blood Transfusion
Authors: H. S. H. Wood
Journal: BMJ (1937)

<h3>ABSTRACT</h3> <h3>Background</h3> Publicly available RNA-seq datasets are often underused although being helpful to improve functional annotation of eukaryotic genomes. This is especially true for filamentous fungi genomes which structure differs from most well annotated yeast genomes. <i>Podospora anserina</i> is a filamentous fungal model, which genome has been sequenced and annotated in 2008. Still, the current annotation lacks information about cis-regulatory elements, including promoters, transcription starting sites and terminators, which are instrumental to integrate epigenomic features into global gene regulation strategies. <h3>Results</h3> Here we took advantage of 37 RNA-seq experiments that were obtained in contrasted developmental and physiological conditions, to complete the functional annotation of <i>P. anserina</i> genome. Out of the 10,800 previously annotated genes, 5’UTR and 3’UTR were defined for 7,554, among which, 3,328 showed differential transcriptional signal starts and/or transcriptional end sites. In addition, alternative splicing events were detected for 2350 genes, mostly due alternative 3’splice site and 1,958 novel transcriptionally active regions (nTARs) in unannotated regions were identified. <h3>Conclusions</h3> Our study provides a comprehensive genome-wide functional annotation release of <i>P. anserina</i> genome, including chromatin features, cis-acting elements such as UTRs, alternative splicing events and transcription of non-coding regions. These new findings will likely improve our understanding of gene regulation strategies in compact genomes, such as those of filamentous fungi. Characterization of alternative transcripts and nTARs paves the way to the discovery of putative new genes, alternative peptides or regulatory non-coding RNAs.
Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis.
Authors: J E Schneider, B C Berk, M B Gravanis, E C Santoian, G D Cipolla, N Tarazona, B Lassegue, S B King
Journal: Circulation (1993)

Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of the long-term success of this procedure. The process of restenosis is similar to an accelerated form of atherosclerosis. Thus, therapeutic interventions that limit the progression and initiation of atherosclerosis may be beneficial in the treatment of restenosis. One such intervention is the antioxidant drug probucol, which has demonstrated benefit in animal models of atherosclerosis.Twenty-six female domestic swine were divided into three study groups (control, n = 9; low-dose probucol, n = 9; high-dose probucol, n = 8) before oversized balloon injury of the left anterior descending and left circumflex coronary arteries. Probucol (1 g/d, low-dose group; 2 g/d, high-dose group) was administered 2 days before balloon injury and was continued until the swine were killed 2 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), maximal intimal thickness (millimeters), and residual lumen (ratio of luminal to intimal plus luminal area). Treatment with high-dose probucol significantly reduced neointimal formation compared with control animals (decreases of 36% in intimal area, P = .007; 20% in maximal intimal thickness, P = NS; and an increase of 15% in residual lumen, P = .02).The major finding of this study is that the antioxidant drug probucol reduces neointimal formation after oversized balloon injury in a swine model of restenosis. This suggests that active oxygen species may play a role in restenosis.