tbuckley/cabot-search huggingface dataset:
Respiratory effects in toluene diisocyanate manufacture: a multidisciplinary approach.
Authors: H Weill, J Salvaggio, A Neilson, B Butcher, M Ziskind
Journal: Environmental Health Perspectives (1975)

A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become
Abstract 5675: Potential use of proteosome pathway inhibitor (bortezomib) in combination with anthracyclines to treat multiple myeloma and pancreatic cancer
Authors: Nicole Frank, Suela Kumbulla, Aditi Jain, Jim Lai, Richard Olson, Barry Cusack, Alok Bhushan
Journal: Cancer Research (2012)

Abstract Anthracyclines are widely used to treat cancers, but may also cause a cumulative dose-related cardiotoxicity. One possible mechanism of cardiotoxicity relates to effects on the cardiomyocyte proteasomal/ubiquitin system (UPS), the major protein recycling system in the cell. The goal of the research is to determine the impact of anthracyclines on the UPS and modulate cardiotoxicity by using other drugs in combination. Rats were treated chronically with a clinically relevant dose of daunorubicin (DNR) or the vehicle (controls) over 9 weeks. Another group received DNR pretreated with ICRF (dexrazoxane; a known protectant against anthracycline cardiotoxicity). The hearts were harvested one week later and analyzed. Isometric atrial preparations from rats treated with DNR showed decreased contractility compared to those pretreated with ICRF or with DNR vehicle only. Ubiquitin ligase atrogin-1 has been associated with muscle atrophy and cancer cachexia. In western blot analysis of common E3 ligases in left ventricle samples from rats treated with DNR, Atrogin-1 showed a significant reduction (P&amp;lt;0.05) compared to animals pretreated with ICRF or DNR vehicle. This suggests that chronic anthracycline cardiotoxicity is accompanied by ubiquitin function. Bortezomib, a proteasomal inhibitor, is approved for treatment of multiple myeloma (MM) and is being investigated for treatment of pancreatic cancer with other drugs. To understand the antineoplastic interaction of a proteosome inhibitor (bortezomib) with an anthracycline (doxorubicin), we performed dose-response assays using MM and pancreatic cancer cell lines. Our studies indicate that, compared to bortezomib alone, 0.05 µM of doxorubicin in combination with bortezomib, enhanced cytotoxicity of bortezomib in the two cell lines. Thus, bortezomib and anthracycline combination therapy may provide enhanced tumoricidal activity for MM and pancreatic cancer compared to bortezomib alone. It is important to understand the mechanisms of the effect of bortezomib and anthracyclines on ubiquitin-proteasome pathway. (Supported by a St. Luke's Health System Mountain States Tumor and Medical Research Institute grant) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5675. doi:1538-7445.AM2012-5675
New Books from the College: Residency Curriculum, Ethics Bibliography, and Clinical Privileges
Authors: Edward J. Huth
Journal: Annals of Internal Medicine (1988)

Editorials15 November 1988New Books from the College: Residency Curriculum, Ethics Bibliography, and Clinical PrivilegesEdward J. Huth, MD, Kathleen Case, MSEdward J. Huth, MDSearch for more papers by this author, Kathleen Case, MSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-10-775 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThree important new guides to improving medical education and practice have just been published by the Publication Division of the American College of Physicians. The books are the latest in the College's growing publishing program. The focus of this program is to provide concise, clinically relevant material by authors outside of the College and to disseminate widely the important guidelines issued by the College's Health and Public Policy Division.A Curriculum for Internal Medicine Residency: The University of Wisconsin Programis the result of a multidisciplinary group's 8-year project to develop an explicit, objective-based curriculum in internal medicine. The increased... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Edward J. Huth, MD; Kathleen Case, MSAffiliations: Publication Division American College of Physicians Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1988Volume 109, Issue 10Page: 775-776KeywordsMedical educationPrevention, policy, and public healthPublic policyResidency ePublished: 1 December 2008 Issue Published: 15 November 1988 PDF downloadLoading ...
Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular liver necrosis
Authors: Hidekazu Tsukamoto, Xiao Ping Xi
Journal: Hepatology (1989)

Centrilobular hypoxia mediated by enhanced hepatic consumption of oxygen has been hypothesized to be a factor of pathogenetic importance in ethanol-induced liver injury. In the present study, this hypothesis was tested in a rat model which developed alcoholic centrilobular liver necrosis. Male Wistar rats were infused with high fat diet plus ethanol or isocaloric glucose for 7 weeks, a duration which resulted in induction of balloon cell degeneration, focal necrosis, and inflammation in the centrilobular region of the liver of the ethanolfed animals. Hepatic blood flow, oxygen consumption and oxygen delivery were determined by the radiolabeled microsphere method and measurement of oxygen content in arterial, portal venous, and hepatic venous blood. Hepatic oxygen consumption was markedly increased by 159% in the ethanol-fed animals compared to that in the controls when results were expressed as relative to body weight. Even after these results were standardized per gram of liver weight, hepatic oxygen consumption was still significantly elevated in the ethanol-fed group, but the magnitude of the elevation was reduced to 70%, due to marked hepatomegaly observed in these animals. There was a concomitant 59% increase in hepatic oxygen delivery in the ethanol-fed rats when expressed per kilogram of body weight, and this effect was attributable entirely to increased portal blood flow. However, the increment of this increase in oxygen delivery was much too small to compensate for the 159% increase in oxygen consumption. In addition, this increase in hepatic oxygen delivery was no longer observable when the results were reexpressed based on the liver weight. These uncoordinated changes in hepatic oxygen consumption and delivery resulted in significantly increased oxygen extraction by livers of the ethanol-fed animals (65.2± 6.4 vs. 43.2± 6.0%) and a 40% reduction in oxygen content in hepatic venous blood of these animals. The observed pathophysiology supports the hypothesis of ethanol-induced centrilobular hypoxia and may contribute to pathogenetic mechanisms of the centrilobular liver necrosis seen in this rat model of alcoholism.
SYSTEMIC MEDICATION IN DENTAL PRACTICE.Read in the Section on Dental and Oral Surgery, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: EDGAR PALMER
Journal: JAMA (1893)

Let us consider first our specialty in its physiologic and pathologic aspect. It is supposed that all who are associated with this Section are of the opinion that "dentistry is a specialty of medicine." It is sufficient for me to base my remarks upon the simple fact that an all-wise Creator has given man organs of mastication much after the same manner and for an equally important service as the organs of hearing and sight, and these organs being subject to abuse, disease and functional derangements, thousands of persons are required to devote their lives to their care and treatment. I am aware it is asserted that this great army of scientific men are, by the mechanical character of their methods, too far removed from the province of general medicine to be entitled to the privileges accorded to the oculist or aurist in giving attention to functional disturbances remote from
Neurotropism and Retrograde Axonal Transport of a Canine Adenoviral Vector: A Tool for Targeting Key Structures Undergoing Neurodegenerative Processes
Authors: Elise Peltékian, Luis Garcia, Olivier Danos
Journal: Molecular Therapy (2002)

Viral tropism refers to the ability of a virus to selectively infect a given subset of cells. It relies on a variety of viral and host determinants that entail virus binding and entry into target cells, in addition to the presence of genetic elements that allow or enhance viral gene expression in a specific manner. Here we report the results of neuroanatomical studies in rat brains injected in different cerebral structures with vectors derived from the canine adenovirus type 2 (CAV2), whose natural target is the respiratory epithelium. Control animals injected with vectors derived from the human adenovirus type 5 (Ad5) displayed the previously documented pattern of gene transfer into both neurons and glial cells. Injection of CAV2 vectors resulted in selective transduction of neuronal cells. Cy3-labeled CAV2 particles allowed us to establish the high affinity of this vector for neuronal processes in vitro and their rapid uptake and retrograde axonal transport in vivo. After intrahippocampal injections, labeled particles were found, within 1 hour, closely associated to the nuclei of the neurons in layer II of the entorhinal cortex. Injections into the striatum resulted in a massive transduction of dopaminergic neurons in the substantia nigra compacta. The high efficiency with which CAV2 vectors are retrogradely transported opens the possibility of targeting a transgene to neuron populations remote from the injection site and difficult to access. Our data support the possibility to target key structures undergoing a degenerative process: the enthorhinal cortex, which is affected first in Alzheimer's disease; and the substantia nigra compacta, which undergoes degeneration in Parkinson's disease.
Process evaluation of complex interventions: Medical Research Council guidance
Authors: G. F. Moore, S. Audrey, M. Barker, L. Bond, C. Bonell, W. Hardeman, L. Moore, A. O'Cathain, T. Tinati, D. Wight, J. Baird
Journal: BMJ (2015)

Process evaluation is an essential part of designing and testing complex interventions.New MRC guidance provides a framework for conducting and reporting process evaluation studiesAttempts to tackle problems such as smoking and obesity increasingly use complex interventions.These are commonly defined as interventions that comprise multiple interacting components, although additional dimensions of complexity include the difficulty of their implementation and the number of organisational levels they target. 1Randomised controlled trials are regarded as the gold standard for establishing the effectiveness of interventions, when randomisation is feasible.However, effect sizes do not provide policy makers with information on how an intervention might be replicated in their specific context, or whether trial outcomes will be reproduced.Earlier MRC guidance for evaluating complex interventions focused on randomised trials, making no mention of process evaluation. 2 Updated guidance recognised the value of process evaluation within trials, stating that it "can be used to assess fidelity and quality of implementation, clarify causal mechanisms and identify contextual factors associated with variation in outcomes." 3However, it did not provide guidance for carrying out process evaluation. Developing guidance for process evaluationIn 2010, a workshop funded by the MRC Population Health Science Research Network discussed the need for guidance on process evaluation. 4There was consensus that researchers, funders, and reviewers would benefit from guidance.A group of researchers with
Identification of a 16,600-dalton outer membrane protein on nontypeable Haemophilus influenzae as a target for human serum bactericidal antibody.
Authors: T F Murphy, L C Bartos, P A Rice, M B Nelson, K C Dudas, M A Apicella
Journal: Journal of Clinical Investigation (1986)

A 16,600-D outer membrane protein is present in all strains of Haemophilus influenzae and antibodies to this protein are present in human serum. This study was designed to assess the role of this outer membrane protein (P6) in nontypeable H. influenzae as a target for human serum bactericidal antibody. P6 was isolated and coupled to an affinity column. Depleting normal human serum of antibodies to P6 by affinity chromatography resulted in reduced bactericidal activity of that serum for nontypeable H. influenzae. Immunopurified antibodies to P6 from human serum were bactericidal. Finally, preincubation of bacteria with a monoclonal antibody that recognizes a surface epitope on P6, inhibited human serum bactericidal killing. Taken together, these experiments establish that P6 is a target for human bactericidal antibodies. This observation provides evidence that P6 plays a potentially important role in human immunity to infection by nontypeable H. influenzae.
Ethical and Legal Issues in AIDS Research
Authors: Ralf Jürgens
Journal: JAMA (1996)

This book addresses the difficult ethical and legal issues involved in conducting psychosocial research on the acquired immunodeficiency syndrome (AIDS). Because the disease has primarily affected people belonging to groups who have suffered discrimination and stigmatization—such as gay men, the poor, and those who engage in drug use (an illegal activity)—many living with human immunodeficiency virus (HIV) infection or AIDS are reluctant to seek treatment and counseling or to participate in research projects. The authors describe the need to handle the cases and records of research participants with extreme care, and they explore the broader implications of conducting socially sensitive research. They begin with a thorough and well-argued exploration of the risks and benefits of doing research on HIV/AIDS for researchers, the public, and participants. They illustrate a point that is seldom given due emphasis in discussions of research ethics: researchers have substantial conflicts of interest, and the more important
Metastatic Myocardial Calcification in Chronic Renal Failure Presenting as Atrioventricular Block
Authors: Robert R. Henderson, Lombardo M. Santiago, Donald A. Spring, Avery R. Harrington
Journal: New England Journal of Medicine (1971)

THE development of hemodialysis for the treatment of chronic renal failure has given rise to a host of new problems in medical management. Atrioventricular block developed in the anephric patient described below who was undergoing hemodialysis and was found to have secondary hyperparathyroidism and metastatic calcification involving the myocardium and its conducting system.Case ReportA.M., a 27-year-old man, was admitted to the University of Wisconsin Hospitals on April 4, 1970. He had had 2 previous admissions in the preceding 20 months for chronic renal failure and had undergone bilateral nephrectomy and splenectomy preparatory to renal transplantation. He had been . . .
Multifunctional Albumin Nanoparticles As Combination Drug Carriers for Intra‐Tumoral Chemotherapy
Authors: Mingjie Cui, Dominik J. Naczynski, Margot Zevon, Craig K. Griffith, Larisa Sheihet, Izmarie Poventud‐Fuentes, Suzie Chen, Charles M. Roth, Prabhas V. Moghe
Journal: Advanced Healthcare Materials (2013)

Current cancer therapies are challenged by weakly soluble drugs and by drug combinations that exhibit non-uniform biodistribution and poor bioavailability. In this study, we have presented a new platform of advanced healthcare materials based on albumin nanoparticles (ANPs) engineered as tumor penetrating, delivery vehicles of combinatorially applied factors to solid tumors. These materials were designed to overcome three sequential key barriers: tissue level transport across solid tumor matrix; uptake kinetics into individual cancer cells; therapeutic resistance to single chemotherapeutic drugs. The ANPs were designed to penetrate deeper into solid tumor matrices using collagenase decoration and evaluated using a three-dimensional multicellular melanoma tumor spheroid model. Collagenase modified ANPs exhibited 1-2 orders of magnitude greater tumor penetration than unmodified ANPs into the spheroid mass after 96 hours, and showed preferential uptake into individual cancer cells for smaller sized ANPs (<100 nm). For enhanced efficacy, collagenase coated ANPs were modified with two therapeutic agents, curcumin and riluzole, with complementary mechanisms of action for combined cell cycle arrest and apoptosis in melanoma. The collagenase coated, drug loaded nanoparticles induced significantly more cell death within 3-D tumor models than the unmodified, dual drug loaded ANP particles and the kinetics of cytotoxicity was further influenced by the ANP size. Thus, multifunctional nanoparticles can be imbued with complementary size and protease activity features that allow them to penetrate solid tumors and deliver combinatorial therapeutic payload with enhanced cancer cytotoxicity but minimal collateral damage to healthy primary cells.
1103-197 Chlamydia pneumoniae-heat shock protein 60 induces a highly specific persistent immune response in patients with unstable angina independently from IgG and IgA seropositivity
Authors: Domenico Cianflone, Alessandra Ciervo, Giulia Angeloni, Marco Magnoni, Claudia Monaco, Gaetano Lanza, Antonio Rebuzzi, Germano Melissano, Roberto Chiesa, Filippo Crea, Antonio Cassone, Attilio Maseri, Francesco Marchi, Giuseppe Ciriello, Aspromonte Nadia, Cesare Volterrani, Paolo Spallarossa, Gianni Destro, Raffaele Bugiardini, Massimo Ciavolella, Gianpietro Leone, Livio Dei Cas
Journal: Journal of the American College of Cardiology (2004)
Re: Reversal of Relation Between Body Mass and Endogenous Estrogen Concentrations With Menopausal Status
Authors: H. V. Thomas, T. J. Key, D. S. Allen, J. W. Moore, M. Dowsett, I. S. Fentiman, D. Y. Wang
Journal: JNCI Journal of the National Cancer Institute (1997)

For more than a decade, results frompublished studies have indicated that therisk of breast cancer may be loweramong heavy premenopausal womenthan among their less obese counterparts(1-8). In heavy postmenopausal women,however, this risk is either increased orunchanged in comparison with non-obese postmenopausal women (9,10).The mechanism explaining this reversalin risk is unknown, although theoreticalexplanations have been proposed. Obesepostmenopausal women may have ele-vated risk from higher levels of circulat-ing estrogens secondary to increasedconversion of androgen to estrogen inadipose tissue (11) and a higher propor-tion of bioavailable estrogen due to thelow levels of sex hormone-bindingglobulin (SHBG) (12,13). Obese pre-menopausal women may exhibit agreater degree of anovulation, resultingin lower levels of both progesterone andestradiol, lower breast cell divisionrates, and, consequently, a lower risk ofbreast cancer (13-15).We had the opportunity to evaluatethe relation of body mass and hormonalprofiles in a group of 195 communityand 103 hospital control subjects from astudy of endometrial cancer describedelsewhere (16,17). Results of both con-trol groups were similar; therefore, thetwo groups were combined. Body massindex (BMI) (kg/m
William Graham Pickering
Authors: J. Spiers
Journal: BMJ (2015)

William Graham Pickering (“Bill”) became the leading national advocate of an independent medical inspectorate, which was intended to improve clinical practices. He published on the subject in The BMJ , the Lancet , and elsewhere. He was also a distinguished field botanist with a national reputation, publishing in leading journals. He had established a solid presence in both worlds. He also contributed many trenchant articles to Private Eye .

His medical practice was in general medicine, in the medicolegal area, in paediatrics, and in occupational medicine. In training he had worked in paediatrics at the Newcastle General Hospital. On qualifying he worked as a paediatrician at the Hospital for Sick Children in Great Ormond Street. London. He …
Abstract 587: Development of brain tumor-specific targeted system by using retroviral-mediated gene therapy with SSX4 promoter
Authors: Keiji Shimizu, Eri Ishida, Masahiro Kitahara, Masakazu Tamura, Toshio Yawata
Journal: Cancer Research (2010)

Abstract Despite many efforts to develop effective therapy, the outcome of malignant glioma remains poor. Previously, we reported the eradication of mouse glioma by retroviral-mediated gene therapy. In this study, a tumor-specific targeting system was studied to develop the effective and safe gene therapy. We first searched for genes expressing at high frequency in brain tumors but not in normal human astrocyte (NHA) among cancer testis antigen (CTA) genes by in silico and RT-PCR screening. MAGEA3 and SSX4 were identified as tumor-specific genes. The promoter activity was measured in glioma, telomerase-immortalized fibroblast and NHA cells. The SSX4 promoter but not MAGEA3 showed the tumor-specific activity. In order to define a useful tumor-specific promoter for targeting in context of retroviral-mediated gene therapy, the SSX4 promoter were used to restrict the expression of suicide gene HSVtk in retroviral vector. The glioma cell lines transduced with the retroviral vector were killed efficiently by addition of ganciclovir (GCV), but telomerase-immortalized fibroblast BJ-5ta cells were not. Mouse glioma RSV-M cells transduced with the retroviral vector were transplanted into S.C. of syngeneic mouse. The administration of GCV suppressed the tumor growth completely. These results suggest that trans-acting factors may play a role for tumor-specific activity of SSX4 promoter while the expression of most CTA genes is regulated by epigenetic factors and the retrovirus vector expressing HSVtk under control of SSX4 promoter is a promising therapeutic reagent for malignant brain tumors. 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 587.