tbuckley/cabot-search huggingface dataset:
Fertility in mice after prenatal exposure to benzo[a]pyrene and inorganic lead.
Authors: P Kristensen, E Eilertsen, E Einarsdóttir, A Haugen, V Skaug, S Ovrebø
Journal: Environmental Health Perspectives (1995)

Experimental evidence suggests that inorganic lead and benzo[a]pyrene (BaP) suppress the development of primordial oocytes during fetal life. We examined the single and combined effects of prenatal exposure to BaP and moderate doses of lead. The fertility and ovarian morphology of F1 female NMRI mice in four treatment groups (nine mice per group) were investigated: control; lead (F0 given 1 g PbCl2/L in drinking water until mating); BaP (10 mg/kg body weight daily by oral intubation on days 7-16 of F0 pregnancy); and combined lead and BaP. F1 groups exposed prenatally to BaP either alone or in combination with inorganic lead showed markedly reduced fertility with few ovarian follicles compared to controls, whereas the group exposed to lead only had measures comparable to the controls. Mice exposed to both lead and BaP had a significantly longer gestation period (days to litter) compared to mice exposed only to BaP, lead, or controls. There is a nonsignificant indication that the compounds together further reduce number of offspring, number of litters, and litter size. These results suggest that lead and BaP have synergistic effects on impairment of fertility. The possibility of synergism may be of human relevance as inorganic lead and BaP are ubiquitous environmental pollutants.
Oral gold for rheumatoid arthritis.
Authors: J M Gumpel
Journal: BMJ (1984)

fore is our recent finding that pulmonary surfactant in the rat contains appreciable concentrations of vitamin E.5 This observation raises the possibility that pulmonary surfactant may exercise a dual role both in physical stabilisation of alveolar structure and also in the biochemical defence of lung tissue.If this hypothesis is correct then the premature infant may prove to be particularly vulnerable to lung injury from oxygen when vitamin E deficient, or when underdevelopment of the mechanisms of biosynthesis and secretion of surfactant prevents the disposition of the vitamin at this crucial site.Artificial surfactant for use in replacement treatment may be more effective if it contains this component.Further research using more appropriate animal models is clearly required.
The Spectrum of Cholestatic Hepatic Disease
Authors: Maurice H. Stauffer
Journal: JAMA (1965)

Hepatic disease has long been a well-documented but rare complication of chronic ulcerative colitis. Early reports, mainly from necropsy studies, showed the hepatic lesions most frequently to be either fatty liver or some form of cirrhosis. During the past 12 years, there have been two important changes in the study of this relationship: (1) increased recognition that liver-function tests give abnormal results in many patients with chronic ulcerative colitis,<sup>1</sup>and (2) increased observation of patients with prolonged hepatic injury characterized by cholestatic features. In some of these patients the lesion progresses to cirrhosis, often exhibiting clinical and laboratory characteristics of the "biliary" type.<sup>1-3</sup> Two reports in 1952<sup>1,4</sup>initiated a changing concept in identifying the hepatic lesions seen with ulcerative colitis. Kleckner and co-workers1 reported on patients with ulcerative colitis and chronic jaundice, "pericholangitis with bile stasis" noted on hepatic biopsy, and clinical and laboratory data suggesting a
The Tamoxifen Metabolite, Endoxifen, Is a Potent Antiestrogen that Targets Estrogen Receptor α for Degradation in Breast Cancer Cells
Authors: Xianglin Wu, John R. Hawse, Malayannan Subramaniam, Matthew P. Goetz, James N. Ingle, Thomas C. Spelsberg
Journal: Cancer Research (2009)

Tamoxifen has been the most important therapeutic agent for the treatment of estrogen receptor (ER)-positive breast cancer for the past three decades. Tamoxifen is extensively metabolized by cytochrome P450 enzymes, and recent in vivo studies have shown that women with genetically impaired cytochrome P450 2D6 have reduced production of endoxifen and a higher risk of breast cancer recurrence. Despite these observations, the contribution of endoxifen to the overall drug effectiveness of tamoxifen remains uncertain. Here, we provide novel evidence that endoxifen is a potent antiestrogen that functions in part by targeting ERalpha for degradation by the proteasome in breast cancer cells. Additionally, we show that endoxifen blocks ERalpha transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation even in the presence of tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxytamoxifen. All of the effects of endoxifen are concentration dependent and do not occur at concentrations observed in human CYP2D6 poor metabolizers. These results support the theory that endoxifen is the primary metabolite responsible for the overall effectiveness of tamoxifen in the treatment of ER-positive breast cancer.
T cell receptor–instructed αβ versus γδ lineage commitment revealed by single-cell analysis
Authors: Taras Kreslavsky, Annette I. Garbe, Andreas Krueger, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2008)

alphabeta and gammadelta T cell lineages develop in the thymus from a common precursor. It is unclear at which stage of development commitment to these lineages takes place and in which way T cell receptor signaling contributes to the process. Recently, it was demonstrated that strong TCR signals favor gammadelta lineage development, whereas weaker TCR signals promote alphabeta lineage fate. Two models have been proposed to explain these results. The first model suggests that commitment occurs after TCR expression and TCR signaling directly instructs lymphocytes to adopt one or the other lineage fate. The second model suggests that commitment occurs before TCR expression and that TCR signaling merely confirms the lineage choice. By tracing the fate of single T cell precursors, this study shows that there is no commitment to either the alphabeta or gammadelta lineage before TCR expression and that modulation of TCR signaling in progeny of a single TCR-expressing cell changes lineage commitment.
Anaerobic cocci populating the deep tissues of chronic wounds impair cellular wound healing responses in vitro
Authors: P. Stephens, I.B. Wall, M.J. Wilson, K.E. Hill, C.E. Davies, C.M. Hill, K.G. Harding, D.W. Thomas
Journal: British Journal of Dermatology (2003)

Summary Background Anaerobic cocci are estimated to be present in the deep tissues of over 50% of chronic skin wounds. While the part they play in the chronicity of these wounds is uninvestigated, anaerobic cocci have previously been shown to be involved in other chronic inflammatory human conditions. Methods In this study the anaerobic microflora of the deep tissues of 18 patients with refractory chronic venous leg ulcers (mean age 80·3 years; mean duration > 24 months) was characterized using strict anaerobic culture conditions. The effect of the anaerobic organisms isolated from these tissues on extracellular matrix (ECM) proteolysis and cellular wound healing responses was studied using in vitro models. Results Anaerobic organisms were present in the deep tissues of 14 of 18 wounds and were principally Peptostreptococcus spp. The effects of three Peptostreptococcus spp. isolated from these wounds (P. magnus, P. vaginalis and P. asaccharolyticus) on cellular wound healing responses were compared with those of two pathogenic organisms also isolated from these wounds (Pseudomonas aeruginosa and Citrobacter diversus). While the direct ECM proteolytic activity exhibited by the Peptostreptococcus spp. was limited, they did significantly inhibit both fibroblast and keratinocyte proliferation, but only at high concentrations. However, at lower concentrations peptostreptococcal supernatants profoundly inhibited keratinocyte wound repopulation and endothelial tubule formation. The magnitude of these effects varied between strains and they were distinct from those demonstrated by Pseudomonas aeruginosa and Citrobacter diversus. Conclusions These studies confirm the importance of anaerobic organisms in chronic wounds and demonstrate an indirect, strain‐specific mechanism by which these microorganisms may play a part in mediating the chronicity of these wounds.
Two cases of telbivudine-induced myopathy in siblings with chronic hepatitis B
Authors: Eun Hye Kim, Hana Park, Kun Ho Lee, Sang Hoon Ahn, Seung-Min Kim, Kwang-Hyub Han
Journal: Clinical and Molecular Hepatology (2013)

Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine has a more potent and sustained antiviral activity with a lower frequency of viral resistance than lamivudine. Although there are several reports concerning the safety profile of telbivudine, most adverse events are described as mild and transient in nature. Here we report two cases of telbivudine-induced myopathy in patients with chronic hepatitis B who were siblings. Keywords: Telbivudine; Hepatitis B; Adverse effects; Myopathy
Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy
Authors: Leisha A. Emens, Elizabeth M. Jaffee
Journal: Cancer Research (2005)

Abstract Engaging the power of the patient's own immune system to actively seek out and destroy transformed cells holds great promise for cancer therapy. Tumor vaccines offer the potential for preventing cancer in high-risk individuals, preventing disease relapse after diagnosis and initial therapy, and shifting the balance of the host-tumor interaction to mitigate the progression of advanced cancers. The therapeutic activity of tumor vaccines is limited by the sheer physical burden of the cancer itself, pathways of local immune tolerance and escape active within the tumor microenvironment, and superimposed potent systemic mechanisms of immune tolerance. In this review, we describe how cytotoxic chemotherapy can be integrated with tumor vaccines using unique doses and schedules to break down these barriers, releasing the full potential of the antitumor immune response to eradicate disease.
New boost for depressed scars
Authors: Gail McBride
Journal: JAMA (1978)

A new technique for the repair and elevation of depressed scars is working well for its developer, dermatologist Sheldon K. Gottlieb, MD, of Washington, DC. Taking his impetus from the work of the late Arthur S. Spangler, MD, who in 1956 reported the use of fibrin foam made from pooled plasma as a filler material for such scars, Gottlieb, who did his residency with Spangler, determined to find another similar filler material. (Fibrin foam is not available to physicians.) Speaking to the recent meeting of the American Academy of Facial Plastic and Reconstructive Surgeons in Palm Beach, Fla, Gottlieb said: "I finally realized the importance of the enzyme fibrinolysin, or plasmin. Present in injured tissue, it destroys or inhibits the action of profibrinogen, fibrinogen, thrombin, fibrin, and other clotting factors. It became clear: An agent that would inhibit or destroy this fibrinolysin and its precursor to allow for the build-up
THE HISTOLOGY OF SUTTON'S NAEVUS
Authors: G. H. FINDLAY
Journal: British Journal of Dermatology (1957)

Journal Article THE HISTOLOGY OF SUTTON'S NAEVUS Get access G. H. FINDLAY G. H. FINDLAY Section of Dermatology, Department of Medicine, University of Pretoria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 11, 1 November 1957, Pages 389–394, https://doi.org/10.1111/j.1365-2133.1957.tb13779.x Published: 01 November 1957
Do Race and Ethnicity Play a Substantial Role in the Quality of Care That Patients Receive in the U.S. Health Care System?
Authors: Victor S. Sloan
Journal: Annals of Internal Medicine (2009)

Letters6 January 2009Do Race and Ethnicity Play a Substantial Role in the Quality of Care That Patients Receive in the U.S. Health Care System?Victor S. Sloan, MDVictor S. Sloan, MDFrom Robert Wood Johnson Medical School, New Brunswick, NJ 08901.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-1-200901060-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:As Dr. Hegedus points out, our health care system is indeed broken. With more than 40 million U.S. residents lacking health insurance, one could hardly argue that point. However, although all U.S. residents are subject to the same broken system, several studies demonstrate that minorities have worse health outcomes. The Institute of Medicine (1) notes that in most studies, differences in care are present even after controlling for other confounding factors. There is ample evidence of racial and ethnic differences in cardiac care (2), cancer care (3), and diabetes (4). Perhaps more important, many physicians erroneously believe that ...References1. Institute of Medicine. Unequal Treatment: What Healthcare Providers Need to Know About Racial and Ethnic Disparities in Healthcare. Washington, DC: National Academies Pr; 2003. Google Scholar2. Lillie-Blanton M, Maddox TM, Rushing O, Mensah GA. Disparities in cardiac care: rising to the challenge of Healthy People 2010. J Am Coll Cardiol. 2004;44:503-8. [PMID: 15358011] CrossrefMedlineGoogle Scholar3. Gross CP, Smith BD, Wolf E, Andersen M. Racial disparities in cancer therapy: did the gap narrow between 1992 and 2002? Cancer. 2008;112:900-8. [PMID: 18181101] CrossrefMedlineGoogle Scholar4. Sequist TD, Fitzmaurice GM, Marshall R, Shaykevich S, Safran DG, Ayanian JZ. Physician performance and racial disparities in diabetes mellitus care. Arch Intern Med. 2008;168:1145-51. [PMID: 18541821] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Robert Wood Johnson Medical School, New Brunswick, NJ 08901.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Content of Their Character Victor S. Sloan Do Race and Ethnicity Play a Substantial Role in the Quality of Care That Patients Receive in the U.S. Health Care System? Steven M. Hegedus Metrics 6 January 2009Volume 150, Issue 1Page: 60KeywordsConflicts of interestEmotionsHealth careHealth care qualityHealth insurancePatients ePublished: 6 January 2009 Issue Published: 6 January 2009 CopyrightCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Mutations of the P Gene in Oculocutaneous Albinism, Ocular Albinism, and Prader-Willi Syndrome Plus Albinism
Authors: Seung-Taek Lee, Robert D. Nicholls, Sarah Bundey, Renata Laxova, Maria Musarella, Richard A. Spritz
Journal: New England Journal of Medicine (1994)

Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal recessive disorder that has recently been mapped to chromosome segment 15q11-q13. The frequency of this disorder is greatly increased in patients with Prader-Willi or Angelman syndrome, both of which involve deletions of chromosome 15q. The P protein is a transmembrane polypeptide that may transport small molecules such as tyrosine, the precursor of melanin. The P gene is located in chromosome segment 15q11-q13.
Epstein-Barr Virus Infection in Relation to Infectious Mononucleosis and Burkitt's Lymphoma
Authors: Richard T. Smith, Judith C. Bausher
Journal: Annual Review of Medicine (1972)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Rethinking the Role of Isolation Practices in the Prevention of Nosocomial Infections
Authors: PATRICIA LYNCH
Journal: Annals of Internal Medicine (1987)

To prevent nosocomial infections, hospitals use two types of procedures: routine patient care practices (handwashing, for example), which are used in appropriate circumstances on all patients, and more intensive isolation precautions, which are implemented only when patients are suspected of having particular infections. Aspects of these current practices, however, may limit their effectiveness. We propose the use of body substance isolation, a simpler alternative system that is used for all patients, not just in response to a specific diagnosis, and that emphasizes the increased use of barrier precautions, especially gloving, when contact with potentially infectious bodily secretions is anticipated. Because of its rationale and simplicity, body substance isolation has been enthusiastically accepted at our hospitals, and we encourage others to consider and evaluate this approach.
Diagnosis of Lung Cancer by the Transbronchial Brush Biopsy Technique
Authors: William J. Bean
Journal: JAMA (1968)

The problem of diagnosis of cancer of the lung has yielded partially to the diagnostic triad of bronchoscopy, sputum cytology, and scalene-node biopsy. There still remains a considerable number of cases in which open-lung biopsy is the only means of arriving at a diagnosis, especially with the small, peripheral lesions. The development of brush biopsy technique by Hattori et al<sup>1</sup>and modifications made by Fennessey<sup>2</sup>make it possible to diagnose peripheral lung cancer nonsurgically in a majority of cases.<sup>3</sup> We first applied this technique in January 1967 in problem cases and have found the method very useful, easy to learn, and safe to use. We therefore present our experiences in the hope that this will encourage others to utilize the method for the benefit of their patients. <h3>Material, Equipment, and Technique</h3> The brushes used in this technique are nylon mounted on a 36.5-inch stainless steel wire. They
Patterns of Ocular Care in a New England Community
Authors: Leon J. Taubenhaus
Journal: New England Journal of Medicine (1963)

THE relation between the medical and paramedical professions produces many problems. The field of eye care provides an excellent example. Here, two licensed professional groups serve the public, One group, the ophthalmologists, comprises licensed physicians who are certified as specialists in the medical and surgical care of the eye by a professional accrediting body, the American Board of Ophthalmology. The other group consists of optometrists, who are trained in their specialty by their own professional schools, but are licensed and qualified by an official body, the State Board of Optometry, to prescribe eyeglasses for the correction of refractive errors. In . . .
Hyaluronic acid derivative-coated nanohybrid liposomes for cancer imaging and drug delivery
Authors: Ju-Hwan Park, Hyun-Jong Cho, Hong Yeol Yoon, In-Soo Yoon, Seung-Hak Ko, Jae-Seong Shim, Jee-Hyun Cho, Jae Hyung Park, Kwangmeyung Kim, Ick Chan Kwon, Dae-Duk Kim
Journal: Journal of Controlled Release (2013)
Inflammatory Skin and Bowel Disease Linked to<i>ADAM17</i>Deletion
Authors: Diana C. Blaydon, Paolo Biancheri, Wei-Li Di, Vincent Plagnol, Rita M. Cabral, Matthew A. Brooke, David A. van Heel, Franz Ruschendorf, Mark Toynbee, Amanda Walne, Edel A. O'Toole, Joanne E. Martin, Keith Lindley, Tom Vulliamy, Dominic J. Abrams, Thomas T. MacDonald, John I. Harper, David P. Kelsell
Journal: New England Journal of Medicine (2011)

We performed genetic and immunohistochemical studies in a sister and brother with autosomal recessive neonatal inflammatory skin and bowel lesions. The girl died suddenly at 12 years of age from parvovirus B19-associated myocarditis; her brother had mild cardiomyopathy. We identified a loss-of-function mutation in ADAM17, which encodes a disintegrin and metalloproteinase 17 (also called tumor necrosis factor α [TNF-α]-converting enzyme, or TACE), as the probable cause of this syndrome. Peripheral-blood mononuclear cells (PBMCs) obtained from the brother at 17 years of age showed high levels of lipopolysaccharide-induced production of interleukin-1β and interleukin-6 but impaired release of TNF-α. Despite repeated skin infections, this young man has led a relatively normal life. (Funded by Barts and the London Charity and the European Commission Seventh Framework Programme.).
Gestalt Bubble and the genesis of space
Authors: Victor Rosenthal, Yves-Marie Visetti
Journal: Behavioral and Brain Sciences (2003)

Lehar (rightly) insists on the volumetric character of our experience of space. He claims that three-dimensional space stems from the functional three-dimensional topology of the brain. But his “Gestalt Bubble” model of volumetric space bears an intrinsically static structure – a kind of theater, or “diorama,” bound to the visual modality. We call attention to the ambivalence of Gestalt legacy and question the status and precise import of Lehar's model and the phenomenology that motivates it.
349. Partial Correction of IL-12 Receptor beta-1 (IL-12Rb1) Deficiency in Mice upon Transplantation of Retrovirally Transduced Hematopoietic Stem Cells
Authors: Marita Bosticardo, Charles Scanga, Francesco Novelli, Jean-Laurent Casanova, Fabio Candotti
Journal: Molecular Therapy (2005)

Patients carrying genetic defects in the IL-12 signaling pathway (IL-12 p40 or IL-12Rb1) show defective immunity against intracellular pathogens, resulting in increased vulnerability to weakly pathogenic strains of Mycobacteria and Salmonella. Despite early diagnosis and treatment with antibiotics and IFN-g, IL12Rb1-deficient patients can still succumb to complications of serious infections. Reversion of patients' susceptibility by corrective gene transfer could be beneficial by preventing the infectious episodes. We showed that gene transfer of IL-12Rb1 chain in PHA-activated T cells blasts of IL-12Rb1 deficient patients through retroviral-mediated transduction restored the expression of the receptor chain and reconstituted IL-12 signaling, as demonstrated by STAT4 phosphorylation and IFN-g production._In addition, to test the feasibility and safety of retroviral-mediated gene correction in vivo, we established a murine model of gene therapy in IL-12Rb1-deficient mice. Treated mice did not show adverse effects upon gene therapy. Transplantation of gene-corrected hematopoietic stem cells resulted in IL-12Rb1 expression in PBMCs, thymocytes and SP cells of IL-12Rb1 KO mice. In addition, splenocytes isolated from gene-corrected IL-12Rb1 KO mice acquired the ability to respond to IL-12, as demonstrated by the production of IFN-g, which is completely impaired in IL-12Rb1 KO mice. However, restoration of IL-12Rb1 membrane expression as well as the production of IFN-g in response to IL-12 where significantly lower than those detected in wild type control mice. Interestingly, we couldn't detect in the periphery of gene corrected mice the presence of cells expressing high levels of IL-12Rb1 chain, comparable to those detected in their thymuses. These data indicate the possibility of a selective elimination of potentially dangerous IL-12Rb1 high expressing cells in the periphery that prevented the achievement of a complete correction of gene therapy treated mice. In addition, production of IFN-g upon challenge with LPS from Salmonella enteriditis provided in vivo evidence of partial correction of IL-12 signaling pathway in IL-12Rb1 KO mice after gene therapy. We are performing experiments of infections with intracellular pathogens, such as Mycobacterium tuberculosis, to establish if the degree of gene correction reached in our experimental model is sufficient to overcome their immunodeficiency