tbuckley/cabot-search huggingface dataset:
Development and stability of Th17 cells in ovarian cancer requires nitric oxide and endogenous NOS2 activity in cancer-associated CD4+ T cells
Authors: Natasa Obermajer, Jeffrey L Wong, Robert P Edwards, Kong Chen, Melanie Scott, Shabaana Khader, Jay K Kolls, Kunle Odunsi, Timothy R Billiar, Pawel Kalinski
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Th17 cells play reciprocal roles in different forms and at different stages of cancer. We report that the presence of Th17 cells in ovarian cancer ascites correlates with local expression of nitric oxide synthase-2 (NOS2). Furthermore, the development of RORγt+IL-23R+IL-17+ Th17
High prevalence of the very rare wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): A genetic and clinical study
Authors: Luis García-Villarreal, Susan Daniels, Sarah H. Shaw, David Cotton, Margaret Galvin, Jeanne Geskes, Paula Bauer, Angel Sierra-Hernández, Alan Buckler, Antonio Tugores
Journal: Hepatology (2000)

The molecular basis of Wilson disease (WD), an autosomal recessive disorder, is the presence of mutations in the ATP7B gene, a copper transporting ATPase. Hospital records indicated a higher prevalence of WD (1 in 2,600) in some counties in the northeastern region of the island of Gran Canaria (Canary Islands, Spain) that was around 10-fold higher than that described for European populations (1 in 30,000). The ATP7B gene was analyzed for mutations in 24 affected subjects, revealing a high prevalence of the rare Leu708Pro mutation present in 12 homozygous and 7 heterozygous individuals. In these patients, who constitute one of the largest described cohorts of WD homozygotes, we found a variable clinical presentation of the disease, although the biochemical picture was homogenous and characteristic, thereby confirming that the Leu708Pro change is indeed a mutation associated with WD. Haplotype analysis of subjects homozygous for the Leu708Pro mutation showed a conserved shared region smaller than 1 centimorgan (cM), and the region of linkage disequilibrium between the Leu708Pro mutation and neighboring microsatellite markers extended approximately 4.6 cM. When comparing the amount of linkage disequilibrium versus genetic distance from the disease mutation, it was estimated that a common ancestral Leu708Pro chromosome may have been introduced in Gran Canaria over 56 generations ago, dating it back to pre-Hispanic times. The prevalence, and the tight geographical distribution of the Leu708Pro chromosome suggests that the Canary Islands can be considered a genetic isolate for linkage disequilibrium studies.
Lipodystrophia centrifugalis abdominalis infantilis
Authors: SADAO IMAMURA, MIZHUA YAMADA
Journal: British Journal of Dermatology (1977)

Journal Article Lipodystrophia centrifugalis abdominalis infantilis Get access SADAO IMAMURA, SADAO IMAMURA Department of Dermatology, Faculty of Medicine, Kyoto University, Shogo‐in, Sakyo‐ku, Kyoto 606, Japan Search for other works by this author on: Oxford Academic Google Scholar MIZHUA YAMADA MIZHUA YAMADA Department of Dermatology, Faculty of Medicine, Kyoto University, Shogo‐in, Sakyo‐ku, Kyoto 606, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 96, Issue 1, 1 January 1977, Page 96, https://doi.org/10.1111/j.1365-2133.1977.tb05195.x Published: 01 January 1977
Diesel exhaust enhances airway responsiveness in asthmatic subjects
Authors: C. Nordenhäll, J. Pourazar, M-C. Ledin, J-O. Levin, T. Sandström, E. Ädelroth
Journal: European Respiratory Journal (2001)

Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation. Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM 10 ) 300 µg·m −3 ) and air during 1 h on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure. Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (p&lt;0.001). DE also induced a significant increase in airway resistance (p=0.004) and in sputum levels of interleukin (IL)-6 (p=0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8. This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings of exacerbations of asthma following exposure to particulate matter.
Points: Management of patients with bilateral amputations
Authors: R. Helsby
Journal: BMJ (1981)

liams's letter (10 October, p 987) about the management of gastrointestinal bleeding, and agree entirely with your comment.I would take exception, however, to his last sentence, which implies that an "alcoholic binge" may lead to an upper gastrointestinal haemorrhage and that this does not require investigation.It is our experience that when alcoholic excess leads to a massive bleed there is usually a chronic underlying cause, and I would suggest that these patients most certainly should be investigated.
Adverse Events following Discharge from the Hospital
Authors: Donald C. Rifas
Journal: Annals of Internal Medicine (2004)

Letters3 February 2004Adverse Events following Discharge from the HospitalDonald C. Rifas, MDDonald C. Rifas, MDFrom Sacramento, CA 95819.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-3-200402030-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Forster and colleagues (1) would have us believe that adverse events occur only as a result of physician lapses, inattention, or simple ignorance. Although these may be important factors, a significant contribution to adverse posthospital events may lie within the medical system itself.Health maintenance organizations and other managed care entities are basking in the profits they make by denial of care; procedures; and, more important for this discussion, certain drugs. My colleagues and I in the United States are aware of consistent posthospital denial of drugs we have prescribed. Days may pass before the correct drug ...References1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse events affecting patients after discharge from the hospital. Ann Intern Med. 2003;138:161-7. [PMID: 12558354] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Donald C. Rifas, MDAffiliations: From Sacramento, CA 95819. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Incidence and Severity of Adverse Events Affecting Patients after Discharge from the Hospital Alan J. Forster , Harvey J. Murff , Josh F. Peterson , Tejal K. Gandhi , and David W. Bates Adverse Events following Discharge from the Hospital Bruce Leff and Chad Boult Adverse Events following Discharge from the Hospital Matthew M. Medlock , Louis R. Cantilena Jr. , and Michael A. Riel Adverse Events following Discharge from the Hospital Rodney A. Hayward and Timothy P. Hofer Adverse Events following Discharge from the Hospital Alan J. Forster and David W. Bates Metrics 3 February 2004Volume 140, Issue 3Page: 231KeywordsAdverse eventsDrugsGastroenterology and hepatologyGastroesophageal reflux diseaseHealth maintenance organizationsHerniaPneumonia ePublished: 3 February 2004 Issue Published: 3 February 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction
Authors: Mallar Bhattacharya, Aparna Sundaram, Makoto Kudo, Jessica Farmer, Previn Ganesan, Amin Khalifeh-Soltani, Mehrdad Arjomandi, Kamran Atabai, Xiaozhu Huang, Dean Sheppard
Journal: Journal of Clinical Investigation (2014)

The intracellular scaffold protein IQGAP1 supports protein complexes in conjunction with numerous binding partners involved in multiple cellular processes. Here, we determined that IQGAP1 modulates airway smooth muscle contractility. Compared with WT controls, at baseline as well as after immune sensitization and challenge, Iqgap1-/- mice had higher airway responsiveness. Tracheal rings from Iqgap1-/- mice generated greater agonist-induced contractile force, even after removal of the epithelium. RhoA, a regulator of airway smooth muscle contractility, was activated in airway smooth muscle lysates from Iqgap1-/- mice. Likewise, knockdown of IQGAP1 in primary human airway smooth muscle cells increased RhoA activity. Immunoprecipitation studies indicated that IQGAP1 binds to both RhoA and p190A-RhoGAP, a GTPase-activating protein that normally inhibits RhoA activation. Proximity ligation assays in primary airway human smooth muscle cells and mouse tracheal sections revealed colocalization of p190A-RhoGAP and RhoA; however, these proteins did not colocalize in IQGAP1 knockdown cells or in Iqgap1-/- trachea. Compared with healthy controls, human subjects with asthma had decreased IQGAP1 expression in airway biopsies. Together, these data demonstrate that IQGAP1 acts as a scaffold that colocalizes p190A-RhoGAP and RhoA, inactivating RhoA and suppressing airway smooth muscle contraction. Furthermore, our results suggest that IQGAP1 has the potential to modulate airway contraction severity in acute asthma.
ApoER2 trafficking, processing and signaling and its participation in neurodegeneration
Authors: María-Paz Marzolo
Journal: Molecular Neurodegeneration (2012)

Background ApoER2, a member of the LDL receptor family, binds to reelin, triggering a signaling pathway that regulates neuronal migration and positioning in the developing brain and dendritic ramification. In the adult, reelin participates in neuronal survival, synaptic plasticity and neurogenesis. Our interest has been to study cell biology aspects of ApoER2, including the molecular and cellular determinants of its endocytic trafficking, how these features regulate the receptor signaling properties and ApoER2 participation in neurodegenerative conditions, such as Alzheimer’s Disease and in the Niemann Pick Type C disease (NPC), a lipid storage and neurodegenerative disorder caused by genetic mutations in npc1 gene that causes cholesterol accumulation in late endosome/lysosomes. In NPC there are alterations in the trafficking and signaling of some receptors however this remains unexplored for ApoER2. As APP, ApoER2 is also processed by proteases and these events are regulated by ligand binding and some cytosolic proteins such as Dab1. By yeast two-hybrid it was found that ApoER2 binds to SNX17, a cytosolic protein that regulates trafficking of membrane proteins in the early endosomal pathway. However SNX17 role in ApoER2 trafficking and signaling has not been evaluated. Methods Endocytic trafficking (internalization and/or recycling) and processing of ApoER2 was evaluated in cell lines transfected with different forms of the receptor to determine the role of 1) its NPxY motif and proline rich insert present in the cytoplasmic domain, 2) Lipid rafts association, 3) dominant negative expression or silencing of adaptor proteins such as Dab2 and SNX17 4) Intracellular cholesterol accumulation. ApoER2 signaling in different conditions (silencing of SNX17; late endosome/lysosome cholesterol accumulation mimicking the NPC condition) were performed in primary cultured neurons activated by reelin, analyzing dendritic branching and determinations of signaling proteins by Western blot. Results ApoER2 internalization is clathrin mediated, determined by its NPXY motif and the adaptor protein Dab2. Lipid rafts association or the presence of the proline-rich insert do not modulate the receptor internalization. The NPXY motif is also responsible of the recycling of ApoER2 from the early endosome, which is mediated by SNX17. Abolishing SNX17 affects ApoER2 signaling in neurons and the receptor processing. ApoER2 processing is stimulated by its own ligand reelin but also by activation of other signaling receptors. In cellular conditions miming NPC there was a decrease in ApoER2 surface levels, explained by a more efficient internalization and less recycling. NPC neurons, exhibited less dendritic ramification while the number of apoptotic cells was increased. Both effects were partial but significantly rescued when exogenous Reelin was added. We found relevant differences in the expression of ApoER2 and its ligand reelin in the brains of the NPC KO mice. Conclusions
Klebsiella pneumoniae Meningitis
Authors: Dennis D. Hickstein
Journal: JAMA (1982)

Despite conventional antibiotic regimens with chloramphenicol and aminoglycosides, mortality from gram-negative bacillary meningitis approaches 40%. With the development of new antibiotics, therapy for this form of meningitis has become an active area of investigation. We describe successful treatment of<i>Klebsiella pneumoniae</i>meningitis with intravenous trimethoprim-sulfamethoxazole, documenting bactericidal levels of the drug in the CSF. (<i>JAMA</i>1982;248:1212-1213)
Underexpression of mRNA in human hepatocellular carcinoma focusing on eight loci
Authors: Moritoshi Kinoshita, Masahiko Miyata
Journal: Hepatology (2002)

Genetic alterations associated with human hepatocellular carcinoma (HCC) have been reported previously, but are not sufficient to specify differences of HCCs from precancerous diseases of the liver, such as hepatitis, hepatic fibrosis, and cirrhosis. In the present study, we performed differential gene display analysis (DGDA) to clarify the specific genetic alterations associated with gene expression changes in the course of development of HCC from chronic viral hepatitis. Four pairs of surgically resected HCCs and hepatitis tissues were investigated. We found 1,028 expression sequence tags (ESTs) that were decreased or increased in HCC tissues compared with hepatitis tissues in the same patient. Nucleotide sequencing showed that they included 55 EST clones in the GenBank database, which were considered candidates for specific messenger RNA (mRNA) expression alterations in HCCs. After excluding 9 ESTs that code mitochondrial DNA, we performed quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) for the 46 remaining EST clones. We found 8 mRNAs underexpressed in primary HCC tissues in 20 patients in higher percentages than found in previous studies, including 18 cases (90%) for aldolase B (ALDOB), 15 cases (75%) for carbamyl phosphate synthetase 1 (CPS1), albumin (ALB), plasminogen (PLG), and EST 51549, 13 cases (65%) for cytochrome P450 subfamily 2E1 (CYP2E1), 12 cases (60%) for human retinol-binding protein 4 (RBP4), and 11 cases (55%) for human organic anion transporter C (OATP-C) gene. In conclusion, underexpression of key gene products may be important in the development and/or progression of HCC.
The Psychiatry of Writing a Will
Authors: Louis L. Lunsky
Journal: JAMA (1990)

The very title of this book creates a paradox. How can a medical discipline, psychiatry, be meaningful in writing a will? Read on. The author, a prominent psychiatrist, weaves a mosaic around the fear of death, loneliness, and the role of money, all of which play a crucial role. This book about the psychological meaning of writing a will should find little competition in the card catalogue. The first person who scholars assume wrote a will was the biblical Jacob, father of Joseph. On the other hand, many prominent persons, such as Lincoln, Andrew Johnson, Grant, Garfield, Jefferson, and, more recently, Picasso, never wrote wills. When Picasso died at the age of 91, he died without leaving instructions on how to distribute his estate of $265 million. What a legal nightmare, which must have delighted probate attorneys! The will is a document in which we distribute significant symbols. Picasso may
Unusual Case of Nutritional Anaemia
Authors: M. McLean
Journal: BMJ (1949)

of the pathological report, the dosage was increased to 500,000 units daily.Pathological Report.-Greenishfoul-smelling pus containing a moderate number of small yellow granules.Stained film: numerous pus cells, numerous fusiform bacilli, small Gram- negative coli and bacilli, a moderate number of clumps of filamentous organisms of fungal morphology.This specimen was referred to the Fungus Reference Laboratory, which reported that Actinomyces israeli was present.On February 22, 2 pints (1.14 litres) of pus was aspirated and 100,000 units of penicillin injected.On February 24, 1 pint (570 ml.) was aspirated.A radiograph on February 28 still showed an encysted collection in the right mid-zone posteriorly.This was much thicker and more difficult to aspirate.Ribresection was considered, but as the fluid was centred under the inferior angle of the scapula it was deciced to continue to aspirate.By March 12 the temperature finally settled.On the 14th a radiograph still showed some encysted fluid.Aspiration failed.On March 18, 6 oz. (170ml.) of pus was aspirated after screening, and penicillin was injected.On April 8, 6 oz. of pus was aspirated and 100,000 units of penicillin injected.Pathological Report of Pus.-On March 9: -Direct smear: numerous pus cells, very scanty Gram-negative bacilli, no actinomyces seen.Cultures: no growth on blood agar.On March 18:-Direct smear: numerous pus cells, no organisms.Culture (aerobic and anaerobic): no growth.An x-ray report on April 12 stated that the fluid seemed to have cleared from the right side and had left some residual pleural thickening.Other Investigations.-Ablood count on February 14 showed: Hb, 68%; red cells, 4,435,000; colour index, 0.77; white cells, 14,000 (eosinophils 81.5%, basophils 0.5%, lymphocytes 11.5%, monocytes 6.5%).Sputum examination on February 17: M. tuberculosis not found; moderate number of pus cells, fairly numerous epithelial cells, a few "dust " cells; no malignant cells seen.Blood sedimentation rate on February 21: first hour, 118 mm.; second hour, 125 mm.(Westergren).Sputum on February 25: moderate number of pus cells, fairly numerous squamous cells, fairly numerous dust cells, no malignant cells; M. tuberculosis not found.Culture :- Mixed: haemolytic streptococci and Neisseria catarrhalis.In addition to intramuscular penicillin (total dosage 25,000,000 units) and intrapleural penicillin (400,000 units)the patient received potassium iodide, 30 gr. (2 g.) thrice daily.He was discharged home on April 18, having been ambulant for ten days.He had gained weight and looked and felt very well.
ENTRANCE OF A NEEDLE INTO THE CHEST: PROBABLE PUNCTURE OF THE HEART
Authors: T. L. Pridham
Journal: BMJ (1856)

Du. 20, 1M w , togther with ntine of urine for three On making an emnion, I found the o0 uteri fuly dilated, the head presnting naturally, and the membranes protrding.The pains being feeble, and the membranes tease and rigid, I waited for about an hour; but, finding no progs in the labour, I ruptured the membranes.As
Vaccine-Induced Tumor Necrosis Factor–Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death
Authors: Tetje C. van der Sluis, Suzanne van Duikeren, Suzanna Huppelschoten, Ekaterina S. Jordanova, Elham Beyranvand Nejad, Arjen Sloots, Louis Boon, Vincent T.H.B.M. Smit, Marij J.P. Welters, Ferry Ossendorp, Bob van de Water, Ramon Arens, Sjoerd H. van der Burg, Cornelis J.M. Melief
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Cancer immunotherapy, such as vaccination, is an increasingly successful treatment modality, but its interaction with chemotherapy remains largely undefined. Therefore, we explored the mechanism of synergy between vaccination with synthetic long peptides (SLP) of human papillomavirus type 16 (HPV16) and cisplatin in a preclinical tumor model for HPV16. Experimental Design: SLP vaccination in this preclinical tumor model allowed the elucidation of novel mechanisms of synergy between chemo- and immunotherapy. By analyzing the tumor immune infiltrate, we focused on the local intratumoral effects of chemotherapy, vaccination, or the combination. Results: Of several chemotherapeutic agents, cisplatin synergized best with SLP vaccination in tumor eradication, without requirement for the maximum-tolerated dose (MTD). Upon SLP vaccination, tumors were highly infiltrated with HPV-specific, tumor necrosis factor-α (TNFα)- and interferon-γ (IFNγ)–producing T cells. Upon combined treatment, tumor cell proliferation was significantly decreased compared with single treated and untreated tumors. Furthermore, we showed that TNFα strongly enhanced cisplatin-induced apoptotic tumor cell death in a JNK-dependent manner. This is consistent with upregulation of proapoptotic molecules and with enhanced cell death in vivo upon combined SLP vaccination and cisplatin treatment. In vivo neutralization of TNFα significantly reduced the antitumor responses induced by the combined treatment. Conclusion: Taken together, our data show that peptide vaccination with cisplatin treatment leads to decreased tumor cell proliferation and TNFα-induced enhanced cisplatin-mediated killing of tumor cells, together resulting in superior tumor eradication. Clin Cancer Res; 21(4); 781–94. ©2014 AACR.
The Future of Chiropractic
Authors: Walter I. Wardwell
Journal: New England Journal of Medicine (1980)

What is to be done about chiropractors? Efforts by organized medicine to eliminate them have been unsuccessful. The label "quack" has not stuck. Despite the most strenuous opposition, they have attained licensure in every state in the United States and in Canada and many foreign countries. Over 23,000 chiropractors treat some 8 million Americans for a wide variety of conditions. Reimbursement for their services has been authorized by Medicare, Medicaid, Workmen's Compensation plans, and by many Blue Shield plans and other private insurance carriers. Chiropractors received more than $30 million of Medicare funds in 1978. Over 2000 new chiropractors will . . .