tbuckley/cabot-search huggingface dataset:
Innocuous IFNγ induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production
Authors: Renu Jain, Danielle M. Tartar, Randal K. Gregg, Rohit D. Divekar, J. Jeremiah Bell, Hyun-Hee Lee, Ping Yu, Jason S. Ellis, Christine M. Hoeman, Craig L. Franklin, Habib Zaghouani
Journal: The Journal of Experimental Medicine (2008)

The role of Th17 cells in type I diabetes (TID) remains largely unknown. Glutamic acid decarboxylase (GAD) sequence 206–220 (designated GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon γ (IFNγ) protect against passive TID. Because IFNγ is known to inhibit Th17 cells, effective presentation of GAD2 peptide under noninflammatory conditions may protect against TID at advanced disease stages. To test this premise, GAD2 was genetically incorporated into an immunoglobulin (Ig) molecule to magnify tolerance, and the resulting Ig-GAD2 was tested against TID at different stages of the disease. The findings indicated that Ig-GAD2 could not prevent TID at the preinsulitis phase, but delayed TID at the insulitis stage. More importantly, Ig-GAD2 sustained both clearance of pancreatic cell infiltration and β-cell division and restored normoglycemia when given to hyperglycemic mice at the prediabetic stage. This was dependent on the induction of splenic IFNγ that inhibited interleukin (IL)-17 production. In fact, neutralization of IFNγ led to a significant increase in the frequency of Th17 cells, and the treatment became nonprotective. Thus, IFNγ induced by an adjuvant free antigen, contrary to its usual inflammatory function, restores normoglycemia, most likely by localized bystander suppression of pathogenic IL-17–producing cells.
Drinking Water as a Source of Lead Pollution
Authors: A. Goldberg
Journal: Environmental Health Perspectives (1974)

Frank lead poisoning was found in some inhabitants of houses in the Scottish Highlands, exposed to soft water and lead-lined drinking water tanks. Further investigations were carried out on the clinical and metabolic effects of lead acquired by drinking soft domestic water from lead plumbing systems in 23 Glasgow households. The lead content of water from cold taps was up to 18 times the upper acceptable limit and was proportional to the amount of lead in the plumbing system. The blood lead of 71 inhabitants of these houses showed a significant positive correlation with water lead content. Delta aminolaevulic acid dehydrase activity, an extremely sensitive indicator of lead exposure, showed a significant negative correlation with water-lead content. Atmospheric lead was within acceptable limits in all but one house and no significant correlation could be found with biochemical measurements. A small number of clinical abnormalities were found but could not be directly attributed to lead toxicity. The results of the study underline the possible danger to health of lead plumbing systems in soft-water regions.
Book Review Epilepsy: Scientific Foundations of Clinical Practice (Neurological Disease and Therapy. Vol. 64.) Edited by Jong M. Rho, Raman Sankar, and José E. Cavazos. 510 pp., illustrated. New York, Marcel Dekker, 2004. $165. 0-8247-5043-8
Authors: Teresa Tran
Journal: New England Journal of Medicine (2005)
Bowel perforation requiring emergency laparotomy and a Hartmann’s procedure after a gas explosion induced by argon plasma coagulation
Authors: A. Townshend, W. Goddard, J. Cid
Journal: Endoscopy (2007)

A 95-year-old woman was scheduled to undergo routine argon plasma coagulation (APC) of a bleeding rectal villous adenoma (Figure [1]). Bowel preparation was performed using a Fletcher’s phosphate enema (Forest Laboratories UK Ltd., Bexley, Kent, UK) approximately 1 hour before the procedure. APC treatment was performed using the Erbe system at the following settings: argon flow rate 1 liter/minute; power 100 W; Endo Cut on; effect 2; spray A65.
Clinical Characteristics, Respiratory Functional Parameters, and Outcome of a Two-Hour T-Piece Trial in Patients Weaning from Mechanical Ventilation
Authors: IMMA VALLVERDÚ, NURIA CALAF, MIREIA SUBIRANA, ALVAR NET, SALVADOR BENITO, JORDI MANCEBO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The discrepancy in results from different studies regarding outcome of weaning from mechanical ventilation may be due to several factors such as the differences in patient populations and weaning indexes used. In order to analyze the clinical characteristics and weaning indexes in patients undergoing a 2-h T-piece weaning trial and the relationship between the etiology of acute respiratory failure (ARF) and the outcome of this weaning trial, we prospectively studied 217 patients receiving mechanical ventilation who met standard weaning criteria. Successful weaning occurred in 57.6% (125 of 217) of patients: 13 of 33 (39.4%) patients with chronic obstructive pulmonary disease (COPD), 27 of 46 (58.7%) neurologic patients, and 85 of 138 (61.6%) patients with ARF. Ventilatory support was reinstituted in 31.8% (69 of 217) patients: 20 of 33 (60.6%) of patients with COPD, four of 46 (8.7%) neurologic patients, and 45 of 138 (32.6%) patients with ARF (p < 0.001). Reintubation was required in 23 of 148 (15.5%) patients: 15 of 42 (35.7%) neurologic patients, and eight of 93 (8.6%) patients with ARF, whereas no patient with COPD was reintubated (p < 0.001). Using a discriminant analysis, the following variables were selected as the best predictors of outcome: (1) in the whole population, days of mechanical ventilation before weaning trial (DMV), frequency-to-tidal volume ratio (f/Vt), maximal inspiratory pressure (MIP), airway occlusion pressure (P0.1), maximal expiratory pressure (MEP), and vital capacity (VC); (2) in patients with ARF, DMV, P0.1/MIP, MIP, f/Vt, and age; (3) in patients with COPD, f/Vt, P0.1, P0.1/MIP, MIP, age, and DMV; (4) in neurologic patients, MIP, MEP, and f/Vt · P0.1. Using these predictors, 74.6% of the whole population, 76.1% of patients with ARF, 93.9% of patients with COPD, and 73.9% of neurologic patients were accurately classified as weaning successes or failures. The highest rate of reintubation occurred in neurologic patients. In this group, the ability to cough and clear respiratory secretions, objectively reflected by MEP, may help in clinical decision-making.
Spectrum of Cancer Risk Among US Solid Organ Transplant Recipients
Authors: Eric A. Engels, Ruth M. Pfeiffer, Joseph F. Fraumeni, Bertram L. Kasiske, Ajay K. Israni, Jon J. Snyder, Robert A. Wolfe, Nathan P. Goodrich, A. Rana Bayakly, Christina A. Clarke, Glenn Copeland, Jack L. Finch, Mary Lou Fleissner, Marc T. Goodman, Amy Kahn, Lori Koch, Charles F. Lynch, Margaret M. Madeleine, Karen Pawlish, Chandrika Rao, Melanie A. Williams, David Castenson, Michael Curry, Ruth Parsons, Gregory Fant, Monica Lin
Journal: JAMA (2011)

Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology.
Investment in health research needs scrutiny
Authors: Nick Smallwood
Journal: BMJ (2006)

Closer tracking of money invested in health research around the world is essential if resources are to be used effectively, says a new report from the Global Forum of Health Research.

Spending on health research has tripled in the past two decades from an estimated $30bn (£16.5bn; 荤24bn) in 1986 to $106bn in 2001 (the latest year for which data are available). It is uncertain, however, whether this increase has narrowed the “10-90” gap—the term coined in 1986 to emphasise the fact that only 10% of the world's …
MYOCARDIAL INJURY IN HYPERTENSIVE HEART
Authors: Erika Yamamoto, Yukihito Sato, Tadashi Miyamoto, Ryoji Taniguchi, Masanao Toma, Rei Fukuhara, Kiyoto Nishi, Sayaka Saijo, Yohei Tanada, Naoki Takahashi, Taisuke Goto, Takuma Sawa, Takashi Kiyonaka, Takako Fujiwara, Hisayoshi Fujiwara, Yoshiki Takatsu
Journal: Journal of the American College of Cardiology (2010)
The Influence of <i>Helicobacter Pylori</i> Infection on Early Rebleeding Rate in Patients with Peptic Ulcer Bleeding
Authors: I. Rácz, K. Bircher, T. Kárász, A. Németh
Journal: Endoscopy (2004)

We read with great interest the article by Schilling et al. [1], investigating the influence of Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the early rebleeding rate in patients who had undergone successful primary endoscopic hemostasis procedures for peptic ulcer bleeding. The highly interesting paper mainly focuses on the question of whether H. pylori infection has any influence on rebleeding episodes during the 3-week period after initial hemostasis. The authors concluded that H. pylori infection does not affect the early rebleeding rate after successful endoscopic hemostasis in patients with peptic ulcer bleeding, and therefore early eradication therapy may not be necessary in order to improve the prognosis in the acute phase. We agree with these conclusions, which accord well with our own results; however we have some suggestions and comments about the study design and data.
The Medical Practitioners in Medieval England: A Biographical Register
Authors: Lester S. King
Journal: JAMA (1966)

Most new books become rapidly outdated. It is indeed refreshing to welcome a new work of tremendous scholarship that will immediately assume a definitive position in the learned world, and will maintain that position for a long time to come. What was medicine like in the Middle Ages? Professors Talbot and Hammond, who began to investigate the problem independently but later joined forces, have published a scholarly and at the same time fascinating answer. Their answer takes the form not of a narrative but of a biographical dictionary. They have compiled all the known medical practitioners in medieval Britain, covering the period from Bede to the early 16th century, arranged them alphabetically, and have presented all the relevant biographical and social data. To find their biographical material they combed the primary sources in British history— both printed and manuscript material, including charters, rolls, chancery and exchequer records, household accounts, monastic
The Nuremberg Code, Informed Consent, and Involuntary Treatment-Reply
Authors: Michael A. Grodin
Journal: JAMA (1997)

<h3>In Reply.</h3> —The major focus of our Editorial was on how physicians and lawyers can work together to promote human rights and medical ethics as a fitting legacy to the way physicians and lawyers worked together at Nuremberg to bring the Nazi physicians to justice. Among other things, we proposed a new organization, Global Physicians and Lawyers for Human Rights, and have been gratified by the positive response to date. Rather than addressing the global challenge of promoting human rights, the letters from Drs Borelli, Tiedt, and Howe reflect narrow and idiosyncratic agendas. Borelli seems to have missed our specific reference to the continuing problem of "using psychiatrists to drug prisoners for easier control." However, we do agree that Dr Szasz deserves to be singled out for his consistent and powerful work supporting the rights of the mentally ill, including his early and strong endorsement of informed consent in his 1963 book,
Hemodynamic effects of intravenous phentolamine in low output cardiac failu;e. Dose-response relationships.
Authors: M A Stern, H K Gohlke, H S Loeb, R P Croke, R M Gunnar
Journal: Circulation (1978)

Nineteen patients with chronic low output cardiac failure were studied before, during and after infusion of phentolamine in doses of 10, 20, 30 and 40 microgram/kg/min. Significant reduction of left- and right-sided pressures and increases in cardiac index and heart rate (HR) were present within 15 minutes of starting phentolamine at the 10 microgram/kg/min dose. Minimal additional effect was observed at 30 minutes. Increased dose from 10 to 20 mu/kg/min resulted in small but significant (P less than 0.05) additional reduction in pressures and increases in HR. No additional significant changes occurred at doses of 30 or 40 microgram/kg/min. Significant hemodynamic changes persisted for at least an hour (53 +/- 3 min) after the phentolamine infusion was discontinued. Near maximal ;emodynamic effects occur within 15 minutes of starting phentolamine infusion and can be achieved at doses of 10 to 20 microgram/kg/min. Increased HR during phentolamine infusion may limit its usefulness in patients with ischemic heart disease.
Authors' reply to Dalzell and Cannon and Satchithananda and colleagues
Authors: K. Dworzynski, E. Roberts, A. Ludman, J. Mant
Journal: BMJ (2014)

We agree with Dalzell and Cannon that, with the possible exception of diuretics, no single drug treatment has been shown to improve outcomes in acute heart failure.1 The National Institute for Health and Care Excellence (NICE) guideline is worded to reflect this lack of evidence.2

Satchithananda and colleagues are correct—we did not formally …
Comparison between autologous noncultured extracted hair follicle outer root sheath cell suspension and autologous noncultured epidermal cell suspension in the treatment of stable vitiligo: a randomized study
Authors: C. Singh, D. Parsad, A.J. Kanwar, S. Dogra, R. Kumar
Journal: British Journal of Dermatology (2013)

Background Vitiligo is an acquired disorder of pigmentation caused by loss of epidermal melanocytes. Autologous noncultured epidermal cell suspension (NCES) and autologous noncultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) are important surgical modalities for the treatment of stable vitiligo. Objectives To compare NCES and NCORSHFS for producing repigmentation in stable vitiligo. Methods We randomized 30 patients with 47 stable vitiligo lesions into two groups. Patients in group 1 were treated with NCES, and those in group 2 with NCORSHFS. They were evaluated 16 weeks postsurgery for the extent of repigmentation, colour match, change in Dermatology Life Quality Index (DLQI) score and patient satisfaction. Results The extent of repigmentation was excellent (90–100% repigmentation) in 83% of lesions in the NCES group and 65% of lesions in the NCORSHFS group (P = 0·154). Repigmentation ≥ 75% (good repigmentation) was observed in 92% of lesions in the NCES group and 78% of lesions in the NCORSHFS group (P = 0·425). There was a significant improvement in DLQI score in both the groups, but the mean decrease among groups did not differ significantly (P = 0·244). However, patients in the NCES group were significantly more satisfied than the patients in the NCORSHFS group. No significant difference was seen in colour match and pattern of repigmentation. Adverse effects were minimal. Conclusions Both NCES and NCORSHFS are safe and effective techniques with comparable efficacy. To the best of our knowledge, this is the first study directly comparing two different cellular techniques.
Abstract 3288: The anti-tumour efficacy of the novel peptide inhibitor of angiogenesis ALM-201
Authors: Martin O'Rourke, Andrea Valentine, Estelle McLean, Natalie Page, Graham Cotton, Tracy Robson, David Hirst, Timothy Harrison, Iain James
Journal: Cancer Research (2011)

Abstract Neovascularization is critical to tumour growth and metastasis and this has led to the development of a number of marketed anti-angiogenic agents which target VEGF/VEGFR2 receptors, for clinical use in specific types of cancer. However, incomplete responses and/or resistance to these therapies has highlighted the need for new agents targeting alternative pathways. Here we describe the characterisation of a novel peptide derived from the natural protein FKBP-like binding protein (FKBPL), which has extremely potent anti-angiogenic activity, is very effective in mouse xenograft models at low doses, and exerts its effects through microtubule binding using CD44 as a cell-entry mechanism. ALM-201 has been profiled in a range of human microvascular endothelial cell (HMEC-1) assays and potently inhibited migration, tubule formation and microvessel formation in vitro and in vivo. Although the peptide has a marked effect on migration, ALM-201 does not inhibit proliferation in a range of growth factor stimulated proliferation assays. Importantly, there is a significant disconnect between the pharmacokinetic and pharmacodynamic profiles of ALM-201 which allows for 3 q.d. dosing in mouse xenograft models. The peptide is well tolerated with no signs of toxicity observed in mouse xenograft models up to 80 days of dosing. The mechanism by which ALM-201 inhibits angiogenesis involves the cell surface receptor CD44, as determined by siRNA depletion of the receptor in migration assays. Furthermore, the peptide potently inhibits microtubule assembly and downstream signalling, thus promoting the anti-migratory phenotype. In summary, ALM-201 is a novel, targeted microtubule binding agent which exhibits potent anti-angiogenic activity in vitro and in vivo. Pre-clinical development is in progress with a Phase 1 clinical study planned for 2011. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3288. doi:10.1158/1538-7445.AM2011-3288
Infant frequent wheezing correlated to Clara cell protein 10 (CC10) polymorphism and concentration, but not allergy sensitization, in a perinatal cohort study
Authors: Kuender D. Yang, Chia-Yu Ou, Jen-Chieh Chang, Rong-Fu Chen, Chieh-An Liu, Hsiu-Mei Liang, Te-Yao Hsu, Li-Chen Chen, Shau-Ku Huang
Journal: Journal of Allergy and Clinical Immunology (2007)
A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).
Authors: H Yano, N Kitano, M Morimoto, K S Polonsky, H Imura, Y Seino
Journal: Journal of Clinical Investigation (1992)

We have identified a 65-yr-old nonobese Japanese man with diabetes mellitus, fasting hyperinsulinemia (150-300 pM), and a reduced fasting C-peptide/insulin molar ratio of 2.5-3.0. Fasting hyperinsulinemia was also found in his son and daughter. Analysis of insulin isolated from the serum of the proband and his son by reverse-phase high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials. The insulin gene of the patient was amplified by the polymerase chain reaction and the products were sequenced. A novel point mutation was identified in which guanine was replaced by thymine. The substitution gives rise to a new HindIII recognition site and results in the amino acid replacement of leucine for arginine at position 65. These results indicate that the amino-acid replacement prevents recognition of the C-peptide-A chain dibasic protease and results in an elevation of proinsulin-like materials in the circulation. Furthermore, in this family the proinsulin-like materials is due to a biosynthetic defect, inherited as an autosomal dominant trait. Rapid detection of this mutation can be accomplished by HindIII restriction enzyme mapping of polymerase chain reaction-generated DNA, which enables us to facilitate the diagnosis and screening.
US to introduce new rules on air pollution
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

The US Environmental Protection Agency is finally introducing the first air quality standard governing fine air particles to make breathing safer for Americans, seven years after it first proposed the changes.

More than 99 million people—a third of the US population—live in areas with unhealthy levels of 2.5 micron particles in the air, says the agency. The smaller the particles, the easier it is for them to get deep into the lungs. The particles …
Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers
Authors: Jiayun Shen, Henry Lik-Yuen Chan, Grace Lai-Hung Wong, Paul Cheung-Lung Choi, Anthony Wing-Hung Chan, Hoi-Yun Chan, Angel Mei-Ling Chim, David Ka-Wai Yeung, Francis Ka-Leung Chan, Jean Woo, Jun Yu, Winnie Chiu-Wing Chu, Vincent Wai-Sun Wong
Journal: Journal of Hepatology (2012)
A scalable controlled-release device for transscleral drug delivery to the retina
Authors: Takeaki Kawashima, Nobuhiro Nagai, Hirokazu Kaji, Norihiro Kumasaka, Hideyuki Onami, Yumi Ishikawa, Noriko Osumi, Matsuhiko Nishizawa, Toshiaki Abe
Journal: Biomaterials (2010)
Experimentally induced complement and immunoglobulin deposition along the basement membrane zone (BMZ) and in dermal blood vessels
Authors: R.A.W. MILLER, W.A.D. GRIFFITHS
Journal: British Journal of Dermatology (1982)

Clinically normal forearm skin often subjects was abraded and biopsied at 24 h and at 5 and 10 day intervals. Biopsy specimens were processed for routine histology and direct immunofluorescence. All ten subjects showed deposition of complement either in the blood vessels and/or along the basement membrane zone 24 h after injury. IgM deposition was found along the BMZ in two patients and in the blood vessels of the papillary dermis in one patient. This immunofluorescence staining was considered a non-specific reaction pattern to injury.
Effective short term treatment of Paget's disease with oral etidronate.
Authors: C J Preston, A J Yates, M N Beneton, R G Russell, R E Gray, R Smith, J A Kanis
Journal: BMJ (1986)

Twelve patients with Paget9s disease of bone were treated with high doses of disodium etidronate for one month and compared with patients given treatments for longer periods. The effects of treatment for one month with etidronate 20 mg/kg daily were indistinguishable from six months9 continuous treatment with the same dose but significantly better than treatment with 5 mg/kg daily in suppressing biochemical indices of disease activity. Treatment for one month was associated with transient osteomalacia but sustained suppression of bone resorption. Short term treatments with high doses of disodium etidronate may maximise suppression of disease activity but decrease exposure to unwanted effects.
Reevaluation of the Role of Cellular Hypoxia and Bioenergetic Failure in Sepsis
Authors: Richard S. Hotchkiss
Journal: JAMA (1992)

Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal "delivery-dependent" oxygen consumption. Two hypotheses have been advanced to explain these metabolic abnormalities: (1) cellular hypoxia resulting from abnormal microcirculatory blood flow or (2) defect(s) in energy-producing metabolic pathways of cells. Results of our studies on rat muscle, liver, heart, brain, and plasma suggest that there is no evidence of bioenergetic failure in these septic tissues and that the increase in lactate production is not necessarily due to cellular hypoxia. The adequacy of cellular oxygenation and bioenergetics was verified using in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, [18F]fluoromisonidazole, and microfluorometric enzymatic techniques. Findings from these studies as well as results from several clinical investigations indicate that neither hypothesis can adequately account for the metabolic features typical of sepsis and that the pathophysiology of sepsis awaits further clarification. These studies and important clinical implications are discussed.