tbuckley/cabot-search huggingface dataset:
Selection of Self-Reactive T Cells in the Thymus
Authors: Gretta L. Stritesky, Stephen C. Jameson, Kristin A. Hogquist
Journal: Annual Review of Immunology (2012)

On the whole, the healthy adaptive immune system is responsive to foreign antigens and tolerant to self. However, many individual lymphocytes have, and even require, substantial self-reactivity for their particular functions in immunity. In this review, we discuss several populations of lymphocytes that are thought to experience agonist stimulation through the T cell receptor during selection: nTreg cells, iNKT cells, nIELs, and nTh17s. We discuss the nature of this self-reactivity, how it compares with conventional T cells, and why it is important for overall immune health. We also outline molecular pathways unique to each lineage and consider possible commonalities to their development and survival.
Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension.
Authors: P R Mills, A P Rae, D A Farah, R I Russell, A R Lorimer, D C Carter
Journal: Gut (1984)

This report uses an enhanced conceptualisation of self-injury mortality (SIM), which comprised registered or known suicides by any method and estimated non-suicide deaths from opioid and other drug self-intoxication. SIM surpassed diabetes as a cause of death in the USA in 2015. The gap expanded in 2016 with respective rates of 29.1 and 24.8 per 100 000 population. Facing similar social and psychologically complex health problems to SIM, the USA has initiated and sustained successful broad-based prevention efforts that have reduced deaths from cardiovascular diseases, smoking-related lung cancer, HIV and motor vehicular injury—given both necessary epidemiological understanding to define the problem and sufficient political will to address it. Development of strategies to prevent SIM will be facilitated by focusing on factors that are common risks for diverse outcomes. Like premature mortality frequently associated with diabetes, deaths from self-injurious behaviours are preventable.
Growth Hormone Treatment during Hemodialysis in a Randomized Trial Improves Nutrition, Quality of Life, and Cardiovascular Risk
Authors: Bo Feldt-Rasmussen, Martin Lange, Wladyslaw Sulowicz, Uzi Gafter, Kar Neng Lai, Jonas Wiedemann, Jens Sandal Christiansen, Meguid El Nahas
Journal: Journal of the American Society of Nephrology (2007)

Nutritional markers, such as lean body mass (LBM) and serum albumin, predict outcome in dialysis patients, in whom protein-energy malnutrition is associated with increased morbidity and mortality. The metabolic effects of human growth hormone (hGH) may improve the nutritional and cardiovascular health of these patients and consequently reduce morbidity and mortality. The aim of this study was to establish clinical proof of concept of hGH treatment for the improvement of the nutritional status in adult patients who are on maintenance hemodialysis. A total of 139 adult patients who were on maintenance hemodialysis and had serum albumin levels < or =40 g/L were randomly assigned to 6 mo of treatment with placebo or 20, 35, or 50 microg/kg per d hGH. Change in LBM and serum albumin (primary outcomes), health-related quality of life, and secondary efficacy and safety parameters were monitored. The study showed that hGH treatment increased LBM significantly at all dosage levels (2.5 kg [95% confidence interval 1.8 to 3.1] versus -0.4 kg [95% confidence interval -1.4 to 0.6]; P < 0.001 for pooled hGH groups versus placebo). Serum albumin tended to increase (P = 0.076), serum transferrin (P = 0.001) and serum HDL (P < 0.038) increased, and plasma homocysteine was reduced (P = 0.029). TNF-alpha also tended to decrease with treatment (P = 0.134). An improvement in the Role Physical SF-36 quality-of-life subscale was observed (P = 0.042). There were no differences in clinically relevant adverse events between groups. In conclusion, hGH therapy safely improves LBM, other markers of mortality and morbidity, and health-related quality of life in adult patients who are on maintenance hemodialysis. A long-term study is warranted to investigate whether these treatment benefits result in reduced mortality and morbidity.
GLUCOSE EXCRETION IN BRIGHT'S DISEASE 1
Authors: James A. Hawkins, Eaton M. MacKay, Donald D. Van Slyke
Journal: Journal of Clinical Investigation (1929)

The occurrence of hyperglycemia and glycosuria in nephritis has been observed and studied by Neubauer in 1910 and a number of subse- quent investigators.A review of this subect has been included in the artide on carbohydrate metabolism in nephritis by Linder, Hiller and, Van Slyke (1925).They found that hyperglycemia and glycosuria were most frequent in cases with marked deficit of renal function; that nephritics with fasting hyperglycemia when fed glucose showed abnormally high and prolonged blood sugar curves, similar to those in mild diabetes; that nevertheless the respiratory quotients after glucose feeding rose as in normal subjects, indicating a normal combustion of glucose.The abnormality appeared to lie in a retarded transfer of glucose from blood to tissues, rather than in a retarded combustion.The renal threshold of sugar excretion appeared to be low in some cases, as evidenced by the appearance of a positive qualitative Bene- di ct test for reducing substances in the urine.However, as shown by Eagle (1926-27) and by Van Slyke and Haw- kins (1929), normal urine may contain substances equivalent in reducing power to 0.1 per cent or more of glucose; but only about one- tenth of the reduction is actually due to sugar capable of fermentation, like glucose.To obtain interpretable data concerning the permeability of nephritic kidneys to glucose it is therefore necessary to base con- clusions upon determinations of the fermentable sugar in the urine.The present studies are based on such determinations.
Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a phase I trial in metastatic melanoma.
Authors: Lone Duval, Henrik Schmidt, Keld Kaltoft, Kirsten Fode, Jens Jorgen Jensen, Steen Mellerup Sorensen, Michael I Nishimura, Hans von der Maase
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with a T-cell receptor encoding gene. EXPERIMENTAL DESIGN: Cells were administered intratumorally in four dose levels ranging from 10(8) to 10(9) cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles. RESULTS: Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient. CONCLUSION: Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.
Sarcoid granulomatosis after zirconium exposure with multiple organ involvement
Authors: U Werfel, J Schneider, K Rodelsperger, J Kotter, W Popp, HJ Woitowitz, G Zieger
Journal: European Respiratory Journal (1998)

To the Editor: A 51 yr old, nonsmoking female suffered from relapsing progressive pneumonia for several years. The patient had worked for 16 yrs in the nuclear industry and was exposed to grinding particles and welding fumes working with zirkaloy, an alloy containing tin, iron, chromium and zirconium. During an exacerbation of the pneumonia radiography of the lung showed interstitial infiltrations of both lower lobes. Extended diagnostic procedures could not confirm an infectious disease. In addition, nodular and painful thickenings appeared in old operation scars on the left breast and right hand, and near former injection points on the buttocks and abdominal wall. The scar tissue of the left breast and an axiliary lymph node were examined histologically after excision. Both tissues showed many epithelioid cell granulomas with giant cells, while foreign bodies were only seen in the skin. Persistent infiltrations of the lung led to lobectomy of the right lower lobe and partial resection of the middle lobe in order to exclude a malignant disease. The histological picture of the lung tissue showed different stages of alterations with pronounced proliferation of the alveolar epithelium, epithelioid cell granulomas between well-presented alveolar walls and additional large areas of scarred tissue [1]. Regression of the pulmonary infiltrations was observed within a few weeks of beginning corticosteroid therapy with 24 mg prednisone daily. The initial pulmonary function test showed a normal vital capacity and a reduced timed vital capacity (Tiffeneau test), which was normal in a control examination 6 months later.
“A Good Personal Scientific Relationship”: Philip Morris Scientists and the Chulabhorn Research Institute, Bangkok
Authors: Ross MacKenzie, Jeff Collin
Journal: PLoS Medicine (2008)

Background This paper examines the efforts of consultants affiliated with Philip Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005. Methods and Findings This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships. Conclusions The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently awarded status as a WHO Collaborating Centre. Since the network of WHO Collaborating Centres rests on the principle of "using national institutions for international purposes," the documents presented below suggest that more rigorous safeguards are required to ensure that such use advances public health goals rather than the objectives of transnational corporations.
Basophils Initiate IL-4 Production during a Memory T-dependent Response
Authors: Marat V. Khodoun, Tatyana Orekhova, Crystal Potter, Suzanne Morris, Fred D. Finkelman
Journal: The Journal of Experimental Medicine (2004)

Experiments were performed to characterize and identify the cellular sources of the secondary interleukin (IL)-4 response to a T cell-dependent antigen. Mice were primed by immunization with goat anti-mouse immunoglobulin (Ig)D antibody (GaMD), which stimulates naive CD4+ T cells to secrete IL-4 in 3-4 d. When challenged with goat serum 14 d after immunization, GaMD-primed mice generated an IL-4 response that exceeded the primary response by approximately 100-fold, started in <2 h, and lasted for 4 d. Studies with 4get mice, in which cells with an accessible Il4 gene express a green fluorescent protein (GFP), revealed CD4+ memory T cells, natural killer T cells, basophils, mast cells, and eosinophils as possible rapid producers of IL-4. GFP(+)CD4+ T cells and basophils expanded more in the spleen than the other cell types during the primary response to GaMD. Quantitation of in vivo IL-4 production by the in vivo cytokine capture assay after individual cell types were selectively stimulated or deleted demonstrated that basophils and memory CD4+ T cells account for most of the secondary IL-4 response, with basophils initiating that response through IgE/FcepsilonRI-mediated signaling but secreting IL-4 for <4 h and memory T cells secreting IL-4 within 4 h and continuing to secrete this cytokine for 4 d.
Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax
Authors: Jamie L. Szocinski, Annette R. Khaled, Julie Hixon, Douglas Halverson, Satoshi Funakoshi, William C. Fanslow, Ann Boyd, Dennis D. Taub, Scott K. Durum, Clay B. Siegall, Dan L. Longo, William J. Murphy
Journal: Blood (2002)
Exocrine pancreatic insufficiency: accuracy and clinical value of the uniformly labelled 13C-Hiolein breath test.
Authors: B Lembcke, B Braden, W F Caspary
Journal: Gut (1996)

BACKGROUND AND AIMS: The 13C-Hiolein breath test (98% [U-13C] labelled long chain triglyceride mixture (highly labelled triolein) was evaluated as a non-invasive, non-radioactive test for exocrine pancreatic insufficiency. Accuracy and clinical validity were examined with reference to both the secretin pancreozymin test and faecal fat analysis. METHODS: A secretin pancreozymin test and faecal fat analysis were performed in 46 patients, 30 with exocrine pancreatic insufficiency and 16 with normal pancreatic function. In all of these patients and in seven healthy volunteers (controls), a 13C-Hiolein breath test was performed using 2 mg/kg [U-13C] labelled Hiolein with a standard risk snack (1.5 g/kg; 25% fat). 13CO2/12CO2 enrichment in the exhaled breath was measured by isotope ratio mass spectrometry. RESULTS: In patients with pancreatic steatorrhoea the 13CO2 response was below the 95% confidence interval of 13CO2 exhalation in the controls. These responses were also diminished (p &lt; 0.001) compared with patients with impaired lipase output but normal fat excretion and with disease as well as healthy controls. There was a linear correlation between stimulated lipase output and the ratio of lipase output/13CO2 response (r = 0.95). Among the 40 patients in whom direct pancreatic function testing was clinically indicated, the sensitivity of the 13C-Hiolein test for detecting steatorrhoea was 91.7%, with a specificity of 85.7%. CONCLUSIONS: In patients with pancreatic disease the 13C-Hiolein breath test reflects impaired lipase output and indicates decompensated lipolysis. The 13C-Hiolein breath test is a convenient alternative to faecal fat analysis.
Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis
Authors: C. Coles, A.M. Thompson, P.A. Elder, B.B. Cohen, I.M. Mackenzie, G. Cranston, J. Mackay, M. Macdonald, C.M. Steel, A.M. Thompson, U. Chetty, J. Mackay, Y. Nakamura, B. Hoyheim
Journal: The Lancet (1990)
Treatment of Hen's Egg- and Cow's Milk-induced Anaphylaxis by Rash Oral Immunotherapy
Authors: N. Yanagida, T. Utsunomiya, S. Sato, M. Iguchi, T. Komata, T. Imai, M. Tomikawa, M. Ebisawa
Journal: Journal of Allergy and Clinical Immunology (2010)
SCREENING DATA FROM THE CANCER CHEMOTHERAPY NATIONAL SERVICE CENTER SCREENING LABORATORIES. XXIV.
Authors: Joseph Leiter, B. J. Abbott, Saul A. Schepartz
Journal: Cancer Research (1965)

Data are reported on 953 synthetic compounds which were tested in the CCNSC primary screens. Almost all of the compounds were tested in Sarcoma 180, Carcinoma 755, Leukemia 1210, and KB cells in culture; some tests were also carried out in Friend virus leukemia and Lewis lung carcinoma. Data are reported only on compounds which have not demonstrated sufficient activity in these systems to warrant further investigation.
Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project
Authors: Youn H. Kim, Mahkam Tavallaee, Uma Sundram, Katrin A. Salva, Gary S. Wood, Shufeng Li, Sima Rozati, Seema Nagpal, Michael Krathen, Sunil Reddy, Richard T. Hoppe, Annie Nguyen-Lin, Wen-Kai Weng, Randall Armstrong, Melissa Pulitzer, Ranjana H. Advani, Steven M. Horwitz
Journal: Journal of Clinical Oncology (2015)

In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored.In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety.Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event.Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.
The human mannose-binding protein functions as an opsonin.
Authors: M Kuhlman, K Joiner, R A Ezekowitz
Journal: The Journal of Experimental Medicine (1989)

The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains: a cysteine-rich NH2-terminal domain that stabilizes the alpha-helix of the second collagen-like domain, and a third COOH-terminal carbohydrate binding region. The function of MBP is unknown, although a role in host defense is suggested by its ability to bind yeast mannans. In this report we show that native and recombinant human MBP can serve in an opsonic role in serum and thereby enhance clearance of mannose rich pathogens by phagocytes. MBP binds to wild-type virulent Salmonella montevideo that express a mannose-rich O-polysaccharide. Interaction of MBP with these organisms results in attachment, uptake, and killing of the opsonized bacteria by phagocytes. These results demonstrate that MBP plays a role in first line host defense against certain pathogenic organisms.
Interferon Induction of TAP1
Authors: Wang Min, Jordan S. Pober, David R. Johnson
Journal: Circulation Research (1998)

Abstract —Interferon (IFN)-γ and IFN-α/β induction of the transporter associated with antigen processing-1 (TAP1) promoter was compared in HeLa cells and endothelial cells (ECs). In HeLa cells, IFN-γ acts through Stat1α/Stat1α homodimers binding to the gamma activating sequence (GAS) and IFN-α/β acts through Stat1/Stat2/p48 binding to the IFN-stimulated response element (ISRE). In ECs, however, IFN-γ and IFN-α/β act through both the GAS and ISRE. The basis of the IFN signaling crossover in ECs was investigated. HeLa and ECs contain similar ratios of Stat1α to Stat2 proteins, and IFN-α/β also activates the same Janus kinases (JAKs) (Jak1 and tyrosine kinase (Tyk) 2 but not Jak2). However, IFN-α/β activates more Stat1α than does IFN-γ in ECs, whereas the reverse occurs in HeLa, and expression of the IFN-α/β receptor-associated phosphatase SHP-1 is much lower in ECs than HeLa cells. Overexpression of SHP-1 in ECs blocks IFN-α/β signaling through GAS, and expression of a dominant negative SHP-1 in HeLa cells permits IFN-α/β signaling through GAS, demonstrating a role for SHP-1 in regulating crossovers between the IFN-α/β and IFN-γ signaling pathways.
The Effect of Lanthanides and Actinides on Blood Coagulation. II. Assay of a New Serum Thromboplastic Factor Vulnerable to These Elements and Its Variations in Health and Disease*
Authors: Robert Colman, Benjamin Alexander
Journal: Journal of Clinical Investigation (1964)

It has been previously reported (1, 2) that some rare earth and related elements progres- sively inactivate a hitherto unrecognized serum component necessary for thromboplastin genera- tion.This factor (thorium vulnerable factor, TVF) 1 is distinct from any previously defined clotting factor or intermediate.It is adsorbable by BaSO4, eluted by citrate, precipitable from serum at 50 to 66% (NH4)2SO4 saturation, and separable from other coagulation constituents by physicochemical means.The thorium-induced in- activation is corrected by substituting normal platelets for phospholipid in the thromboplastin generating mixture.Inactivation can be com- pletely reversed by citrate or oxalate, but not by -extensive dialysis.TVF also differs from all known serum factors by its relative lability.This report includes an assay procedure, based on a modification of the thromboplastin generation test (TGT), the normal variation of TVF, and its levels in newborn infants, pregnant subjects, pa- tients under coumarin therapy, and individuals with liver disease. MethodsThorium chloride (ThCl4, chemically pure)2 was ana- lyzed as: rare earths, 0.03%; Fe, 0.01%; and 1Ng, 0.01%.BaSO4-adsorbed oxalated plasma (BaSO4 plasma) was prepared by mixing fresh oxalated human plasma with 100 mg BaSO4 (chemically pure)3 per ml for 15 min- utes at 250 C.