tbuckley/cabot-search huggingface dataset:
Abstract 5311: Myeloid-derived suppressor cells and immune cell responsiveness in tumor-bearing mice
Authors: Bethany L. Mundy, Gregory Lesinski, Kristen Benninger, Mahmood Khan, Periannan Kuppusamy, Kristan Guenterberg, Sri Vidya Kondadasula, Abhik Ray Chaudhury, Melanie Kreiner, Gregory Young, Denis C. Guttridge, William E. Carson
Journal: Cancer Research (2010)

Abstract Conditions that inhibit IFN-induced signal transduction and gene transcription can dampen the host immune system and its ability to recognize and eliminate tumors leading to impaired immunoediting. We hypothesized that in the setting of cancer, myeloid-derived suppressor cells (MDSC) could impair the responsiveness of immune effector cells to interferons. We used the murine adenocarcinoma cell line C26 which induces MDSC generation when implanted in C2DF1 mice. C26-bearing mice had significantly elevated levels of GR1+CD11b+ MDSC (p&amp;lt;0.0001) and plasma IL-6 as compared to controls (p&amp;lt;0.0001). The ability of IFNa or IFNy to stimulate phosphorylation of the STAT1 transcription factor (P-STAT1, a direct measure of IFN action) was measured by intracellular flow cytometry. Induction of P-STAT1 following a 15 minute stimulation of splenocytes with IFNa (102-104 U/mL) was significantly reduced in C26-bearing mice (Mean P-STAT1 = 18.8; Range = 4.0 - 33.4) as compared to control mice (Mean P-STAT1 = 37.9; Range = 27.0 - 50.0; p&amp;lt;0.0001). A similar decrease in P-STAT1 in splenocytes of C26-bearing mice was observed following IFNy stimulation (1 ng/mL; 15 min; p=0.002). This decrease in IFN responsiveness was also observed in cells derived from inguinal lymph nodes following IFN-stimulation. The level of IFNa induced P-STAT1 was inversely correlated with the plasma IL-6 levels (Pearson correlation = −0.635; p=0.019). However, direct exogenous treatment of mice with IL-6 did not decrease splenic IFN response. In vitro co-culture experiments revealed that MDSC inhibited IFN-responsiveness of splenocytes from normal mice. Reduction of MDSC with either gemcitabine or anti-GR1 antibody treatment restored IFN responsiveness in splenocytes from C26-bearing mice as compared to tumor-bearing mice treated with vehicle or isotype control antibody. Spleens from C26-bearing animals displayed elevated levels of iNOS protein and nitric oxide (NO). The elevation in NO in C26-bearing mice was associated with increased levels of nitration on STAT1. In vitro treatment of splenocytes with a nitric oxide donor led to a decreased STAT1 IFN response. Taken together, these data suggest a novel link between MDSC and a decreased molecular response of the immune effectors responsible for promoting functional anti-tumor responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5311.
Evaluation of a Subcutaneous Glucose Sensor out to 3 Months in a Dog Model
Authors: Barbara J Gilligan, Mark C Shults, Rathbun K Rhodes, Stuart J Updike
Journal: Diabetes Care (1994)

OBJECTIVE To advance the feasibility of an impiantatile long-term glucose sensor with bioprotective sensor membranes and test protocols using a somatostatin analog (octreotide). RESEARCH DESIGN AND METHODS Implantable sensors were constructed with one of eight bioprotective membranes and screened in vitro for stable response to glucose. Sensors were implanted subcutaneously into nondiabetic mongrel dogs and monitored at 4-min intervals via radiotelemetry. When implanted sensor responses showed evidence of tracking blood glucose after glucagon challenge (8–21 days postimplant), a glucose infusion protocolwas used to assess performance. Sensor data were collected every 4 s after octreotide inhibition of endogenous insulin release. Reference plasma glucose samples were taken every 4–10 min. RESULTS Preimplant in vitro testing of sensors verified linearity to 33.3 mM glucose and response times to 90% of equilibrium in 2–7 min. Ten implanted sensors tracked glucose for 20–114 days, during which 25 separate glucose infusion studies were conducted. The resulting regression data yielded a mean slope of 0.99 ± 0.06, an intercept of 0.24 ± 0.53 mM glucose, and a correlation coefficient 0.98 ± 0.01. Long-term sensor stability was not judged adequate for clinical application, although two sensors tracked within ±15% for 33 and 42 days. In vivo oxygen delivery was shown toaffect sensor performance. On expiant, two of eight tested bioprotective membranes were found to be biostable and to fully protect the sensor's enzyme membrane. The foreign body capsule was adequately vascularized adjacent to the sensor up to 91 days postimplant. Sensor units eventually failed because of electronic problems (package leakage) or because of biodegradation or biofouling of test bioprotective membranes. CONCLUSION Further development of this type of sensor may provide diabetic patients with a better means of monitoring blood glucose.
Impairment of vascular regeneration precedes progressive glomerulosclerosis in anti-Thy 1 glomerulonephritis
Authors: Yoko Wada, Tetsuo Morioka, Yukiko Oyanagi-Tanaka, Jian Yao, Yasuhito Suzuki, Fumitake Gejyo, Masaaki Arakawa, Takashi Oite
Journal: Kidney International (2002)
Persistent warts protected from immune attack by a blocking factor
Authors: D.L.J. FREED, KAREN E. EYRES
Journal: British Journal of Dermatology (1979)

Severe warts of 20 years duration, highly resistant to therapy, were found to contain a soluble factor which blocked the local expression of cellular immunity, without affecting systemic immune respon‐ siveness. This finding enabled us to propose therapy by infection, and this had a limited success.
Prognostic factors and prevention of radioembolization-induced liver disease
Authors: Belen Gil-Alzugaray, Ana Chopitea, Mercedes Iñarrairaegui, Jose I. Bilbao, Macarena Rodriguez-Fraile, Javier Rodriguez, Alberto Benito, Inés Dominguez, Delia D'Avola, Jose I. Herrero, Jorge Quiroga, Jesus Prieto, Bruno Sangro
Journal: Hepatology (2012)

Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)
Pigmentation Related to Amiodarone
Authors: W A High, S D Weiss
Journal: New England Journal of Medicine (2001)

Figure 1. A 55-year-old man had blue-gray discoloration of the auricular and periauricular areas of his ears. In 1985, he had had a large anterior myocardial infarction during aortic-valve replacement. Three years later, he had begun to take 400 mg of amiodarone per day for persistent ventricular tachycardia. While taking amiodarone, he began to have photosensitivity, followed by progressive blue-gray pigmentation of areas of his head and face that were exposed to the sun. This pigment has been shown to consist of electron-dense, compact, lamellar granules in the lysosomes of dermal macrophages, similar to lipofuscin. The use of protective clothing . . .
Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect.
Authors: R A Cooper, E C Arner, J S Wiley, S J Shattil
Journal: Journal of Clinical Investigation (1975)

Cholesterol-rich membranes are the hallmark of "spur" red cells. Spur cells accumulate cholesterol from cholesterol-rich serum lipoproteins. Previous studies suggested that this added cholesterol is responsible for both the altered morphology and the destruction of spur cells. To examine this process in the absence of other serum factors, cholesterol-lecithin dispersions with varying amounts of unesterified cholesterol (C) relative to phospholipid (P) were prepared, and their influence on normal human red cells was studied. Cholesterol-rich lipid dispersions (C/P mole ration greater 1.0) transferred cholesterol to both red cell membranes and serum lipoproteins, and cholesterol-poor dispersions (C/P mole ration less 1.0) depleted red cells of cholesterol. Changes in membrane cholesterol paralleled changes in membrane surface area, as calculated from osmotic fragility, with a 0.22 percent variation in surface area per 1.0 percent variation in cholesterol content. Cold-induced compression of membrane surface area was increased in cholesterol-poor red cells (C/P equals 0.4), whereas the surface area of cholesterol-rich membranes (C/P equals 1.80) underwent no compression. Although the Na and K permeability of red cells severely depleted of cholesterol was increased, lesser degrees of depletion had no effect, and the permeability of cholesterol-rich cells was normal. However, increasing membrane cholesterol caused a progressive decrease in red cell deformability, as measured by filtration. Cholesterol-poor red cells were spherocytic in appearance and cholesterol-rich cells were broad and flat, indicative of their surface areas. In addition, cholesterol-rich cells had an irregular contour due to folding of the periphery of the cell. This shape abnormality was identical to that of both spur cells after splenectomy and normal red cells incubated in spur serum. Normalization of the C/P of spur serum by added phospholipid prevented the increase in membrane cholesterol and surface area and the transformation of cell shape. These studies establish that the cholesterol content of red cells is dependent on the C/P of their milieu, either lipoproteins or cholesterol-lecithin dispersions. Moreover, the surface area, deformability, and contour of cholesterol-rich red cells are a direct function of their increased membrane C/P. Although cholesterol-rich spur cells are further modified in the circulation of patients with spleens, this abnormality of the membrane lipid bilayer, induced by cholesterol-rich cholesterol-lecithin dispersions, represents the primary spur cell defect.
Alterations in the K-ras and p53 genes in rat lung tumors.
Authors: S A Belinsky, D S Swafford, G L Finch, C E Mitchell, G Kelly, F F Hahn, M W Anderson, K J Nikula
Journal: Environmental Health Perspectives (1997)

Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. Only two agents, TNM and plutonium, led to mutation frequencies of > 10%. In both cases, the transition mutations formed could have been derived from deamination of cytosine. The identification of non-ras transforming genes in rat lung tumors induced by mutagenic and nonmutagenic exposures such as NNK and beryllium would help define some of the mechanisms underlying cancer induction by different types of DNA damage. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarcinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 to 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors.
Reduction in Pulmonary Vascular Resistance with Long-Term Epoprostenol (Prostacyclin) Therapy in Primary Pulmonary Hypertension
Authors: Vallerie V. McLaughlin, Diane E. Genthner, Maureen M. Panella, Stuart Rich
Journal: New England Journal of Medicine (1998)

Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed.
Uric Acid Levels and Renal Blood Flow
Authors: CHARLES J. DISKIN
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 July 1981Uric Acid Levels and Renal Blood FlowCHARLES J. DISKIN, M.D.CHARLES J. DISKIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-1-123 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recently Messerli and colleagues (1) in an interesting paper related elevated serum uric acid levels to decreased renal blood flow as measured by131I aminohippurate collections. They concluded that early hypertensive vascular involvement was probably to blame. They neglected to consider, however, that both hippurate and urate depend in part on tubular secretion for elimination in the urine. Aminohippurate is not an accurate measure of renal blood flow if there is a disruption of tubular secretion. Sera from spontaneously hypertensive rats have been shown to inhibit aminohippurate secretion (2). Also, it has been shown that when renal...References1. MESSERLIFROHLICHDRESLINSKISUAREZARISTIMUNO FEGDG. Serum uric acid in essential hypertension: an indicator of renal involvement. Ann Intern Med. 1980;93:817-20. LinkGoogle Scholar2. PREUSSGRANTPARRISZMUDKASLOTKOFF HKRML. Effects of sera and sera fractions from spontaneously hypertensive rats on renal organic anion and cation transport. Proc Soc Exp Biol Med. 1974;145:397-402. CrossrefMedlineGoogle Scholar3. BERGERÜATSMONKUPFERGUTMAN LTASA. Effect of reducing renal arterial blood pressure by balloon catheter on urate excretion in the dog. Proc Soc Exp Biol Med. 1964;115:58-61. CrossrefMedlineGoogle Scholar1. REUBIWEIDMANNHODLERCOTTIER FPJP. Changes in renal function in essential hypertension. Am J Med. 1978;64:556-63. CrossrefMedlineGoogle Scholar2. YÜBERGERDORPHSMITH TLDH. Renal function in gout: V. Factors influencing the renal hemodynamics. Am J Med. 1979;67:766-71. CrossrefMedlineGoogle Scholar3. DIAMONDMEISELHOLDEN HAD. The natural history of urate overproduction in sickle cell anemia. Ann Intern Med. 1979;90:752-7. LinkGoogle Scholar4. BONERSTEELE GT. Relationship of urate and p-aminohippurate secretion in man. Am J Physiol. 1973;225:100-4. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Stanford University Medical Center Stanford, CA 94305 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCurrent approaches in the treatment of hypertensionCurrent issues in hypertension: Old Questions With New Answers and New Questions 1 July 1981Volume 95, Issue 1Page: 123-124KeywordsRenal circulationUric acidUrine Issue Published: 1 July 1981 PDF DownloadLoading ...
The Hippocratic oath
Authors: I Loudon
Journal: BMJ (1994)

EDITOR, - In the Editor's Choice in the issue of 9 July the editor asked, “When did medical schools stop administering the Hippocratic oath and why?” Perhaps the question should be, was it ever administered in any medical school at any time, and if so where and when?

There is a widespread public belief that the oath is still administered to all doctors …
Histocompatibility antigens in discoid and systemic lupus erythematosus
Authors: L.G. MILLARD, N.R. ROWELL, S.M. RAJAH
Journal: British Journal of Dermatology (1977)

A study of histocompatibility (HLA) antigens in 69 patients with discoid lupus erythematosus (DLE) showed an increased incidence of HLA-B7 and HLA-B8 related to the age at onset and sex of the patient. Young females and males aged 15-39 years at onset were associated with HLA-B7 and females aged over 40 years with HLA-B8. This supports previous studies concerning sex and age specific onset rates in DLE which suggests that there is more than one genotype in this disorder. Female patients with systemic lupus erythematosus (SLE) at all ages of onset showed a significant association with HLA-B8. Female patients, with onset 15-39 years, with either SLE or DLE which has transformed to SLE, show a significant increase in HLA-B8 compared with the females in the same age onset group who have the discoid disease. The presence of HLA-B8 in a young female with DLE may represent a risk factor for the development of the systemic disease.
BODY T1-201.Cl REDISTRIBUTION AFTER EXERCISE AND A POSSIBLE RELATIONSHIP TO "REVERSE" REDISTRIBUTION.
Authors: J. A. Vento, L. T. Swing, R. P. Spencer
Journal: Clinical Nuclear Medicine (1999)

Scientific Abstracts And Posters From The 44Th Annual Meeting Of The Southwestern Chapter Of The Society Of Nuclear Medicine, And From The 12Th Northeastern Regional Scientific Meeting Of The New England And New York Chapters Of The Society Of Nuclear Medicine
Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes
Authors: Shannon M. Bailey, Carol C. Cunningham
Journal: Hepatology (1998)

Although reactive oxygen species (ROS) have been implicated in the etiology of alcohol–induced liver disease, neither their relative contribution to cell death nor the cellular mechanisms mediating their formation are known. The purpose of this study was to test the hypothesis that acute and chronic ethanol exposure enhances the mitochondrial generation of ROS in fresh, isolated hepatocytes. Acute ethanol exposure stimulated ROS production, increased the cellular NADH/NAD + ratio, and decreased hepatocyte viability slightly, which was prevented by pretreatment with 4–methylpyrazole (4–MP), an inhibitor of alcohol dehydrogenase. Similarly, xylitol, an NADH–generating compound, enhanced hepatocyte ROS production and decreased viability. Incubation with pyruvate, an NADH–oxidizing compound, and cyanamide, an inhibitor of aldehyde dehydrogenase, significantly decreased ROS levels in acute ethanol–treated hepatocytes. Chronic ethanol consumption produced a sixfold increase in hepatocyte ROS production compared with levels measured in controls. Hepatocytes from ethanol–fed rats were less viable compared with controls, e.g., viability was 68% ± 2% (ethanol) versus 83% ± 1% (control) after 60 minutes of incubation. Antimycin A increased ROS production and decreased cell viability; however, the toxic effect of antimycin A was more pronounced in ethanol–fed hepatocytes. These results suggest that acute and chronic ethanol exposure exacerbates mitochondrial ROS production, contributing to cell death.
Scintigraphic characteristics of experimental myocardial infarct extension.
Authors: M W Kronenberg, N E Wooten, G C Friesinger, D L Page, S B Higgins, J C Collins, J L O'Connor, R R Price, A B Brill
Journal: Circulation (1979)

Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p less than 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria.
A Prospective Study of Delirium in Hospitalized Elderly
Authors: Joseph Francis
Journal: JAMA (1990)

The prevalence, risk factors, and outcomes of delirium were studied in 229 elderly patients. Fifty patients (22%) met criteria for delirium; nondelirious elderly constituted the control group. Abnormal sodium levels, illness severity, dementia, fever or hypothermia, psychoactive drug use, and azotemia were associated with risk of delirium. Patients with three or more risk factors had a 60% rate of delirium. Delirious patients stayed 12.1 days in the hospital vs 7.2 days for controls and were more likely to die (8% vs 1%) or be institutionalized (16% vs 3%). Illness severity predicted 6-month mortality, but the effect of delirium was not significant. Delirium occurs commonly in hospitalized elderly, is associated with chronic and acute problems, and identifies elderly at risk for death, longer hospitalization, and institutionalization. The increased mortality associated with delirium appears to be explained by greater severity of illness. (<i>JAMA</i>. 1990;263:1097-1101)