tbuckley/cabot-search huggingface dataset:
Gangliosides Drive the Tumor Infiltration and Function of Myeloid-Derived Suppressor Cells
Authors: Assefa Wondimu, Yihui Liu, Yan Su, Daniel Bobb, Jennifer S.Y. Ma, Lina Chakrabarti, Saša Radoja, Stephan Ladisch
Journal: Cancer Research (2014)

Abstract Although it is now widely appreciated that antitumor immunity is critical to impede tumor growth and progression, there remain significant gaps in knowledge about the mechanisms used by tumors to escape immune control. In tumor cells, we hypothesized that one mechanism of immune escape used by tumors involves the synthesis and extracellular shedding of gangliosides, a class of biologically active cell surface glycosphingolipids with known immunosuppressive properties. In this study, we report that tumor cells engineered to be ganglioside deficient exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in the numbers and function of tumor-infiltrating myeloid-derived suppressor cells (MDSC) in ganglioside-deficient tumors, in contrast with the large MDSC infiltrates seen in ganglioside-rich littermate control tumors. Transient ganglioside reconstitution of the tumor cell inoculum was sufficient to increase MDSC infiltration, supporting a direct connection between ganglioside production by tumor cells and the recruitment of immunosuppressive MDSC into the tumor microenvironment. Our results reveal a novel mechanism of immune escape that supports tumor growth, with broad implications given that many human tumors produce and shed high levels of gangliosides. Cancer Res; 74(19); 5449–57. ©2014 AACR.
Role of Anions in Metabolic Alkalosis and Potassium Deficiency
Authors: William B. Schwartz, Charles van Ypersele de Strihou, Jerome P. Kassirer
Journal: New England Journal of Medicine (1968)

STUDIES of acid–base physiology in recent years have defined many factors that influence the pH of the body fluids. A key step contributing to this progress has been the long delayed acceptance by renal physiologists of the modern physicochemical theory that considers acids as proton donors and bases as proton acceptors.1 , 2 It is now generally agreed that secretion of hydrogen ion by the renal tubule has a fundamental role in regulating body alkali stores and that the process of sodium-hydrogen exchange is the basic mechanism responsible for both acid excretion and bicarbonate reabsorption. A variety of studies suggest that the . . .
Tropical Problems in Nutrition
Authors: TELFORD H. WORK
Journal: Annals of Internal Medicine (1973)

The terms kwashiorkor, marasmus, defective cellular immunity, and famine are exotic terms to most Americans, but they have foreboding implications for both present and future American medicine. This conference reviews some recent studies of these problems abroad. Endemic and epidemic malnutrition may underlie cellular and immunological incapacity to resist microbiological parasitism. The clinician should be aware of the consequences of limitations on food production and distribution, which could result in malnutrition and famine.
Non-cirrhotic portal hypertension in the HIV-infected individual
Authors: Ka Fernando, S Bhaduri, S Hubscher, Kw Radcliffe
Journal: Journal of the Royal Society of Medicine (2013)

We report two cases of non-cirrhotic portal hypertension (NCPH) in persons infected with HIV, one of which was unusual in occurring in the absence of exposure to any antiretroviral therapy (ART).
Clinical Aspects of Eosinophilia in Atopic Disease
Authors: Francis C. Lowell
Journal: JAMA (1967)

There is a striking relationship between eosinophilia and allergenic exposure among atopic patients, and the existence of eosinophilia is an indication of such exposure. The term "eosinophilosis" is suggested as an appropriate descriptive designation embracing all patients with atopic manifestations whether or not specific allergic causes are recognizable. There are many advantages to the total eosinophil count (TEC) in diagnosis and in the assessment of response to treatment with steroids.
1141 Complete genotypic and phenotypic analyses of HBV mutations identified in HBEAG-negative chronic hepatitis B patients receiving 96 weeks of adefovir dipivoxil (ADV)
Authors: H YANG, C WESTLAND, W DELANEYIV, P ANGUS, S LOCARNINI, G KITIS, M WULFSOHN, C GIBBS, M MILLER, C BROSGART
Journal: Hepatology (2003)

Nucleos(t)ide analogues (NAs) including lamivudine (LAM), telbivudine (LDT), adefovir dipivoxil(ADV), and entecavir (ETV) have been widely used as anti-HBV drugs. We aimed to study the effectiveness and safety of various NAs.Two thousand three hundred and eighty patients with chronic hepatitis B (CHB) were enrolled. The rate of virologic response, optimization therapy, and serologic responses were analyzed.HBV DNA inhibitory capacity was shown to be LAM + ADV ≈ ETV > LDT > LAM > ADV. Virologic breakthrough rate and proportion of optimized treatment were LAM > ADV > LDT > LAM + ADV > ETV. However, virological response rate showed the opposite trend. The selection of anti-virals, HBeAg-negative, and lower HBV DNA levels after one year of anti-viral treatment, are favorable factors for the maintenance of virologic response.This study's results were consistent with the major clinical guidelines to recommend ETV and TDF as the preferred treatment for CHB patients. LAM could be used for patients with lower HBV DNA load; ADV may be more applicable to non-cirrhotic patients with HBeAg-negative and lower HBV DNA load. LDT can be used to treat patients with HBeAg-positive, low HBV DNA load, and higher ALT levels due to higher HBeAg conversion rate in a baseline optimized population. The effectiveness of LAM + ADV is similar to and sometimes better than ETV treatment in a CHB population.
Tremetol Poisoning—Not Yet Extinct
Authors: Alexis F. Hartmann
Journal: JAMA (1963)

IN THE BEDSIDE TEACHING of medical students and housestaff, one always finds most stimulating the challenge of the unusual problems which first demand clinical control of potentially lethal conditions and, because of unusual interest or importance, will then prompt investigation into their causes. The following cases describe such an experience. <h3>Report of Cases</h3><h3>Case 1.—</h3> On Dec 23, 1962, a 7-month-old female baby weighing 8 kg was admitted to the St. Louis Children's Hospital with what clinically suggested very severe ketosis and acidosis, such as might be expected in diabetes. Acetone could be detected on the breath, and nitroprusside and ferric chloride tests of the urine indicated heavy ketonuria. The serum CO<sub>2</sub>content was but 4.5 mEq/liter. The urine was free of sugar, however, and also of salicylate, and the blood sugar was quite normal—82 mg/100 ml. If not diabetes or salicylate intoxication, what then was the cause of
Usefulness of Negative and Weak–Diffuse Pattern of SDHB Immunostaining in Assessment of SDH Mutations in Paragangliomas and Pheochromocytomas
Authors: Esmeralda Castelblanco, Maria Santacana, Joan Valls, Aguirre de Cubas, Alberto Cascón, Mercedes Robledo, Xavier Matias-Guiu
Journal: Endocrine Pathology (2013)
Nodular regenerative hyperplasia in the rat induced by a selenium-enriched diet: Study of a model
Authors: Paulette Bioulac-Sage, Liliane Dubuisson, Christiane Bedin, Pierre Gonzalez, Eliane de Tinguy-Moreaud, Henri Garcin, Charles Balabaud
Journal: Hepatology (1992)

Weaned male rats were fed a 4 ppm selenium diet. Compared after 2 mo with a control group fed a 0.4 ppm diet, the rats' body weights had not significantly decreased and liver function was normal, but portal pressure was 1.8 times higher (p &lt; 0.05). Liver weight was slightly increased (10.3%; p &lt; 0.05). All livers had an abnormal appearance. In the less severe cases the surface was only slightly irregular, but in the more severe cases, atrophic micronodular lobes and hypertrophic lobes, with mildly irregular surfaces, were present. On light microscopy, atrophic lobes displayed a peripheral nodular zone with micronodules separated by rows of atrophic hepatocytes without fibrosis, characteristic of nodular regenerative hyperplasia, and a central atrophic zone that was sometimes peliotic. Hypertrophic lobes and livers in the less severe cases had only minor and relatively localized evidence of nodular regenerative hyperplasia; occasional peliosis was seen. In all cases portal veins, hepatic veins and hepatic arteries were normal. By electron microscopy, in nonnodular zones with no obvious evidence of parenchymal atrophy, the endothelial wall showed signs of complete or incomplete capillarization with frequent enlargement of the Disse space. The selenium–enriched diet is a reproducible model of liver nodular regenerative hyperplasia. In this model, damage to the sinusoidal wall could represent the primum movens of microcirculatory disturbances. (Hepatology 1992;16:418-425.)
The Role of Lead in Gout Nephropathy
Authors: Vecihi Batuman, John K. Maesaka, Bassam Haddad, Eric Tepper, Elaine Landy, Richard P. Wedeen
Journal: New England Journal of Medicine (1981)

UNTIL recently, renal disease was considered a major cause of death among patients with gout.1 Modern long-term follow-up studies of renal function, however, have indicated that hyperuricemia and gout rarely result in kidney damage unless other renal disease supervenes.2 3 4 These conflicting views of the occurrence of renal disease in gout might be reconciled if a single agent could be identified as a cause of both gout and renal disease in some patients. Lead is a likely candidate for such an agent, since this heavy metal has long been recognized as a causative factor in both gout and nephropathy.5 To test . . .
The Archbishop and the neurosurgeon.
Authors: B Jennett
Journal: BMJ (1977)

Aliskiren (2(<i>S</i>),4(<i>S</i>),5(<i>S</i>),7(<i>S</i>)-<i>N</i>-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamid hemifumarate) is the first in a new class of orally active, nonpeptide direct renin inhibitors developed for the treatment of hypertension. The absorption, distribution, metabolism, and excretion of [<sup>14</sup>C]aliskiren were investigated in four healthy male subjects after administration of a single 300-mg oral dose in an aqueous solution. Plasma radioactivity and aliskiren concentration measurements and complete urine and feces collections were made for 168 h postdose. Peak plasma levels of aliskiren (<i>C</i><sub>max</sub>) were achieved between 2 and 5 h postdose. Unchanged aliskiren represented the principal circulating species in plasma, accounting for 81% of total plasma radioactivity (AUC<sub>0–∞</sub>), and indicating very low exposure to metabolites. Terminal half-lives for radioactivity and aliskiren in plasma were 49 h and 44 h, respectively. Dose recovery over 168 h was nearly complete (91.5% of dose); excretion occurred almost completely via the fecal route (90.9%), with only 0.6% recovered in the urine. Unabsorbed drug accounted for a large dose proportion recovered in feces in unchanged form. Based on results from this and from previous studies, the absorbed fraction of aliskiren can be estimated to approximately 5% of dose. The absorbed dose was partly eliminated unchanged via the hepatobiliary route. Oxidized metabolites in excreta accounted for at least 1.3% of the radioactive dose. The major metabolic pathways for aliskiren were <i>O</i>-demethylation at the phenyl-propoxy side chain or 3-methoxy-propoxy group, with further oxidation to the carboxylic acid derivative.
Book: Infections and Inequalities: The Modern Plagues
Authors: J. Collazos
Journal: BMJ (2000)

Paul Farmer ![Graphic][1]</img> University of California Press, £18.95, pp 375 ISBN 0520215443 Rating: ![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> The slogan of the otherwise successful 11th World Conference on AIDS, held in 1996 in Vancouver, Canada, was “One World, One Hope.” This book reminds us that not one but two worlds exist and that, at least for the moment, there is almost no hope for one of them. Through his description of the sociocultural environment of one of the world's poorest countries, Haiti, and of two highly prevalent diseases there, tuberculosis and AIDS, Paul Farmer, an experienced medical anthropologist, shows that … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Full, not selective, information needed for melanoma risk
Authors: M. Hayes
Journal: BMJ (2011)

Spence may be guilty of the same “whiff of propaganda” and contradictions that he alleges from others.1

UK melanoma figures are 54% for head, neck, and limbs (38% trunk) in men and 77% (17% trunk) in women. In the west of Scotland, 69% of melanomas occurred on the face, whereas only 55% did so …
Inverse Relation of Dietary Protein Markers With Blood Pressure
Authors: J. Stamler, P. Elliott, H. Kesteloot, R. Nichols, G. Claeys, A.R. Dyer, R. Stamler
Journal: Circulation (1996)

Background The purpose of this study was to assess relations to blood pressure (BP) in individuals of markers of dietary protein in their 24-hour urine collections. Methods and Results INTERSALT (INTERnational study of SALT and blood pressure) was a cross-sectional study of 10 020 men and women aged 20 to 59 years in 52 population-based samples in 32 countries worldwide, with quality-controlled standardized procedures and assessment of multiple possible confounders. Three measurements of dietary protein in 24-hour urine of each individual participant were studied: total nitrogen and urea as indexes of total protein intake, and sulfate as an index of sulfur-containing dietary amino acids. Repeat examination was performed in a random 8% of participants to assess reliability and to correct for regression-dilution bias. Significant independent inverse relationships were found between BP (systolic and diastolic) and both 24-hour urinary total nitrogen and urea nitrogen, with adjustment for age, sex, alcohol intake, body mass, and 24-hour urinary sodium, potassium, calcium, and magnesium. With adjustment for regression-dilution bias, it was estimated that systolic and diastolic BP were on average 3.0 and 2.5 mm Hg lower, respectively, for persons with dietary total protein intake 30% above the overall mean than for those whose dietary protein intake was 30% below the overall mean (12.94 versus 6.96 g/d urinary total nitrogen, equivalent to 81 versus 44 g/d dietary protein, respectively). For the association of these markers with diastolic BP, results were similar for younger (20- to 39-year-old) and older (40- to 59-year-old) persons and for women and men. For their relation to systolic BP, regression coefficients were larger both for those aged 40 to 59 years than for those aged 20 to 39 years and for women than for men. Nonsignificant inverse relations were recorded for urinary sulfate and BP. Conclusions These INTERSALT findings lend support to the hypothesis that higher dietary protein intake has favorable influences on BP.
An Address ON THE RELATION OF PHYSIOLOGY TO PHYSICS AND CHEMISTRY: Delivered before the Physiological Section of the British Association for the Advancement of Science, Dublin, 1908
Authors: J. S. Haldane
Journal: BMJ (1908)

<h3>Objective</h3> The purpose of this literature review was to identify educational approaches addressing low health literacy for people with type 2 diabetes. Low health literacy can lead to poor management of diabetes, low engagement with health care providers, increased hospitalization rates, and higher health care costs. These challenges can be even more profound among minority populations and non-English speakers in the United States. <h3>Methods</h3> A literature search and standard data extraction were performed using PubMed, Medline, and EMBASE databases. A total of 1,914 articles were identified, of which 1,858 were excluded based on the inclusion criteria, and 46 were excluded because of a lack of relevance to both diabetes management and health literacy. The remaining 10 articles were reviewed in detail. <h3>Results</h3> Patients, including ethnic minorities and non-English speakers, who are engaged in diabetes education and health literacy improvement initiatives and ongoing follow-up showed significant improvement in A1C, medication adherence, medication knowledge, and treatment satisfaction. Clinicians considering implementing new interventions to address diabetes care for patients with low health literacy can use culturally tailored approaches, consider ways to create materials for different learning styles and in different languages, engage community health workers and pharmacists to help with patient education, use patient-centered medication labels, and engage instructors who share cultural and linguistic similarities with patients to provide educational sessions. <h3>Conclusion</h3> This literature review identified a variety of interventions that had a positive impact on provider-patient communication, medication adherence, and glycemic control by promoting diabetes self-management through educational efforts to address low health literacy.
Ringworm in the South-West of England, 1960-1970, with special reference to onychomycosis
Authors: MARY P. ENGLISH, LINDA LEWIS
Journal: British Journal of Dermatology (2006)

The numbers of dermatophytes isolated from specimens sent to a mycological diagnostic service in the West of England from i960 to 1970 are reported. An increasing rate of failure to culture from microscopically positive specimens is noted. One reason for this was the large number of nail clippings sent in unaccompanied by scrapings from skin lesions. The cultural failure rate from nail clippings makes the diagnosis of the causal fungi in onychomycosis very unsatisfactory. For treatment purposes, means of deducing the nature of these uncultured fungi by combining clinical and laboratory observations are proposed. It is suggested that two features of mycological diagnostic services—(a) failure to culture from a proportion of microscopically positive specimens, and (b) the fact that only the more severe, widespread and recalcitrant lesions are usually seen by dermatologists—result in a very misleading picture if these figures are used to assess the incidence of the various dermatophyte species in the general population.
Hepatic excretion of circulating bilirubin photoproducts in the Gunn rat.
Authors: A F McDonagh, L A Palma
Journal: Journal of Clinical Investigation (1980)

To investigate the origin and metabolism of the intermediates that occur in blood during phototherapy of neonatal jaundice, serum from irradiated homozygous Gunn rats was injected intravenously into other homozygous Gunn rats fitted with bile fistulas, and the excretion of pigment in the bile of the recipient rats was studied. In some experiments the donor rats were labeled with [14C]bilirubin; in others the recipient rats were labeled. Injection of donor serum from irradiated rats caused a transient burst of pigment excretion in the bile of the recipient rats. However, simultaneous bursts of pigment and 14C excretion were observed only when the donor rat was labeled and the recipient rat was not, and not when the donor rat was unlabeled and the recipient rat was labeled. In addition, there was simultaneous transient enhanced excretion of pigment and label when labeled recipient rats were exposed briefly to blue light. We conclude that (a) the phototherapy intermediates previously detected spectroscopically in serum are formed from bilirubin and are excreted in bile independently of bilirubin; (b) the enhanced excretion of pigment in bile during phototherapy is not caused by complex formation between bilirubin and photoproducts, or by liver damage produced by photoproducts or light.
Kinetic differences in the induction of interferon stimulated genes by interferon-α and interleukin 28B are altered by infection with hepatitis C virus
Authors: Nikolaus Jilg, Wenyu Lin, Jian Hong, Esperance A. Schaefer, David Wolski, James Meixong, Kaku Goto, Cynthia Brisac, Pattranuch Chusri, Dahlene N. Fusco, Stephane Chevaliez, Jay Luther, Kattareeya Kumthip, Thomas J. Urban, Lee F. Peng, Georg M. Lauer, Raymond T. Chung
Journal: Hepatology (2013)

Several genome-wide association studies (GWAS) have identified a genetic polymorphism associated with the gene locus for interleukin 28B (IL28B), a type III interferon (IFN), as a major predictor of clinical outcome in hepatitis C. Antiviral effects of the type III IFN family have previously been shown against several viruses, including hepatitis C virus (HCV), and resemble the function of type I IFN including utilization of the intracellular Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Effects unique to IL28B that would distinguish it from IFN-α are not well defined. By analyzing the transcriptomes of primary human hepatocytes (PHH) treated with IFN-α or IL28B, we sought to identify functional differences between IFN-α and IL28B to better understand the roles of these cytokines in the innate immune response. Although our data did not reveal distinct gene signatures, we detected striking kinetic differences between IFN-α and IL28B stimulation for interferon stimulated genes (ISGs). While gene induction was rapid and peaked at 8 hours of stimulation with IFN-α in PHH, IL28B produced a slower, but more sustained increase in gene expression. We confirmed these findings in the human hepatoma cell line Huh7.5.1. Interestingly, in HCV-infected cells the rapid response after stimulation with IFN-α was blunted, and the induction pattern resembled that caused by IL28B.The kinetics of gene induction are fundamentally different for stimulations with either IFN-α or IL28B in hepatocytes, suggesting distinct roles of these cytokines within the immune response. Furthermore, the observed differences are substantially altered by infection with HCV.
How Well Do Angiogenesis Inhibitors Work? Biomarkers of Response Prove Elusive
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2009)

I n 2007, the late Judah Folkman noted “a major obstacle” to the development of drugs targeted at angiogenesis, or new blood vessel growth, in tumors: the lack of noninvasive biomarkers for identifying patients most likely to respond to the drugs. Now, with three approved angiogenesis inhibitors (AIs) on the market — bevacizumab, sunitinib, and sorafenib — and hundreds of trials for others under way, the need for accurate, inexpensive, and noninvasive biomarkers has become even more pressing. “Among researchers, there is a consensus that we need to step back and better understand how angiogenesis inhibitors work, and don’t work as well as we’d hoped,” said Curzio Ruegg, M.D. , professor and head of ex perimental oncology at Switzerland’s University of Lausanne. “Better biomarkers should also help us answer the nagging question why AIs often improve progression-free survival but don’t result in better overall survival.” AI biomarkers that are detectable in blood or serum are especially intriguing because they would be relatively low cost and accessible, in contrast to the advanced imaging tools used to gauge response. And they could aid in diagnosis, staging, prognosis, and treatment selection, said Sam Gambhir, M.D., Ph.D., director of the molecular imaging program at Stanford University. For all these reasons, AI biomarker research is booming. Much of the research has focused on cytokines, including the protein targets of AI drugs, such as vascular endothelial growth factor (VEGF). But intense interest also surrounds biological markers such as circulating endothelial cells (CECs), and a subset of those cells, circulating endothelial progenitors (CEPs).