tbuckley/cabot-search huggingface dataset:
Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins
Authors: Miguel F. Sanmamed, Omar Carranza-Rua, Carlos Alfaro, Carmen Oñate, Salvador Martín-Algarra, Guiomar Perez, Sara F. Landazuri, Álvaro Gonzalez, Stefanie Gross, Inmaculada Rodriguez, Cecilia Muñoz-Calleja, María Rodríguez-Ruiz, Bruno Sangro, José M. López-Picazo, Manglio Rizzo, Guillermo Mazzolini, Juan I. Pascual, Maria Pilar Andueza, Jose Luis Perez-Gracia, Ignacio Melero
Journal: Clinical Cancer Research (2014)

Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden.IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis.IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n = 16), renal cell carcinoma (RCC; n = 23), non-small cell lung cancer (NSCLC; n = 21), or hepatocellular carcinoma (HCC; n = 30), serum IL8 concentrations correlated with tumor burden and stage, survival (melanoma, n = 16; RCC, n = 23; HCC, n = 33), and objective responses to therapy, including those to BRAF inhibitors (melanoma, n = 16) and immunomodulatory monoclonal antibodies (melanoma, n = 8). IL8 concentrations in urine (n = 18) were mainly elevated in tumors with direct contact with the urinary tract.IL8 levels correlate with tumor burden in preclinical models and in patients with cancer. IL8 is a potentially useful biomarker to monitor changes in tumor burden following anticancer therapy, and has prognostic significance.
Excessive Matrix Accumulation in the Kidneys of MRL/lpr Lupus Mice Is Dependent on Complement Activation
Authors: Lihua Bao, Jian Zhou, V. Michael Holers, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Complement receptor 1–related gene/protein y (Crry) in rodents is a potent membrane complement regulator that inhibits complement C3 activation by both classical and alternative pathways. Complement inhibition with Crry as the recombinant protein Crry-Ig has been demonstrated to prevent MRL/MpJ-<i>Tnfrsf6</i><sup><i>lpr</i></sup> (MRL/<i>lpr</i>) mice from developing proteinuria and renal failure. Crry-Ig–treated mice also showed less glomerulosclerosis compared with control MRL/<i>lpr</i> mice. To clarify how complement inhibition with Crry might affect renal scarring in lupus nephritis, gene transcript profiling was performed comparing Crry-Ig–treated MRL/<i>lpr</i> mice to control-treated MRL/<i>lpr</i> mice as well as to the MRL/+ strain control. Altered gene expression was confirmed by quantitative PCR, and protein quantity with either immunoblotting or immunofluorescence microscopy. Collagens I, III, IV, and VI were overexpressed in control MRL/<i>lpr</i> mice, whereas complement inhibition with Crry reduced the overexpression of these extracellular matrix components toward normal. Plasminogen activator inhibitor 1, connective tissue growth factor, and TGF-β1 were upregulated in MRL/<i>lpr</i> mice compared with MRL/+ mice and were normalized by Crry-Ig treatment, suggesting that the product of these genes may contribute to the progressive glomerulosclerosis in MRL/<i>lpr</i> mice in a complement-dependent fashion. Thus, complement inhibition with Crry has a prominent effect on matrix-related genes and proteins, which translates into improvement in functional renal disease. E-mail: rquigg@medicine.uchicago.edu
BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients
Authors: Senait Ashenafi, Getachew Aderaye, Martha Zewdie, Rubhana Raqib, Amsalu Bekele, Isabelle Magalhaes, Beede Lema, Meseret Habtamu, Rokeya Sultana Rekha, Getachew Aseffa, Markus Maeurer, Abraham Aseffa, Mattias Svensson, Jan Andersson, Susanna Brighenti
Journal: Thorax (2012)

<h3>Background</h3> Diagnosis of active tuberculosis (TB) among sputum-negative cases, patients with HIV infection and extra-pulmonary TB is difficult. In this study, assessment of BCG-specific IgG-secreting peripheral plasmablasts, was used to identify active TB in these high-risk groups. <h3>Methods</h3> Peripheral blood mononuclear cells were isolated from patients with TB and controls and cultured in vitro using an assay called Antibodies in Lymphocyte Supernatant, which measures spontaneous IgG antibody release from migratory plasmablasts. A BCG-specific ELISA and flow cytometry were used to quantify in vivo activated plasmablasts in blood samples from Ethiopian subjects who were HIV negative or HIV positive. Patients diagnosed with different clinical forms of sputum-negative active TB or other diseases (n=96) were compared with asymptomatic individuals including latent TB and non-TB controls (n=85). Immunodiagnosis of TB also included the tuberculin skin test and the interferon (IFN)-γ release assay, QuantiFERON. <h3>Results</h3> This study demonstrated that circulating IgG+ plasmablasts and spontaneous secretion of BCG-specific IgG antibodies were significantly higher in patients with active TB compared with latent TB cases and non-TB controls. BCG-specific IgG titres were particularly high among patients coinfected with TB and HIV with CD4 T-cell counts &lt;200 cells/ml who produced low levels of <i>Mycobacterium tuberculosis</i>-specific IFNγ in vitro. <h3>Conclusions</h3> These results suggest that BCG-specific IgG-secreting peripheral plasmablasts could be successfully used as a host-specific biomarker to improve diagnosis of active TB, particularly in people who are HIV positive, and facilitate administration of effective treatment to patients. Elevated IgG responses were associated with impaired peripheral T-cell responses, including reduced T-cell numbers and low <i>M tuberculosis</i>-specific IFNγ production.
BT-04 * A STANDARDIZED AUTOPSY PROCUREMENT ALLOWS FOR THE COMPREHENSIVE STUDY OF DIPG BIOLOGY
Authors: M. Kambhampati, J. Perez, S. Yadavilli, A. Saratsis, A. Hill, C.-Y. Ho, E. Panditharatna, M. Markel, R. Packer, J. Nazarian
Journal: Neuro-Oncology (2015)

Diffuse intrinsic pontine glioma (DIPG) is one of the least understood and most deadly childhood cancers. Historically, there has been a paucity of DIPG specimens for molecular analysis. However, due to the generous participation of DIPG families in programs for postmortem specimen donation, there has been a recent surge in molecular analysis of newly available tumor specimens. Collaborative efforts to share data and tumor specimens have resulted in rapid discoveries in other pediatric brain tumors, such as medulloblastoma, and therefore have the potential to shed light on the biology of DIPG. Given the generous gift of postmortem tissue donation from DIPG patients, there is a need for standardized postmortem specimen accrual to facilitate rapid and effective multi-institutional molecular studies. We developed and implemented an autopsy protocol for rapid procurement, documenting and storing these specimens. Sixteen autopsies were performed throughout the United States and Canada and were processed using a standard protocol and inventory method, including specimen imaging, fixation, snap freezing, orthotopic injection, or preservation. This allowed for comparative clinical and biological studies of rare postmortem DIPG tissue specimens, generation of in vivo and in vitro models of DIPG, and detailed records to facilitate collaborative analysis.
Adult respiratory distress syndrome and pancytopenia associated with miliary tuberculosis in a HIV-infected patient
Authors: A Mofredj, JM Guerin, F Leibinger, R Masmoudi
Journal: European Respiratory Journal (1996)

Adult respiratory distress syndrome (ARDS) is a rare but severe complication of miliary tuberculosis, which may appear even after introduction of antituberculosis therapy. Mortality has been reported to be as high as 100% if there is associated pancytopenia. We report a case of a patient infected with the human immunodeficiency virus who presented with miliary tuberculosis associated with pancytopenia and adult respiratory distress syndrome.
Prevalence, risk factors, and genotype distribution of hepatitis C virus infection in the general population: A community-based survey in southern Italy
Authors: V Guadagnino, T Stroffolini, M Rapicetta, A Costantino, L A Kondili, F Menniti-Ippolito, B Caroleo, C Costa, G Griffo, L Loiacono, V Pisani, A Foca, M Piazza
Journal: Hepatology (1997)

In 1996 the prevalence, risk factors, and genotype distribution of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample was selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects (11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-confirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to 33.1% in those ≥ 60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females tested positive more frequently than males (14.1% vs. 10.5%; P &lt; .05). Alanine transaminase (ALT) concentrations were abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening is not useful in the detection of anti-HCV-positive subjects in a general population. The results of multiple logistic regression analysis showed that an age of less than 45 years, the use of glass syringes, and dental therapy were all independent predictors of anti-HCV positivity. HCV RNA was detected by polymerase chain reaction in 75.9% of the 195 anti-HCV EIA-positive subjects: in 84.7% (144/170) of the RIBA-confirmed subjects; in 17.4% (4/23) tested as RIBA indeterminate; and in neither of the two subjects who tested RIBA negative. HCV type 1b was detected in 75 subjects (50.7%), type 2b in 1 subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individuals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general population with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epidemic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease.
Physiologic benefits of exercise training in rehabilitation of patients with severe chronic obstructive pulmonary disease.
Authors: R Casaburi, J Porszasz, M R Burns, E R Carithers, R S Chang, C B Cooper
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We determined the effect on exercise tolerance and physiological exercise responses of rigorous rehabilitative exercise training in chronic obstructive pulmonary disease (COPD). Fifteen men and 10 women (mean age, 68 +/- 6 yr; FEV1, 0.93 +/- 0.27 L) participated in a rehabilitation program with an exercise component of three per week 45-min sessions of cycle ergometer training for 6 wk with exercise intensity kept near maximal targets. Before and after rehabilitation, patients performed an incremental test and a constant work rate (CWR) test at 80% of the peak work rate in the preprogram incremental test. Ventilation (V(E)) and gas exchange were measured breath by breath; arterialized venous blood was analyzed for blood gas determinations and lactate. Rehabilitation yielded an average increase in peak work rate in the incremental test of 36% (p < 0.001), and in the duration of the CWR test of 77% (p < 0.001). In the CWR test, the kinetics of O2 uptake, CO2 output, V(E), and heart rate were markedly slower than those of healthy subjects. After training, mean response time decrease averaged 17, 22, 34, and 29%, respectively (p < 0.02), evidence of a physiologic training effect. Further, for identical CWR tasks, V(E) was 10% lower (p < 0.02) after training, attributable to altered breathing pattern: tidal volume increased by 8% and respiratory rate decreased by 19%, yielding lower V(D) /V(T) (0.46 versus 0.53 p < 0.005). Rigorous exercise training for patients with severe COPD yields more efficient exercise breathing pattern and lower V(E); this is associated with improved exercise tolerance.
A paired comparison of tuberculin skin test results in health care workers using 5 TU and 10 TU tuberculin
Authors: R. L Stuart
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Historically, 10 TU has been employed in Australia and the United Kingdom to perform the tuberculin skin test (TST). However, this makes it difficult to compare the rates of TST positivity with other countries such as the USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a comparison was made of TST responses in health care workers given a TST with both 5 and 10 TU. <h3>METHODS</h3> Two TSTs were performed simultaneously in each health care worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to the right or left forearm and read at 48–72 hours by a single nurse who was blinded to the assignment of the 5 and 10 TU doses. <h3>RESULTS</h3> A total of 128 health care workers were enrolled, 119 (93%) of whom had a past history of BCG vaccination. The overall mean difference in paired reaction sizes for the two doses was 1.5 mm with 95% limits of agreement of –3.6 to 6.5 mm. <h3>CONCLUSION</h3> A slightly larger TST reading was seen with 10 TU than with 5 TU. The mean difference of 1.5 mm between the two doses should be considered when comparing rates of TST positivity between countries who use different doses of tuberculin to perform the tuberculin skin test.
MOBILIZATION OF BASOPHILE SUBSTANCE (RIBONUCLEIC ACID) IN THE CYTOPLASM OF LIVER CELLS WITH THE PRODUCTION OF TUMORS BY BUTTER YELLOW
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1946)

Butter yellow (dimethylaminoazobenzene) causes degenerative changes in liver cells accompanied by chromatolysis of cytoplasmic structures that stain with basic dyes because they contain ribonucleic acid. These changes are profoundly modified by the protein content of the diet. Chromatolysis is succeeded by focal regeneration with reaccumulation of ribonucleic acid in the cytoplasm of liver cells; these foci of basophile hyperplasia have their origin in the parenchyma surrounding portal spaces and consist of cells arranged in columns or as tubules with lumina. Hepatomas arise from foci of basophile hyperplasia and corresponding with the arrangement of cells in these foci may be trabecular or adenomatous. Butter yellow causes new formation of bile ducts which arise chiefly in the immediate neighborhood of secondary portal spaces and produce the precancerous lesion, designated cholangiofibrosis. These bile ducts may accumulate ribonucleic acid in their cytoplasm and undergo hyperplasia. Cholangiomas arise from newly formed bile ducts that are the site of basophile hyperplasia. Changes accompanying chromatolysis and basophile hyperplasia aid in the definition of structural elements of the cytoplasm and in the localization of ribonucleic acid with relation to the mitochondria.
A perspective for viewing the history of psychophysics
Authors: David J. Murray
Journal: Behavioral and Brain Sciences (1993)

Abstract Fechner's conception of psychophysics included both “outer psychophysics” the relation between stimulus intensity and the response reflecting sensation strength, and “inner psychophysics” the relation between neurelectric responses and sensation strength. In his own time outer psychophysics focussed on the form of the psychophysical law, with Fechner espousing a logarithmic law, Delboeuf a variant of the logarithmic law incorporating a resting level of neural activity, and Plateau a power law. One of the issues on which the dispute was focussed concerned the appearance of contrasts if the overall illumination was increased or decreased; another issue was the question of whether a sensation of a “just noticeable difference” established for one value of a sensory dimension appeared the same for a value elsewhere on the dimension. The development of “inner psychophysics” led through the works of Delboeuf, Solomons, Jastrow, and Thurstone to modern signal detection theory. A third line of research, devoted to the question of what was meant by the “measurement” of sensation strength, stemmed from the criticism of Fechner's work by von Kries (1882) and others. Although a valid body of science could be built up without the intervening variable called “sensation strength,” such a science might be a cumbersome representation of reality. When an optical contrast is set up, and its overall illumination is increased or decreased, subjective contrasts involving medium levels of lightness vary little as illumination varies (as a power law based on sensation ratios or a logarithmic law based on sensation differences predict), but subjective contrasts involving extreme levels of lightness might be subject to the effects of other variables.
Association between colon cancer and adenocarcinoma of the oesophagus Reply
Authors: R MARIC
Journal: Gut (2000)

Editor,—Recently, Lagergren and Nyren ( Gut 1999; 44 :819–821) concluded that results from a population based cohort study in Sweden did not support a common link between colon cancer and oesophageal adenocarcinoma. However, there is consistent evidence that low intake of dietary fibre is associated with both diseases. In an analysis of 13 case control studies involving more than 5000 colorectal cancer cases, Howe and colleagues reported an inverse association between fibre intake and risk of colorectal cancer in 12 of the 13 studies, and an odds ratio of 0.53 (95% confidence interval 0.47 to 0.61) for the highest quintile of fibre intake compared with the lowest, in the combined analysis.1 Similarly, four case control studies have reported a significant inverse association between fibre intake and adenocarcinoma of the oesophagus and gastric cardia (table1).2-5 In contrast, two studies which included cases of squamous cell carcinoma found no significant link between fibre intake and squamous cell carcinoma of the oesophagus.2 5

View this table:

Table 1 
Dietary fibre intake and adenocarcinoma of the oesophagus and gastric cardia



Clearly, the dramatic increase in the incidence of adenocarcinoma of the oesophagus in …
Aortic Stiffness Increases Upon Receipt of Anthracycline Chemotherapy
Authors: Narumol Chaosuwannakit, Ralph D'Agostino, Craig A. Hamilton, Kimberly S. Lane, William O. Ntim, Julia Lawrence, Susan A. Melin, Leslie R. Ellis, Frank M. Torti, William C. Little, W. Gregory Hundley
Journal: Journal of Clinical Oncology (2009)

PURPOSE Cancer survivors exposed to anthracyclines experience an increased risk of cardiovascular (CV) events. We hypothesized that anthracycline use may increase aortic stiffness, a known predictor of CV events. PATIENTS AND METHODS We performed a prospective, case-control study involving 53 patients: 40 individuals who received an anthracycline for the treatment of breast cancer, lymphoma, or leukemia (cases), and 13 age- and sex-matched controls. Each participant underwent phase-contrast cardiovascular magnetic resonance measures of pulse wave velocity (PWV) and aortic distensibility (AoD) in the thoracic aorta at baseline, and 4 months after initiation of chemotherapy. Four one-way analyses of covariance models were fit in which factors known to influence thoracic aortic stiffness were included as covariates in the models. Results At the 4-month follow-up visit, aortic stiffness remained similar to baseline in the control participants. However, in the participants receiving anthracyclines, aortic stiffness increased markedly (relative to baseline), as evidenced by a decrease in AoD (P < .0001) and an increase in PWV (P < .0001). These changes in aortic stiffness persisted after accounting for age, sex, cardiac output, administered cardioactive medications, and underlying clinical conditions known to influence aortic stiffness, such as hypertension or diabetes (P < .0001). CONCLUSION A significant increase in aortic stiffness occurs within 4 months of exposure to an anthracycline which was not seen in an untreated control group. These results indicate that previously regarded cardiotoxic cancer therapy adversely increases thoracic aortic stiffness, a known independent predictor of adverse cardiovascular events.
Zinc Protoporphyrin to Prevent Iron Deficiency
Authors: Robert D. Baker
Journal: JAMA Pediatrics (2013)

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