tbuckley/cabot-search huggingface dataset:
Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis
Authors: Srikanth Nagalla, Jeff W Chou, Mark C Willingham, Jimmy Ruiz, James P Vaughn, Purnima Dubey, Timothy L Lash, Stephen J Hamilton-Dutoit, Jonas Bergh, Christos Sotiriou, Michael A Black, Lance D Miller
Journal: Genome biology (2013)

Gene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified. To investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes. These findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.
Has the Yearly Increase in the Renal Replacement Therapy Population Ended?
Authors: Steven Jay Rosansky, William F. Clark
Journal: Journal of the American Society of Nephrology (2013)

The recent decline in the number of new patients undergoing dialysis and transplantation in the United States may be linked to a reduction in the incidence of early-start dialysis, defined as the initiation of renal replacement therapy (RRT) at an estimated GFR ≥10 ml/min per 1.73 m2. We examined the most recent data from the U.S. Renal Data System to determine how this trend will affect the future incidence of ESRD in the United States. The percentage of early dialysis starts grew from 19% to 54% of all new starts between 1996 and 2009 but remained stable between 2009 and 2011. Similarly, the incident RRT population increased substantially in all age groups between 1996 and 2005, with the largest increase occurring in patients aged ≥75 years. Early dialysis starts accounted for most of the increase in the incident RRT population in all age groups during this time period, and between 2005 and 2010, the increase slowed dramatically. Although the future incident RRT population will be determined in part by population growth, these results suggest that later dialysis starts and greater use of conservative and palliative care, which may improve quality of life for elderly patients with advanced renal failure, will continue to attenuate the increase observed in previous years.
Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease
Authors: Long Truong Hoang, Chisato Shimizu, Ling Ling, Ahmad Nazri Mohamed Naim, Chiea Chuen Khor, Adriana H Tremoulet, Victoria Wright, Michael Levin, Martin L Hibberd, Jane C Burns
Journal: Genome Medicine (2014)

Abstract Background Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD. Methods To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes. Results The overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target. Conclusion Our study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.
Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias
Authors: B. You, M. Pollet-Villard, L. Fronton, C. Labrousse, A.-M. Schott, T. Hajri, P. Girard, G. Freyer, M. Tod, B. Tranchand, O. Colomban, B. Ribba, D. Raudrant, J. Massardier, S. Chabaud, F. Golfier
Journal: Annals of Oncology (2010)
Genetic Testing in Clinical Practice
Authors: Steven W.J. Lamberts, André G. Uitterlinden
Journal: Annual Review of Medicine (2008)

In the practice of internal medicine, the value of genetic testing in common (mono)genetic diseases such as familial hemochromatosis, hypercholesterolemia, Mediterranean fever, and thrombophilia is limited. The genotype insufficiently predicts the phenotype because of the powerful effects of other modifying genes, environmental influences, and lifestyle factors. Many common diseases, including diabetes mellitus, osteoporosis, and cardiovascular disease, have strong genetic influences but are called complex genetic traits. The underlying genetic factors are currently investigated using new molecular tools such as genome-wide association studies, analyzing up to 500,000 markers in huge numbers of patients. Many new (often unexpected) markers have been identified, and in many instances their functional significance is unknown. Genomic profiles play a rapidly growing role in the field of pharmacogenomics. A number of recently identified pharmacogenomic biomarkers are helpful to predict drug-related toxic effects.
Anger and acne: implications for quality of life, patient satisfaction and clinical care
Authors: D.A. Rapp, G.A. Brenes, S.R. Feldman, A.B. Fleischer, G.F. Graham, M. Dailey, S.R. Rapp
Journal: British Journal of Dermatology (2004)

Background Acne is a common skin disorder with a significant psychological and social impact for some people. Little is known about how personality and emotional traits affect acne and its impact on quality of life and treatment. Trait anger (TA), which is related to heart disease and other morbidities, may also affect acne and patients' adjustment to it. Objectives To evaluate the relationship between TA and acne severity, skin-related quality of life, satisfaction with treatment, and adherence to treatment. Participants and methods A sample of 479 individuals with acne completed a survey instrument to assess acne severity, skin care practices, skin-related quality of life, satisfaction with treatment, adherence, TA and demographic variables. Respondents who reported high TA were compared with individuals with low TA on outcome variables. Regression analyses adjusted for covariates and identified the significant predictors of quality of life, satisfaction and adherence. Results High TA was unrelated to acne severity (P = 0·2) or frequency of face washing (P = 0·9). Anger was significantly related to both global quality of life (P < 0·001) and skin-related quality of life (P = 0·002) as well as to satisfaction with treatment (P = 0·001) and adherence to treatment advice (P = 0·05) in bivariate analyses. Regression analyses revealed that high TA remained a significant predictor of global (P < 0·001) and skin-related quality of life (P = 0·003) and satisfaction with treatment (P = 0·04), but not adherence to treatment advice (P = 0·8) after controlling for covariates. Conclusions Anger is associated with the quality of patients' lives and with their satisfaction with treatment. Care of acne patients should include attention to anger and other chronic emotional states, quality of life, as well as to clinical severity. Simple guidelines are suggested for how clinicians might approach this important aspect of care.
Male Fertility in Hot Environment
Authors: Richard J. Levine
Journal: JAMA (1984)

<h3>To the Editor.—</h3> The American Medical Association Council on Scientific Affairs has recently noted that adequate studies of adverse effects on male reproductive function from working in hot environments do not exist.<sup>1</sup>Unfortunately, the Council has also made the premature judgment that such effects are not to be expected under normal working conditions. It cites a study of workers in sugar refineries and railroads by Fonio et al,<sup>2</sup>which is poorly documented and lacks a control group. Although Fonio et al state that heat had no negative influence on fertility since 94% of surveyed persons were reported to have had children during exposure, no attempt was made to determine if the number of children conceived might have been fewer than usual. While temporary hot exposures should, as the Council has concluded, cause no permanent effects and no substantial decrease in fertility, exposures of up to several hours experienced
Glyceraldehyde-3-phosphate dehydrogenase gene over expression correlates with poor prognosis in non small cell lung cancer patients
Authors: Roberto Puzone, Graziana Savarino, Sandra Salvi, Maria Dal Bello, Giulia Barletta, Carlo Genova, Erika Rijavec, Claudio Sini, Alessia Esposito, Giovanni Ratto, Mauro Truini, Francesco Grossi, Ulrich Pfeffer
Journal: Molecular Cancer (2013)

Glycolysis in presence of oxygen with high glucose consumption is known to be the metabolism of choice in many tumors. In lung cancer this phenomenon is routinely exploited in diagnostic PET imaging of fluorodeoxyglucose uptake, but not much is known about the prognostic capabilities of glycolysis level assessment in resected lung tumor samples. In this retrospective study, we used real time polymerase chain reaction(RQ-PCR) to assess the expression level of the gene for Glyceraldehyde 3-phosphate dehydrogenase(GAPDH), key enzyme for glucose breakdown, in tumor samples from 82 consecutive early stages resected non small cell lung cancer(NSCLC) patients. We then compared our results in six large publicly available NSCLC microarray datasets collecting data from over 1250 total patients. In our study GAPDH gene over expression was found to be an adverse prognostic factor in early stages NSCLC (n = 82 HR = 1.30 p = 0.050). This result was confirmed in 5 of 6 public datasets analyzed: Shedden et al. 2008: n = 442 HR = 1.54 p < 0.0001; Lee et al. 2008: n = 138 HR = 1.31 p = 0.043; Tomida et al. 2009: n = 117 HR = 1.59 p = 0.004; Roepman et al. 2009: n = 172 (TPI1 gene) HR = 1.51 p = 0.009; Okayama et al. 2012: n = 226 HR = 3.19 p < 0.0001; Botling et al. 2013: n = 196 HR = 1.00 p = 0.97). Furthermore, in the large and clinically well annotated Shedden et al. microarray dataset, GAPDH hazard ratio did not change whether calculated for the whole dataset or for the subgroup of adjuvant naive patients only (n = 330 HR = 1.49 p < 0.0001). GAPDH gene over expression in resected tumor samples is an adverse prognostic factor in NSCLC. Our results confirm the prognostic value of glucose metabolism assessment in NSCLC.
Clinical Activity of Rituximab in Gastric Marginal Zone Non-Hodgkin's Lymphoma Resistant to or Not Eligible for Anti–<i>Helicobacter Pylori</i> Therapy
Authors: Giovanni Martinelli, Daniele Laszlo, Andrés J.M. Ferreri, Giancarlo Pruneri, Maurilio Ponzoni, Annarita Conconi, Cristiano Crosta, Ennio Pedrinis, Francesco Bertoni, Liliana Calabrese, Emanuele Zucca
Journal: Journal of Clinical Oncology (2005)

Purpose Preliminary results using rituximab in extranodal marginal zone (MALT) non-Hodgkin's lymphoma (NHL) patients seem to indicate a relevant clinical activity. Aim of the present study is to investigate the efficacy of conventional weekly treatment using rituximab in gastric MALT NHL patients resistant/refractory or not suitable for eradication treatment, and to evaluate the relevance of the t(11; 18)(q21; q21) translocation and its possible role as a predictive criteria of response. Patients and Methods Twenty-seven patients presenting with gastric MALT NHL at any stage, relapsed/refractory to initial treatment or not suitable for eradication were treated with rituximab in a weekly conventional schedule and evaluated for response and relapse. Flourescence in situ hybridization (FISH) analysis for the presence of 18q21 translocation was performed in 21 patients and was evaluated with clinical outcome. Results Among the 26 evaluated patients, 20 (77%) achieved an objective response. Twelve patients (46%) had a pathological and clinical complete remission, and eight (31%) had a partial response. With a median follow-up of 33 months, only two patients relapsed at 26 and 14 months, respectively. No correlation was founded between FISH analysis and response or relapse. Conclusion Our experience seems to confirm the clinical activity of rituximab in gastric MALT NHL patients resistant/refractory to antibiotics treatment or not presenting with clinical evidence of Helicobacter pylori infection. The t(11; 18)(q21; q21) translocation seems not to be a predictive marker to response or to subsequent relapse.
Dietary Patterns and Risk of Mortality From Cardiovascular Disease, Cancer, and All Causes in a Prospective Cohort of Women
Authors: Christin Heidemann, Matthias B. Schulze, Oscar H. Franco, Rob M. van Dam, Christos S. Mantzoros, Frank B. Hu
Journal: Circulation (2008)

The impact of overall dietary patterns that reflect actual eating behaviors on mortality caused by cardiovascular or other chronic diseases is largely unknown.We prospectively evaluated the relation between dietary patterns and risk of cardiovascular, cancer, and all-cause mortality among 72,113 women who were free of myocardial infarction, angina, coronary artery surgery, stroke, diabetes mellitus, or cancer and were followed up from 1984 to 2002. Dietary patterns were derived by factor analysis based on validated food frequency questionnaires administered every 2 to 4 years. Two major dietary patterns were identified: High prudent pattern scores represented high intakes of vegetables, fruit, legumes, fish, poultry, and whole grains, whereas high Western pattern scores reflected high intakes of red meat, processed meat, refined grains, french fries, and sweets/desserts. During 18 years of follow-up, 6011 deaths occurred, including 1154 cardiovascular deaths and 3139 cancer deaths. After multivariable adjustment, the prudent diet was associated with a 28% lower risk of cardiovascular mortality (95% confidence interval [CI], 13 to 40) and a 17% lower risk of all-cause mortality (95% CI, 10 to 24) when the highest quintile was compared with the lowest quintile. In contrast, the Western pattern was associated with a higher risk of mortality from cardiovascular disease (22%; 95% CI, 1 to 48), cancer (16%; 95% CI, 3 to 30), and all causes (21%; 95% CI, 12 to 32).Greater adherence to the prudent pattern may reduce the risk of cardiovascular and total mortality, whereas greater adherence to the Western pattern may increase the risk among initially healthy women.
Cell surface immunoglobulin. XVIII. Functional differences of B lymphocytes bearing different surface immunoglobulin isotypes.
Authors: E S Vitetta, J Forman, J R Kettman
Journal: The Journal of Experimental Medicine (1976)

Three populations of murine splenic B lymphocytes have been characterized previously (6, 7, 9) as those bearing only IgM, those bearing only IgD, and a population bearing both isotopes. These studies were designed to test the response of the IgM+ cells (IgM-only or IgM plus IgD) vs. the IgD-only cells to the B-cell mitogen, lipopolysaccharide. Results that after 1-4 days of culture, in the presence of mitogen, the IgM+ cells enlarge and elaborate an IgM polyclonal response. The IgD-only cells, in contrast, do not exhibit an IgM polyclonal response, but instead undergo blastogenesis and proliferation.
High Expression of Neutral Endopeptidase in Idiopathic Diffuse Hyperplasia of Pulmonary Neuroendocrine Cells
Authors: ANDREA J. COHEN, TALMADGE E. KING, LAURA B. GILMAN, CATHERINE MAGILL-SOLC, YORK E. MILLER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a clinicopathological entity characterized by a diffuse hyperplasia of neuroendocrine cells involving distal bronchi and bronchioles. The pathogenesis of this syndrome remains unknown. The hyperplastic neuroendocrine (NE) cells contain multiple neuropeptides, including the bombesinlike peptides (BLP), which are likely important in the pathogenesis of the disorder by stimulating proliferation of fibroblasts in a paracrine fashion and the NE cells themselves in an autocrine manner. Neutral endopeptidase (NEP) is a cell-surface enzyme that hydrolyzes BLP and other bioactive peptides. Low or undetectable NEP is present in many primary lung cancers and cell lines. Low NEP expression could increase neuropeptide-induced autocrine effects by increasing local levels of neuropeptides. We hypothesized that IDHPNC was associated with low or absent NEP expression. NEP expression was assayed in patients with IDHPNC (n = 3) and was compared with expression in patients with idiopathic pulmonary fibrosis (n = 5), hypersensitivity pneumonitis (n = 5), and normal lung (n = 4) using immunohistochemistry, ELISA, activity assay, and Western blot analysis. By these assays, NEP expression was highest in lungs affected by IDHPNC. NEP mRNA, as assessed in IDHPNC lung tissue by RT-PCR, was the expected size and free of mutation between bp 238–2437. Therefore, IDHPNC is unlikely to be the result of a defect in NEP expression. The apparent increase in NEP expression in lung tissue from patients with IDHPNC may reflect a compensatory increase that partly counteracts abundant neuropeptides, including BLP, present in this disorder.
Rh Isoimmunization from Ruptured Tubal Pregnancy
Authors: G. d. B. Mitford-Barberton
Journal: BMJ (1972)

The spontaneous group of abortions in this series includes those cases where the evidence was not clear enough to call the abortion legal or illegal and the group prob- ably includes quite a number of self-induced abortions.It is interesting that since the start of the Abortion Act in 1968 it is particularly this group of doubtfully-classified abortions which have decreased among the deaths counted by the Registrar General, as is shown in Table II.
Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles.
Authors: J H Morse, R J Barst, S Itescu, E R Flaster, G Sinha, Y Zhang, M Fotino
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Primary pulmonary hypertension (PPH) may have an autoimmune basis that is influenced by host immunogenetics. The pathogenesis of primary pulmonary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patients with PPH and HIV infection have distinctive immunogenetic profiles. Ten racially mixed HIV-infected patients with PPH were typed for human leukocyte antigen (HLA) class II (DRB1, 3, 4, 5 and DQB1) by DNA-PCR sequence-specific oligonucleotide probes. Results were compared with two control groups: 128 HIV-negative Caucasians and a previously reported group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (-DRB1*1301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findings suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major histocompatibility complex. The same HLA-DR6 subtype found at increased frequency in our patients has previously been associated with the development of a CD8 lymphocytic host response to HIV-1, termed diffuse infiltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjogren's disease and is associated with prolonged survival. Together, these findings suggest that HIV-positive PPH may represent a clinical outcome that has similarities with that resulting from the immunogenetically determined host response present in DILS.
Reduced Alveolar–Capillary Membrane Diffusing Capacity in Chronic Heart Failure
Authors: Sundeep Puri, B. Leigh Baker, David P. Dutka, Celia M. Oakley, J. Michael B. Hughes, John G. F. Cleland
Journal: Circulation (1995)

Background The pulmonary diffusing capacity for carbon monoxide ( dlco ) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLco into its membrane conductance (D M ) and capillary blood volume components (Vc) and to assess if alveolar–capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. Methods and Results The classic Roughton and Forster method of measuring single-breath DLco at varying alveolar oxygen concentrations was used to determine D M and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLco was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in D M (7.0±2.6 versus 12.9±3.8 versus 20.0±6.1 mmol · min −1 · kPa −1 in New York Heart Association class III, class II, and normal subjects, respectively, P &lt;.0001), even when the reduction in lung volumes was accounted for by the division of D M by the effective alveolar volume. The Vc component of DLco was not impaired. D M significantly correlated with maximal exercise oxygen uptake ( r =.72, P &lt;.0001) and inversely correlated with pulmonary vascular resistance ( r =.65, P &lt;.01) in CHF. Conclusions Reduced alveolar–capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. D M may be a useful marker for the alveolar–capillary barrier damage induced by raised pulmonary capillary pressure.