tbuckley/cabot-search huggingface dataset:
Socioeconomic status and chronic obstructive pulmonary disease
Authors: E. Prescott, J. Vestbo
Journal: Thorax (1999)

Socioeconomic status, whether measured by education, income, or other indices of social class, has long been known to be associated with mortality from different diseases.1-7 This knowledge for the major part stems from studies conducted in the UK where there is a tradition of interest in socioeconomic differences. A milestone within recent years was the “Black Report” prepared by a committee appointed by the UK Minister of Health in 1980.7 This report showed that there were still large socioeconomic differences in morbidity and mortality in men and women of all ages in England. Since then a number of epidemiological studies have been published, both in England and other European and North American countries, which confirm this relationship.8-12 

Socioeconomic differences have been shown to exist for a number of diseases including ischaemic heart disease, many types of cancer, respiratory diseases and, in particular, mortality related to alcohol and violence. In addition, despite a general fall in mortality during recent decades, the relative disadvantage of low socioeconomic status continues to increase.3 7 The number of papers published on socioeconomic factors and morbidity and mortality is increasing sharply.13 The social gradient in ischaemic heart disease has been extensively studied but, although there are indicators that socioeconomic differences in respiratory diseases are greater still,2 very few studies have focused on this disease entity.

A social class gradient in the prevalence of respiratory symptoms in adults, in particular cough and sputum, was first observed in early studies in the UK.1 This has later been confirmed in other studies, most of which date from the 1970s.2 14-26 The relationship between socioeconomic factors and symptoms, lung function parameters, and respiratory morbidity in studies in adults is summarised in table 1. Most of these studies have adjusted for smoking …
Assessing Cell and Organ Senescence Biomarkers
Authors: Bruno Bernardes de Jesus, Maria A. Blasco
Journal: Circulation Research (2012)

A major goal in cancer and aging research is to discriminate the biochemical modifications that happen locally that could account for the healthiness or malignancy of tissues. Senescence is one general antiproliferative cellular process that acts as a strong barrier for cancer progression, playing a crucial role in aging. Here, we focus on the current methods to assess cellular senescence, discriminating the advantages and disadvantages of several senescence biomarkers.
Predictors of mortality in acute heart failure: interaction between diabetes and impaired left ventricular ejection fraction
Authors: Yun Yun Go, John Carson Allen, Shaw Yang Chia, Ling Ling Sim, Fazlur Rehman Jaufeerally, Jonathan Yap, Chi Keong Ching, David Sim, Bernard Kwok, Reginald Liew
Journal: European Journal of Heart Failure (2014)
Chromosomal Instability in Unirradiated Hemaopoietic Cells Induced by Macrophages Exposed <i>In vivo</i> to Ionizing Radiation
Authors: Sally A. Lorimore, Jennifer A. Chrystal, Joanne I. Robinson, Philip J. Coates, Eric G. Wright
Journal: Cancer Research (2008)

Abstract The tumorigenic potential of ionizing radiation has conventionally been attributed to DNA damage in irradiated cells induced at the time of exposure. Recently, there have been an increasing number of reports of damage in unirradiated cells that are either neighbors or descendants of irradiated cells, respectively, regarded as bystander effects and genomic instability and collectively termed nontargeted effects. In this study, we show that descendants of normal murine hemaopoietic clonogenic stem cells exposed to bone marrow–conditioned medium derived from γ-irradiated mice exhibit chromosomal instability unlike the descendants of directly γ-irradiated cells. The instability is expressed in bone marrow cells of the radiation-induced acute myeloid leukemia (r-AML) susceptible strain (CBA/Ca) but not in mice resistant to r-AML (C57BL/6). Furthermore, crossgenetic experiments show the induction of the instability phenotype requires both the producer and responder cells to be of the susceptible CBA/Ca genotype. Macrophages are the source of the bystander signals, and the signaling mechanism involves tumor necrosis factor-α, nitric oxide, and superoxide. The findings show a genotype-dependent chromosomal instability phenotype induced by radiation-induced macrophage-mediated bystander signaling. As the majority of accidental, occupational, and therapeutic exposures to ionizing radiation are partial body exposures, the findings have implications for understanding the consequences of such exposure. [Cancer Res 2008;68(19):8122–6]
Identification and Validation of a Gene Expression Signature That Predicts Outcome in Adult Men With Germ Cell Tumors
Authors: James E. Korkola, Jane Houldsworth, Darren R. Feldman, Adam B. Olshen, Li-Xuan Qin, Sujata Patil, Victor E. Reuter, George J. Bosl, R.S.K. Chaganti
Journal: Journal of Clinical Oncology (2009)

Purpose Germ cell tumor (GCT) is the most common malignancy in young adult men. Currently, patients are risk-stratified on the basis of clinical presentation and serum tumor markers. The introduction of molecular markers could improve outcome prediction. Patients and Methods Expression profiling was performed on 74 nonseminomatous GCTs (NSGCTs) from cisplatin-treated patients (ie, training set) and on 34 similarly treated patients with NSGCTs (ie, validation set). A gene classifier was developed by using prediction analysis for microarrays (PAM) for the binary end point of 5-year overall survival (OS). A predictive score was developed for OS by using the univariate Cox model. Results In the training set, PAM identified 140 genes that predicted 5-year OS (cross-validated classification rate, 60%). The PAM model correctly classified 90% of patients in the validation set. Patients predicted to have good outcome had significantly longer survival than those with poor predicted outcome (P &lt; .001). For the OS end point, a 10-gene model had a predictive accuracy (ie, concordance index) of 0.66 in the training set and a concordance index of 0.83 in the validation set. Dichotomization of the samples on the basis of the median score resulted in significant differences in survival (P = .002). For both end points, the gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P &lt; .01 for both). Conclusion We have identified gene expression signatures that accurately predict outcome in patients with GCTs. These predictive genes should be useful for the prediction of patient outcome and could provide novel targets for therapeutic intervention.
Isolation and Characterization of Multipotent Progenitor Cells from the Bowman’s Capsule of Adult Human Kidneys
Authors: Costanza Sagrinati, Giuseppe Stefano Netti, Benedetta Mazzinghi, Elena Lazzeri, Francesco Liotta, Francesca Frosali, Elisa Ronconi, Claudia Meini, Mauro Gacci, Roberta Squecco, Marco Carini, Loreto Gesualdo, Fabio Francini, Enrico Maggi, Francesco Annunziato, Laura Lasagni, Mario Serio, Sergio Romagnani, Paola Romagnani
Journal: Journal of the American Society of Nephrology (2006)

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman’s capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell–specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24 + CD133 +  PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24 + CD133 +  PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24 + CD133 +  PEC but not of CD24 − CD133 −  renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24 + CD133 +  PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.
Adipose Tissue–Derived Human Mesenchymal Stem Cells Mediated Prodrug Cancer Gene Therapy
Authors: Lucia Kucerova, Veronika Altanerova, Miroslava Matuskova, Silvia Tyciakova, Cestmir Altaner
Journal: Cancer Research (2007)

Abstract Human adipose tissue–derived mesenchymal stem cells (AT-MSC) are considered to be a promising source of autologous stem cells in personalized cell-based therapies. Tumor tracking properties of MSC provide an attractive opportunity for targeted transgene delivery into the sites of tumor formation. In the present study, we addressed whether the suicide gene introduction into human AT-MSC could produce a tumor-specific prodrug converting cellular vehicle for targeted chemotherapy. We prepared yeast fusion cytosine deaminase::uracil phosphoribosyltransferase gene–expressing cells [cytosine deaminase (CD)–expressing AT-MSC (CD-AT-MSC)] by retrovirus transduction. We explored their therapeutic potential on a model of human colon cancer in the presence of prodrug 5-fluorocytosine (5-FC). Gene manipulation of human AT-MSC did not sensitize CD-AT-MSC to 5-FC, thus overcoming the inherent disadvantage of suicide effect on cellular vehicle. CD-AT-MSC in combination with 5-FC augmented the bystander effect and selective cytotoxicity on target tumor cells HT-29 in direct coculture in vitro. We confirmed directed migration ability of AT-MSC and CD-AT-MSC toward tumor cells HT-29 in vitro. Moreover, we achieved significant inhibition of s.c. tumor xenograft growth by s.c. or i.v. administered CD-AT-MSC in immunocompromised mice treated with 5-FC. We confirmed the ability of CD-AT-MSC to deliver the CD transgene to the site of tumor formation and mediate strong antitumor effect in vivo. Taken together, these data characterize MSC derived from adipose tissue as suitable delivery vehicles for prodrug converting gene and show their utility for a personalized cell-based targeted cancer gene therapy. [Cancer Res 2007;67(13):6304–13]
Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity
Authors: Giulia Pinton, Arcangela G Manente, Antonio Daga, Michele Cilli, Maurizio Rinaldi, Stefan Nilsson, Laura Moro
Journal: Molecular Cancer (2014)

Estrogen receptor (ER) β acts as a tumor suppressor in malignant mesotheliomas. Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERβ agonist, KB9520, in human mesothelioma cell lines in vitro and in a mesothelioma mouse model in vivo. KB9520 showed significant anti-proliferative effect in ERβ positive human malignant pleural mesothelioma cells in vitro. Selective activation of ERβ with KB9520 sensitized the cells to treatment with cisplatin, resulting in enhanced growth inhibition and increased apoptosis. Furthermore, in CD1 nude mice mesothelioma tumor growth was significantly inhibited when KB9520 was added on top of the standard of care chemo combination cisplatin/pemetrexed, as compared to the cisplatin/pemetrexed alone group. Importantly, KB9520 exerted a protective effect to cisplatin toxicity in the non-malignant mesothelium derived MET5A cells. Together, the data presented suggest that selective targeting of ERβ may be an efficacious stand-alone treatment option and/or become an important add-on to existing malignant mesothelioma therapy.
Development of a Miniaturized Glucose Monitoring System by Combining a Needle-Type Glucose Sensor With Microdialysis Sampling Method: Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients
Authors: Yasuhiro Hashiguchi, Michiharu Sakakida, Kenro Nishida, Takero Uemura, Ken-Ichiro Kajiwara, Motoaki Shichiri
Journal: Diabetes Care (1994)

OBJECTIVE To develop a reliable and practical glucose monitoring system by combining a needle-type glucose sensor with a microdialysis sampling technique for long-term subcutaneous tissue glucose measurements. RESEARCH DESIGN AND METHODS A microdialysis Cuprophan hollowfiber probe (inner diameter, 0.20 mm; length, 15 mm) was perfused with isotonic saline solution (120 μl/h) and glucose concentrations in the dialysate were measured by a needle-type glucose sensor extracorporeally. This system was tested both in vitro and in vivo. Subcutaneous tissue glucose concentrations were then monitored continuously in 5 healthy and 8 diabetic volunteers for 7 to 8 days. A hollow-fiber probe was inserted into the abdominal subcutaneous tissue. RESULTS This monitoring system achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to &amp;gt;027.8 mM glucose, with a time delay of 6.9 ±1.2 min associated with a rise in glucose and 8.8 ±1.6 min with a fall in the glucose level (means ± SE). The overall correlation between subcutaneous tissue (Y) and blood (X) glucose concentration was Y = 1.08X ± 0.19 (r = 0.99). The subcutaneous tissue glucose concentration could be monitored precisely for 4 days without any in vivo calibrations and for 7 days by introducing in vivo calibrations. CONCLUSIONS Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.
Activation of CPP32-like Proteases Is Not Sufficient to Trigger Apoptosis: Inhibition of Apoptosis by Agents that Suppress Activation of AP24, but Not CPP32-like Activity
Authors: Susan C. Wright, Ute Schellenberger, Hong Wang, David H. Kinder, Jamil W. Talhouk, James W. Larrick
Journal: The Journal of Experimental Medicine (1997)

The 24-kD apoptotic protease (AP24) is a serine protease that is activated during apoptosis and has the capacity to activate internucleosomal DNA fragmentation in isolated nuclei. This study examined the following: (a) the functional relationship between AP24 and the CPP32-like proteases of the caspase family; and (b) whether activation of CPP32-like proteases is sufficient to commit irreversibly a cell to apoptotic death. In three different leukemia cell lines, we showed that agents that directly (carbobenzoxy-Ala-Ala-borophe (DK120) or indirectly inhibit activation of AP24 (protein kinase inhibitors, basic fibroblast growth factor, tosylphenylalaninechloromethylketone, and caspase inhibitors) protected cells from apoptosis induced by TNF or UV light. Only the caspase inhibitors, however, prevented activation of CPP32-like activity as revealed by cleavage of the synthetic substrate, DEVD-pNa, by cell cytosols, and also by in vivo cleavage of poly (ADP-ribosyl) polymerase, a known substrate of CPP32. Activation of DEVD-pNa cleaving activity without apoptosis was also demonstrated in two variants derived from the U937 monocytic leukemia in the absence of exogenous inhibitors. Cell-permeable peptide inhibitors selective for CPP32-like proteases suppressed AP24 activation and apoptotic death. These findings indicate that CPP32-like activity is one of several upstream signals required for AP24 activation. Furthermore, activation of CPP32-like proteases alone is not sufficient to commit irreversibly a cell to apoptotic death under conditions where activation of AP24 is inhibited.
Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90
Authors: Ming Zhao, Jian Ma, Hai-Yan Zhu, Xu-Hui Zhang, Zhi-Yan Du, Yuan-Ji Xu, Xiao-Dan Yu
Journal: Molecular Cancer (2011)

Abstract Background Multiple myeloma (MM) is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.
Consumer Reports in Health Care: Do They Make a Difference?
Authors: Helen Halpin Schauffler, Jennifer K Mordavsky
Journal: Annual Review of Public Health (2001)

▪ Abstract The public release of health care–quality data into more formalized consumer health report cards is intended to educate consumers, improve quality of care, and increase competition in the marketplace The purpose of this review is to evaluate the evidence on the impact of consumer report cards on the behavior of consumers, providers, and purchasers. Studies were selected by conducting database searches in Medline and Healthstar to identify papers published since 1995 in peer-review journals pertaining to consumer report cards on health care. The evidence indicates that consumer report cards do not make a difference in decision making, improvement of quality, or competition. The research to date suggests that perhaps we need to rethink the entire endeavor of consumer report cards. Consumers desire information that is provider specific and may be more likely to use information on rates of errors and adverse outcomes. Purchasers may be in a better position to understand and use information about health plan quality to select high-quality plans to offer consumers and to design premium contributions to steer consumers, through price, to the highest-quality plans.
Influence of Neck Muscles on Mouth Pressure Response to Cervical Magnetic Stimulation
Authors: VALÉRIE ATTALI, SELMA MEHIRI, CHRISTIAN STRAUS, FRANÇOIS SALACHAS, ISABELLE ARNULF, VINCENT MEININGER, JEAN-PHILIPPE DERENNE, THOMAS SIMILOWSKI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Measurement of mouth pressure (Pm) in response to electrical phrenic nerve stimulation (Es) provides a simple noninvasive means to assess diaphragm function. An even simpler measure would be to use the Pm twitch response (Pm,t) to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects diaphragm function only if the corresponding INM contraction does not produce inspiratory pressures by itself. In patients with recent-onset bilateral diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero; however, INM hypertrophy could change this situation and lead CMS-Pm,t to overestimate the performance of the diaphragm. To address this issue, we studied nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of inspiratory neck muscles. The response to CMS was described in terms of diaphragm electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG response to CMS could be observed in most cases, and CMS was always associated with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck muscle hypertrophy can significantly influence the Pm response to CMS. This should be taken into account when using the CMS-Pm combination in patients with possible chronic diaphragm dysfunction.
Pelvic Irradiation With Concurrent Chemotherapy Versus Pelvic and Para-Aortic Irradiation for High-Risk Cervical Cancer: An Update of Radiation Therapy Oncology Group Trial (RTOG) 90-01
Authors: Patricia J. Eifel, Kathryn Winter, Mitchell Morris, Charles Levenback, Perry W. Grigsby, Jay Cooper, Marvin Rotman, David Gershenson, David G. Mutch
Journal: Journal of Clinical Oncology (2004)

To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix.Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation.The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms.Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.