tbuckley/cabot-search huggingface dataset:
Clinical Correlates of MDR1 (P-glycoprotein) Gene Expression in Ovarian and Small-Cell Lung Carcinomas
Authors: T. A. Holzmayer, S. Hilsenbeck, D. D. Von Hoff, I. B. Roninson
Journal: JNCI Journal of the National Cancer Institute (1992)

Background: Expression of the MDR1 (P-glycoprotein) gene causes resistance to several classes of lipophilic anti-cancer drugs, but MDR1 expression in untreated ovarian and lung carcinomas is rarely detectable by standard assays. Purpose: This study was designed to measure the MDR1 messenger RNA (mRNA) content of ovarian and lung carcinomas and to analyze clinical correlations of MDR1 expression in these tumors. Methods: A sensitive assay based on the polymerase chain reaction (PCR) was used in a retrospective study to measure MDR1 mRNA in biopsy samples of 100 solid tumors, including 60 ovarian and 32 lung carcinomas. The levels of MDR1 mRNA were correlated with history of chemotherapeutic treatment for all tumors; for ovarian and small-cell lung carcinomas (SCLCs), these levels were also correlated with subsequent tumor response to chemotherapy. Results: Among previously untreated patients, MDR1 mRNA was expressed in 68% (50 of 74) of all tumors. Among patients pretreated with chemotherapy regimens that included at least one P-glycoprotein-transported drug (MDR regimens), 95% (20 of 21) of all tumors expressed MDR1 mRNA though the incidence of high-level MDR1 expression was decreased among the treated tumors. MDR1 mRNA was expressed in only one of five tumors treated with regimens that included no P-glycoprotein substrates (non-MDR regimens). Subsequent tumor response to chemotherapy was evaluated in 35 patients with ovarian carcinoma and seven patients with SCLC. The presence of even very low levels of MDR1 mRNA correlated with the lack of response to MDR regimens in these tumor types ( P <.035 for ovarian carcinomas, P <.029 for SCLCs, and P <.0005 for both tumor types; Fisher's Exact Test). Conclusions: Low-level expression of MDR1 mRNA correlates with clinical resistance to combination chemotherapy in ovarian cancer and SCLC. We hypothesize that MDR1 is expressed in a sub-population of more malignant tumor cells possessing multiple mechanisms of drug resistance. Implications: The presence of MDR1-expressing tumor cells may be useful as a predictive marker for clinical resistance to combination chemotherapy in ovarian cancer and SCLC. Prospective studies are needed to confirm this hypothesis. [J Natl Cancer Inst 84:1486–1491, 1992]
Mortality in ankylosing spondylitis: results from a nationwide population-based study
Authors: Sofia Exarchou, Elisabeth Lie, Ulf Lindström, Johan Askling, Helena Forsblad-d'Elia, Carl Turesson, Lars Erik Kristensen, Lennart TH Jacobsson
Journal: Annals of the Rheumatic Diseases (2015)

Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population.Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort.There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (age-adjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery.Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.
Loss of Krox20 results in aortic valve regurgitation and impaired transcriptional activation of fibrillar collagen genes
Authors: Gaëlle Odelin, Emilie Faure, Frank Kober, Corinne Maurel-Zaffran, Alexis Théron, Fanny Coulpier, Benjamin Guillet, Monique Bernard, Jean-François Avierinos, Patrick Charnay, Piotr Topilko, Stéphane Zaffran
Journal: Cardiovascular Research (2014)

AimsHeart valve maturation is achieved by the organization of extracellular matrix (ECM) and the distribution of valvular interstitial cells. However, the factors that regulate matrix components required for valvular structure and function are unknown. Based on the discovery of its specific expression in cardiac valves, we aimed to uncover the role of Krox20 (Egr-2) during valve development and disease.
Nanoparticle-based flow virometry for the analysis of individual virions
Authors: Anush Arakelyan, Wendy Fitzgerald, Leonid Margolis, Jean-Charles Grivel
Journal: Journal of Clinical Investigation (2013)

While flow cytometry has been used to analyze the antigenic composition of individual cells, the antigenic makeup of viral particles is still characterized predominantly in bulk. Here, we describe a technology, "flow virometry," that can be used for antigen detection on individual virions. The technology is based on binding magnetic nanoparticles to virions, staining the virions with monoclonal antibodies, separating the formed complexes with magnetic columns, and characterizing them with flow cytometers. We used this technology to study the distribution of two antigens (HLA-DR and LFA-1) that HIV-1 acquires from infected cells among individual HIV-1 virions. Flow virometry revealed that the antigenic makeup of virions from a single preparation is heterogeneous. This heterogeneity could not be detected with bulk analysis of viruses. Moreover, in two preparations of the same HIV-1 produced by different cells, the distribution of antigens among virions was different. In contrast, HIV-1 of two different HIV-1 genotypes replicating in the same cells became somewhat antigenically similar. This nanotechnology allows the study of virions in bodily fluids without virus propagation and in principle is not restricted to the analysis of HIV, but can be applied to the analysis of the individual surface antigenic makeup of any virus.
Vascular Endothelial Cell Growth Factor Receptor 3–Mediated Activation of Lymphatic Endothelium Is Crucial for Tumor Cell Entry and Spread via Lymphatic Vessels
Authors: Yulong He, Iiro Rajantie, Katri Pajusola, Michael Jeltsch, Tanja Holopainen, Seppo Yla-Herttuala, Thomas Harding, Karin Jooss, Takashi Takahashi, Kari Alitalo
Journal: Cancer Research (2005)

Abstract Lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to promote lymphatic metastasis by inducing tumor-associated lymphangiogenesis. In this study, we have investigated how tumor cells gain access into lymphatic vessels and at what stage tumor cells initiate metastasis. We show that VEGF-C produced by tumor cells induced extensive lymphatic sprouting towards the tumor cells as well as dilation of the draining lymphatic vessels, suggesting an active role of lymphatic endothelial cells in lymphatic metastasis. A significant increase in lymphatic vessel growth occurred between 2 and 3 weeks after tumor xenotransplantation, and lymph node metastasis occurred at the same stage. These processes were blocked dose-dependently by inhibition of VEGF receptor 3 (VEGFR-3) signaling by systemic delivery of a soluble VEGFR-3-immunoglobulin (Ig) fusion protein via adenoviral or adeno-associated viral vectors. However, VEGFR-3-Ig did not suppress lymph node metastasis when the treatment was started at a later stage after the tumor cells had already spread out, suggesting that tumor cell entry into lymphatic vessels is a key step during tumor dissemination via the lymphatics. Whereas lymphangiogenesis and lymph node metastasis were significantly inhibited by VEGFR-3-Ig, some tumor cells were still detected in the lymph nodes in some of the treated mice. This indicates that complete blockade of lymphatic metastasis may require the targeting of both tumor lymphangiogenesis and tumor cell invasion.
Frequency, Clinical Associations, and Longitudinal Course of Major Depressive Disorder in Adults With Cerebral Glioma
Authors: Alasdair G. Rooney, Shanne McNamara, Mairi Mackinnon, Mary Fraser, Roy Rampling, Alan Carson, Robin Grant
Journal: Journal of Clinical Oncology (2011)

There is a need for high-quality evidence regarding the frequency, independent clinical associations, and longitudinal course of depression in patients with cerebral glioma.This was a twin-center, prospective, observational cohort study with 6-month follow-up. Consenting adults with a new diagnosis of cerebral glioma received the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to diagnose major depressive disorder (MDD). Interviews occurred shortly after the start of radiotherapy (T1), with follow-up interviews 3 months later (T2) and 6 months later (T3). Independent associations between MDD and clinical variables were analyzed using logistic regression.One hundred fifty-five patients participated. The frequency of MDD was 13.5% ± 5.4% at T1 (n = 155); 14.8% ± 6.7% at T2 (n = 108); and 6.8% ± 5.3% at T3 (n = 88). Overall, 32 individuals were diagnosed with MDD during the study period (20.6% ± 6.4%). Inter-rater diagnostic agreement for MDD was good (κ = 0.81; 95% CI, 0.60 to 1.00). Independent predictors of MDD were functional impairment (odds ratio, 3.9; 95% CI, 1.5 to 10.8) and a previous history of depression (odds ratio, 2.7; 95% CI, 0.99 to 7.3). MDD persisted for at least 3 months in half of the patients with adequate follow-up, but many depressed patients also dropped out of the study as a result of clinical deterioration.In this longitudinal study, one in five patients with glioma developed clinical depression in the 6 months after starting radiotherapy. Patients with functional impairment or previous depression were at higher risk. MDD often persisted for at least 3 months. Clinicians should seek and treat depression in adults with glioma.
The Association Between IGF-I and Insulin Resistance
Authors: Nele Friedrich, Betina Thuesen, Torben Jørgensen, Anders Juul, Christin Spielhagen, Henri Wallaschofksi, Allan Linneberg
Journal: Diabetes Care (2012)

IGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate the association between IGF-I level and insulin resistance in a Danish general population.Included were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin resistance. Serum IGF-I levels were determined by an immunoassay and grouped into quintiles (Q1-Q5). Linear or multinomial logistic regression analyses were performed.In the study population, 520 subjects (15.5%) had increased HOMA-IR values above 2.5. After adjustment for age, sex, physical activity, and waist-to-height ratio, a U-shaped association between IGF-I and HOMA-IR was found. Low IGF-I (Q1: odds ratio [OR] 1.65 [95% CI 1.16-2.34], P < 0.01) as well as high IGF-I (Q5: 1.96 [1.38-2.79], P < 0.01) levels were related to a higher odds of increased HOMA-IR values compared with subjects with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.Low- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism of this complex phenomenon has to be elucidated in more detail for future risk stratification.
Fine Mapping of Chromosome 6q23-25 Region in Familial Lung Cancer Families Reveals <i>RGS17</i> as a Likely Candidate Gene
Authors: Ming You, Daolong Wang, Pengyuan Liu, Haris Vikis, Michael James, Yan Lu, Yian Wang, Min Wang, Qiong Chen, Dongmei Jia, Yan Liu, Weidong Wen, Ping Yang, Zhifu Sun, Susan M. Pinney, Wei Zheng, Xiao-Ou Shu, Jirong Long, Yu-Tang Gao, Yong-Bing Xiang, Wong-Ho Chow, Nat Rothman, Gloria M. Petersen, Mariza de Andrade, Yanhong Wu, Julie M. Cunningham, Jonathan S. Wiest, Pamela R. Fain, Ann G. Schwartz, Luc Girard, Adi Gazdar, Colette Gaba, Henry Rothschild, Diptasri Mandal, Teresa Coons, Juwon Lee, Elena Kupert, Daniela Seminara, John Minna, Joan E. Bailey-Wilson, Christopher I. Amos, Marshall W. Anderson
Journal: Clinical Cancer Research (2009)

Abstract Purpose: We have previously mapped a major susceptibility locus influencing familial lung cancer risk to chromosome 6q23-25. However, the causal gene at this locus remains undetermined. In this study, we further refined this locus to identify a single candidate gene, by fine mapping using microsatellite markers and association studies using high-density single nucleotide polymorphisms (SNP). Experimental Design: Six multigenerational families with five or more affected members were chosen for fine-mapping the 6q linkage region using microsatellite markers. For association mapping, we genotyped 24 6q-linked cases and 72 unrelated noncancer controls from the Genetic Epidemiology of Lung Cancer Consortium resources using the Affymetrix 500K chipset. Significant associations were validated in two independent familial lung cancer populations: 226 familial lung cases and 313 controls from the Genetic Epidemiology of Lung Cancer Consortium, and 154 familial cases and 325 controls from Mayo Clinic. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Results: A region-wide scan across 6q23-25 found significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene. This association was further confirmed in two independent familial lung cancer populations. By quantitative real-time PCR analysis of matched tumor and normal human tissues, we found that RGS17 transcript accumulation is highly and consistently increased in sporadic lung cancers. Human lung tumor cell proliferation and tumorigenesis in nude mice are inhibited upon knockdown of RGS17 levels. Conclusion: RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25.
Long-Term Outcome of Psychodynamic Therapy and Cognitive-Behavioral Therapy in Social Anxiety Disorder
Authors: Falk Leichsenring, Simone Salzer, Manfred E. Beutel, Stephan Herpertz, Wolfgang Hiller, Juergen Hoyer, Johannes Huesing, Peter Joraschky, Bjoern Nolting, Karin Poehlmann, Viktoria Ritter, Ulrich Stangier, Bernhard Strauss, Susan Tefikow, Tobias Teismann, Ulrike Willutzki, Joerg Wiltink, Eric Leibing
Journal: American Journal of Psychiatry (2014)

Relatively few studies have examined the long-term outcome of psychotherapy in social anxiety disorder. The authors previously reported findings of a clinical trial comparing cognitive-behavioral therapy (CBT), psychodynamic therapy, and a wait-list control. The purpose of the present study was to follow the participants' status over the ensuing 24 months.Outpatients with social anxiety disorder who were treated with CBT (N=209) or psychodynamic therapy (N=207) in the previous trial were assessed 6, 12, and 24 months after the end of therapy. Primary outcome measures were rates of remission and response.For both CBT and psychodynamic therapy, response rates were approximately 70% by the 2-year follow-up. Remission rates were nearly 40% for both treatment conditions. Rates of response and remission were stable or tended to increase for both treatments over the 24-month follow-up period, and no significant differences were found between the treatment conditions after 6 months.CBT and psychodynamic therapy were efficacious in treating social anxiety disorder, in both the short- and long-term, when patients showed continuous improvement. Although in the short-term, intention-to-treat analyses yielded some statistically significant but small differences in favor of CBT in several outcome measures, no differences in outcome were found in the long-term.
Extended Transthoracic Resection Compared with Limited Transhiatal Resection for Adenocarcinoma of the Esophagus
Authors: Jan B.F. Hulscher, Johanna W. van Sandick, Angela G.E.M. de Boer, Bas P.L. Wijnhoven, Jan G.P. Tijssen, Paul Fockens, Peep F.M. Stalmeier, Fiebo J.W. ten Kate, Herman van Dekken, Huug Obertop, Hugo W. Tilanus, J. Jan B. van Lanschot
Journal: New England Journal of Medicine (2002)

Controversy exists about the best surgical treatment for esophageal carcinoma.We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined.A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died--74 (70 percent) after transhiatal resection and 68 (60 percent) after transthoracic resection (P=0.12). Although the difference in survival was not statistically significant, there was a trend toward a survival benefit with the extended approach at five years: disease-free survival was 27 percent in the transhiatal-esophagectomy group, as compared with 39 percent in the transthoracic-esophagectomy group (95 percent confidence interval for the difference, -1 to 24 percent [the negative value indicates better survival with transhiatal resection]), whereas overall survival was 29 percent as compared with 39 percent (95 percent confidence interval for the difference, -3 to 23 percent).Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy. Although median overall, disease-free, and quality-adjusted survival did not differ statistically between the groups, there was a trend toward improved long-term survival at five years with the extended transthoracic approach.
THE ORGANIZATION AND ADMINISTRATION OF A STATE HOSPITAL INSULIN-METRAZOL-ELECTRIC SHOCK THERAPY UNIT
Authors: HARRY J. WORTHING, NEWTON BIGELOW, RICHARD BINZLEY, HENRY BRILL
Journal: American Journal of Psychiatry (1943)

Imperfect and unsatisfactory as it is at the present time shock therapy is economically, medically and socially justifiable. It is indicated in the treatment of mental disturbances unassociated with gross organic brain disease, where illness has been serious enough to lead to recent commitment to a state hospital, unless there are severe physical contraindications or unless there is a clear history of continuous illness outside of the hospital for several years. It appears to be a treatment of choice. From a five-year experience with this method in a large state hospital the authors conclude that the treatment is very conveniently and efficiently applied in a central unit where all patients are housed and where insulin, metrazol and electric shock therapy are given in parallel, with the idea of finding which treatment or what combination of treatments will produce the best result in each individual case. Costs per capita fall rapidly as the capacity of the treatment unit rises and it may be said that a unit with a capacity of 30 to 40 patients with two physicians is quite satisfactory from the operational point of view. Experience with the method and with choices of patients and therapies has somewhat the characteristic of an art. One cannot therefore expect good results from such an organization until it has had a year or two in which to develop its technique and experience. Finally, we feel that the treatment pays for itself in an improved parole rate, better public relations and intangible human values, both for the hospital staff and the community which it serves.
Information gaps have the same causes as wealth gaps
Authors: R. Stott
Journal: BMJ (2000)

Editor—If I substituted the words “financial wealth” for “information flow” in the editorial by Godlee et al on global information flow in this issue,1 I could imagine myself reading an upbeat briefing on the virtues of trickle down economics from the 1970s. Information gaps have the same causes as wealth gaps. They are a consequence of a powerful elite parading their culture and ideas as if these were universal. When there is the remotest opposition, the powerful will do everything to overcome it.

The notion that thoughtful articulation of alternative views about health and society might, through the information revolution, modify the behaviour of the powerful in a way which will improve the health of the poor is fanciful and misguided. The information gap can be closed only when we are closer to securing the economic, social, and environmental justice within which all societies can flourish and express themselves as equal partners. The question, therefore, is, can we expect the flow of information to move us closer to this desired state?

I fear the answer is no, and we are in danger of falling into an information revolution abyss. Haven't we got enough problems with the International Monetary Fund and the World Bank?
Mourning in Japan
Authors: JOE YAMAMOTO, KEIGO OKONOGI, TETSUYA IWASAKI, SABURO YOSHIMURA
Journal: American Journal of Psychiatry (1969)

The authors examine the process of mourning in a culture whose religions sanction the implied presence of the deceased through ancestor worship, as compared to a culture where this is not acceptable or encouraged. Most of 20 Japanese widows interviewed during the acute grief phase of mourning adhered to the cultural beliefs and were less depressed and anxious and had less difficulty accepting the loss than those who did not. The authors suggest that the almost universal Japanese custom of ancestor worship serves an important adaptive function in the work of mourning.