tbuckley/cabot-search huggingface dataset:
Relative versus absolute change in forced vital capacity in idiopathic pulmonary fibrosis
Authors: Luca Richeldi, Christopher J Ryerson, Joyce S Lee, Paul J Wolters, Laura L Koth, Brett Ley, Brett M Elicker, Kirk D Jones, Talmadge E King, Jay H Ryu, Harold R Collard
Journal: Thorax (2012)

<h3>Background</h3> Decline in forced vital capacity (FVC) over time reliably predicts mortality in patients with idiopathic pulmonary fibrosis. The use of this measure in clinical practice is recommended by current evidence-based guidelines. It is unknown if the method of calculating decline in FVC (relative vs absolute change) impacts its frequency or its ability to predict mortality. <h3>Methods</h3> Patients with idiopathic pulmonary fibrosis from two prospective cohorts were included if they had a baseline and 12-month follow-up FVC. A ≥10% decline in FVC from baseline was calculated in two ways: a relative decline of 10% (eg, from 60% predicted to 54% predicted) and an absolute decline of 10% (eg, from 60% predicted to 50% predicted). The frequency of a ≥10% decline in FVC and its ability to predict 2-year transplant-free survival were compared between these two methods. Declines in FVC of ≥5% and ≥15% were similarly compared. Analyses were performed unadjusted and adjusted for age, gender, use of oxygen, baseline FVC and baseline diffusion capacity for carbon monoxide. <h3>Results</h3> The frequency of any given FVC decline was significantly greater using the relative change in FVC method. For ≥10% decline, both methods predicted 2-year transplant-free survival with similar accuracy, and remained significant predictors after adjusting for baseline characteristics. The absolute change method appeared more predictive for ≥5% decline. <h3>Conclusions</h3> Using the relative change in FVC maximises the chance of identifying a ≥10% decline in FVC without sacrificing prognostic accuracy. This may not hold true for ≥5% decline in FVC. These findings have important implications for clinical practice and the design of clinical trials.
Functional CXCR4-Expressing Microparticles and SDF-1 Correlate with Circulating Acute Myelogenous Leukemia Cells
Authors: Alexander Kalinkovich, Sigal Tavor, Abraham Avigdor, Joy Kahn, Alexander Brill, Isabelle Petit, Polina Goichberg, Melania Tesio, Neta Netzer, Elizabeth Naparstek, Izhar Hardan, Arnon Nagler, Igor Resnick, Alexander Tsimanis, Tsvee Lapidot
Journal: Cancer Research (2006)

Abstract Stromal cell–derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 are implicated in the pathogenesis and prognosis of acute myelogenous leukemia (AML). Cellular microparticles, submicron vesicles shed from the plasma membrane of various cells, are also associated with human pathology. In the present study, we investigated the putative relationships between the SDF-1/CXCR4 axis and microparticles in AML. We detected CXCR4-expressing microparticles (CXCR4+ microparticles) in the peripheral blood and bone marrow plasma samples of normal donors and newly diagnosed adult AML patients. In samples from AML patients, levels of CXCR4+ microparticles and total SDF-1 were elevated compared with normal individuals. The majority of CXCR4+ microparticles in AML patients were CD45+, whereas in normal individuals, they were mostly CD41+. Importantly, we found a strong correlation between the levels of CXCR4+ microparticle and WBC count in the peripheral blood and bone marrow plasma obtained from the AML patients. Of interest, levels of functional, noncleaved SDF-1 were reduced in these patients compared with normal individuals and also strongly correlated with the WBC count. Furthermore, our data indicate NH2-terminal truncation of the CXCR4 molecule in the microparticles of AML patients. However, such microparticles were capable of transferring the CXCR4 molecule to AML-derived HL-60 cells, enhancing their migration to SDF-1 in vitro and increasing their homing to the bone marrow of irradiated NOD/SCID/β2mnull mice. The CXCR4 antagonist AMD3100 reduced these effects. Our findings suggest that functional CXCR4+ microparticles and SDF-1 are involved in the progression of AML. We propose that their levels are potentially valuable as an additional diagnostic AML variable. (Cancer Res 2006; 66(22): 11013-20)
Predictors of COPD symptoms: does the sex of the patient matter?
Authors: L. Watson, J. P. Schouten, C-G. Löfdahl, N. B. Pride, L. A. Laitinen, D. S. Postma
Journal: European Respiratory Journal (2006)

Although chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV 1 % pred); annual increase in FEV 1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV 1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV 1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52–0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14–1.70)) and wheeze (1.24 (1.03–1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.
Cofactors With Human Papillomavirus in a Population-Based Study of Vulvar Cancer
Authors: M. M. Madeleine, J. R. Daling, S. M. Schwartz, J. J. Carter, G. C. Wipf, A. M. Beckmann, B. McKnight, R. J. Kurman, M. E. Hagensee, D. A. Galloway
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Human papillomavirus (HPV) has been previously associated with vulvar cancer. In a population-based study, we examined whether exposure to HPV, cigarette smoking, or herpes simplex virus 2 (HSV2) increases the risk of this cancer. Methods: Incident cases of in situ (n = 400) and invasive (n = 110) squamous cell vulvar cancer diagnosed among women living in the Seattle area from 1980 through 1994 were identified. Serum samples were analyzed for antibodies against specific HPV types and HSV2. HPV DNA in tumor tissue was detected by means of the polymerase chain reaction. In most analyses, case subjects were compared with population-based control subjects (n = 1403). Relative risks of developing vulvar cancer were estimated by use of adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Increased risks of in situ or invasive vulvar cancer were associated with HPV16 seropositivity (ORs = 3.6 [95% CI = 2.6-4.8] and 2.8 [95% CI = 1.7-4.7], respectively), current cigarette smoking (ORs = 6.4 [95% CI = 4.4-9.3] and 3.0 [95% CI = 1.7-5.3], respectively), and HSV2 seropositivity (ORs = 1.9 [95% CI = 1.4-2.6] and 1.5 [95% CI = 0.9-2.6], respectively). When the analysis was restricted to HPV16 DNA-positive tumors ( in situ or invasive), the OR associated with HPV16 seropositivity was 4.5 (95% CI = 3.0-6.8). The OR for vulvar cancer was 18.8 (95% CI = 11.9-29.8) among current smokers who were HPV16 seropositive in comparison with never smokers who were HPV16 seronegative. Conclusions: Current smoking, infection with HPV16, and infection with HSV2 are risk factors for vulvar cancer. Risk appears particularly strong among women who are both current smokers and HPV16 seropositive.
Amiodarone Therapy for Drug-Refractory Fetal Tachycardia
Authors: Janette F. Strasburger, Bettina F. Cuneo, Maaike M. Michon, Nina L. Gotteiner, Barbara J. Deal, Scott N. McGregor, Martijn A. Oudijk, Erik J. Meijboom, Leonard Feinkind, Michael Hussey, Barbara V. Parilla
Journal: Circulation (2004)

Background— Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. Methods and Results— Fetuses with incessant tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2) for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for &lt;1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. Conclusions— Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.
Relationships between membrane antigens of human leukemic cells and oncogenic RNA virus structural components.
Authors: R S Metzgar, T Mohanakumar, D P Bolognesi
Journal: The Journal of Experimental Medicine (1976)

Leukemic cells from all human chronic granulocytic leukemia (CGL) and some acute myelomonocytic leukemia (AMML) donors are lysed by rabbit antisera to a purified glycoprotein of Friend murine leukemia virus (FLV gp71) in a microcytotoxicity assay. These antisera are not cytotoxic to cells from patients with acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or to peripheral blood lymphocytes from normal donors. A goat antiserum to gradient purified FLV in addition to reacting with cells from CGL and AMML donors also reacted with cells from AML patients and some ALL donors. However, this antiserum failed to react with cells from CLL patients. Peripheral blood and bone marrow leukocytes prepared from leukemic patients in clinical remission failed to react with antisera to FLV and FLV gp71. Absorption experiments demonstrated that the antigen on CGL cells which is reacting with the antiserum to FLV gp71 is also present on normal human platelets and neutrophils. Similar absorption studies showed that the antigen on AML cells detected by the FLV antiserum is not present on normal leukocytes and platelets and appears to be related to the major internal p30 antigens of mammalian RNA tumor viruses. Another antigenic relationship between oncornaviruses and membrane antigens of human leukemia cells was shown by the ability of FLV antigens to absorb the cytotoxic reactivity of nonhuman primate antisera detecting human leukemia-associated antigens. FLV and FLV gp71 antigens were able to absorb all cytotoxic activity of monkey and chimpanzee antisera to human myeloid leukemia antigens when these antisera were tested with CGL cells. These two approaches to an analysis of cross-reactivity indicate that the antigenic determinant(s) detected by the cytotoxic reactions of the FLV gp71 antiserum with human CGL cells is different from the determinant on FLV gp71 which is responsible for the inhibition of the reactivity of simian antisera with CGL cells. Since the goat and rabbit antisera to FLV and FLV gp71 are able to distinguish AML from CGL cells by direct cytotoxicity testing and absorption, they may be valuable reagents for the serological diagnosis of myeloid leukemia. In addition, since peripheral blood cells from AML and CGL patients in clinical remission were seronegative, the antisera may be valuable as management aids. The data in this report indicates that whatever the mechanism of leukemogenesis is in man, cells from CGL and AML patients possess certain membrane antigens which cross-react with FLV structural components such as p30 and gp71.
No Role for Chemoradiotherapy When Compared with Chemotherapy Alone in Elderly Patients with Localized Low Risk Aggressive Lymphoma: Final Results of the LNH93-4 GELA Study.
Authors: Georges Fillet, C. Bonnet, N. Mounier, G. Ganem, T. Molina, C. Thieblemont, C. Fermé, B. Quesnel, C. Martin, C. Gisselbrecht, H. Tilly, F. Reyes
Journal: Blood (2005)
THE STRUCTURE OF THE T CELL ANTIGEN RECEPTOR
Authors: Graham A. Bentley, Roy A. Mariuzza
Journal: Annual Review of Immunology (1996)

Recent crystallographic studies of T cell antigen receptor (TCR) fragments from the alpha and beta chains have now confirmed the expected structural similarity to corresponding immunoglobulin domains. Although the three-dimensional structure of a complete TCR alpha beta heterodimer has not yet been determined, these results support the view that the extracellular region should resemble an immunoglobulin Fab fragment with the antigen-binding site formed from peptide loops homologous to immunoglobulin complementarity-determining regions (CDR). These preliminary results suggest that CDR1 and CDR2 may be less variable in structure than their immunoglobulin counterparts, consistent with the idea that they may interact preferentially with the less polymorphic regions of the molecules of the major histocompatibility complex. The region on the variable beta domain responsible for superantigen recognition is analyzed in detail. The implications for T cell activation from the interactions observed between domains of the alpha and beta chains are also discussed in terms of possible dimerization and allosteric mechanisms.
Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor
Authors: Kim M. Holwerda, Suzanne D. Burke, Marijke M. Faas, Zsuzsanna Zsengeller, Isaac E. Stillman, Peter M. Kang, Harry van Goor, Amy McCurley, Iris Z. Jaffe, S. Ananth Karumanchi, A. Titia Lely
Journal: Journal of the American Society of Nephrology (2013)

Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with therapeutic potential in several diseases. Therefore, we evaluated the potential therapeutic effect and mechanisms of action of hydrogen sulfide in an animal model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide-donor sodium hydrosulfide (NaHS) (50 µmol/kg, twice daily) or vehicle (n=7 per group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and an increase of free plasma vascular endothelial growth factor (VEGF) after treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels with a VEGF receptor 2-neutralizing antibody significantly attenuated NaHS-induced vasodilation. These results suggest that hydrogen sulfide ameliorates sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by increasing VEGF expression. Further studies are warranted to evaluate the role of hydrogen sulfide as a novel therapeutic agent for vascular disorders such as preeclampsia.
Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage.
Authors: D D Dean, J Martel-Pelletier, J P Pelletier, D S Howell, J F Woessner
Journal: Journal of Clinical Investigation (1989)

Cartilage specimens from tibial plateaus, obtained from 13 osteoarthritic (OA) patients and seven controls, were selected from three regions: zone A, center of fibrillated area; zone B, area adjacent to fibrillation, and zone C, remote region of plateau. Acid and neutral metalloproteinases and tissue inhibitor of metalloproteinase (TIMP) were extracted with 2 M guanidine. Methods were developed to selectively destroy either proteinases or TIMP to prevent cross-reaction during assay. Acid and neutral proteinases were elevated approximately 150% in OA; TIMP was elevated approximately 50%. A positive correlation (r = 0.50) was found between acid and neutral proteinase activities in OA, but not in controls. Both proteinases were elevated two-to threefold in zones A, B, and C. However, the self-active form of the acid metalloproteinase was elevated only in zones A and B (200%); it correlated well with the Mankin scores, whereas the total activities did not. TIMP was elevated (50%) only in zones A and B. Both the proteinase levels and the Mankin score were elevated to a greater extent in the medial, than in the lateral, compartment. Titration of TIMP against the two metalloproteinases indicates that there is a small excess of inhibitor over enzymes in normal cartilage. In OA, TIMP does not increase to the same extent as the proteinases; the resultant excess of proteinases over TIMP may contribute to cartilage breakdown.
Achievements in Congenital Heart Defect Surgery
Authors: Gunnar Erikssen, Knut Liestøl, Egil Seem, Sigurd Birkeland, Kjell Johan Saatvedt, Tom Nilsen Hoel, Gaute Døhlen, Helge Skulstad, Jan Ludvig Svennevig, Erik Thaulow, Harald Lauritz Lindberg
Journal: Circulation (2014)

This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades.From 1971 to 2011, all 7038 patients <16 years of age undergoing surgical treatment for CHD at Rikshospitalet (Oslo, Norway) were enrolled prospectively. CHD diagnosis, date, and type of all operations were recorded, as was all-cause mortality until December 31, 2012. CHDs were classified as simple (3751/7038=53.2%), complex (2918/7038=41.5%), or miscellaneous (369/7037=5.2%). Parallel to a marked, sequential increase in operations for complex defects, median age at first operation decreased from 1.6 years in 1971 to 1979 to 0.19 years in 2000 to 2011. In total, 1033 died before January 1, 2013. Cumulative survival until 16 years of age in complex CHD operated on in 1971 to 1989 versus 1990 to 2011 was 62.4% versus 86.9% (P<0.0001). In the comparison of patients operated on in 2000 to 2004 versus 2005 to 2011, 1-year survival was 90.7% versus 96.5% (P=0.003), and 5-year cumulative survival was 88.8% versus 95.0% (P=0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% (P=0.0001).Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality.
Metallothionein-overexpression as a prognostic factor for progression and survival in melanoma. A prospective study on 520 patients
Authors: G. Weinlich, W. Bitterlich, V. Mayr, P.O. Fritsch, B. Zelger
Journal: British Journal of Dermatology (2003)

Background Metallothioneins (MTs) are ubiquitous proteins with high affinity for heavy metal ions, e.g. zinc, copper and cadmium. In the last decade it has been shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and radiotherapy, and with a poor prognosis. Objectives To examine the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Methods In a prospective cohort study 760 patients with primary cutaneous melanoma were investigated over 5 years (1993–98) by using a monoclonal antibody (E9) against MT on routinely fixed and paraffin‐embedded tissues. In total, 520 patients were able to be followed up for progression of their disease or death due to melanoma and were included for statistical analysis (Fisher's exact test, Mantel–Haenszel χ2 test, Kaplan–Meier curves). MT data, progress‐free interval and overall survival were compared univariately and multivariately with other prognostic factors, e.g. Breslow thickness, Clark level, ulceration, localization, age and gender (Cox regression analysis). Results The immunohistochemical overexpression of MT in tumour cells (cut‐off level > 10% of all tumour cells) in patients with primary melanoma (156 of 520; 30%) was associated with a higher risk for progression of the disease (33 of 45; 73%) and reduced survival (24 of 30; 80%) than MT‐negative lesions [364 of 520 (70%), 12 of 45 (27%) and six of 30 (20%), respectively (P < 0·0001)]. Similarly, Kaplan–Meier tumour‐free survival and overall survival curves for the comparison of MT‐positive and MT‐negative tumours gave highly significant advantages for the MT‐negative group. In a univariate analysis (comparison with Breslow thickness: relative risk 2·9, 95% confidence interval, CI 1·46–5·76, P = 0·0023 for progression; relative risk 4·19, 95% CI 1·73–10·19, P = 0·0015 for survival), as well as in a multivariate analysis with other prognostic markers, MT overexpression turned out to be a highly significant and independent factor for prognosis in primary melanoma. Conclusions MT overexpression in primary melanoma is associated with an increased risk for disease progression. This marker is independent from Breslow thickness and helps to identify those thin melanomas (< 1·5 mm) that are at increased risk of progression. Moreover, the immunohistochemical staining of paraffin material is a cheap, easy and widely available technique to gain these results.