tbuckley/cabot-search huggingface dataset:
Postrelapse Survival in Osteosarcoma of the Extremities: Prognostic Factors for Long-Term Survival
Authors: Stefano Ferrari, Antonio Briccoli, Mario Mercuri, Franco Bertoni, Piero Picci, Amelia Tienghi, Adalberto Brach Del Prever, Franca Fagioli, Alessandro Comandone, Gaetano Bacci
Journal: Journal of Clinical Oncology (2003)

To identify factors that influence postrelapse survival (PRS) in patients with nonmetastatic osteosarcoma of the extremity.One hundred sixty-two patients with recurrent osteosarcoma of the extremity were retrospectively reviewed. The first-line treatment included surgery of the primary lesion and chemotherapy with methotrexate, doxorubicin, cisplatin, and ifosfamide.The projected 5-year PRS rate was 28%. Patients who had complete surgery of recurrence had a 5-year PRS of 39%, whereas for those who did not have complete surgery, PRS was 0% at 3 years (P <.0001). In the latter group, PRS was not influenced by site of recurrence and relapse-free interval (RFI), although it was influenced (P =.006) by the use of second-line chemotherapy (PRS, 53% at 12 months for patients who received chemotherapy v 12% for those who did not). In patients who had complete surgery, PRS was influenced by site of relapse (5-year PRS, lung 44%, other 19%; P <.06), RFI (5-year PRS at < or = 24 months, 20%; at > 24 months, 60%; P <.0001), and number of lung metastases (5-year PRS, two or fewer nodules, 59%; more than two nodules, 14%; P <.0001) but not by the use of a second-line chemotherapy treatment.RFI, site of metastases, and number of pulmonary nodules are the main prognostic factors for PRS in osteosarcoma. Complete surgery of recurrence is pivotal in the strategy of treatment. Patients with unresectable recurrence benefit from second-line chemotherapy, whereas our data do not support a generalized use of chemotherapy after complete surgery of first recurrence.
S58 Prospective Health Economic Evaluation Of Different Recommended Strategies For Tb Testing In A Contemporary Hiv Positive Cohort
Authors: S. Capocci, J. Sewell, C. Smith, I. Cropley, S. Bhagani, S. Morris, M. Johnson, M. Lipman
Journal: Thorax (2014)

<h3>Introduction</h3> The risk of active tuberculosis (TB) disease is estimated to be increased 40-fold in people with HIV (PHIV). Effective antiretroviral treatment (ART) may reduce this significantly. UK national guidance recommends using blood interferon gamma release assay (IGRA) +/- tuberculin skin testing (TST) for latent TB (LTBI) diagnosis but there are little supporting health economic data. We sought to evaluate the cost-effectiveness of different testing strategies using data from a prospective contemporary cohort. <h3>Methods</h3> Subjects receiving ambulatory HIV care were recruited by stratified selection within our HIV centre. TST, IGRA (TSpot. TB), frontal chest radiograph (CXR) and single induced sputum for mycobacterial culture were performed. The yield was used to model a screening programme that utilised current UK HIV demographics (Public Health England). Costs were based on the BNF, local costs or published literature (TST £16, IGRA £60, CXR £50, induced sputum £42, treatment for latent and active TB £786 and £7619 respectively). Uptake and LTBI treatment efficacy were both estimated at 65%. We assumed a lifetime reactivation rate with TST+/IGRA+ of 10% and TST+/IGRA- of 2%; and that all those with evidence of LTBI would be given treatment. <h3>Results</h3> Over 13 months, 211 people were recruited. 26% were female and 26% black African. LTBI rates amongst subjects from sub-Saharan Africa, medium and low TB incidence countries were 8/55 (15%), 2/31 (6%) and 4/125 (3%) respectively. One patient had a persistently indeterminate IGRA. Subclinical TB disease was diagnosed in two (1%) subjects. Using these data to model TB testing nationally, the British HIV Association (BHIVA) testing algorithm was the most cost-effective with an incremental cost effectiveness ratio (ICER) of £21,475. The NICE algorithm both cost more and prevented fewer cases of active TB (Table 1). More comprehensive strategies were associated with increasing cost. <h3>Conclusion</h3> Testing only those at highest risk of progression to active TB disease in an HIV population with high ART use was cost-effective, whilst most strategies testing all comers and for active TB cost considerably more than the £20–30,000/QALY gained threshold used in the UK.
Herpesvirus type 1–8 in BAL fluid from HIV-1-infected patients with suspected pneumonia and from healthy individuals
Authors: B. Tarp, S. Jensen-Fangel, R. Dahl, N. Obel
Journal: European Respiratory Journal (2001)

Pneumonia is still a major problem in human immunodeficiency virus (HIV)-infected patients, and despite extensive investigation the aetiology remains unknown in many cases. The prevalence of the eight human herpesviruses was determined by polymerase chain reaction in 91 samples of bronchoalveolar lavage (BAL) fluid from 72 HIV-infected patients with 91 episodes of suspected pneumonia. The presence of herpesviruses was related to clinical and immunological findings and the prevalence of herpesviruses in HIV-infected patients was compared with the prevalence in BAL fluid from 50 healthy, immunocompetent individuals. Epstein-Barr virus, cytomegalovirus and human herpesvirus-8 (HHV8) were found in 5.5%, 36%, and 5.5% of BAL fluid samples from HIV-infected patients. No herpesviruses were detectable in BAL fluid from healthy, immunocompetent individuals. The herpesviruses occurred mainly in patients with CD4+ counts &lt;200×10 6 L −1 . All patients with herpesviruses recovered without specific antiviral treatment. Two patients with HHV8 had the diagnosis of Kaposi's sarcoma. It is concluded that cytomegalovirus, Epstein-Barr virus, and human herpesvirus-8 are frequently present in bronchoalveolar lavage fluid from severely immunocompromised human immunodeficiency virus-infected patients with pulmonary symptoms. In bronchoalveolar lavage fluid from healthy, immunocompetent individuals, herpesviruses are absent. Apart from human herpesvirus-8, the present results indicate that the herpesviruses do not play a serious pathogenic role in the development of pulmonary symptoms in human immunodeficiency virus-infected patients.
Cardiac events in football and strategies for first-responder treatment on the field
Authors: Christian Schmied, Jonathan Drezner, Efraim Kramer, Jiri Dvorak
Journal: British Journal of Sports Medicine (2013)

The incidence and outcomes of sudden cardiac arrest (SCA) and global strategies for prevention of sudden cardiac death (SCD) in football are not known. The aim of this study was to estimate the occurrence of cardiac events in football and to investigate the preventive measures taken among the Fédération International de Football Association (FIFA) member associations internationally.A questionnaire was sent to the member associations of FIFA. The first section addressed the previous events of SCA, SCD or unexplained sports-related sudden death within the last 10 years. Further questions focused on football player medical screening strategies and SCA resuscitation response protocols on the field.126 of 170 questionnaires were returned (response rate 74.1%), and 103 questionnaires (60.6%) were completed sufficiently to include in further analysis. Overall, 107 cases of SCA/SCD and 5 unexplained football-associated sudden deaths were reported. These events occurred in 52 of 103 responding associations (50.5%). 23 of 112 (20.5%) footballers survived. 12 of 22 (54.5%) players treated with an available automated external defibrillators (AED) on the pitch survived. A national registry to monitor cardiac events was established in only 18.4% of the associations. Most associations (85.4%) provide regular cardiac screening for their national teams while 75% screen teams of the national leagues. An AED is available at all official matches in 68% of associations.National registries to accurately measure SCA/SCD in football are rare and greatly needed. Deficiencies in emergency preparations, undersupply of AEDs on the field during matches, and variability in resuscitation response protocols and training of team-staff members should be addressed to effectively prevent SCD in football.
The DNA repair protein ALKBH2 mediates temozolomide resistance in human glioblastoma cells
Authors: Tor-Christian Aase Johannessen, Lars Prestegarden, Amra Grudic, Monika E. Hegi, Berit Bølge Tysnes, Rolf Bjerkvig
Journal: Neuro-Oncology (2012)

Glioblastoma multiforme (GBM; World Health Organization astrocytoma grade IV) is the most frequent and most malignant primary brain tumor in adults. Despite multimodal therapy, all such tumors practically recur during the course of therapy, causing a median survival of only 14.6 months in patients with newly diagnosed GBM. The present study was aimed at examining the expression of the DNA repair protein AlkB homolog 2 (ALKBH2) in human GBM and determining whether it could promote resistance to temozolomide chemotherapy. ALKBH2 expression in GBM cell lines and in human GBM was determined by quantitative real-time PCR (qRT-PCR) and gene expression analysis, respectively. Drug sensitivity was assessed in GBM cells overexpressing ALKBH2 and in cells in which ALKBH2 expression was silenced by small-interfering (si)RNA. ALKBH2 expression following activation of the p53 pathway was examined by western blotting and qRT-PCR. ALKBH2 was abundantly expressed in established GBM cell lines and human GBM, and temozolomide exposure increased cellular ALKBH2 expression levels. Overexpression of ALKBH2 in the U87 and U251 GBM cell lines enhanced resistance to the methylating agents temozolomide and methyl methanesulfonate but not to the nonmethylating agent doxorubicin. Conversely, siRNA-mediated knockdown of ALKBH2 increased sensitivity of GBM cells to temozolomide and methyl methanesulfonate but not to doxorubicin or cisplatin. Nongenotoxic activation of the p53 pathway by the selective murine double minute 2 antagonist nutlin-3 caused a significant decrease in cellular ALKBH2 transcription levels. Our findings identify ALKBH2 as a novel mediator of temozolomide resistance in human GBM cells. Furthermore, we place ALKBH2 into a new cellular context by showing its regulation by the p53 pathway.
Intercellular adhesion molecule-1 and CD18 are involved in neutrophil adhesion and its cytotoxicity to cultured sinusoidal endothelial cells in rats
Authors: S Sakamoto, T Okanoue, Y Itoh, K Sakamoto, K Nishioji, Y Nakagawa, N Yoshida, T Yoshikawa, K Kashima
Journal: Hepatology (1997)

The expression of several adhesion molecules is increased on the hepatic sinusoidal endothelial cells (SECs) in various liver diseases. The objective of this study is to assess the roles of intercellular adhesion molecule 1 (ICAM-1) and of CD18 in the interaction between the neutrophils (polymorphonuclear leukocytes [PMNs]) and SECs and in the injury to SECs mediated by PMNs. Rat PMNs was perfused on SECs stimulated with tumor necrosis factor alpha (TNF-alpha) using an in vitro flow system. The number of adhered PMNs to SECs and that of PMNs migrated under SECs was counted and the effects of anti-ICAM-1, anti-CD18, and dexamethasone were studied. We also define the effect of these antibodies on the SEC injury mediated by PMNs stimulated with phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). TNF-alpha significantly increased the adhesion of PMNs to SECs (322 +/- 26 cells/mm2) compared with controls (194 +/- 22 cells/mm2). Anti-ICAM-1 and anti-CD18 significantly inhibited the adhesion of PMNs (131 +/- 10 and 51 +/- 30 cells/mm2, respectively). These antibodies also decreased the migration rate of PMNs (6.0% and 7.9%, respectively) compared with controls (migration rate, 21.2%). The SEC injury induced by PMA- and fMLP-activated PMNs was prevented by anti-ICAM-1 and anti-CD18. The adhesion of PMNs induced by TNF-alpha was inhibited by the treatment with dexamethasone (160 +/- 20 cells/mm2) via a down-regulation of ICAM-1 expression on SECs. The interactions between ICAM-1 and CD18 appeared to be important in the adhesion and the migration of PMNs to SECs. The injury to SECs was induced by the close interaction between the activated PMNs and SECs mediated via ICAM-1 and CD18.
STUDIES ON THE RELATIONSHIP OF THE CHEMICAL CONSTITUENTS OF BLOOD AND CEREBROSPINAL FLUID
Authors: Lawrence S. Kubie, Gertrude M. Shults
Journal: The Journal of Experimental Medicine (1925)

1. If due allowance is made for the slow rate of elaboration of cerebrospinal fluid and for the time that it takes for newly formed fluid to emerge from a needle in the cistema, the amount of sugar, chloride, and non-protein nitrogen in the fluid seems to follow in a general way their concentrations in the blood stream. 2. It is equally evident, however, that for any substance other factors besides its concentration in the blood stream play a part in its distribution between blood and cerebrospinal fluid.
Nocardia infections in lung transplant recipients (LxTR)
Authors: Jeremy Bismuth, Clotilde Fournier de Lesquen, Carine Gomez, Nadine Dufeu, Berengere Coltey, Pascal Thomas, Jean Marc Rolain, Martine Reynaud Gaubert
Journal: European Respiratory Journal (2014)

INTRODUCTION: The various species of  Nocardia  are pathogenic staining Gram-positive bacteria which frequently occurs as an opportunistic infection in immunocompromised patients. There are few data in the literature regarding nocardia infections after LTx.  METHODS: A retrospective observational study was conducted in patients who developed postoperative nocardiosis. From 01/2005 to 01/2014, 241 patients underwent consecutively LTx (n=241) at the Marseille transplant center (France).  RESULTS: Nocardia infection was encountered in 4 patients (1.7%) who were transplanted for sarcoidosis (2), emphysema (1) cystic fibrosis (1). All patients experienced slowly progressive pneumonia, fever, fatigue, dyspnea with no concomitant extrapulmonary involvement. Mean time for diagnosis was 5.8 po months. The mean duration of follow up was 9.6 mo (26-832). An acute rejection requiring corticosteroids was noted in the previous 6 mo (n=2). Nocardia species cultured from sputum (2), BAL (2), mediastinal lymphadenopathy (1) samples with N.cyriacigeorgica (2), N.wallacei (1), no specified (1).None of the recipients received an antibiotic trimethoprim-sulfamethoxazole prophylaxis on diagnosis. Antibiotic therapy consisted of amoxicillin (n=2) + clavulanic acid (n=2), with a mean total duration of 4.5 mo. Total recovery, with good clinical outcome and no recurrence of nocardiosis were observed in all cases. One patient died at 22 po months, with no evident link such infection.  Nocardiosis is a rare complication after LTx. The diagnosis remains difficult due to nonspecific clinical symptoms and imaging. Prolonged amoxicillin therapy has been effective and well tolerated in the 4 LTR patients avoiding the potential toxicities of TMP-SMX prophylaxis.
High Serum Transforming Growth Factor-β1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib
Authors: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Clinical Cancer Research (2015)

The TGF-β signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-β1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC).We selected patients who had received sorafenib-containing regimens as first-line therapy for advanced HCC between 2007 and 2012. Serum TGF-β1 levels were measured and correlated with the treatment outcomes. The expression TGF-β1 and the sensitivity to sorafenib were examined in HCC cell lines.Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (+), and 11 (12%) were anti-hepatitis C virus (+). High (≥ median) pretreatment serum TGF-β1 levels (median 13.7 ng/mL; range, 3.0-41.8) were associated with high α-fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF-β1 levels exhibited significantly shorter progression-free survival (median, 2.5 vs. 4.3 months; P = 0.022) and overall survival (median 5.6 vs. 11.6 months; P = 0.029) than did patients with low serum TGF-β1 levels. Compared with pretreatment levels, the serum TGF-β1 levels were significantly increased at disease progression (n = 29, P = 0.010). In preclinical models of HCC, higher TGF-β1 expression levels were associated with poorer sensitivity to sorafenib.High pretreatment serum TGF-β1 levels were associated with poor prognoses, and increased serum TGF-β1 levels were associated with the disease progression of advanced HCC patients. TGF-β pathway may be explored as a therapeutic target for advanced HCC.
Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
Authors: Barbara Wassmann, Heike Pfeifer, Michael Stadler, Martin Bornhaüser, Gesine Bug, Urban J. Scheuring, Patrick Brück, Matthias Stelljes, Rainer Schwerdtfeger, Nadezda Basara, Jolanta Perz, Donald Bunjes, Georg Ledderose, Rolf Mahlberg, Anja Binckebanck, Harald Gschaidmeier, Dieter Hoelzer, Oliver G. Ottmann
Journal: Blood (2005)
Private specificities of CD8 T cell responses control patterns of heterologous immunity
Authors: Sung-Kwon Kim, Markus Cornberg, Xiaoting Z. Wang, Hong D. Chen, Liisa K. Selin, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (2005)

CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Rα by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.
Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene
Authors: June Yun, Torsten Schöneberg, Jie Liu, Angela Schulz, Carolyn A. Ecelbarger, Dominique Promeneur, Soren Nielsen, Hui Sheng, Alexander Grinberg, Chu-xia Deng, Jürgen Wess
Journal: Journal of Clinical Investigation (2000)

The V2 vasopressin receptor (V2R) plays a key role in the maintenance of a normal body water balance. To generate an in vivo model that allows the physiological and molecular analysis of the role of V2Rs in kidney function, we have created mouse lines that lack functional V2Rs by using targeted mutagenesis in mouse embryonic stem cells. Specifically, we introduced a nonsense mutation known to cause X-linked nephrogenic diabetes insipidus (XNDI) in humans (Glu242stop) into the mouse genome. V2R-deficient hemizygous male pups showed a decrease in basal urine osmolalities and were unable to concentrate their urine. These pups also exhibited an enlargement of renal pelvic space, failed to thrive, and died within the first week after birth due to hypernatremic dehydration. Interestingly, female mice heterozygous for the V2R mutation showed normal growth but displayed an XNDI-like phenotype, characterized by reduced urine concentrating ability of the kidney, polyuria, and polydipsia. Western blot analysis and immunoelectron microscopic studies showed that the loss of functional V2Rs had no significant effect on the basal expression levels of aquaporin-2 and the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1). The V2R mutant mice described here should serve as highly useful tools for the development of novel therapeutic strategies for the treatment of XNDI.
Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum
Authors: Yuko Kawakami, Yoshiaki Tomimori, Kenji Yumoto, Shunji Hasegawa, Tomoaki Ando, Yutaka Tagaya, Shane Crotty, Toshiaki Kawakami
Journal: The Journal of Experimental Medicine (2009)

Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.
Variable major proteins of Borrelia hermsii. Epitope mapping and partial sequence analysis of CNBr peptides.
Authors: P A Barstad, J E Coligan, M G Raum, A G Barbour
Journal: The Journal of Experimental Medicine (1985)

The variable major proteins (VMP) of serotypes 7 and 21 of the relapsing fever agent Borrelia hermsii were isolated by detergent extraction and high performance liquid chromatography. Cyanogen bromide (CNBr) digestion of the isolated VMP yielded two peptides of apparent molecular weights 20,000 (20 K) and 16 K from VMP7, and three peptides of 14.5, 14, and 7 K mol wt from VMP21. Serotype-specific monoclonal antibodies bound in Western blots to one of each of the two or three CNBr fragments from the homologous VMP. A single monoclonal antibody bound to the whole cells, the isolated VMP, and a CNBr fragment of both serotype 7 and serotype 21. (This crossreactive antibody did not, however, bind to any of four other serotypes examined.) Regional conservation of structure between VMP7 and VMP21 was also shown by amino acid sequence analysis of the N-termini of the five CNBr fragments. One pair of aligned fragments from VMP7 and VMP21 had 80% amino acid homology in sequence; a second pair had 40% homology. The partial amino acid homologies between two VMP suggest that these proteins are products of members of a polygene family.