tbuckley/cabot-search huggingface dataset:
Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data
Authors: Antonio Rossi, Massimo Di Maio, Paolo Chiodini, Robin Michael Rudd, Hiroaki Okamoto, Dimosthenis Vasilios Skarlos, Martin Früh, Wendi Qian, Tomohide Tamura, Epaminondas Samantas, Taro Shibata, Francesco Perrone, Ciro Gallo, Cesare Gridelli, Olga Martelli, Siow-Ming Lee
Journal: Journal of Clinical Oncology (2012)

Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments.A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test.Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio [HR], 1.08; 95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference between the cisplatin and carboplatin arms according to sex, stage, performance status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin, respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%, respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity profile was significantly different for each of the arms: hematologic toxicity was higher with carboplatin, and nonhematologic toxicity was higher with cisplatin.Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.
Identification of HLA-DRB1*1501–Restricted T-cell Epitopes from Prostate-Specific Antigen
Authors: Elena N. Klyushnenkova, Jason Link, Warren T. Oberle, James Kodak, Cathleen Rich, Arthur A. Vandenbark, Richard B. Alexander
Journal: Clinical Cancer Research (2005)

Abstract The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 T cells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II–restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)–derived MHC class II–restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA171-190 and PSA221-240, which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.
Rectal Administration of Artemisinin Derivatives for the Treatment of Malaria
Authors: Harin A. Karunajeewa, Laurens Manning, Ivo Mueller, Kenneth F. Ilett, Timothy M. E. Davis
Journal: JAMA (2007)

Rectal administration of artemisinin derivatives is a potentially lifesaving emergency treatment of severe malaria. Many different preparations are marketed in tropical countries, but their pharmacokinetic disposition and clinical efficacy may vary.To review the pharmacokinetics, efficacy, and safety of rectally administered artesunate, artemisinin, dihydroartemisinin, and artemether.We searched the MEDLINE, EMBASE, Cochrane Database of Clinical Reviews, Global Health, Web of Science, and CINAHL computerized databases up to December 2006, along with reviewing unpublished data from conference proceedings, pharmaceutical companies, and regulatory applications. Studies in languages other than English were translated.Studies were included involving rectal administration of an artemisinin derivative to healthy volunteers or patients with measurement of plasma drug concentrations or rates of initial parasite clearance. Both single-arm and comparative trials were included.Forty-five studies were identified, of which 39 eligible studies were included in the review. Primary efficacy outcome measures included parasite density as a percentage of baseline at 12 and 24 hours following the first dose. Pharmacokinetic variables included maximum plasma concentration (C(max)), time to C(max) (T(max)), and area under the plasma concentration-time curve. Weighted means were calculated from available data.Thirty-two studies provided valid clinical efficacy data: 19 of artesunate, 10 of artemisinin, 2 of dihydroartemisinin, and 1 of artemether. All demonstrated prompt parasite clearance, with evidence of a dose-dependent effect for artesunate. Mortality rates in severe malaria (weighted means, 0%-13%) were consistent with those expected. Eight studies compared rectal artemisinin with conventional parenteral treatment (quinine, artemether, or artesunate) for severe malaria. Despite similar clinical outcomes, rectal artemisinin derivatives initiated parasite clearance more rapidly than parenteral treatment (percentage of baseline at 12 hours, < or =27% vs > or =56%, respectively). Eighteen pharmacokinetic studies were identified, including 13 of artesunate. There was marked interindividual variability in most pharmacokinetic variables, but artesunate achieved an earlier T(max) and higher C(max) and area under the plasma concentration-time curve than other artemisinin derivatives.Available rectal preparations of artemisinin derivatives differ in their pharmacokinetic disposition. Most available evidence pertains to artesunate and artemisinin. Despite marked interindividual variability in bioavailability, rectal preparations appear to have acceptable therapeutic efficacy, including in severe illness.
Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1.
Authors: P P Nawroth, I Bank, D Handley, J Cassimeris, L Chess, D Stern
Journal: The Journal of Experimental Medicine (1986)

Tumor necrosis factor/cachectin (TNF) has been implicated as a mediator of the host response in sepsis and neoplasia. Recent work has shown that TNF can modulate endothelial cell hemostatic properties, suggesting that endothelium is a target tissue for TNF. This led us to examine whether endothelial cells have specific binding sites for TNF and augment the biological response to TNF by elaborating the inflammatory mediator, IL-1. Incubation of 125I-recombinant human TNF with confluent, cultured human umbilical vein endothelial cells resulted in time-dependent, reversible, and saturable binding. Binding was half-maximal at a TNF concentration of 105 +/- 40 pM, and at saturation 1,500 molecules were bound per cell. Heat-treated TNF, which is biologically inactive, did not bind to endothelium. In addition to surface binding, TNF induced the elaboration of IL-1 activity by endothelial cells in a time-dependent manner. Generation of IL-1 activity required protein synthesis and was half-maximal at a TNF concentration of 50 +/- 20 pM. IL-1 activity from TNF-treated endothelium could be adsorbed by an immobilized antibody to IL-1. Heat-treated TNF was ineffective in eliciting endothelial cell IL-1. These data indicate that TNF can bind specifically to endothelium and initiate a cascade of inflammatory and coagulant events on the vessel surface potentially central to the host response to neoplasia and sepsis.
Low tidal volume ventilation is associated with reduced mortality in HIV-infected patients with acute lung injury
Authors: J L Davis, A Morris, R H Kallet, K Powell, A S Chi, M Bensley, J M Luce, L Huang
Journal: Thorax (2008)

<h3>Background:</h3> Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996–2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. <h3>Methods:</h3> A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. <h3>Results:</h3> In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference −5.4%, 95% CI −21% to 11%, p = 0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with <i>Pneumocystis</i> pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, p = 0.043), after controlling for <i>Pneumocystis</i> pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. <h3>Conclusions:</h3> Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.
Mobile Elements and the Genesis of Microsatellites in Dipterans
Authors: Jason Wilder, Hope Hollocher
Journal: Molecular Biology and Evolution (2001)

Factors that influence the genesis and genomic distribution of microsatellite DNA are poorly understood. We have identified a novel class of Dipteran mobile elements, mini-me elements, which help elucidate both of these issues. These retroposons contain two internal proto-microsatellite regions that commonly expand into lengthy microsatellite repeats. These elements are highly abundant, accounting for approximately 1.2% of the Drosophila melanogaster genome, giving them the potential to be a prolific source of microsatellite DNA variation. They also give us the opportunity to observe the outcomes of multiple microsatellite genesis events (initiating from the same proto-microsatellite) at separate mini-me loci. Based on these observations, we determined that the genesis of microsatellites within mini-me elements occurs through two separate mutational processes: the expansion of preexisting tandem repeats and the conversion of sequence with high cryptic simplicity into tandemly repetitive DNA. These modes of microsatellite genesis can be generalized beyond the case of mini-me elements and help to explain the genesis of microsatellites in any sequence region that is not constrained by selection.
A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis
Authors: C.C.J.M. Simons, L.A.E. Hughes, K.M. Smits, C.A. Khalid-de Bakker, A.P. de Bruïne, B. Carvalho, G.A. Meijer, L.J. Schouten, P.A. van den Brandt, M.P. Weijenberg, M. van Engeland
Journal: Annals of Oncology (2013)
Merkel Cell Polyomavirus-Specific CD8+ and CD4+ T-cell Responses Identified in Merkel Cell Carcinomas and Blood
Authors: Jayasri G. Iyer, Olga K. Afanasiev, Christopher McClurkan, Kelly Paulson, Kotaro Nagase, Lichen Jing, Joshua O. Marshak, Lichun Dong, Joseph Carter, Ivy Lai, Erik Farrar, David Byrd, Denise Galloway, Cassian Yee, David M. Koelle, Paul Nghiem
Journal: Clinical Cancer Research (2011)

Merkel cell polyomavirus (MCPyV) is prevalent in the general population, integrates into most Merkel cell carcinomas (MCC), and encodes oncoproteins required for MCC tumor growth. We sought to characterize T-cell responses directed against viral proteins that drive this cancer as a step toward immunotherapy.Intracellular cytokine cytometry, IFN-γ enzyme-linked immunospot (ELISPOT) assay, and a novel HLA-A*2402-restricted MCPyV tetramer were used to identify and characterize T-cell responses against MCPyV oncoproteins in tumors and blood of MCC patients and control subjects.We isolated virus-reactive CD8 or CD4 T cells from MCPyV-positive MCC tumors (2 of 6) but not from virus-negative tumors (0 of 4). MCPyV-specific T-cell responses were also detected in the blood of MCC patients (14 of 27) and control subjects (5 of 13). These T cells recognized a broad range of peptides derived from capsid proteins (2 epitopes) and oncoproteins (24 epitopes). HLA-A*2402-restricted MCPyV oncoprotein processing and presentation by mammalian cells led to CD8-mediated cytotoxicity. Virus-specific CD8 T cells were markedly enriched among tumor infiltrating lymphocytes as compared with blood, implying intact T-cell trafficking into the tumor. Although tetramer-positive CD8 T cells were detected in the blood of 2 of 5 HLA-matched MCC patients, these cells failed to produce IFN-γ when challenged ex vivo with peptide.Our findings suggest that MCC tumors often develop despite the presence of T cells specific for MCPyV T-Ag oncoproteins. The identified epitopes may be candidates for peptide-specific vaccines and tumor- or virus-specific adoptive immunotherapies to overcome immune evasion mechanisms in MCC patients.
* The effects of antimuscarinic agents on rectal compliance in patients with supraconal spinal cord injury
Authors: A. J. Paily, G. Preziosi, A. Raeburn, A. Emmanuel
Journal: Gut (2011)

<h3>Introduction</h3> Constipation affects up to 80% of spinal cord injury (SCI) patients and is cause of significant reduction of quality of life. Rectal compliance is determined by the rectal wall properties and by the supra-spinal modulation of the thoracic sympathetic and para-sympathetic lumbosacral efferents; it is increased in SCI patients with injury level above T5. Often this patient group has associated bladder dysfunction, and requires antimuscarinic agents (Tolterodine or Solifenacin), which are known to cause constipation. The authors aimed to assess the physiological effect of antimuscarinic agents on the anorectal function of patients with SCI above T5. <h3>Methods</h3> The authors prospectively collected data from 17 SCI patients (11 males, mean age 41, mean disease duration 13 months) attending a neuro-gastroenterology clinic at a tertiary centre. All had an established SCI above T5, and 11 had a complete injury. Anal manometry, assessment of rectoanal inhibitory reflex (RAIR) and rectal compliance were measured at baseline, and after antimuscarinic treatment was started (mean follow-up 12 weeks). <h3>Results</h3> Anal sphincter function parameters of squeeze and cough pressure were unchanged after antimuscarinic treatment (pre vs post 123±40 vs 122±36 p=0.827; 88±24 vs 87±26 p=0.859 respectively). However, resting anal pressure and rectal compliance were significantly raised after antimuscarinic treatment (82±18 vs 88±16 p=0.058; 19.2±5.0 vs 24.2±4.1 p&lt;0.001). When analysing the three components of the RAIR, the percent amplitude of maximal sphincter relaxation was decreased (pre vs post 48%±8% vs 37%±6%, p=0.026) and excitation latency was increased (1.2±0.6 vs 1.5±0.7 s, p&lt;0.001). <h3>Conclusion</h3> In SCI patients the use of antimuscarinic agents causes increased rectal compliance, reduced reflex relaxation of the anal sphincter and delayed latency of this reflex. These physiological changes all predispose towards constipation. In the absence of cortical modulation, in patients with a SCI level above T-5, sympathetic activity is effectively enhanced. The effect of these drugs underlines the importance of tonic parasympathetic input to rectal compliance and anorectal reflex function.
Treatment of Osteo-Arthritis of the Knees
Authors: V. Wright
Journal: Annals of the Rheumatic Diseases (1964)

<h3>AIM</h3> To describe leprosy characteristics, ocular features, and type of organisms that produce infective corneal ulcers in leprosy patients. <h3>METHOD</h3> The records of all leprosy patients admitted for treatment of corneal ulcers between 1992 and 1997 were reviewed. <h3>RESULTS</h3> 63 leprosy patients, 53 males and 10 females, are described. 16 were tuberculoid and 47 lepromatous. 25 patients had completed multidrug therapy. 10 patients had face patches, eight had type I reaction, and 10 had type II reaction. 43 (68%) patients had hand deformities. In 54% of patients pain was absent as a presenting symptom. 19 patients gave a history of trauma. In 15 patients ulcers had also occurred on the other eye, five of them having occurred during the study period and the rest before 1992. Of the 68 eyes with corneal ulcers, 28 had madarosis, 34 had lagophthalmos, nine had ectropion, three had trichiasis, six had blocked nasolacrimal ducts, and 39 decreased corneal sensation. In 14 eyes, a previous lagophthalmos surgery had been done. 16 patients were blind at presentation. 32% of ulcers were located centrally. After treatment only 18% of the eyes showed visual improvement. Five types of fungus were cultured, two of them rare ocular pathogens. <h3>CONCLUSIONS</h3> Corneal ulcers occur more in males and in the lepromatous group of patients. Decreased corneal sensation, lagophthalmos and hand deformity are closely associated. Indigenous treatment and late presentations were notable in many patients. Visual outcome is not good. There is increased risk of developing an ulcer in the other eye. Fungal corneal ulcers are not uncommon.
Update of the <scp>WHO</scp>/<scp>IUIS A</scp>llergen <scp>N</scp>omenclature <scp>D</scp>atabase based on analysis of allergen sequences
Authors: C. Radauer, A. Nandy, F. Ferreira, R. E. Goodman, J. N. Larsen, J. Lidholm, A. Pomés, M. Raulf‐Heimsoth, P. Rozynek, W. R. Thomas, H. Breiteneder
Journal: Allergy (2014)

The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages researchers to use these updated allergen names in future publications.
Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans
Authors: Koji Miyamoto, Kazuhiro Nishigami, Noritoshi Nagaya, Koichi Akutsu, Masaaki Chiku, Masataka Kamei, Toshihiro Soma, Shigeki Miyata, Masahiro Higashi, Ryoichi Tanaka, Takeshi Nakatani, Hiroshi Nonogi, Satoshi Takeshita
Journal: Circulation (2006)

The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.