tbuckley/cabot-search huggingface dataset:
STUDIES ON THE SOMATIC C POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Theodore J. Abernethy, Thomas Francis
Journal: The Journal of Experimental Medicine (1937)

A study of 46 cases of pneumococcus pneumonia has shown that a characteristic response may be elicited by the intracutaneous injection of 0.1 mg. of the somatic C polysaccharide of pneumococcus. During the acute febrile period in patients who recover, the response consists of a delayed erythema which reaches its maximum intensity in 18 to 24 hours. During convalescence the reaction is not demonstrable. In patients in whom the disease is prolonged by complications the capacity of the skin to react persists. In 7 fatal cases the skin failed to react to C polysaccharide. Parallel studies of the reaction of the patients' serum with C have confirmed and extended the observations of Tillett and Francis on the appearance of the precipitation phenomenon during the acute stages and its disappearance in recovery. That the cutaneous and serological reactions are not specific for pneumococcus infection is shown by the results in 29 control cases. 8 patients with infectious febrile diseases not of pneumococcus origin gave responses similar to those noted in pneumonia. 2 patients with non-infectious fevers and 18 of 19 normal individuals failed to give either skin or serum reactions. These observations emphasize the importance of using separate components of the bacterial cell in the interpretation of cutaneous and serological reactions in pneumonia. The parallelism in results of the skin and serum tests in pneumococcus pneumonia with the somatic carbohydrate C, the significance of the reactions in relation to the clinical course and outcome of the disease, and the frequency of occurrence of both reactions in bacterial infections other than those of pneumococcal origin, are discussed.
Genomic characterization of the Yersinia genus
Authors: Peter E Chen, Christopher Cook, Andrew C Stewart, Niranjan Nagarajan, Dan D Sommer, Mihai Pop, Brendan Thomason, Maureen P Kiley Thomason, Shannon Lentz, Nichole Nolan, Shanmuga Sozhamannan, Alexander Sulakvelidze, Alfred Mateczun, Lei Du, Michael E Zwick, Timothy D Read
Journal: Genome biology (2010)

Abstract Background New DNA sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. Prior to this study, three species of the enterobacterial genus Yersinia that cause invasive human diseases ( Yersinia pestis , Yersinia pseudotuberculosis , and Yersinia enterocolitica ) had been sequenced. However, there were no genomic data on the Yersinia species with more limited virulence potential, frequently found in soil and water environments. Results We used high-throughput sequencing-by-synthesis instruments to obtain 25- to 42-fold average redundancy, whole-genome shotgun data from the type strains of eight species: Y. aldovae , Y. bercovieri , Y. frederiksenii , Y. kristensenii , Y. intermedia , Y. mollaretii, Y. rohdei , and Y. ruckeri . The deepest branching species in the genus, Y. ruckeri , causative agent of red mouth disease in fish, has the smallest genome (3.7 Mb), although it shares the same core set of approximately 2,500 genes as the other members of the species, whose genomes range in size from 4.3 to 4.8 Mb. Yersinia genomes had a similar global partition of protein functions, as measured by the distribution of Cluster of Orthologous Groups families. Genome to genome variation in islands with genes encoding functions such as ureases, hydrogeneases and B-12 cofactor metabolite reactions may reflect adaptations to colonizing specific host habitats. Conclusions Rapid high-quality draft sequencing was used successfully to compare pathogenic and non-pathogenic members of the Yersinia genus. This work underscores the importance of the acquisition of horizontally transferred genes in the evolution of Y. pestis and points to virulence determinants that have been gained and lost on multiple occasions in the history of the genus.
Reply to F. Puglisi
Authors: Stephen Chan
Journal: Journal of Clinical Oncology (2009)

Puglisi 1 expressed an interest in our study and we appreciate his detailed review.In this study, the primary objective was to compare progression-free survival (PFS) in the two treatment arms: capecitabine plus docetaxel (CD) and gemcitabine plus docetaxel (GD).We wrote that no significant difference in PFS was seen between the two arms.We concluded that the efficacy is similar in the two treatment arms, not only based on PFS but on a number of end points: PFS (log-rank P ϭ .121),overall response rate (32% in both arms), and overall survival (log-rank P ϭ .983).Since PFS, ORR, and OS cannot be combined in a weighted overall efficacy measure, we used the word "similar" as a nontechnical term to summarize our message.Additionally, patients treated with GD experienced fewer nonhematological toxicities (P Ͻ .05) and had a statistically significant longer time to treatment failure, with a median of 4.24 months compared with 4.07 months for CD (log-rank P ϭ .059;P Ͻ .1 was prespecified to demonstrate statistical significance).Based on the effi-cacy results combined with a better tolerability profile, we proposed that GD "may be a better option."In conclusion, we did not intend to claim equivalence from a superiority study, but to describe and compare the results for efficacy and tolerability observed with GD and CD in this phase III randomized study.
β-Catenin Inhibitor ICAT Modulates the Invasive Motility of Melanoma Cells
Authors: Mélanie J. Domingues, Florian Rambow, Bastien Job, Laura Papon, Wanguo Liu, Lionel Larue, Jacky Bonaventure
Journal: Cancer Research (2014)

Inhibitor of β-catenin and TCF (ICAT) inhibits β-catenin transcriptional activity by competing with T-cell factor/lymphoid enhancer factor. We documented high ICAT levels in human melanoma cells, in which β-catenin signaling is frequently deregulated, finding a correlation with the capacity to form metastases in nude mice. Ectopic expression of ICAT in melanoma cells did not affect their proliferation but increased cell motility and Matrigel invasion of metastatic cells in a manner relying upon stable ICAT-β-catenin interaction. This effect was associated with conversion of an elongated/mesenchymal phenotype to a round/amoeboid phenotype in the absence of similar effects on elongated morphology of nonmetastatic melanoma cells. Transition from mesenchymal to amoeboid movement was associated with decreased levels of NEDD9 and activated Rac1, a positive regulator of mesenchymal movement. Ectopic ICAT promoted colonization of melanoma cells in the lungs of nude mice, suggesting an increase in metastatic potential. Together, our results showed that by downregulating Rac signaling in metastatic melanoma cells, ICAT increased their invasive motility by promoting a morphologic variation that facilitates a favorable adaptation to their microenvironment.
THE EFFECT OF HEXAMETHONIUM AS COMPARED TO PROCAINE OR METYCAINE LUMBAR BLOCK ON THE BLOOD FLOW TO THE FOOT OF NORMAL SUBJECTS 12
Authors: Harold W. Schnaper, Robert L. Johnson, Edward B. Tuohy, Edward D. Freis
Journal: Journal of Clinical Investigation (1951)

Blood flow was measured in the left foot using the venous occlusion plethysmograph described by Abramson (10), but with certain modifications. These changes were introduced because of the necessity of removing the foot from the plethysmograph at the time of the regional block and then replacing it rapidly to avoid delaying the determinations of blood flow. Therefore, instead of cementing the edge of a thick rubber sheeting to the ankle, a thin rubber boot was prepared, the edges of which were everted and sealed permanently to the inlet of the plethysmograph in a manner similar to that described by Krogh, Landis and Turner (11) for use with the limb segment plethysmograph. The boot was made of rubber thin and pliable enough for the pressure of the water filling the plethysmograph to press the rubber membrane snugly against the contours of the foot.4 Since an air pocket usually formed at the upper end of the boot, the air was removed by means of small-bore plastic tubing leading from the toe of the boot to one of the two outlets of the plethysmograph. The trapped air could then be removed by applying suction to the plastic tube with a syringe. By means of this device, the foot could be sealed quickly
Partial liquid ventilation improves lung function in ventilation-induced lung injury
Authors: G.F. Vazquez de Anda, R.A. Lachmann, S.J.C. Verbrugge, D. Gommers, J.J. Haitsma, B. Lachmann
Journal: European Respiratory Journal (2001)

Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL·kg −1 , 20 mL·kg −1 , and 20 ml·kg −1 plus an additional 5 mL·kg −1 after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation.
Microevolutionary analysis of Clostridium difficile genomes to investigate transmission
Authors: Xavier Didelot, David W Eyre, Madeleine Cule, Camilla LC Ip, M Azim Ansari, David Griffiths, Alison Vaughan, Lily O'Connor, Tanya Golubchik, Elizabeth M Batty, Paolo Piazza, Daniel J Wilson, Rory Bowden, Peter J Donnelly, Kate E Dingle, Mark Wilcox, A Sarah Walker, Derrick W Crook, Tim E A Peto, Rosalind M Harding
Journal: Genome biology (2012)

Abstract Background The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing. Results Here we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions. Conclusions Our results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.
Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.
Authors: W E Paul, E M Shevach, S Pickeral, D W Thomas, A S Rosenthal
Journal: The Journal of Experimental Medicine (1977)

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.
Comparison of Sertraline and Nortriptyline in the Treatment of Major Depressive Disorder in Late Life
Authors: W Bondareff, M Alpert, A J Friedhoff, E M Richter, C M Clary, E Batzar
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults. METHOD: A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50–150 mg/day) or nortriptyline (25–100 mg/day). RESULTS: The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment. CONCLUSIONS: Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.
Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer
Authors: D. Strumberg, S. Brügge, M.W. Korn, S. Koeppen, J. Ranft, G. Scheiber, C. Reiners, C. Möckel, S. Seeber, M.E. Scheulen
Journal: Annals of Oncology (2002)
Hot off the breath: a big step forward for idiopathic pulmonary fibrosis
Authors: Christopher J Ryerson, Harold R Collard
Journal: Thorax (2014)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown etiology1 with a median survival of 3 years from the time of diagnosis.2 The recent decade has seen a tremendous investment in IPF clinical research, and as a result, we have moved beyond traditional treatment approaches (prednisone and other immunomodulatory therapies) toward clinical trials of potential antifibrotic therapies.3 As recently as 2011, however, an international guideline committee concluded that there remained insufficient evidence to support the regular use of any IPF pharmacotherapy.1 Because of this, there has been no consensus standard of care for IPF patients.

This will likely change with the recent publication of three landmark studies.4–6 Two novel therapies, pirfenidone and nintedanib, were found to slow disease progression in patients with IPF, while a third therapy, acetylcysteine, was found to have no effect. We believe these studies will transform IPF management and lead to the establishment of a universal standard of care. We discuss each of the three trials below, followed by a discussion of their clinical and clinical research implications.

Pirfenidone is an orally available antifibrotic agent with multiple potential mechanisms of action. Early clinical trials suggested that pirfenidone could slow lung function decline in patients with IPF,7–9 prompting two parallel, randomised, double-blind, placebo-controlled, phase III clinical trials (the CAPACITY studies).10 There was a significant benefit in the primary endpoint of change in FVC over 72 weeks in one of the CAPACITY studies but not in the other. Pirfenidone was associated with an increased risk of gastrointestinal (eg, nausea and stomach discomfort) and dermatological (eg, photosensitivity) adverse effects, however, these were generally manageable, and most patients were able to continue at the full dose for the duration of the study. Based largely on the CAPACITY results, pirfenidone was approved …
Enhancement of Lexatumumab-Induced Apoptosis in Human Solid Cancer Cells by Cisplatin in Caspase-Dependent Manner
Authors: Xiu-Xian Wu, Yoshiyuki Kakehi
Journal: Clinical Cancer Research (2009)

This study was designed to evaluate the apoptotic effect of mapatumumab or lexatumumab, human agonistic antibodies that target the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2), in combination with chemotherapeutic agents, against human solid cancer cells.Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis.Treatment of ACHN human renal cell carcinoma cells with cisplatin combined with mapatumumab did not overcome resistance to these agents. However, treatment with cisplatin in combination with lexatumumab had a synergistic cytotoxicity. Synergy was also achieved in six primary renal cell carcinoma cell cultures. Lexatumumab and cisplatin also synergistically enhanced apoptosis. Pretreatment with cisplatin followed by lexatumumab resulted in high cytotoxicity compared with the reverse sequence. Cisplatin significantly increased TRAIL-R2 expression at both the mRNA and the protein levels. Furthermore, the combination of lexatumumab and cisplatin significantly enhanced caspase-8 activity, Bid cleavage, up-regulation of Bax, cytochrome c release, and caspase-9, caspase-6, and caspase-3 activities. Importantly, the activation of caspase-8 was significantly abrogated by the specific inhibitors of caspase-9, caspase-6, and caspase-3. Furthermore, combination-induced cytotoxicity was significantly suppressed by the DR5:Fc chimeric protein and the specific inhibitors of caspase-8, caspase-9, caspase-6, and caspase-3. A similar effect was observed in prostate cancer, bladder cancer, lung cancer, and cervical cancer cells.Cisplatin sensitizes solid cancer cells to lexatumumab-induced apoptosis by potentiation of the extrinsic and intrinsic apoptotic pathways that lead to amplification of caspase activation, particularly caspase-8, suggesting the combination treatment of solid cancers with cisplatin and lexatumumab might overcome their resistance.
Making Progress on Progression in Metastatic Prostate Cancer
Authors: Andrew J. Armstrong, Susan Halabi
Journal: Journal of Clinical Oncology (2015)

Determiningclinicalbenefittotherapyisamongthemostcritical aspects of oncology care. At the individual level, this determination influences cessation or continuation of therapy and can dramatically affect patient and family perceptions of hope and optimism. At the trial level, these determinations affect regulatory approvals, optimal care delivery, and the chance of a therapy reaching the clinic. In men with metastatic castration-resistant prostate cancer (CRPC),anumberofchallengesexistinassessingclinicalbenefitto therapies. First, the vast majority of men have metastatic disease confined predominantly to bone, making response challenging to assess using traditional RECIST criteria 1 that were developed for other cancer types. Second, prostate-specific antigen (PSA) as a marker of response may be valuable in some contexts such as with androgen-receptor directed therapies, 2 but in other settings, PSA may not drop to arbitrary degrees despite the use of chemotherapies or immunotherapies known to prolong life. 3-6 Pain responses are valuable, particularly if durable, and patient-reported outcomes are certainly helpful, but these outcomes are highly subjective, hard to quantify across a trial, and heterogeneous and dependent on baseline symptoms. 4,7 Technetium-99 methylene diphosphonate bone scans have traditionally been used to quantify progression in bone, but this nuclear tracer only indirectly measures the tumor and instead more likely images osteoblastic activity in the tumor microenvironment. The problem of imaging bone metastases with traditional bone scans becomes apparent during the common observation of bone scan flare (new lesions seen during response) during treatment with novel hormonal therapies, such as abiraterone acetate or enzalutamide. 8
Comparison of docetaxel and docetaxel–irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial
Authors: D. Pectasides, M. Pectasides, D. Farmakis, V. Kostopoulou, M. Nikolaou, A. Gaglia, M. Koumpou, N. Mylonakis, N. Xiros, T. Economopoulos, S.A. Raptis
Journal: Annals of Oncology (2005)
Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation
Authors: Henrique Bittencourt, Vanderson Rocha, Sylvie Chevret, Gérard Socié, Hélène Espérou, Agnès Devergie, Liliane Dal Cortivo, Jean-Pierre Marolleau, Federico Garnier, Patricia Ribaud, Eliane Gluckman
Journal: Blood (2002)