tbuckley/cabot-search huggingface dataset:
S86 The anti-inflammatory effects of pneumolysin
Authors: JN Periselneris, T James, M Noursadeghi, JS Brown
Journal: Thorax (2015)

<h3></h3> The inflammatory response to bacteria requires the interaction of pattern recognition receptors with bacterial surface constituents, and humans deficient in components of inflammatory signalling pathways such as IRAK4 are prone to invasive pneumococcal disease. Pneumolysin is a well-recognised virulence factor for Streptococcus pneumoniae that has multiple effects on the host immune response that are primarily thought to be pro-inflammatory; including causing IL1β release due to pore formation, and epithelial cell layer breakdown. We hypothesised that pneumolysin deficient TIGR4 (a serotype 4 strain) would induce less inflammatory cytokines than wildtype from human monocyte derived macrophages. While both pore forming and non-cytolytic purified pneumolysin induced dose dependent inflammatory cytokine release, the pneumolysin deficient bacteria induced greater TNF and IL6 than wildtype, by qPCR and ELISA measurement of protein. This was reduced by inhibition of phagocytosis with cytochalasin D. Given the pore forming effects of pneumolysin we assessed whether differential cell death contributed to the differences in inflammatory response. While wildtype bacteria caused more cell death at 24 h, inhibition of caspases had no effect on the cytokine response suggesting that apoptosis pathways don’t directly influence the early inflammatory response. Transcriptome analysis confirmed increased pro-inflammatory and interferon gene signalling with the mutant strain, with reduction of the inflammatory and interferon signature with inhibition of phagocytosis. Wildtype bacteria induced less NFκB translocation, but more IRF3 translocation than <i>Δply.</i> An <i>in vivo</i> intranasal mouse infection showed wildtype was more virulent, with more bacteria recovered from bronchoalveolar lavage fluid at 4 h. However, this was associated with reduced TNF compared to <i>Δply. </i>Neutralising TNF intranasally abrogated the difference in bacteria recovered between wildtype and Δ<i>ply. </i>Thus, the early inflammation dampening effects of pneumolysin released within the phagolysosome may be an important contribution to its virulence by allowing bacterial replication at mucosal surfaces. This may be due to IRF3 mediated inhibition of inflammatory cytokine transcription. Better understanding of the biology of pneumolysin may aid in adjuvant treatment o<i>f S. pneumoniae.</i>
Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes
Authors: M Delforge, H Demuynck, P Vandenberghe, G Verhoef, P Zachee, V van Duppen, P Marijnen, H Van den Berghe, MA Boogaerts
Journal: Blood (1995)
Environmental Remediation to Address Childhood Lead Poisoning Epidemic due to Artisanal Gold Mining in Zamfara, Nigeria
Authors: Simba Tirima, Casey Bartrem, Ian von Lindern, Margrit von Braun, Douglas Lind, Shehu Mohammed Anka, Aishat Abdullahi
Journal: Environmental Health Perspectives (2016)

From 2010 through 2013, integrated health and environmental responses addressed an unprecedented epidemic lead poisoning in Zamfara State, northern Nigeria. Artisanal gold mining caused widespread contamination resulting in the deaths of > 400 children. Socioeconomic, logistic, and security challenges required remediation and medical protocols within the context of local resources, labor practices, and cultural traditions.Our aim was to implement emergency environmental remediation to abate exposures to 17,000 lead poisoned villagers, to facilitate chelation treatment of children ≤ 5 years old, and to establish local technical capacity and lead health advocacy programs to prevent future disasters.U.S. hazardous waste removal protocols were modified to accommodate local agricultural practices. Remediation was conducted over 4 years in three phases, progressing from an emergency response by international personnel to comprehensive cleanup funded and accomplished by the Nigerian government.More than 27,000 m3 of contaminated soils and mining waste were removed from 820 residences and ore processing areas in eight villages, largely by hand labor, and disposed in constructed landfills. Excavated areas were capped with clean soils (≤ 25 mg/kg lead), decreasing soil lead concentrations by 89%, and 2,349 children received chelation treatment. Pre-chelation geometric mean blood lead levels for children ≤ 5 years old decreased from 149 μg/dL to 15 μg/dL over the 4-year remedial program.The unprecedented outbreak and response demonstrate that, given sufficient political will and modest investment, the world's most challenging environmental health crises can be addressed by adapting proven response protocols to the capabilities of host countries.Tirima S, Bartrem C, von Lindern I, von Braun M, Lind D, Anka SM, Abdullahi A. 2016. Environmental remediation to address childhood lead poisoning epidemic due to artisanal gold mining in Zamfara, Nigeria. Environ Health Perspect 124:1471-1478; http://dx.doi.org/10.1289/ehp.1510145.
Lack of Effect of Lovastatin on Restenosis after Coronary Angioplasty
Authors: William S. Weintraub, Stephen J. Boccuzzi, J. Larry Klein, Andrzej S. Kosinski, Spencer B. King, Russell Ivanhoe, John C. Cedarholm, Michael E. Stillabower, J. David Talley, Samuel J. DeMaio, William W. O'Neill, John E. Frazier, Caryn L. Cohen-Bernstein, David C. Robbins, Charles L. Brown, R. Wayne Alexander
Journal: New England Journal of Medicine (1994)

Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty.
A Randomized Trial of Intensive Insulin Therapy in Newly Diagnosed Insulin-Dependent Diabetes Mellitus
Authors: Shirish C. Shah, John Malone, Norma E. Simpson
Journal: New England Journal of Medicine (1989)

A period of early, intensive insulin treatment is thought to improve subsequent beta-cell function in insulin-dependent diabetes mellitus (IDDM). To study this hypothesis, we randomly assigned adolescents with newly diagnosed IDDM to receive either conventional treatment (n = 14) (NPH insulin, 1 U per kilogram of body weight per day, in two divided doses) or an experimental treatment (n = 12) (a two-week hospitalization with maintenance of blood glucose levels between 3.3 and 4.4 mmol per liter by continuous insulin infusion delivered by an external artificial pancreas [Biostator]). During the two-week intervention, the experimental-therapy group received four times more insulin than the conventionally treated group, and their endogenous insulin secretion was more completely suppressed, as evidenced by a urinary C-peptide excretion rate one seventh that of the conventionally treated group. After the first two weeks, both groups were treated similarly and received similar amounts of insulin. At one year, the mean (±SEM) plasma level of C peptide was significantly higher after mixed-meal stimulation in the experimental-therapy group than in the conventionally treated group (0.51 ±0.07 vs. 0.27±0.06; P<0.01). The experimental-therapy group also had better metabolic control, as evidenced by lower glycohemoglobin values (7.2±0.7 vs. 10.8±1.2 percent; P<0.01). We conclude that suppression of endogenous insulin by intensive, continuous insulin treatment during the first two weeks after the diagnosis of IDDM may improve beta-cell function during the subsequent year. (N Engl J Med 1989; 320:550–4.)
A Meta-Analysis of Thoracic Radiotherapy for Small-Cell Lung Cancer
Authors: Jean-Pierre Pignon, Rodrigo Arriagada, Daniel C. Ihde, David H. Johnson, Michael C. Perry, Robert L. Souhami, Ola Brodin, Rudolf A. Joss, Merrill S. Kies, Bernard Lebeau, Taisuke Onoshi, Kell Østerlind, Martin H.N. Tattersall, Henry Wagner
Journal: New England Journal of Medicine (1992)

In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer.
ABCF2 expression may predict the prognosis of cervical cancer
Authors: S. Nishimura, H. Tsuda, K. Kajitani, Y. Hashiguchi, N. Kawamura, R. S. Berkowitz, S. C. Mok
Journal: Journal of Clinical Oncology (2006)

5045 Background: ABCF2 is a new member of the ATP-binding cassette transporter superfamily gene. We previously reported that ABCF2 protein is new biomarker in clear cell adenocarcinoma (CC) of the ovary and its expression may predict the response to chemotherapy and survival of CC patients (Proc ASCO 2005, Clin Cancer Res 2005). In this study, we examined ABCF2 expression in cervical cancer (CACX) and evaluated the relationship between ABCF2 expression and clinical factor. Methods: Formalin-fixed surgical samples from one hundred fourty CACX were included in this study. ABCF2 expression was investigated by immunohistochemistry. Positive expression of ABCF2 was &gt;10% based on the cytoplasmic staining. Results: One hundred fourty patients were included in this study. The clinical stage was I in 86 patients, II in 38 patients, III in 10 patients, and IV in 6 patients. Histologic types were squamous cell carcinoma (SC) in 101 patients and non-squamous cell carcinoma (NSC) in 39 patients. The positive rate of ABCF2 in advanced stage (III + IV) was significantly higher than it in early stage (I + II) (p = 0.03). However, histologic type was not related with ABCF2 expression (SC 49.5% vs NSC 59.0%, p = 0.35). ABCF2-negative tumors had longer overall survival (OS) than ABCF2-positive tumors (p = 0.0014). The ABCF2 expression were correlated with further biological variables such as age, tumor stage, and histologic type for OS rate by univariate and multivariate Cox regression analysis. Multivariate analysis revealed that stage and ABCF2 were independent prognostic factor (Hazards ratio (HR) = 4.66, p = 0.0005; HR = 0.34, p = 0.025). Conclusions: The role of ABCF2 protein may predict the prognosis of CACX. [Table: see text] No significant financial relationships to disclose.
P-002 The therapeutic effect of irreversible electroporation according to tissue properties of upper gastrointestinal tract: feasibility study for esophageal neoplasm
Authors: H.S. Choi, H.J. Chun, I.K. Yoo, J.M. Lee, S.H. Kim, E.S. Kim, B. Keum, Y.T. Jeen, H.S. Lee, C.D. Kim
Journal: Annals of Oncology (2015)
The clinician-researcher in psychiatry
Authors: J D Burke, H A Pincus, H Pardes
Journal: American Journal of Psychiatry (1986)

As clinical research in psychiatry has grown in importance and promise in the past decade, the need for a growing pool of skilled clinician-researchers has been increasingly recognized. Compared with physicians in other specialties, psychiatrists in academic positions have less training in research and devote less time to it, which is reflected in the growing concentration of research funds from the National Institute of Mental Health in just a few of the strongest medical school departments. To focus attention on the need for developing the role of clinician-researchers, the authors examine four major tasks faced by clinician-researchers and present a developmental perspective on the transition to research.
Images of the mind: psychiatry in the commercial film
Authors: I Schneider
Journal: American Journal of Psychiatry (1977)

There are many striking temporal and cultural parallels in the development of commercial films and psychiatry. The psychiatrist has been depicted in widely varying ways--as madman, as a powerful force for tinkering with the soul, and as a wonder worker who cures patients by uncovering a single traumatic event. The early years, in which psychiatric issues were often treated simplistically or sensationally, were followed by a "latency period". After the war there was a deluge of psychological films, which also began to deal with emerging social issues. Contemporary films tend to focus on madness as a metaphor or on the struggle of seemingly normal, successful people to find fulfillment. Psychiatry and film are "toys that have grown up together," along with the consumers of both.
Interaction Between the R501X Filaggrin Mutation and Disease Severity Associates with Increased Staphylococcus Aureus Colonization in European American Subjects with Atopic Dermatitis
Authors: Nicholas M. Rafaels, Alexandre Lockhart, Denise C. Babineau, Keli Artis, Gloria L. David, Takeshi Yoshida, Mark Boguniewicz, Peck Y. Ong, Anna De Benedetto, Jon M. Hanifin, Eric L. Simpson, Amy S. Paller, Emma Guttman-Yassky, Lynda C. Schneider, Rasika A. Mathias, Kathleen C. Barnes, Donald Y. Leung, Lisa A. Beck
Journal: Journal of Allergy and Clinical Immunology (2016)
Hereditary Choreoathetosis, Self-Mutilation and Hyperuricemia in Young Males
Authors: Dick Hoefnagel, E. Donald Andrew, Norman G. Mireault, William O. Berndt
Journal: New England Journal of Medicine (1965)

IN 1964 Lesch and Nyhan1 described a syndrome in 2 young brothers, characterized by a nervous-system disorder dating from early infancy, a behavioral abnormality manifested by self-mutilation and a consistent elevation of the levels of uric acid in blood and urine. Single cases conforming to this syndrome had previously been reported by Catel and Schmidt2 and Riley,3 and, since the paper of Lesch and Nyhan, another report of the syndrome in a young boy has appeared.4 The present paper is concerned with a description of clinical, biochemical and genetic features in 2 further families with boys suffering from this syndrome. . . .
Factors influencing fatigue in breast cancer patients undergoing breast irradiation.
Authors: Edward Belk Perry, Sudhanshu Bharat Mulay, Jayesh Kamath, Robert J. Dowsett, Jacob Neuwirth, James Grady, Courtney Gold, Bruce Liang, Susan Tannenbaum
Journal: Journal of Clinical Oncology (2015)

96 Background: We are conducting an exploratory, prospective study to investigate factors associated with radiation-induced fatigue in women with early breast cancer undergoing radiation therapy (RT) for breast conservation. Our hypothesis is that fatigue associated with adjuvant RT is related to tissue damage by apoptosis and inflammation, and to baseline psychological profiles. Methods: All subjects were assessed immediately before RT (T1), mid-point of RT (T2), end of RT (T3), 6 months (T4) and 1 year (T5) after completing RT. Clinical evaluations of skin toxicity, laboratory measures, fatigue, distress, depression, anxiety, sleep, energy and pain were assessed using validated measures. Results: Thirty-one subjects (target 50) have been enrolled to date; 23 have completed T3 and are presented here. 35% had a history of depression and 17% are currently depressed; 22% had past and current anxiety. BCTOS breast pain, tenderness and sensitivity increased during RT and were consistent with functional pain scores. No clinically relevant changes in energy or distress were seen. Despite a notable prevalence of depression and anxiety at baseline, there were no relevant changes in depression or anxiety. Most IL-1β, IL-4, IL-6 and IL-10 levels were undetectable. 39% of subjects showed increases in fatigue and were 14 years younger than non-fatigued subjects. Fatigued subjects had more frequent past (44%) and current (33%) depression than non-fatigued subjects (29% and 7%, respectively), and woke up tired more frequently (44% versus 0%). Current depression, but not fatigue, was associated with decreased a.m. cortisol levels during RT. 56% of fatigued subjects had an RTOG Acute Skin Toxicity score &gt; 1 and 78% had BCTOS breast-specific pain subscales scores ≥ 3 during RT vs. 21% and 14% of non-fatigued subjects, respectively. Serum caspase-1 (inflammation) and caspase-3 (apoptosis), hs-CRP and TNF-α were increased but not associated with fatigue. Conclusions: Our preliminary findings suggest that radiation-associated fatigue is complex and, as hypothesized, is dependent on a patient’s psychological profile in the setting of skin toxicity and insomnia. If this data holds at study completion, it may guide clinical interventions.
Retrospective Analysis of Survival in Patients with Acute Erythroid Leukemia (AML-6) Treated with Conventional Chemotherapy Versus Hypomethylating Agents
Authors: Binsah George, Elias Jabbour, Monica Cabrero, Nitin Jain, Naval Daver, Farhad Ravandi, Gautam Borthakur, Zach Bohannan, Jorge E. Cortes, Michael J Keating, Susan O'Brien, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2014)
P67 Combined innate and adaptive immune responses are needed to control hepatitis B virus replication in children with infancy-acquired infection
Authors: I Carey, A Mendes, S Bansal, G Mieli-Vergani, D Vergani
Journal: Gut (2010)

Introduction  Innate/adaptive immunity interplay is crucial to control hepatitis B virus (HBV) replication. In infancy-acquired chronic hepatitis B, low viral load is associated with high numbers of natural killer cells (NKC), high expression of their activation markers/receptors (CD69, CD107a, CD161 and NKG2D) and possibly of their inhibitory receptor NKG2A, but there is no information on NKC functional subsets and their interaction with adaptive immunity.  Aim  To investigate NKC functional subsets ex-vivo and after exposure to K562 cells in relation to HBV-specific Th1 immune response and viral load.  Method  30 infancy-acquired chronic hepatitis B children (median age 13 y, 14 boys) divided into: group A (HBeAg+/HBsAg+/normal ALT; n=8), group B (HBeAg+/HBsAg+/elevated ALT; n=8), group C (HBeAg-/HBsAg+; n=9) and group D (HBeAg-/HBsAg-; n=5). NKC were obtained by negative magnetic bead isolation from PBMC and after exposure to K562 cells (post-K562). CD107a degranulation, IFN-g intracellular staining and NKC receptor expression (NKG2A/2D) were assessed concomitantly by flow cytometry. HBV-specific immune response was tested by IFN-g intracellular staining after PBMC incubation with HBV core antigen (HBcAg) and HBV DNA viral load by real-time PCR.  Results  Frequency of NKC producing IFNg only (CD107a-IFNg+), polyfunctional NKC (CD107a+IFNg+) and NKC expressing NKG2A or NKG2D only (CD107a-NKG2A/D+) was higher in group D than in groups A–C, both ex-vivo ((%CD107a-IFNg+: 24.5vs7.3, 11.3, 16.3, p=0.03) (%CD107a+IFNg+: 25.5vs14.6, 18.6, 20.2, p=0.04) (%CD107a-NKG2A+: 10.9vs3.1, 4.5, 4.6, p=0.02) and (% CD107a-NKG2D+: 27.3 vs 16.7, 20.2, 22.6, p=0.05)) and post-K562 ((%CD107a-IFNg+: 31.1 vs 13.2, 16.4, 19.6, p=0.04) (%CD107a+IFNg+: 39.5 vs 20.3, 24.1, 31.1, p=0.05) (%CD107a-NKG2A+: 12.3 vs 3.7, 4.1, 5.6, p=0.03) and (%CD107a-NKG2D+: 35.3 vs 20.1, 22.6, 23.4, p=0.05)). % NKG2D+CD107a+ NKC was higher in group D than in groups A-C ex-vivo (32.4 vs 17.1, 20.1, 22.4, p=0.03) and post-K562 (39.7 vs 17.9, 21.7, 26.2, p=0.04), while NKG2A+/CD107a+ NKC number was similar in all groups. % HBcAg-specific IFN-g producing cells was higher in group D than groups A–C (CD4+/IFN-g+: 7.2±1.2 vs 2.3±0.3, 2.7±0.5, 3.1±0.9, p=0.04). Polyfunctional NKC CD107a+/IFN-g+ number correlated with that of HBcAg-specific IFN-g producing cells (r=0.5, p=0.04) and negatively with HBV DNA viral load (r=−0.42, p=0.05).  Conclusion  High numbers of NKC producing IFN-g, polyfunctional, and with high NKG2D expression are associated with low HBV DNA replication. The strong correlations between polyfunctional NKC and HBV-specific T-helper 1 cells and HBV DNA viral load indicate a joint action between innate and adaptive immunity in controlling HBV infection.
Neoadjuvant chemotherapy with docetaxel and cisplatin followed by concomitant chemoradiotherapy (CT-RT) in the management of locally advanced laryngeal carcinoma
Authors: F. S. Sayed, A. Karim, M. Hossain, D. Ahmed, M. A. Khan, M. Momin, J. Sobhan
Journal: Journal of Clinical Oncology (2007)

16507 Background: Neoadjuvant chemotherapy has been used effectively in the treatment of locally advanced head and neck cancers. We conducted a study to evaluate the efficacy and adverse events associated with neoadjuvant chemotherapy schedule comprising of docetaxel and cisplatin followed by concomitant CT-RT from July 2004 to June 2006. Methods: 25 patients with locally advanced supraglottic laryngeal cancer were enrolled to receive docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 every 3 weekly for 3 cycles followed by one cycle of concomitant external beam radiotherapy (6000 cGy) and docetaxel 75 mg/m 2 +cisplatin 75 mg/m 2 on day 7 of radiotherapy. All patients after completion of neoadjuvant chemotherapy were evaluated by CT scan and direct laryngoscopy and biopsy from any residual disease. All patients were followed up every month up to disease progression. Follow-up was done by physical examination and indirect laryngoscopy and by 3 monthly CT scan. Adverse events were treated mostly on outpatient basis. Results: Out of 25 patients, 9 had residual disease after completion of treatment and 2 had a disease relapse within 5 months of disease completion. The remaining 14 patients were disease free from a duration of 6 to14 months follow-up period. Median progress free survival had not been reached. 9 (36%) patients had severe mucositis and neutropenia while receiving concomitant CT-RT. 6 (24%) patients had grade III mucositis and rest 3 (12%) patients had grade II mucositis and all the 9 (36%) patients had grade III neutropenia. All of them were treated with G-CSF and prophylactic antibiotics. All the rest had grade I and grade II mucositis and neutropenia Conclusions: In our experience, neoadjuvant chemotherapy with docetaxel and cisplatin (3 cycles) followed by 1 cycle of concomitant CT-RT may be a good choice in treating locally advanced supraglottic laryngeal cancer. The toxicity profile was also manageable. No significant financial relationships to disclose.
Superior Pulmonary Sulcus Tumors and Pancoast's Syndrome
Authors: Selim M. Arcasoy, James R. Jett
Journal: New England Journal of Medicine (1997)

Pancoast's syndrome is a constellation of characteristic symptoms and signs that includes shoulder and arm pain along the distribution of the eighth cervical nerve trunk and first and second thoracic nerve trunks, Horner's syndrome, and weakness and atrophy of the muscles of the hand, most commonly caused by local extension of an apical lung tumor at the superior thoracic inlet.13 These tumors are called superior pulmonary sulcus tumors or Pancoast's tumors. Nearly 90 years after the first documented case,4 Pancoast described the clinical and radiologic findings of thoracic-inlet tumors. Pancoast mistakenly believed that these tumors emanated from epithelial rests . . .