tbuckley/cabot-search huggingface dataset:
Discovery of β-lactam-resistant variants in diverse pneumococcal populations
Authors: Regine Hakenbeck
Journal: Genome Medicine (2014)

Understanding of antibiotic resistance in Streptococcus pneumoniae has been hindered by the low frequency of recombination events in bacteria and thus the presence of large linked haplotype blocks, which preclude identification of causative variants. A recent study combining a large number of genomes of resistant phenotypes has given an insight into the evolving resistance to β-lactams, providing the first large-scale identification of candidate variants underlying resistance.
Impaired Cognitive Flexibility and Motor Inhibition in Unaffected First-Degree Relatives of Patients With Obsessive-Compulsive Disorder
Authors: Samuel R. Chamberlain, Naomi A. Fineberg, Lara A. Menzies, Andrew D. Blackwell, Edward T. Bullmore, Trevor W. Robbins, Barbara J. Sahakian
Journal: American Journal of Psychiatry (2007)

Objective: Obsessive-compulsive disorder (OCD) is highly heritable. Attempts to delineate precise genetic contributions have met with limited success. There is an ongoing search for intermediate cognitive brain markers (endophenotypes) that may help clarify genetic contributions. The aim was to assess inhibitory control processes in unaffected first-degree relatives of OCD patients for the first time with objective tests. Method: The Intradimensional/Extradimensional Shift, Stop-Signal, and Cambridge Gamble tasks were administered to 20 unaffected first-degree relatives, 20 OCD patient probands with washing/checking symptoms, and 20 healthy matched comparison subjects without a family history of OCD. Results: Unaffected first-degree relatives and OCD patient probands showed cognitive inflexibility (extradimensional set shifting) and motor impulsivity (stop-signal reaction times). Decision making (Cambridge Gamble task) was intact. Conclusions: Deficits in cognitive flexibility and motor inhibition may represent cognitive endophenotypes for OCD. Such measures will play a key role in understanding genotype/phenotype associations for OCD and related spectrum conditions.
Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency
Authors: Carsten Speckmann, Ulrich Pannicke, Elisabeth Wiech, Klaus Schwarz, Paul Fisch, Wilhelm Friedrich, Tim Niehues, Kimberly Gilmour, Karin Buiting, Michael Schlesier, Hermann Eibel, Jan Rohr, Andrea Superti-Furga, Ute Groß-Wieltsch, Stephan Ehl
Journal: Blood (2008)
Role of Androgen Deprivation Therapy for Node-Positive Prostate Cancer
Authors: Yu-Ning Wong, Stephen Freedland, Brian Egleston, Gary Hudes, J. Sanford Schwartz, Katrina Armstrong
Journal: Journal of Clinical Oncology (2008)

To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era.We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT.A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition.Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.
Interleukin-6 in relation to other proinflammatory cytokines, chemotactic activity and neutrophil activation in rheumatoid synovial fluid.
Authors: M A van Leeuwen, J Westra, P C Limburg, P L van Riel, M H van Rijswijk
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To evaluate the relation between synovial fluid (SF) concentrations of interleukin-6 (IL-6) and other mediators of inflammation which are responsible for joint degradation in rheumatoid arthritis (RA). METHODS--We measured IL-6, IL-1 beta, tumour necrosis factor alpha (TNF alpha), granulocyte macrophage colony stimulating factor, IL-8, and polymorphonuclear leucocyte (PMNL) chemotaxis and degranulation in SF from patients with RA (n = 30) in the early phase of the disease. RESULTS--In a cross-sectional study IL-6 concentrations correlated with those of IL-1 beta, IL-8 and with PMNL activation as reflected by lactoferrin concentrations. In a longitudinal study, changes in IL-6 concentrations correlated with changes in TNF alpha, IL-8 and lactoferrin concentrations. CONCLUSION--IL-6 in SF appears to reflect the local proinflammatory, potentially erosive activity in RA. This supports the use of acute phase proteins, which are mainly induced by IL-6, as variables to monitor the course of RA.
THE STATUS OF THE KIDNEYS IN ALKALOSIS
Authors: EDMUND H. BERGER
Journal: JAMA (1935)

It is an established fact that the kidneys play an important part in maintaining the acid-base equilibrium and thus also in maintaining a constant<i>p</i><sub>H</sub>in the blood and tissues. When this renal function is impaired, the acid-base mechanism is more readily disturbed and the compensating mechanism is more subject to deflection by the ingestion of either acid or basic salts. Conversely, primary renal impairment is very frequently accentuated by overzealous administration of acid or basic salts. We frequently hear of and see instances of depletion of the alkali reserve resulting in compensated or uncompensated acidosis, but rarely do we consider a depletion of the acid reserve with compensated or uncompensated alkalosis and the distressing symptoms associated with this condition. Our present paper concerns itself primarily with the relationships of renal function to alkalosis resulting from the administration of alkalis. It was early recognized that it was dangerous to
Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex.
Authors: S D Miller, M S Sy, H N Claman
Journal: The Journal of Experimental Medicine (1978)

Genetic restrictions governing the induction and expression of suppressor T cells (Ts) in tolerance to 1-fluoro-2,4-dinitrogenzene (DNFB) contract sensitivity were studied. Tolerance was induced by using 2,4-dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogen. Two kinds of Ts were found-those produced by DNP-LC syngeneic to the donor of the Ts (syninduced Ts), and those produced by DNP-LC allogeneic to the donor of Ts (alloinduced Ts). Studies employing congenic resistant mouse strains indicated that recognition of DNP-modified-major histocompatibility region determinants on the tolerogenic DNP-LC was essential for the induction of both types of Ts. Non-H-2 genetic background was irrelevant to Ts induction. Mapping studies indicated that induction of both syninduced and alloinduced Ts was associated with recognition of DNP-modified-MHC region determinants which map to the right of the H-2G region (i.e., H-2D gene products). Tolerization of donor mice with DNP-LC which were H-2D region compatible, but not with H-2K or I region compatible DNP-LC, was both sufficient and required for the induction of hapten-specific syninduced Ts. Tolerization of donor mice with DNP-LC which were incompatible only at the H-2D region was sufficient for the induction of alloinduced Ts. These Ts were capable of suppressing recipient mice only if the recipients shared the H-2D region with the strain providing the DNP-LC tolerogen, and were not capable of suppressing recipients sharing all but the H-2D region with the tolerogen.
Phase I Study of Combined Pegylated Liposomal Doxorubicin with Protracted Daily Topotecan for Ovarian Cancer
Authors: Deepu Mirchandani, Howard Hochster, Anne Hamilton, Leonard Liebes, Herman Yee, John P. Curtin, Sang Lee, Joan Sorich, Cornelia Dellenbaugh, Franco M. Muggia
Journal: Clinical Cancer Research (2005)

To determine the maximum tolerated dose and dose-limiting toxicity of Doxil with low-dose continuous infusion topotecan and subsequently with low-dose oral topotecan. Other specific aims were preliminary assessment of activity in advanced ovarian and tubal malignancies, pharmacokinetics of oral topotecan, and correlation of response with topoisomerase I and II expression in tumors.Eligible patients had histopathologically documented advanced cancers beyond standard therapy, performance status <2, and adequate organ functions. Doxil (30-40 mg/m2 i.v.) was given on day 1, with topotecan either oral topotecan 0.4 mg/m2 bid for 14 days or continuous infusion topotecan (0.3-0.4 mg/m2/d) for 14 to 21 days, in 28-day cycles. Fifty-seven patients, 23 with epithelial ovarian or tubal cancers were enrolled. Plasma levels of lactone form of topotecan were determined on patients receiving oral topotecan.Grade 4 neutropenia and thrombocytopenia and grade 3 diarrhea were dose-limiting toxicities at the highest dose levels explored. Doxil (40 mg/m2/day 1) and continuous infusion topotecan at 0.4 mg/m2/days 1 to 14 could be safely given and is the recommended phase II dose. Oral topotecan was limited by low and erratic plasma topotecan levels and frequent gastrointestinal toxicity. Particularly long partial responses and stable disease were observed in patients with epithelial ovarian or tubal cancers. Clinical benefit (objective responses and stable diseases) correlated with elevated expression of both topoisomerases by immunohistochemistry in four of six epithelial ovarian or tubal cancer tumor samples.Doxil with 14-day topotecan infusion is a well-tolerated regimen and suitable for study in platinum-resistant or refractory ovarian or tubal cancers. Frequent gastrointestinal toxicity and/or erratic absorption complicate treatment with a longer topotecan infusion or with oral topotecan, respectively, and these combinations are not recommended.
Role of p53 in murine macrophages and alveolar epithelial cells response to nanoparticles
Authors: E. Belade, C. Bussy, L. Armand, A. Simon-Deckers, S. Lanone, J.-C. Pairon, J. Boczkowski
Journal: European Respiratory Journal (2011)

Introduction:  The mechanisms of toxicity of manufactured nanoparticles (NP) are poorly characterized, but may involve oxidative stress. p53 is a key protein implicated in cellular responses to oxidative stress.   Aim of the study:  To examine the induction and the roles of p53 in murine macrophages and alveolar epithelial cells exposed to different NP.   Methods:  Murine macrophages (RAW 264.7 cell line and peritoneal macrophages from C57Bl6 mice) and alveolar epithelial cells (MLE-12 cell line) were exposed to 2 carbon black (CB) NP (13 and 20 nm diameter), single-wall carbon nanotubes (SWCNT, diameter: 4-7 nm) and 2 titanium dioxide (TiO 2 ) NP (10 and 15 nm diameter). p53 protein activation, cellular viability, apoptosis, oxidative stress, and proinflammatory cytokines levels were quantified 6 to 48h after cells exposure to NP.   Results:  The 5 NP activated p53 concomitantly with a decreased cellular viability (except CB), and an induction of apoptosis (except TiO 2 ), oxidative stress and inflammation in macrophages, whereas no effect in alveolar epithelial cells was found after exposure to all NP.  In macrophages, the antioxidant N-acetylcysteine prevented p53 activation only in response to SWCNT. Pifithrin-α, an inhibitor of the transcriptional effects of p53, did not significantly modify the effects of NP on macrophages viability, apoptosis and inflammation.   Conclusion:  In macrophages p53 was activated by the 5 NP, but only SWCNT did it via oxidative stress. Since p53 was not involved in the loss of viability and inflammation induced by the different NP, the role of p53 in macrophages response to NP deserves further investigations. p53 is not involved in alveolar epithelial cells responses to NP.
The influence of cutaneous factors on the transcutaneous pO2 and pO2 at various body sites
Authors: H. TAKIWAKI, H. NAKANISHI, Y. SHONO, S. ARASE
Journal: British Journal of Dermatology (1991)

The transcutaneous partial pressures of oxygen (tcpO2) and carbon dioxide (tcpCO2) were measured at eight different sites in 10 adult male subjects with an electrode at a temperature of 44 degrees C. The mean tcpO2 values (mmHg) were significantly lower on the face (forehead 26.6, cheek 29.6) and the palm (26.4) than at other sites (60.6-69.6). The tcpCO2 values (mmHg) were only slightly higher on the face. Removal of the stratum corneum produced an average increase of the tcpO2 on the palm of 37.6 mmHg and on the forehead of 19.6 mmHg. However, in 10 children with an age range of 3-9 years, the difference in the mean pO2 between the cheek and forearm was very small. There was no significant difference in the cutaneous blood flow at 44 degrees C between the cheek, palm and forearm.
Andrew Philip Thomas
Authors: S. Fraser
Journal: BMJ (2010)

When first appointed to the Royal Wolverhampton Hospital as a consultant in 1990, Andrew Philip Thomas made it clear from the outset that he intended to deliver the highest quality service to as many patients as possible. In this, “APT” as he became known, was singularly successful. Those with initial doubts soon lost them. His slightly autocratic style was well considered and effective. His daily routine would start with an early morning ward round and a hand written entry in the notes, a practice he continued until his retirement in 2007 as a result of ill health. Organisational effectiveness was combined with clinical and operative skills …
Rational development and characterization of humanized anti–EGFR variant III chimeric antigen receptor T cells for glioblastoma
Authors: Laura A. Johnson, John Scholler, Takayuki Ohkuri, Akemi Kosaka, Prachi R. Patel, Shannon E. McGettigan, Arben K. Nace, Tzvete Dentchev, Pramod Thekkat, Andreas Loew, Alina C. Boesteanu, Alexandria P. Cogdill, Taylor Chen, Joseph A. Fraietta, Christopher C. Kloss, Avery D. Posey, Boris Engels, Reshma Singh, Tucker Ezell, Neeraja Idamakanti, Melissa H. Ramones, Na Li, Li Zhou, Gabriela Plesa, John T. Seykora, Hideho Okada, Carl H. June, Jennifer L. Brogdon, Marcela V. Maus
Journal: Science Translational Medicine (2015)

A chimeric antigen receptor redirects T cells to treat glioblastoma.
Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris
Authors: C Segala, B Fauroux, J Just, L Pascual, A Grimfeld, F Neukirch
Journal: European Respiratory Journal (1998)

There is controversy as to whether low levels of air pollution affect the symptoms and lung function in asthma. We addressed this by examining the short-term effects of winter air pollution on childhood asthma in Paris. We performed a 6 month follow-up of 84 medically diagnosed asthmatic children classified into two groups of severity. The outcomes included incidence and prevalence of asthma attacks, symptoms and use of supplementary beta2-agonists, peak expiratory flow (PEF) value and its variability. The statistical analysis controlled the lack of independence between daily health outcomes, trends and meteorology. Air pollution was associated with an increase in reports and duration of asthma attacks and asthma-like symptoms in mild asthmatic children. The strongest association was the risk of asthma attack for an increase of 50 microg x m(-3) of sulphur dioxide (SO2) on the same day (odds ratio (OR)=2.86). Maximum reduction in morning peak expiratory flow (PEF) (5%) and maximum increase in PEF variability (2%) were observed at a lag of 3 days for an increase of 50 microg x m(-3) of SO2 in the subgroup of mild asthmatics receiving no regular inhaled medication. In moderate asthmatic children, the duration of supplementary beta2-agonist use was strongly associated with air pollution. The general pattern of our results provides evidence of the effect of the low levels of air pollution encountered in Western Europe on symptoms and lung function in childhood asthma.
Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma
Authors: Philippe Gevaert, Lien Calus, Thibaut Van Zele, Katrien Blomme, Natalie De Ruyck, Wouter Bauters, Peter Hellings, Guy Brusselle, Dirk De Bacquer, Paul van Cauwenberge, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2012)
Primary Prevention of Cardiovascular Events With Low-Dose Aspirin and Vitamin E in Type 2 Diabetic Patients
Authors: Michele Sacco, Fabio Pellegrini, Maria C. Roncaglioni, Fausto Avanzini, Gianni Tognoni, Antonio Nicolucci
Journal: Diabetes Care (2003)

OBJECTIVE—We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes. RESEARCH DESIGN AND METHODS—The Primary Prevention Project (PPP) is a randomized, open trial with a two-by-two factorial design aimed to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors. The primary end point was a composite end point of cardiovascular death, stroke, or myocardial infarction. A total of 1,031 people with diabetes in the PPP, aged ≥50 years, without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics. RESULTS—The PPP trial was prematurely stopped (after a median of 3.7 years) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors. In diabetic patients, aspirin treatment was associated with a nonsignificant reduction in the main end point (relative risk [RR] = 0.90, 95% CI 0.50–1.62) and in total cardiovascular events (0.89, 0.62–1.26) and with a nonsignificant increase in cardiovascular deaths (1.23, 0.69–2.19). In nondiabetic subjects, RRs for the main end point, total cardiovascular events, and cardiovascular deaths were 0.59 (0.37–0.94), 0.69 (0.53–0.90), and 0.32 (0.14–0.72), respectively. No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects. CONCLUSIONS—Our data suggest a lower effect of primary prevention of cardiovascular disease (CVD) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors. If confirmed, these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation, thus making the balance between benefits and harms of aspirin treatment unfavorable. Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed.
Decreased Cardiovascular Disease and Increasing Cancer-Reply
Authors: D. L. Davis, G. E. Dinse, D. G. Hoel
Journal: JAMA (1994)

<h3>In Reply.</h3> —Efforts to find simple explanations for complex patterns are commendable. Dr Lemon carries Ockam's razor to an untenable extreme, however, when asserting that increased cancer risks are caused entirely by active and passive smoking. Like all disease, cancer has multiple causes. Only crude analyses that classified cancer sites, not individual cases, as related or unrelated to smoking were possible. In addition to lung and oral cancers, Lemon and others suggested that the smoking-related category should include pancreas, kidney, blasder, and colon. The Table indicates that even after reclassifying cancer sites, men born from 1948 to 1957 had three to four times the risk of developing cancers unrelated to smoking, and women had a 30% to 40% greater risk than their grandparents had at the same ages. The cancer sites in this new nonsmoking category exhibiting increased risks are brain, breast, lymphoma, melanoma, and prostate. Lemon speculates that all
High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration
Authors: Turiddu Lombardo, Gabriella Ferro, Viviana Frontini, Sebastiano Percolla
Journal: American Journal of Hematology (1996)

To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of IV therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the IV route. © 1996 Wiley-Liss, Inc.