tbuckley/cabot-search huggingface dataset:
Pathogenesis of Respiratory Syncytial Virus Vaccine-augmented Pathology
Authors: Barney S. Graham
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Respiratory syncytial virus (RSV) is an important respiratory pathogen for which vaccine development has been thwarted by the legacy of vaccine-enhanced illness. A formalin-inactivated, alum-precipitated, whole virus vaccine did not protect children from infection and was associated with severe illness. Clues from clinical studies of RSV and vaccine-induced a typical measles illness suggest that an aberrant CD4+ lymphocyte response occurred in vaccinees. There is a growing body of evidence from murine models that show vaccine formulations can selectively activate different populations of CD4+ T helper lymphocytes that produce distinct cytokine expression patterns. The cytokine milieu in turn can influence the composition of the immune response and thereby impact the efficiency of virus clearance, type of pathology, and magnitude of illness. Major priorities of current vaccine development are to define the optimal combination of T lymphocyte subsets to safely clear RSV and to learn ways to modulate the composition of the immune response to vaccine antigens. Graham BS. Pathogenesis of respiratory syncytial virus vaccine-augmented pathology.
Impaired T cell capping and receptor regeneration in active systemic lupus erythematosus. Evidence for a disorder intrinsic to the T lymphocyte.
Authors: G M Kammer
Journal: Journal of Clinical Investigation (1983)

It is currently unclear whether the T cell dysfunctions observed during active systemic lupus erythematosus (SLE) reflect a disorder intrinsic to the T cell or defects that result from interaction with anti-T cell autoantibody. To determine whether a disorder intrinsic to the T cell exists in SLE, the T cell capping mechanism was selected as a model of cellular function. The normal T cell capping mechanism is a rapid, energy-dependent and coordinated sequence of membrane events that consists of microaggregation, capping, endocytosis, and regeneration of the surface molecule. The monoclonal antibodies OKT3, OKT4, and OKT8, directed against the T cell-specific membrane glycoproteins T-3, T-4, T-8, served as specific probes of the glycoproteins' mobility within the membrane and membrane glycoprotein regeneration. When compared with greater than 91% T cell capping in normal and control subjects with active Sjögren's syndrome, active rheumatoid arthritis and active tuberculosis, only 49-60% of T cells from active SLE patients completed the capping sequence (SLE vs. healthy controls; T-3, P less than 0.002; T-4, P less than 0.004; T-8, P less than 0.002). Colchicine (10(-5) M), which inhibits microtuble polymerization and augments the rate of normal T cell capping, failed to restore the abnormal capping. However, as judged by the elapsed time intervals to half-maximal capping, the capping kinetics of the T cells able to initiate capping were not significantly different from controls. Fluorescence microscopy demonstrated an abnormal staining pattern characterized by microaggregation of ligand-glycoprotein complexes on resting T cells, coarse aggregation of ligand-glycoprotein complexes over the surfaces of cells that failed to cap, and cleaved or disrupted caps. After clearance of determinants by capping, greater than 94% of T cells from healthy controls regenerated T-3, -4, and -8 within 24 h. In contrast, only 20-40% of capped T cells from active SLE patients reexpressed new determinants. With improving disease activity, the proportion of cells capping and regenerating T-3, -4, and -8 increased, but remained significantly below control levels. In conclusion, this study has identified a disorder of T cell surface glycoprotein mobility and regeneration affecting the majority (60-80%) of both the T-3+, T-4+, (inducer/helper), and T-3+, T-8+ (suppressor) subsets during active SLE. Although the impaired capping and reexpression improve with disease remission, a residual defect persists. The data support the concept of a disorder intrinsic to the T cell in SLE.
Economic evaluations of single- versus double-embryo transfer in IVF
Authors: A.A.A. Fiddelers, J.L. Severens, C.D. Dirksen, J.C.M. Dumoulin, J.A. Land, J.L.H. Evers
Journal: Human Reproduction Update (2006)

Multiple pregnancies lead to complications and induce high costs. The most successful way to decrease multiple pregnancies in IVF is to transfer only one embryo, which might reduce the efficacy of treatment. The objective of this review is to determine which embryo-transfer policy is most cost-effective: elective single-embryo transfer (eSET) or double-embryo transfer (DET). Several databases were searched for (cost* or econ*) and (single embryo* or double embryo* or one embryo* or two embryo* or elect* embryo or multip* embryo*). On the basis of five exclusion criteria, titles and abstracts were screened by two individual reviewers. The remaining papers were read for further selection, and data were extracted from the selected studies. A total of 496 titles were identified through the searches and resulted in the selection of one observational study and three randomized studies. Study characteristics, total costs and probability of live births were extracted. Besides this, cost-effectiveness and incremental cost-effectiveness were derived. It can be concluded that DET is the most expensive strategy. DET is also most effective if performed in one fresh cycle. eSET is only preferred from a cost-effectiveness point of view when performed in good prognosis patients and when frozen/thawed cycles are included. If frozen/thawed cycles are excluded, the choice between eSET and DET depends on how much society is willing to pay for one extra successful pregnancy.
IL28B rs12979860 is not associated with histologic features of NAFLD in a cohort of Caucasian North American patients
Authors: Melanie E. Garrett, Manal F. Abdelmalek, Allison Ashley-Koch, Michael A. Hauser, Cynthia A. Moylan, Herbert Pang, Anna Mae Diehl, Hans L. Tillmann
Journal: Journal of Hepatology (2012)
Effect of strategies to reduce exposure of infants to environmental tobacco smoke in the home: cross sectional survey
Authors: C. Blackburn
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To examine parents9 reported knowledge and use of harm reduction strategies to protect their infants from exposure to tobacco smoke in the home, and the relation between reported use of strategies and urinary cotinine to creatinine ratios in the infants. <b>Design</b> Cross sectional survey. <b>Settings</b> Coventry and Birmingham. <b>Main outcome measures</b> Parents9 reported knowledge and use of harm reduction strategies and urinary cotinine to creatinine ratios in their infants. <b>Participants</b> 314 smoking households with infants. <b>Results</b> 86% of parents (264/307) believed that environmental tobacco smoke is harmful, 90% (281/314) believed that infants can be protected from it in the home, and 10% (32/314) were either unaware of measures or reported using none. 65% of parents (205/314) reported using two or more measures, but only 18% (58/314) reported not allowing smoking in the home. No difference was found in mean log e transformed urinary cotinine to creatinine ratio in infants from households that used no measures compared with households that used less strict measures. Mean log cotinine to creatinine ratios were significantly different in households banning smoking in the home compared with those using less strict or no measures. Banning smoking in the home was independently associated with a significant reduction in urinary cotinine to creatinine ratio by a factor of 2.6 (1.6 to 4.2) after adjustment for average household cigarette consumption, tenure, and overcrowding. <b>Conclusions</b> Less than a fifth of parents in smoking households ban smoking in the home. Banning smoking was associated with a small but significant reduction in urinary cotinine to creatinine ratio in infants, whereas less strict measures compared with no measures had no effect on the infants9 exposure to environmental tobacco smoke.
Efficacy and safety of imatinib in adult patients with c-kit–positive acute myeloid leukemia
Authors: Thomas Kindler, Frank Breitenbuecher, Andreas Marx, Joachim Beck, Georg Hess, Birgit Weinkauf, Justus Duyster, Christian Peschel, Charles J. Kirkpatrick, Matthias Theobald, Harald Gschaidmeier, Christoph Huber, Thomas Fischer
Journal: Blood (2004)
Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea
Authors: A. S. L. Chan, R. W. W. Lee, V. K. Srinivasan, M. A. Darendeliler, R. R. Grunstein, P. A. Cistulli
Journal: European Respiratory Journal (2009)

This study aimed to explore the effect of mandibular advancement splints (MAS) on upper airway anatomy during wakefulness in obstructive sleep apnoea (OSA). Patients commencing treatment for OSA with MAS were recruited. Response to treatment was defined by a ≥50% reduction in the apnoea/hypopnoea index. Nasopharyngoscopy was performed in the supine position. Nasopharyngoscopy was performed in 18 responders and 17 nonresponders. Mandibular advancement caused an increase in the calibre of the velopharynx (mean± sem +40±10%), with relatively minor changes occurring in the oropharynx and hypopharynx. An increase in cross-sectional area of the velopharynx with mandibular advancement occurred to a greater extent in responders than nonresponders (+56±16% versus +22±13%; p&lt;0.05). Upper airway collapse during the Müller manoeuvre, relative to the baseline cross-sectional area, was greater in nonresponders than responders in the velopharynx (-94±4% versus -69±9%; p&lt;0.01) and oropharynx (-37±6% versus -16±3%; p&lt;0.01). When the Müller manoeuvre was performed with mandibular advancement, airway collapse was greater in nonresponders than responders in the velopharynx (-80±11% versus +9±37%; p&lt;0.001), oropharynx (-36±6% versus -20±5%; p&lt;0.05) and hypopharynx (-64±6% versus -42±6%; p&lt;0.05). These results indicate that velopharyngeal calibre is modified by MAS treatment and this may be useful for predicting treatment response.
Building Research Capacity in Africa: Equity and Global Health Collaborations
Authors: Kathryn M. Chu, Sudha Jayaraman, Patrick Kyamanywa, Georges Ntakiyiruta
Journal: PLoS Medicine (2014)

Kathryn Chu and colleagues discuss the impact of high-income country investigators conducting research in low- and middle-income countries and explore lessons from the effective and equitable relationships that exist. Please see later in the article for the Editors' Summary
How Well Do Clinical Pain Assessment Tools Reflect Pain in Infants?
Authors: Rebeccah Slater, Anne Cantarella, Linda Franck, Judith Meek, Maria Fitzgerald
Journal: PLoS Medicine (2008)

Background Pain in infancy is poorly understood, and medical staff often have difficulty assessing whether an infant is in pain. Current pain assessment tools rely on behavioural and physiological measures, such as change in facial expression, which may not accurately reflect pain experience. Our ability to measure cortical pain responses in young infants gives us the first opportunity to evaluate pain assessment tools with respect to the sensory input and establish whether the resultant pain scores reflect cortical pain processing. Methods and Findings Cortical haemodynamic activity was measured in infants, aged 25–43 wk postmenstrual, using near-infrared spectroscopy following a clinically required heel lance and compared to the magnitude of the premature infant pain profile (PIPP) score in the same infant to the same stimulus (n = 12, 33 test occasions). Overall, there was good correlation between the PIPP score and the level of cortical activity (regression coefficient = 0.72, 95% confidence interval [CI] limits 0.32–1.11, p = 0.001; correlation coefficient = 0.57). Of the different PIPP components, facial expression correlated best with cortical activity (regression coefficient = 1.26, 95% CI limits 0.84–1.67, p < 0.0001; correlation coefficient = 0.74) (n = 12, 33 test occasions). Cortical pain responses were still recorded in some infants who did not display a change in facial expression. Conclusions While painful stimulation generally evokes parallel cortical and behavioural responses in infants, pain may be processed at the cortical level without producing detectable behavioural changes. As a result, an infant with a low pain score based on behavioural assessment tools alone may not be pain free.
New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals
Authors: Jingjing Qi, Yong Yu, Özlem Akilli Öztürk, Jane D Holland, Daniel Besser, Johannes Fritzmann, Annika Wulf-Goldenberg, Klaus Eckert, Iduna Fichtner, Walter Birchmeier
Journal: Gut (2015)

We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis.We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems.Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways.We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis.
Asymptomatic Gonorrhea, the Gonococcal Carrier State, and Gonococcemia in Men
Authors: A. Bernard Ackerman
Journal: JAMA (1966)

GONOCOCCEMIA occurring in the male without symptoms of gonococcal urethritis is an uncommonly reported phenomenon. Gonococcal septicemia in men has generally been associated with recent or concomitant acute gonorrhea,<sup>1,2</sup>whereas gonococcemia is women frequently develops in asymptomatic carriers of<i>Neisseria gonorrhoeae</i>. Recent observations indicate that males, like females, can acquire asymptomatic gonorrhea and carry gonococci covertly in their urogenital tracts despite apparently successful therapy.<sup>3,4</sup>Diagnosis of gonococcal septicemia is facilitated by recognition of the characteristic clinical features; fever, arthropathy, and specific skin lesions.<sup>5</sup>This report describes a male patient with bacteriologically proved gonococcemia in the absence of urogenital signs and symptoms. <h3>Report of a Case</h3> A 26-year-old Negro man was admitted to USAF Hospital Andrews on May 5, 1965, for recurrent fever, polyarthralgia, and a skin eruption of nine weeks' duration. His health has been excellent except for gonococcal urethritis treated with one injection of an unknown
Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI-a systematic review
Authors: K.J. Middelburg, M.J. Heineman, A.F. Bos, M. Hadders-Algra
Journal: Human Reproduction Update (2008)

The effect of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) on the developing human brain is unclear. The objective of this study is to evaluate neurodevelopmental (ND) outcome of children born following these techniques.This systematic review includes studies which compare a group of children born following IVF/ICSI to children born after natural conception by assessing outcome in terms of neuromotor development, cognition, speech/language and behaviour. Specific attention is paid to the studies' methodological quality based on study design, attrition, blinding of the assessor, validity of ND tests used, confounders included and group size or power analysis.Twenty-three out of 59 studies had a good methodological quality including 9 register-based (RB) and 14 controlled studies. RB studies suggested that IVF/ICSI per se does not increase the risk for severe cognitive impairment (i.e. mental retardation) or neuromotor handicaps such as cerebral palsy (CP), the association of IVF/ICSI and CP being brought about by the association of assisted conception with risk factors, like preterm birth. In general, controlled studies of good quality did not report an excess of ND disorders in IVF/ICSI-children. However, the majority of studies followed the children during infancy only, thereby precluding pertinent conclusions on the risk of ND disorders that come to the expression at older ages, such as fine manipulative disability or dyslexia.A negative effect of assisted conception on the developing human brain is not identified; however, further research of high methodological quality in children beyond pre-school age is needed.
Leukaemia and lymphoma among young people near Sellafield: Authors' reply
Authors: M. J Gardner, M. P Snee
Journal: BMJ (1990)

The cauterising iris scissors described here are a modification achieved by suitably insulating the standard De Wecker9s iris scissors. This modification provides in addition to cutting an advantageous cauterising effect, which could prove useful in the surgery of eye conditions with high risk of bleeding or metastasis. It utilises the optimum electric current range of 20-40 mA.
Lung Cancer Risk Among Female Textile Workers Exposed to Endotoxin
Authors: G. Astrakianakis, N. S. Seixas, R. Ray, J. E. Camp, D. L. Gao, Z. Feng, W. Li, K. J. Wernli, E. D. Fitzgibbons, D. B. Thomas, H. Checkoway
Journal: JNCI Journal of the National Cancer Institute (2007)

Reduced risk of lung cancer among workers in the cotton textile industry has been observed since the 1970s. Bacterial endotoxin, a contaminant of raw cotton fiber and cotton dust, has been proposed as a protective agent that may act through the innate and acquired immune systems. We examine the association between endotoxin exposure and lung cancer risk in a cohort of female textile workers. We conducted a case–cohort study nested within a cohort of 267 400 female textile workers in Shanghai, China. We compared the cumulative exposure histories of 628 case patients diagnosed with incident lung cancer from January 1, 1989, through December 31, 1998, with those of a lung cancer–free reference subcohort of 3184 workers who were frequency matched by 5-year age-groups to all cancer patients in the cohort. Cumulative endotoxin exposure for all participants was based on historic measurements and on additional measurements for this study. Relative risks and 95% confidence intervals (CIs) were estimated by hazard ratios (HRs) from Cox proportional hazards models. We conducted exposure–response trend analyses by use of cumulative exposures with lag times of 0, 5, 10, 15, or 20 years to account for disease latency. All analyses controlled for age and smoking status. All statistical tests were two-sided. Cumulative exposure to endotoxin was strongly, statistically significantly, and inversely associated with lung cancer risk. The inverse trend was greatest with a 20-year lag time, for which highest endotoxin exposure was associated with a statistically significantly 40% less risk of lung cancer (HR = 0.60, 95% CI = 0.43 to 0.83; Ptrend across quintiles = .002) than nonexposure. From a reported population rate of lung cancer among women in Shanghai of 19.1 per 100 000 for the year 2000 and the estimated reduction in risk of lung cancer observed for 20 years of endotoxin exposure in this population of workers, the incidence of lung cancer in this cohort was reduced by approximately 7.6 per 100 000 (range = 3.2–10.9 per 100 000). Long-term and high-level exposure to endotoxin, compared with no exposure, appears to be associated with a reduced risk of lung cancer in this cohort.
Probing the Validity of the Probe-to-Bone Test in the Diagnosis of Osteomyelitis of the Foot in Diabetes
Authors: Alison Shone, Jaclyn Burnside, Susan Chipchase, Fran Game, William Jeffcoate
Journal: Diabetes Care (2006)

The ability to probe the base of a wound to periosteum or bone (the “probe-to-bone” test) is increasingly used to indicate the likelihood of underlying osteomyelitis. The original study (1) reported sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of 66, 85, 89, and 56%, respectively. However, this work has been criticized on the grounds of the high pretest probability of the disease (2), since the prevalence of osteomyelitis in the chosen sample (in-patients with clinically overt infection) was 66%. It follows that the usefulness of the test may be very different in less-selected populations. We have therefore determined the validity of the probe-to-bone test in a consecutive series of outpatients attending our own multi
Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages.
Authors: R M Steinman, N Nogueira, M D Witmer, J D Tydings, I S Mellman
Journal: The Journal of Experimental Medicine (1980)

Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (M phi). Acquisition of Ia paralleled M phi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal M phi was lost during the 1st d of culture. In the continued presence of immune LK, Ia was re-expressed on virtually all M phi by the 2nd and 3rd d. Alternatively, &amp;gt; 95% Ia negative populations were obtained by culturing the cells 3 d; then, addition of LK induced Ia on most cells within 1 d. Once induced, Ia persisted on the M phi surface for at least 2 d. [35S]methionine radiolabeling indicated that immune LK selectively increased radiolabeling of M phi Ia, again with other non-MHC-linked plasma membrane polypeptides as controls. LK-induced Ia-bearing M phi were tested as primary mixed leukocyte reaction stimulators. 1 x 10(5)-2 x 10(5) M phi did not stimulate 4.5 x 10(6) responding T cells, whereas 10(4) dendritic cells induced strong responses, as previously described. Because Ia-positive M phi do not actively sensitize T cells in a model immune response, we propose that M phi MHC products serve primarily as recognition sites for previously sensitized T cells, thereby enhancing T cell-mediated M phi activation.