tbuckley/cabot-search huggingface dataset:
Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice
Authors: Hyunsoo Kim, Han Kyoung Choi, Ji Hye Shin, Kyung Hee Kim, Ji Young Huh, Seung Ah Lee, Chang-Yong Ko, Han-Sung Kim, Hong-In Shin, Hwa Jeong Lee, Daewon Jeong, Nacksung Kim, Yongwon Choi, Soo Young Lee
Journal: Journal of Clinical Investigation (2009)

Regulation of the formation and function of bone-resorbing osteoclasts (OCs) is a key to understanding the pathogenesis of skeletal disorders. Gene-targeting studies have shown that the RANK signaling pathway plays a critical role in OC differentiation and function. Although pharmaceutical blockade of RANK may be a viable strategy for preventing bone destruction, RANK is implicated in multiple biological processes. Recently, a cytoplasmic motif of RANK was identified that may be specifically involved in OC differentiation. Here, we developed a cell-permeable inhibitor termed the RANK receptor inhibitor (RRI), which targets this motif. The RRI peptide blocked RANKL-induced OC formation from murine bone marrow-derived macrophages. Furthermore, RRI inhibited the resorptive function of OCs and induced OC apoptosis. Treatment with the peptide impaired downstream signaling of RANK linked to Vav3, Rac1, and Cdc42 and resulted in disruptions of the actin cytoskeleton in differentiated OCs. In addition, RRI blocked inflammation-induced bone destruction and protected against ovariectomy-induced bone loss in mice. These data may be useful in the development of selective therapeutic agents for the treatment of osteoporosis and other bone diseases.
Late Gadolinium Enhancement Cardiovascular Magnetic Resonance of the Systemic Right Ventricle in Adults With Previous Atrial Redirection Surgery for Transposition of the Great Arteries
Authors: Sonya V. Babu-Narayan, Omer Goktekin, James C. Moon, Craig S. Broberg, George A. Pantely, Dudley J. Pennell, Michael A. Gatzoulis, Philip J. Kilner
Journal: Circulation (2005)

Background— Patients treated for transposition of the great arteries by atrial redirection surgery have a right ventricle (RV) that sustains systemic pressures long term. Late RV dysfunction occurs in these patients; the reasons for this are unclear, but myocardial fibrosis may be important. Myocardial fibrosis can be visualized by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). We hypothesized that LGE would be present in the systemic RV and relate to adverse clinical features. Methods and Results— We performed CMR on 36 consecutive adult patients (mean age, 27 years) after atrial redirection surgery for transposition of the great arteries. Late gadolinium RV enhancement was seen in 22 patients (61%) with various patterns. Patients with RV LGE were older (30 versus 22 years; P &lt;0.001) and had increased RV end-systolic volume index (43 versus 35 mL/m 2 ; P =0.03), decreased RV ejection fraction (57% versus 62%; P =0.02), increased QRS duration (108 versus 97 ms; P =0.01), and increased QT dispersion (93 versus 71 ms; P =0.002). The extent of LGE correlated with age ( r =0.59, P &lt;0.001) and QRS duration ( r =0.67, P &lt;0.001) and inversely with RV ejection fraction ( r =−0.76, P &lt;0.001). The incidence of documented arrhythmia and/or syncope (10 of 36) was significantly higher in the late gadolinium-positive group (9/22 versus 1/14; P =0.03). Conclusions— LGE CMR suggestive of myocardial fibrosis occurs in the systemic RV of patients after atrial redirection surgery. The extent of LGE correlates with age, ventricular dysfunction, electrophysiological parameters, and clinical events, suggesting prognostic importance that merits further investigation.
Cryptosporidiosis in an urban community.
Authors: D A Hunt, R Shannon, S R Palmer, A E Jephcott
Journal: BMJ (1984)

Over three months Cryptosporidium oocysts were identified in faecal samples from 43 (5%) of 867 patients presenting to their general practitioners with gastrointestinal symptoms. Cryptosporidium was the second most common enteric pathogen identified. Of the 867 patients, 329 were children aged under 5, of whom 24 (7%) excreted Cryptosporidium. A characteristic clinical presentation of infection with Cryptosporidium was recognised--namely, mild gastroenteritis with four to six watery, mucoid, and offensive motions a day, which lasted for one to two weeks. The source of infection was not identified, but direct contact with farm animals was not a feature and no association with a common water supply could be established.
Tamoxifen and the uterus
Authors: P Neven, X D Muylder, Y V Belle, R Campo, G Vanderick
Journal: BMJ (1994)

The effects of tamoxifen on the endometrium have caused concern since the late 1980s,1,2 and clear evidence of endometrial changes has now emerged from three studies in postmenopausal women - one case-control study of breast cancer3 and two randomised controlled trials, one in women with early breast cancer4 and one in healthy women with a family history of the disease.5 In most women treated with tamoxifen the endometrium remains atrophic, but epithelial metaplasia, simple hyperplasia, atypical hyperplasia, endometrial polyps, and endometrial cancers have all been reported in women taking a dose of 20 mg/day.6 There is evidence that local expression of insulinlike growth factor I and insulin-like growth factor binding protein-3 are important in tamoxifen's uterotrophic effect.7

In patients with breast cancer the risk of endometrial changes is justified by the protective effect of tamoxifen against the cancer and against osteoporosis and cardiovascular disease.8 The risk-benefit equations are, however different in healthy postmenopausal women taking tamoxifen for as yet unestablished benefits, and in such women pelvic assessment should not be confined to those who have abnormal …
Prevalence of alcohol histories in medical and nursing notes of patients admitted with self poisoning
Authors: R. M Shepherd, T. H S Dent, G. J M Alexander, M. London
Journal: BMJ (1995)

to be less accurate than data from these cohort studies, we found similar decreases after starting donor screen- ing policies for antibodies to hepatitis C virus in Italy (-66% and -93% after introduction of ELISA-I and ELISA-IH, respectively).These findings suggest that, although non-notified or asymptomatic blood associated cases of non-A, non-B hepatitis may still occur, in Italy the current risk is likely to be very low.
Drugs which modulate nitric oxide homeostasis are likely to provide therapeutic benefit in cardiovascular disease
Authors: C. Thiemermann
Journal: Cardiovascular Research (1993)

Journal Article Drugs which modulate nitric oxide homeostasis are likely to provide therapeutic benefit in cardiovascular disease Get access Christoph Thiemermann Christoph Thiemermann The William Harvey Research Institute, St Bartholomew's Hospital Medical College, Charterhouse Square, London EC 1M 6BQ: Dr C Thiemermann. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 12, December 1993, Page 2104, https://doi.org/10.1093/cvr/27.12.2104 Published: 01 December 1993
Omalizumab Improves Quality of Life (QoL) in Patients with Refractory Chronic Spontaneous/Idiopathic Urticaria (CSU/CIU) As Assessed By the Dermatology Life Quality Index (DLQI): A Post-Hoc Analysis of Percent Change from Baseline to Week 12
Authors: Karin Rosén, Sam Khalil, Maria-Magdalena Balp, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2015)
Translationally Optimal Codons Associate with Structurally Sensitive Sites in Proteins
Authors: T. Zhou, M. Weems, C. O. Wilke
Journal: Molecular Biology and Evolution (2009)

The mistranslation-induced protein misfolding hypothesis predicts that selection should prefer high-fidelity codons at sites at which translation errors are structurally disruptive and lead to protein misfolding and aggregation. To test this hypothesis, we analyzed the relationship between codon usage bias and protein structure in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse. Using both the Mantel–Haenszel procedure, which applies to categorical data, and a newly developed association test for continuous variables, we find that translationally optimal codons associate with buried residues and also with residues at sites where mutations lead to large changes in free energy (ΔΔG). In each species, only a subset of all amino acids show this signal, but most amino acids show the signal in at least one species. By repeating the analysis on a reduced data set that excludes interdomain linkers, we show that our results are not caused by an association of rare codons with solvent-accessible linker regions. Finally, we find that our results depend weakly on expression level; the association between optimal codons and buried sites exists at all expression levels, but increases in strength as expression level increases.
Prolonged treatment of high-renin hypertension with a converting enzyme inhibitor.
Authors: M J Vandenburg, V L Sharman, F P Marsh, E J Rucinska
Journal: BMJ (1978)

in two of our cases raises the question whether the sensitivity to mustine is really allergic.The latency and nature of the skin reaction and the results of patch testing, however, indicate that allergy is concerned, and the occurrence of contact urticaria and bronchial asthma in one case further supports the idea of an allergic mechanism.We think that it is important to investigate the effect of PUVA on other forms of allergic contact dermatitis as well as urticaria.
Cerebral vessel laminins and IFN-γ define Trypanosoma brucei brucei penetration of the blood-brain barrier
Authors: Willias Masocha, Brita Robertson, Martin E. Rottenberg, Jama Mhlanga, Lydia Sorokin, Krister Kristensson
Journal: Journal of Clinical Investigation (2004)

Subspecies of Trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. We investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence T. brucei neuroinvasion. Migration of a rodent pathogenic T. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in IFN-γ–/–, IFN-γ receptor–/– (IFN-γR–/–), IL-12p40–/–, and recombinant activating gene–1–/– (RAG-1–/–) mice as compared with their WT littermates despite higher levels of parasitemia in the mutant strains. Parasites accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the brains of IFN-γ–/–, IFN-γR–/–, and RAG-1–/– mice. This accumulation occurred around endothelial basement membranes containing the laminin α4 chain, while blood vessels showing robust laminin α5 chain immunostaining were not associated with parasite infiltration. The number of CD4+ and CD8+ T cells infiltrating the brain parenchyma was also reduced in the IFN-γ–/– and IFN-γR–/– mice. Our findings suggest that lymphocyte-derived IFN-γ facilitates trypanosome penetration across cerebral blood vessels and that the site of penetration is determined by the composition of the basement membranes of these vessels.
Evaluation of endosonography in TN staging of oesophageal cancer.
Authors: K Ziegler, C Sanft, M Zeitz, M Friedrich, H Stein, R Haring, E O Riecken
Journal: Gut (1991)

Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis. Resection, the only curative treatment, is confined to early tumour stages. Tumours with local infiltration are usually unresectable and require palliative treatment. Computed tomography has been widely used for preoperative staging but often fails to define this correctly. Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours. In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement. Thirty seven of these patients underwent operation, resection, or dissection and entered the study. The intraoperative findings or the histopathological assessment, or both, were taken as a reference. For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test). This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.
Pertussis toxin inhibits activation-induced cell death of human thymocytes, pre-B leukemia cells and monocytes.
Authors: R Ramírez, J Carracedo, N Zamzami, M Castedo, G Kroemer
Journal: The Journal of Experimental Medicine (1994)

Activation of human thymocytes and pre-B cells via the CD3/T cell receptor (TCR) complex or the IgM/B cell receptor complex, respectively, results in apoptotic cell death. Similarly, cross-linking of the activation marker CD69, which belongs to the natural killer complex, causes apoptosis of lipopolysaccharide-preactivated monocytes. Here we show that pertussis toxin (PTX) inhibits the activation-induced apoptosis of these three cell types, though it fails to prevent the programmed cell death that follows exposure of cells to the synthetic glucocorticoid dexamethasone (thymocytes, pre-B cells) or to interleukin 4 (monocytes). The capacity of pertussis toxin to suppress activation-induced death is not due to quenching of the activation signal, because thymocytes exposed to PTX are still capable of mobilizing Ca2+ after TCR-alpha/beta cross-linking and proliferate in response to costimulation with PTX and CD3/TCR ligation. The apoptosis-inhibitory effect of PTX depends on the presence of an intact adenosine diphosphate (ADP)-ribosylating moiety, since a mutant pertussis toxin molecule that lacks enzymatic activity, but still possesses the membrane translocating activity, fails to interfere with activation-induced cell death. A toxin that induces a different spectrum of ADP ribosylation than PTX, cholera toxin, fails to inhibit apoptosis. To suppress apoptosis, the intact PTX holotoxin must be added to cells before the lethal activation step; its addition 30 min after initial activation remains without effect on apoptosis. These data unravel a PTX sensitive signal transduction event that intervenes during an early step of activation-induced cell death of immune cells.
Deaths in children with a diagnosis of acute appendicitis in England and Wales 1980-4.
Authors: H G Pledger, L T Fahy, G A van Mourik, G H Bush
Journal: BMJ (1987)

Thirty five children died of acute appendicitis in England and Wales in 1980-4 compared with 204 in 1963-7. Thirteen of the 35 deaths in 1980-4 took place at home or on the day of admission to hospital before operation and a further 18 on the day of operation or the first day after it. Thirty one of the children had peritonitis. A third of the deaths were in children aged 0-4 years, and the hospital fatality rate in this age group was one death in 320 cases compared with one death in 4760 cases in children aged 5-14 years. The fall in the number of deaths between the 1960s and the 1980s was due to improvements in medical care, a reduction in the incidence of appendicitis, and changes in the age structure of the child population. Difficulty and delay in diagnosis and inadequate intravenous therapy are now the main factors contributing to death.
Antenatal, perinatal, or postnatal brain damage
Authors: W. Savage
Journal: BMJ (1987)

jogging or brisk walking three times a week), yet only 15% of the population of the United Kingdom do this.The real benefits of exercise have not yet been emphasised, either by this campaign or by previous attempts, and the few hazards of exercise have been overemphasised.Mass screening and drug treatment are costly, exercise is cheap, and all that is required is a positive attitude by health authority managers and general practitioners.For these reasons and the financial state of the NHS exercise deserves a higher priority.
Isolation of Bordetella pertussis from swabs.
Authors: P W Ross, C G Cumming
Journal: BMJ (1981)

Four varieties of swabs held in plastic containers and three swab transport media kits, all obtainable in the United Kingdom, were tested to assess their effectiveness in the isolation of Bordetella pertussis. The highest isolation rates up to 48 hours were obtained with Dacron swabs held in plastic containers. Swab-transport media kits proved unsatisfactory. B pertussis may have a stronger affinity to Dacron than to cotton-wool, and pernasal swabs should be made of Dacron to improve the recovery of B pertussis.
Long term effects of exposure to viral infections in utero.
Authors: P E Fine, A M Adelstein, J Snowman, J A Clarkson, S M Evans
Journal: BMJ (1985)

An analysis was conducted of the major findings of a long term follow up study of 3076 subjects who were exposed to viral infections in utero and who at the time of analysis were up to 40 years of age. Mortality and morbidity were compared with those in a control population matched for sex and date and area of birth. An excess of cancers (16 cases against seven) appeared to be clustered among those exposed to herpes viruses (varicella or cytomegalovirus). There was evidence of an increased risk of diabetes among those exposed to mumps during the first trimester (four cases among 128 subjects against none in 148 controls). The most surprising finding was a decrease of diseases of the skin and subcutaneous tissue and of the nervous system among subjects exposed to antenatal varicella zoster infection. The mechanism for the association may include production of fetal anti-idiotype antibodies in response to transplacentally acquired maternal autoantibodies.
S119 Variation in pharyngeal pH in the diagnosis of airway reflux
Authors: I. D. Molyneux, W. Jackson, A. H. Morice
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Reflux of gastric contents to the laryngopharynx has been implicated in the pathogenesis of chronic cough and may exacerbate other respiratory conditions. Direct measurement of pharyngeal pH is available but standard analysis relies on the pH crossing a lower threshold. Non-acid gaseous reflux may cause respiratory symptoms without producing a significant drop in pharyngeal pH. We theorised that variation in pharyngeal pH might be a useful marker of airway reflux. <h3>Methods</h3> Measurements of pH in the pharynx over 24 h were made in patients with a variety of respiratory diagnoses suspected to have reflux contributing to their symptoms. Diagnoses included chronic cough, cystic fibrosis and asthma. Results were analysed using a pre-defined, threshold-based scoring system and our novel system based on variation in pH. Comparison was also made with oesophageal physiology where available. <h3>Results</h3> 60 studies were performed on 58 patients; median age 48 years (range 17–81). 43 studies had an abnormal threshold score. 31 patients had an abnormal variation score (&gt;30 events per hour). Both were positive in 21 patients and both negative in 7. Cough symptom scores were similarly high in patients with abnormal variation to those with abnormal threshold scores (mean 34.7 and 38.3 respectively) and higher than patients with both negative (23.0; n/s). Cough patients who had undergone fundoplication demonstrated less variation than those who had not (mean events 55 per hour vs 115; n/s). Asthma patients had similar overall variation to other groups but had higher numbers of events over fewer peak hours (468 vs 368 events per peak hour; p=0.08) with the opposite seen in cystic fibrosis patients (276; p=0.26). Of 25 patients with an abnormal pharyngeal study and an oesophageal study available, 15 had normal oesophageal studies. <h3>Conclusions</h3> These results show that the interaction between pharyngeal pH and airway symptoms is complex, not easily assessed using a pH threshold alone and not well correlated with oesophageal physiology. Assessment of variation suggests different patterns of reflux may relate to disease phenotypes. The ideal analysis should include correlation of clinical symptoms with peaks in variation and pH threshold events.
Ceruletide increases dose dependently both jejunal motor activity and threshold and tolerance to experimentally induced pain in healthy man.
Authors: G Stacher, H Steinringer, G Schmierer, C Schneider, S Winklehner, G Mittelbach, C De Paolis, C Praga
Journal: Gut (1984)

The effects of ceruletide on jejunal motility and experimentally induced pain were studied in 16 healthy men, who participated each in four experiments and received in random double blind fashion 5, 10, or 20 micrograms ceruletide intramuscularly or placebo. Jejunal pressures were recorded by three perfused catheters with orifices between 10 and 20 cm aboral of the ligament of Treitz. Ceruletide dose dependently diminished phase I and increased phase II type activity and tended to reduce the number, but not the duration, of activity fronts. The number and amplitude of contractions as well as the area under the curve increased significantly and dose dependently as did threshold and tolerance to electrically and threshold to thermally induced pain. Only mild sedative and other side effects occurred.
Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis
Authors: Benjamin C. Ling, Jianqiang Wu, Shyra J. Miller, Kelly R. Monk, Rania Shamekh, Tilat A. Rizvi, Gabrielle DeCourten-Myers, Kristine S. Vogel, Jeffrey E. DeClue, Nancy Ratner
Journal: Cancer Cell (2005)
Binding of Estrogenic Compounds to Recombinant Estrogen Receptor-α: Application to Environmental Analysis
Authors: Arnaud Pillon, Anne-Marie Boussioux, Aurélie Escande, Sélim Aït-Aïssa, Elena Gomez, Hélène Fenet, Marc Ruff, Dino Moras, Françoise Vignon, Marie-Josèphe Duchesne, Claude Casellas, Jean-Claude Nicolas, Patrick Balaguer
Journal: Environmental Health Perspectives (2004)

Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity compounds for estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low-affinity compounds such as alkylphenols, phthalates, and polychlorinated biphenyls are present in water and sediment samples. Furthermore, compounds such as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen activity by means of the aryl hydrocarbon receptor (AhR). In order to characterize compounds that mediate estrogenic activity in river water and sediment samples, we developed a tool based on the ER-alphaligand-binding domain, which permitted us to estimate contaminating estrogenic compound affinities. We designed a simple transactivation assay in which compounds of high affinity were captured by limited amounts of recombinant ER-alpha and whose capture led to a selective inhibition of transactivation. This approach allowed us to bring to light that water samples contain estrogenic compounds that display a high affinity for ERs but are present at low concentrations. In sediment samples, on the contrary, we showed that estrogenic compounds possess a low affinity and are present at high concentration. Finally, we used immobilized recombinant ER-alpha to separate ligands for ER and AhR that are present in river sediments. Immobilized ER-alpha, which does not retain dioxin-like compounds, enabled us to isolate and concentrate ER ligands to facilitate their further analysis.