tbuckley/cabot-search huggingface dataset:
Evolution of the Sulfide-Binding Function Within the Globin Multigenic Family of the Deep-Sea Hydrothermal Vent Tubeworm Riftia pachyptila
Authors: Xavier Bailly, Didier Jollivet, Stephano Vanin, Jean Deutsch, Franck Zal, François Lallier, André Toulmond
Journal: Molecular Biology and Evolution (2002)

The giant extracellular hexagonal bilayer hemoglobin (HBL-Hb) of the deep-sea hydrothermal vent tube worm Riftia pachyptila is able to transport simultaneously O2 and H2S in the blood from the gills to a specific organ: the trophosome that harbors sulfide-oxidizing endosymbionts. This vascular HBL-Hb is made of 144 globins from which four globin types (A1, A2, B1, and B2) coevolve. The H2S is bound at a specific location (not on the heme site) onto two of these globin types. In order to understand how such a function emerged and evolved in vestimentiferans and other related annelids, six partial cDNAs corresponding to the six globins known to compose the multigenic family of R. pachyptila have been identified and sequenced. These partial sequences (ca. 120 amino acids, i.e., 80% of the entire protein) were used to reconstruct molecular phylogenies in order to trace duplication events that have led to the family organization of these globins and to locate the position of the free cysteine residues known to bind H2S. From these sequences, only two free cysteine residues have been found to occur, at positions Cys + 1 (i.e., 1 a.a. from the well-conserved distal histidine) and Cys + 11 (i.e., 11 a.a. from the same histidine) in globins B2 and A2, respectively. These two positions are well conserved in annelids, vestimentiferans, and pogonophorans, which live in sulfidic environments. The structural comparison of the hydrophobic environment that surrounds these cysteine residues (the sulfide-binding domain) using hydrophobic cluster analysis plots, together with the cysteine positions in paralogous strains, suggests that the sulfide-binding function might have emerged before the annelid radiation in order to detoxify this toxic compound. Moreover, globin evolutionary rates are highly different between paralogous strains. This suggests that either the two globin subfamilies involved in the sulfide-binding function (A2 and B2) have evolved under strong directional selective constraints (negative selection) and that the two other globins (A1 and B1) have accumulated more substitutions through positive selection or have evolved neutrally after a relaxation of selection pressures. A likely scenario on the evolution of this multigenic family is proposed and discussed from this data set.
Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor
Authors: Li Yang, Noboru Yamagata, Rajwardhan Yadav, Suzanne Brandon, Regina L. Courtney, Jason D. Morrow, Yu Shyr, Mark Boothby, Sebastian Joyce, David P. Carbone, Richard M. Breyer
Journal: Journal of Clinical Investigation (2003)

Prostaglandin E2 (PGE2), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE2 EP2 receptor to cancer-associated immune deficiency using EP2–/– mice. EP2–/– mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates. While no differences in T cell function were observed, PGE2 suppressed differentiation of DCs from wild-type bone marrow progenitors, whereas EP2-null cells were refractory to this effect. Stimulation of cells in mixed lymphocyte reactions by wild-type DCs was suppressed by treatment with PGE2, while EP2–/–-derived DCs were resistant to this effect. In vivo, DCs, CD4+, and CD8+ T cells were significantly more abundant in draining lymph nodes of tumor-bearing EP2–/– mice than in tumor-bearing wild-type mice, and a significant antitumor cytotoxic T lymphocyte response could be observed only in the EP2–/– animals. Our data demonstrate an important role for the EP2 receptor in PGE2-induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo.
Prevention of thermal and condensation errors in pneumotachographic recordings of the maximal forced expiratory manoeuvre
Authors: MR Miller, T Sigsgaard
Journal: European Respiratory Journal (1994)

When recording respiratory manoeuvres using a pneumotachograph (PT), it is customary to heat the pneumotachograph head to avoid condensation errors. It is technically demanding to heat the PT correctly, and this increases the complexity of the equipment. We have studied whether a simpler method can eradicate condensation errors and preserve thermal stability of the PT. We tested the accuracy of a PT by recording the discharge of 1,000 ml of air through the PT before and after a subject had blown through it, thus causing both condensation within the PT and a rise in its temperature. We then determined whether the thermal and condensation errors could be avoided by placing the PT, between blows, on a fan that was blowing air at a constant 1.65 l.s-1. With ambient temperature at 20 degrees C, a single blow through the PT was found to cause a subsequent 4% over-reading in volume, due to condensation and temperature changes in the PT. After five consecutive blows the error was 7%. Placing the PT on the fan for 15 s after a single blow abolished these errors, whereas a wait of 15 s did not. At an ambient temperature of 14 degrees C there was a 5% over-reading of volume after a single blow, and an over-reading of 9% after five blows. At an ambient temperature of 26 degrees C these errors were 3 and 5%, respectively. All of these errors were abolished by placing the PT on the fan for 15 s and 30 s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Transiently Beneficial Insertions Could Maintain Mobile DNA Sequences in Variable Environments
Authors: Richard J. Edwards, John F. Y. Brookfield
Journal: Molecular Biology and Evolution (2003)

The maintenance of mobile DNA sequences in clonal organisms has been seen as a paradox.If selfish mobile sequences spread through genomes only by overreplication in transposition, then sexuality is necessary for their spread through populations.The persistence of bacterial transposable elements without obvious dominant selectable markers has previously been explained by horizontal transfer.However, advantageous insertions of mobile DNAs are known in bacteria.Here we model maintenance of an otherwise selfish mobile DNA element in a clonal species in which selection for null mutations occurs during one of two temporally alternating environments.Large areas of parameter space permit maintenance of mobile DNAs where, without selection, they would have gone extinct.Horizontal transfer diminishes, rather than enhances, mean copy number.In finite populations, effective population sizes are greatly reduced by selective sweeps, and mean copy number can be increased as the reduced variance in copy number results in reduced selection.
Diffuse Dystrophic Calcinosis Cutis of the Scalp in a Patient With Scalp Discoid Lupus Erythematosus and Systemic Lupus Erythematosus
Authors: A. Brooke Eastham, Nicole F. Velez, Allyson L. Chesebro, Henry B. Townsend, Ruth Ann Vleugels
Journal: JAMA Dermatology (2013)
The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea
Authors: A. S. L. Chan, K. Sutherland, R. J. Schwab, B. Zeng, P. Petocz, R. W. W. Lee, M. A. Darendeliler, P. A. Cistulli
Journal: Thorax (2010)

<h3>Background</h3> The mechanisms by which mandibular advancement splints (MAS) improve obstructive sleep apnoea (OSA) are not well understood. This study aimed to evaluate the mechanism of action of MAS by assessing their effect on upper airway structure in patients with OSA. <h3>Methods</h3> Patients were recruited from a sleep disorders clinic for treatment with a custom-made MAS. MRI of the upper airway was performed during wakefulness in the supine position, with and without the MAS. <h3>Results</h3> Sixty-nine patients with OSA were recruited. Treatment with the MAS reduced the apnoea–hypopnoea index (AHI) from 27.0±14.7 events/h to 12.2±12.5 events/h (p&lt;0.001). There was an increase in the total airway volume with mandibular advancement (16.5±0.7 cm<sup>3</sup> vs 18.1±0.8 cm<sup>3</sup>; p&lt;0.01) that occurred predominantly because of an increase in the volume of the velopharynx (5.7±0.3 cm<sup>3</sup> vs 6.5±0.3 cm<sup>3</sup>; p&lt;0.001). This increase in airway calibre was associated with an increase in the lower anterior facial height (6.8±0.1 cm vs 7.5±0.1 cm; p&lt;0.001), reduction in the distance between the hyoid and posterior nasal spine (7.4±0.1 cm vs 7.2±0.1 cm; p&lt;0.001), lateral displacement of the parapharyngeal fat pads away from the airway (right parapharyngeal fat pad 0.17±0.02 cm; left parapharyngeal fat pad 0.22±0.02 cm) and anterior movement of the tongue base muscles (0.33±0.03 cm). Subanalyses in responders and non-responders to MAS treatment showed that the increase in upper airway calibre with mandibular advancement occurred only in responders. <h3>Conclusion</h3> These results suggest that the mechanism of action of MAS is to increase the volume of the upper airway, predominantly by increasing the volume of the velopharynx, and this increased volume is associated with changes in the surrounding bony and soft tissue structures.
Evidence for a Dispersed Hox Gene Cluster in the Platyhelminth Parasite Schistosoma mansoni
Authors: Raymond J. Pierce, Wenjie Wu, Hirohisa Hirai, Al Ivens, Lee D. Murphy, Christophe Noël, David A. Johnston, François Artiguenave, Martin Adams, Jocelyne Cornette, Eric Viscogliosi, Monique Capron, Guillaume Balavoine
Journal: Molecular Biology and Evolution (2005)

In most bilaterian organisms so far studied, Hox genes are organized in genomic clusters and determine development along the anteroposterior axis. It has been suggested that this clustering, together with spatial and temporal colinearity of gene expression, represents the ancestral condition. However, in organisms with derived modes of embryogenesis and lineage-dependent mechanisms for the determination of cell fate, temporal colinearity of expression can be lost and Hox cluster organization disrupted, as is the case for the ecdysozoans Drosophila melanogaster and Caenorhabditis elegans and the urochordates Ciona intestinalis and Oikopleura dioica. We sought to determine whether a lophotrochozoan, the platyhelminth parasite Schistosoma mansoni, possesses a conserved or disrupted Hox cluster. Using a polymerase chain reaction (PCR)-based strategy, we have cloned and characterized three novel S. mansoni genes encoding orthologues of Drosophila labial (SmHox1), deformed (SmHox4), and abdominal A (SmHox8), as well as the full-length coding sequence of the previously described Smox1, which we identify as an orthologue of fushi tarazu. Quantitative reverse transcriptase-PCR showed that the four genes were expressed at all life-cycle stages but that levels of expression were differentially regulated. Phylogenetic analysis and the conservation of "parapeptide" sequences C-terminal to the homeodomains of SmHox8 and Smox1 support the grouping of platyhelminths within the lophotrochozoan clade. However, Bacterial Artificial Chromosome (BAC) library screening followed by genome walking failed to reconstitute a cluster. The BAC clones containing Hox genes were sequenced, and in no case were other Hox genes found on the same clone. Moreover, the SmHox4 and SmHox8 genes contained single very large introns (>40 kbp) further indicating that the schistosome Hox cluster is highly extended. Localization of the Hox genes to chromosomes using fluorescence in situ hybridization showed that SmHox4 and SmHox8 are on the long arm of chromosome 4, whereas SmHox1 and Smox1 are on chromosome 3. In silico screening of the available genome sequences corroborated results of Southern blotting and BAC library screening that indicate that there are no paralogues of SmHox1, SmHox4, or SmHox8. The schistosome Hox cluster is therefore not duplicated, but is both dispersed and disintegrated in the genome.
Fluoroscopically guided laser lithotripsy versus extracorporeal shock wave lithotripsy for retained bile duct stones: a prospective randomised study.
Authors: R Jakobs, H E Adamek, M Maier, M Kromer, C Benz, W R Martin, J F Riemann
Journal: Gut (1997)

BACKGROUND AND AIMS: To compare extracorporeal shock wave lithotripsy (ESWL) and laser induced shock wave lithotripsy (LISL) of retained bile duct stones to stone free rate, number of therapeutic sessions, and costs. PATIENTS: Thirty four patients were randomly assigned to either ESWL or LISL therapy. The main reasons for failure of standard endoscopy were due to stone impaction (n = 12), biliary stricture (n = 8), or large stone diameter (n = 14). METHODS: An extracorporeal piezoelectic lithotripter with ultrasonic guidance and a rhodamine 6G laser with an integrated stone tissue detection system were used. LISL was performed exclusively under radiological control. RESULTS: Using the initial methods complete stone fragmentation was achieved in nine of 17 patients (52.4%) of the ESWL group and in 14 of 17 patients (82.4%) in the LISL group, or combined with additional fragmentation techniques 31 of the 34 patients (91.2%) were stone free at the end of treatment. In comparison LISL tended to be more efficient in clearing the bile ducts (p = 0.07, NS). Significantly less fragmentation sessions (1.29 v 2.82; p = 0.0001) and less additional endoscopic sessions (0.65 v 1.6; p = 0.002) were necessary in the LISL group. There were no major complications in either procedure. CONCLUSIONS: Compared with ESWL, fluoroscopically guided LISL achieves stone disintegration more rapidly and with significantly less treatment sessions, which leads to a significant reduction in cost.
Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer
Authors: Soundararajan Krishnaswamy, Rajani Kanteti, Jonathan S. Duke-Cohan, Sivakumar Loganathan, Wanqing Liu, Patrick C. Ma, Martin Sattler, Patrick A. Singleton, Nithya Ramnath, Federico Innocenti, Dan L. Nicolae, Zheng Ouyang, Jie Liang, John Minna, Mark F. Kozloff, Mark K. Ferguson, Viswanathan Natarajan, Yi-Ching Wang, Joe G.N. Garcia, Everett E. Vokes, Ravi Salgia
Journal: Clinical Cancer Research (2009)

Abstract Purpose: African Americans have higher incidence and poorer response to lung cancer treatment compared with Caucasians. However, the underlying molecular mechanisms for the significant ethnic difference are not known. The present study examines the ethnic differences in the type and frequency of MET proto-oncogene (MET) mutation in lung cancer and correlated them with other frequently mutated genes such as epidermal growth factor receptor (EGFR), KRAS2, and TP53. Experimental Design: Using tumor tissue genomic DNA from 141 Asian, 76 Caucasian, and 66 African American lung cancer patients, exons coding for MET and EGFR were PCR amplified, and mutations were detected by sequencing. Mutation carriers were further screened for KRAS2 and TP53 mutations. Functional implications of important MET mutations were explored by molecular modeling and hepatocyte growth factor binding studies. Results: Unlike the frequently encountered somatic mutations in EGFR, MET mutations in lung tumors were germline. MET-N375S, the most frequent mutation of MET, occurred in 13% of East Asians compared with none in African Americans. The frequency of MET mutations was highest among male smokers and squamous cell carcinoma. The MET-N375S mutation seems to confer resistance to MET inhibition based on hepatocyte growth factor ligand binding, molecular modeling, and apoptotic susceptibility to MET inhibitor studies. Conclusions: MET in lung cancer tissues contained nonsynonymous mutations in the semaphorin and juxtamembrane domains but not in the tyrosine kinase domain. All the MET mutations were germline. East Asians, African-Americans, and Caucasians had different MET genotypes and haplotypes. MET mutations in the semaphorin domain affected ligand binding. (Clin Cancer Res 2009;15(18):5714–23)
PROCEEDINGS OF THE FORTY-FOURTH ANNUAL MEETING OF THE AMERICAN SOCIETY FOR CLINICAL INVESTIGATION HELD IN ATLANTIC CITY, N. J., MAY 5, 1952
Authors: W. Barry Wood
Journal: Journal of Clinical Investigation (1952)

By custom the presiding officer of this society is ex- pected to open the scientific session with a presidential address.This obligation, which I accept with grave mis- givings, I shall try to fulfill in as short a time as possible, so that we may proceed promptly to the main program.The thesis which I should like to present briefly, is that today we find ourselves in, or rapidly approaching, the "logarithmic phase" of medical progress.The choice of my crude analogy is, of course, condi- tioned by my own past training and interests.Reference to the bacterial growth curve may be justified, however, on the grounds that it is familiar to nearly everyone in medicine (Figure 1).You will recall that the logarithm c 0.
Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.
Authors: K T Tung, A U Wells, M B Rubens, J M Kirk, R M du Bois, D M Hansell
Journal: Thorax (1993)

Open lung biopsy is often performed to confirm the diagnosis in patients with suspected fibrosing alveolitis. The superior sensitivity and specificity of high resolution computed tomography (CT) over chest radiography in various diffuse lung diseases suggest that the characteristic appearance of fibrosing alveolitis on high resolution CT might render biopsy confirmation unnecessary.The chest radiographs and high resolution CT scans of 86 patients (41 with fibrosing alveolitis and 45 with various other diffuse lung diseases) were examined individually and independently by two observers. No clinical information was given and the observers gave a level of confidence when the diagnosis was thought to be fibrosing alveolitis.The observers correctly and confidently discriminated between fibrosing alveolitis and other diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest radiography with an accuracy of 76%. The false negative rate for fibrosing alveolitis diminished from 29% on chest radiography to 11% on high resolution CT. The false positive rate on chest radiography was 19% and on high resolution CT 13%; the false positive diagnoses on CT were the result of a few conditions (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia, and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing alveolitis. The superficial similarity of the CT patterns of these conditions are discussed.High resolution CT is superior to chest radiography in establishing the diagnosis of fibrosing alveolitis and the typical CT appearances are virtually pathognomonic. The diagnostic advantages of CT over chest radiography should further reduce the need for open lung biopsy in this condition.
Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma at the Time of Second or Subsequent Remission: Long-Term Follow-Up
Authors: Ama Z.S. Rohatiner, Lee Nadler, Andrew J. Davies, John Apostolidis, Donna Neuberg, Janet Matthews, John G. Gribben, Peter M. Mauch, T. Andrew Lister, Arnold S. Freedman
Journal: Journal of Clinical Oncology (2007)

Purpose The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. Patients and Methods One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. Results Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY+TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. Conclusion These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up.
Inhaled isotonic alkaline versus saline solution and radioaerosol clearance in chronic cough
Authors: P. Haidl, B. Schonhofer, K Siemon, D Kohler
Journal: European Respiratory Journal (2000)

The aim of the present study was to test the influence of inhaled isotonic Ems salt (brine from the spa of Bad Ems, Germany) compared to isotonic saline on radioaerosol clearance (RC) in patients with chronic cough. Ems salt is an alkaline solution (pH 8.0-9.0) containing largely bicarbonate ions rather than the chloride ions present in isotonic saline (pH 6.4). RC was assessed with a radioaerosol technique using technetium-99m albumin in supine patients. After a 30-min baseline measurement of RC according to a single blind and randomized design, patients inhaled Ems salt (n=22, 20-77 yrs) or isotonic saline (n=21, 34-72 yrs) via a jet nebulizer (Pari Boy) for 10 min and were scanned for an additional 30 min. There was no difference between the two groups before intervention in terms of deposition pattern, lung function and baseline RC rate. After inhalation of Ems salt, the RC rate (1/tau) improved significantly from 0.15+/-0.14 (mean+/-SD) to 0.53+/-0.70 L.h(-1) (p&lt;0.005); no change was found after isotonic saline (0.13+/-0.13 to 0.08+/-0.09 L.h(-1), NS). Voluntary coughs performed after 60 min had no effect on the RC rate. However, in the Ems salt group, significantly more patients reported an inhalation induced cough. Compared to the Ems salt patients, who did not cough during and after inhalation, the RC rate in the cough group was enhanced significantly (0.10+/-0.12 versus 0.73+/-0.83, p=0.017), this effect being seen more frequently in females (p=0.003). It is concluded that Ems salt improves radioaerosol clearance significantly in patients with chronic cough. The underlying mechanism, regarding whether induced cough, increased water content in the mucus or enhanced ciliary beat frequency is the leading cause of Ems salt action, remains unclear.
Staff shortages threaten public health in London
Authors: A. Vass
Journal: BMJ (2002)

Staff shortages threaten to limit the effectiveness of London's new primary care trusts, a King's Fund study has warned.

The report says that although there is “a wealth of public health experience in London,” shortages of some staff could hamper the efforts of the 30 London trusts to deliver public health. For example, the rate of health …