tbuckley/cabot-search huggingface dataset:
Rhesus Macaque Class I Duplicon Structures, Organization, and Evolution Within the Alpha Block of the Major Histocompatibility Complex
Authors: J. K Kulski
Journal: Molecular Biology and Evolution (2004)

The alpha block of the human and chimpanzee major histocompatibility complex (MHC) class I genomic region contains 10 to 11 duplicated MHC class I genes, including the HLA/Patr-A, -G, and -F genes. In comparison, the alpha block of the rhesus macaque (Macaca mulatta, Mamu) has an additional 20 MHC class I genes within this orthologous region. The present study describes the identification and analysis of the duplicated segmental genomic structures (duplicons) and genomic markers within the alpha block of the rhesus macaque and their use to reconstruct the duplication history of the genes within this region. A variety of MHC class I genes, pseudogenes, transposons, and retrotransposons, such as Alu and ERV16, were used to categorize the 28 duplicons into four distinct structural categories. The phylogenetic relationship of MHC class I genes, Alu, and LTR16B sequences within the duplicons was examined by use of the Neighbor-Joining (NJ) method. Two single-duplicon tandem duplications, two polyduplicon tandem duplications with an accompanying inversion product per duplication, eight polyduplicon tandem duplications steps, 12 deletions, and at least two recombinations were reconstructed to explain the highly complex organization and evolution of the 28 duplicons (nine inversions) within the Mamu alpha block. On the basis of the phylogenetic evidence and the reconstructed tandem duplication history of the 28 duplicons, the Mamu/Patr/HLA-F ortholog was the first MHC class I gene to have been fixed without further duplication within the alpha block of primates. Assuming that the rhesus macaque and the chimpanzee/human lineages had started with the same number of MHC class I duplicons at the time of their divergence approximately 24 to 31 MYA, then the number of genes within the alpha block have been duplicated at an approximately three times greater rate in the rhesus macaque than in either the human or chimpanzee.
Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations
Authors: A Lanas, L A Garcia-Rodriguez, M T Arroyo, F Gomollon, F Feu, A Gonzalez-Perez, E Zapata, G Bastida, L Rodrigo, S Santolaria, M Guell, C M de Argila, E Quintero, F Borda, J M Pique
Journal: Gut (2006)

<b>Background:</b> The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. <b>Objective:</b> To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. <b>Methods:</b> A hospital-based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. <b>Results:</b> Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. <b>Conclusions:</b> Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.
Sensitive cancer test developed
Authors: D. Josefson
Journal: BMJ (1998)

A sensitive blood test capable of detecting certain cancers before they are clinically apparent has been developed by scientists from the University of Texas Southwestern Medical Center.

The test, which can detect a single cancer cell in a millilitre of blood, may one day revolutionise the screening of and treatment for cancer and enable doctors to catch malignant tumours earlier than is currently possible (Proceedings of the National Academy of Sciences 1998:95:4589-94).

The researchers searched for epithelial cells in blood samples taken from 30 patients with breast cancer, 3 with prostate cancer, and …
Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo
Authors: Magdalena S Mroz, Niamh Keating, Joseph B Ward, Rafiquel Sarker, Silvie Amu, Gabriella Aviello, Mark Donowitz, Padraic G Fallon, Stephen J Keely
Journal: Gut (2013)

<h3>Objective</h3> Bile acids are important regulators of intestinal physiology, and the nuclear bile acid receptor, farnesoid X receptor (FXR), is emerging as a promising therapeutic target for several intestinal disorders. Here, we investigated a role for FXR in regulating intestinal fluid and electrolyte transport and the potential for FXR agonists in treating diarrhoeal diseases. <h3>Design</h3> Electrogenic ion transport was measured as changes in short-circuit current across voltage-clamped T<sub>84</sub> cell monolayers or mouse tissues in Ussing chambers. NHE3 activity was measured as BCECF fluorescence in Caco-2 cells. Protein expression was measured by immunoblotting and cell surface biotinylation. Antidiarrhoeal efficacy of GW4064 was assessed using two in vivo mouse models: the ovalbumin-induced diarrhoea model and cholera toxin (CTX)-induced intestinal fluid accumulation. <h3>Results</h3> GW4064 (5 μmol/L; 24 h), a specific FXR agonist, induced nuclear translocation of the receptor in T<sub>84</sub> cells and attenuated Cl<sup>−</sup> secretory responses to both Ca<sup>2+</sup> and cAMP-dependent agonists. GW4064 also prevented agonist-induced inhibition of NHE3 in Caco-2 cells. In mice, intraperitoneal administration of GW4064 (50 mg/mL) also inhibited Ca<sup>2+</sup> and cAMP-dependent secretory responses across ex vivo colonic tissues and prevented ovalbumin-induced diarrhoea and CTX-induced intestinal fluid accumulation in vivo. At the molecular level, FXR activation attenuated apical Cl<sup>−</sup> currents by inhibiting expression of cystic fibrosis transmembrane conductance regulator channels and inhibited basolateral Na<sup>+</sup>/K<sup>+</sup>-ATPase activity without altering expression of the protein. <h3>Conclusions</h3> These data reveal a novel antisecretory role for the FXR in colonic epithelial cells and suggest that FXR agonists have excellent potential for development as a new class of antidiarrheal drugs.
Response of an <i>ERBB2</i>-Mutated Inflammatory Breast Carcinoma to Human Epidermal Growth Factor Receptor 2–Targeted Therapy
Authors: Siraj M. Ali, R. Katherine Alpaugh, Sean R. Downing, Philip J. Stephens, Jian Q. Yu, Hong Wu, Jamie K. Buell, Vincent A. Miller, Doron Lipson, Gary A. Palmer, Jeffrey S. Ross, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2014)
A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative
Authors: O. Brouckaert, R. Paridaens, G. Floris, E. Rakha, K. Osborne, P. Neven
Journal: Annals of Oncology (2012)

Steroid receptors have been around in the field of breast cancer for decades now. Still, controversy remains on how best to report steroid receptors. In this review, we will convince the reader why benefits outweigh pitfalls, when reporting steroid receptors in a quantitative rather than qualitative way. Summarizing decades of research in this field, we will explore the evidence why quantitative reporting is superior in all settings (neoadjuvant, adjuvant and metastatic settings). Furthermore, we will also summarize different staining methods, definitions and pitfalls that have shown to be important points of discussion in earlier debates. Although the molecular unraveling of breast cancer in the past decade has revolutionized the way we think about breast cancer, we should not easily abandon the classical pathological variables such as steroid receptors in favor of molecular tools.
Long-Term Efficacy and Safety of Recombinant Human Hyaluronidase (rHuPH20)- Facilitated Subcutaneous Infusion of Immunoglobulin G (IgG) (HyQvia; IGHy) in Patients with Primary Immunodeficiencies (PI)
Authors: Richard L. Wasserman, Mark R. Stein, Isaac Melamed, Lisa J. Kobrynski, Sudhir Gupta, Jennifer M. Puck, Arye Rubinstein, Werner Engl, Barbara McCoy, Heinz Leibl, Leman Yel
Journal: Journal of Allergy and Clinical Immunology (2015)
An intrapulmonary teratoma associated with thymic tissue.
Authors: D W Day, S A Taylor
Journal: Thorax (1975)

A benign teratoma was removed by segmental resection from the upper lobe of the right lung in a girl aged 19 years. This is the twentieth case report of a teratoma occurring in the lung substance and is of special interest because of the identification of thymic tissue histologically. The significance of this in relation to the pathogenesis of intrathoracic teratoma is discussed.
Segmental Bronchoprovocation in Allergic Rhinitis Patients Affects Mast Cell and Basophil Numbers in Nasal and Bronchial Mucosa
Authors: GERT-JAN BRAUNSTAHL, SHELLEY E. OVERBEEK, WYTSKE J. FOKKENS, ALEX KLEINJAN, ALAN R. McEUEN, ANDREW F. WALLS, HENK C. HOOGSTEDEN, JAN–BAS PRINS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Mast cells and basophils are cells that play an important role in the initiation and control of allergic inflammation in asthma and rhinitis. This study was undertaken to determine the presence and dynamics of mast cells and basophils in the nasal and bronchial mucosa of allergic rhinitis patients after segmental bronchial provocation (SBP). Eight nonasthmatic, grass pollen-allergic rhinitis patients and eight healthy controls were included. Bronchial and nasal biopsies, as well as blood samples, were taken before (T0) and 24 h (T24) after SBP. Immunohistochemical staining was performed for mast cells (tryptase and chymase; phenotypes MCT, MCTC, MCC) and basophils (BB1). In the bronchial mucosa, the number of BB1+ cells increased significantly (p < 0.05) in allergic rhinitis patients after SBP. In the nasal mucosa, the numbers of MCC and MCTC cells decreased significantly, whereas the numbers of [BB1+] cells increased significantly in allergic rhinitis patients after SBP (p < 0.05). In blood, the number of basophils decreased (p < 0.05) and the level of interleukin (IL)-5 increased (p < 0.05) in atopic patients after SBP. No significant changes could be observed in healthy controls. This study shows that SBP in nonasthmatic allergic rhinitis patients reduces numbers of mast cells in the nose as a result of enhanced degranulation. At the same time, there is evidence for an influx of basophils from the blood into the nasal and bronchial mucosae.Keywords: bronchoprovocation; asthma; rhinitis; biopsy; inflammation
Intermittent Claudication Secondary to Idiopathic Fibrous Retroperitonitis
Authors: RICHARD E. LARSON, JAMES V. ROSS
Journal: Circulation (1963)

In the case of idiopathic fibrous retroperitonitis presented, the only symptoms were those of arterial insufficiency of the lower limbs and testicular and inguinal pain of uncertain origin. Relief of claudication and return of normal pulsations were achieved after surgical lysis of the common iliac arteries and the terminal segment of the aorta. Numerous reports in the literature indicate that idiopathic fibrous retroperitonitis is not rare but retroperitoneal arterial obstruction by the fibrous plaque is apparently unusual, and intermittent claudication without urinary symptoms is unique. Idiopathic fibrous retroperitonitis, therefore, should be included in the differential diagnosis of the causes of intermittent claudication. Although the aortogram may not permit differentiation of arteriosclerosis obliterans from external compression of the aorta by this fibrosing process, the excretory urogram should be helpful in making or excluding the diagnosis. Treatment is primarily surgical with thorough excision of the fibrous mass and with ureteral transplantation; vascular resection or bypass grafting is not necessary. Advisability of postoperative roentgen and adrenal corticoid therapy is not clearly established.
Carbon Monoxide From Heme Oxygenase-2 Is a Tonic Regulator Against NO-Dependent Vasodilatation in the Adult Rat Cerebral Microcirculation
Authors: Mami Ishikawa, Mayumi Kajimura, Takeshi Adachi, Kayo Maruyama, Nobuya Makino, Nobuhito Goda, Tokio Yamaguchi, Eiichi Sekizuka, Makoto Suematsu
Journal: Circulation Research (2005)

Although the brain generates NO and carbon monoxide (CO), it is unknown how these gases and their enzyme systems interact with each other to regulate cerebrovascular function. We examined whether CO produced by heme oxygenase (HO) modulates generation and action of constitutive NO in the rat pial microcirculation. Immunohistochemical analyses indicated that HO-2 occurred in neurons and arachnoid trabecular cells, where NO synthase 1 (NOS1) was detectable, and also in vascular endothelium–expressing NOS3, suggesting colocalization of CO- and NO-generating sites. Intravital microscopy using a closed cranial window preparation revealed that blockade of the HO activity by zinc protoporphyrin IX significantly dilates arterioles. This vasodilatation depended on local NOS activities and was abolished by CO supplementation, suggesting that the gas derived from HO-2 tonically regulates NO-mediated vasodilatory response. Bioimaging of NO by laser-confocal microfluorography of diaminofluorescein indicated detectable amounts of NO at the microvascular wall, the subdural mesothelial cells, and arachnoid trabecular cells, which express NOS in and around the pial microvasculature. On CO inhibition by the HO inhibitor, regional NO formation was augmented in these cells. Such a pattern of accelerated NO formation depended on NOS activities and was again attenuated by the local CO supplementation. Studies using cultured porcine aortic endothelial cells suggested that the inhibitory action of CO on NOS could result from the photo-reversible gas binding to the prosthetic heme. Collectively, CO derived from HO-2 appears to serve as a tonic vasoregulator antagonizing NO-mediated vasodilatation in the rat cerebral microcirculation.
Determinants in Canadian Health Care Workers of the Decision to Withdraw Life Support From the Critically Ill
Authors: Deborah J. Cook
Journal: JAMA (1995)

Objective.  —To examine the attitudes of health care workers regarding the withdrawal of life support.  Design.  —Cross-sectional survey.  Participants.  —Attending staff, house staff, and intensive care unit (ICU) nurses in 37 Canadian university-affiliated hospitals.  Main Outcome Measures.  —Health care workers' ratings of the importance of 17 factors considered in the decision to withdraw life support, and their ratings of five levels of care ranging from comfort measures to intensive care in two of 12 different clinical scenarios.  Results.  —We surveyed 1361 respondents (149 of 167 potentially eligible ICU attending staff, 142 of 173 ICU house staff, and 1070 of 1455 ICU nurses, with response rates of 89%, 82% and 74%, respectively). The most important factors were likelihood of surviving the current episode, likelihood of long-term survival, premorbid cognitive function, and age of the patient. In choosing the level of care for the patient scenarios, the same option was chosen by more than 50% of respondents in only one of 12 scenarios; opposite extremes of care were chosen by more than 10% of the respondents in eight of 12 scenarios. Respondent characteristics affecting choices included the number of years since graduation, the city and province in which they worked, the number of beds in their ICU, and their assessment of the likelihood that they would withdraw life support in comparison with their colleagues (P  Conclusions.  —While ICU health care workers consistently identify a number of patient factors as important in decisions to withdraw care, there is extreme variability, which may be explained in part by the values of individual health care providers.  (JAMA. 1995;273:703-708)
Lifetime exposure to a soluble TGF-β antagonist protects mice against metastasis without adverse side effects
Authors: Yu-an Yang, Oksana Dukhanina, Binwu Tang, Mizuko Mamura, John J. Letterio, Jennifer MacGregor, Sejal C. Patel, Shahram Khozin, Zi-yao Liu, Jeffrey Green, Miriam R. Anver, Glenn Merlino, Lalage M. Wakefield
Journal: Journal of Clinical Investigation (2002)

TGF-βs play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-β antagonist of the soluble type II TGF-β receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-β null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-β associated with metastasis, while sparing the regulatory roles of TGF-βs in normal tissues. Thus this soluble TGF-β antagonist has potential for long-term clinical use in the prevention of metastasis.
High-altitude treatment in atopic and nonatopic patients with severe asthma
Authors: Lucia H. Rijssenbeek-Nouwens, Karin B. Fieten, Adriaan O. Bron, Simone Hashimoto, Elisabeth H. Bel, Els J. Weersink
Journal: European Respiratory Journal (2012)

The beneficial effects of high-altitude treatment in asthma have been attributed to allergen avoidance. Recent evidence shows that this treatment also improves airway inflammation in nonallergic patients. We hypothesised that high-altitude treatment is clinically equally effective in patients with severe refractory asthma, with or without allergic sensitisation. In a prospective observational cohort study, 137 adults with severe refractory asthma (92 with allergic sensitisation), referred for high-altitude (1,600 m) treatment in Davos, Switzerland, were consecutively included. We measured asthma control (Asthma Control Questionnaire (ACQ)), asthma-related quality of life (Asthma-Related Quality of Life Questionnaire (AQLQ)), sino-nasal symptoms (Sino-Nasal Outcome Test (SNOT-20)), medication requirement, postbronchodilator (post-BD) forced expiratory volume in 1 s (FEV(1)), 6-min walking distance (6MWD), total immunoglobulin (Ig)E, blood eosinophils and exhaled nitric oxide fraction (F(eNO)) at admission and after 12 weeks. Sensitised and nonsensitised patients showed similar improvements in ACQ (-1.4 and -1.5, respectively; p = 0.79), AQLQ (1.6 and 1.5, respectively; p = 0.94), SNOT-20 (-0.7 and -0.5, respectively; p = 0.18), post-BD FEV(1) (6.1% and 5.8% pred, respectively; p = 0.87), 6MWD (+125 m and +147 m, respectively; p = 0.43) and oral steroids (40% versus 44%, respectively; p = 0.51). Sensitised patients showed a larger decrease in total IgE, blood eosinophils and F(eNO). High-altitude treatment improves clinical and functional parameters, and decreases oral corticosteroid requirement in patients with severe refractory asthma, irrespective of allergic sensitisation.
INFLUENCE OF ERYTHROCYTE MEMBRANE COMPONENTS ON MALARIA MEROZOITE INVASION
Authors: Louis H. Miller, James A. Dvorak, Tsugiye Shiroishi, John R. Durocher
Journal: The Journal of Experimental Medicine (1973)

Chymotrypsin- and Pronase-treated human erythrocytes were refractory to invasion by P. knowlesi merozoites; invasion was not inhibited by trypsin or neurammidase treatment. These data implicate a surface protein other than sialoglycoprotein as the receptor site for merozoites. Invasion of rhesus erythrocytes was unaffected by pretreatment with these enzymes. Differences in membrane structure of erythrocytes from various species may explain the absence of an enzyme effect on rhesus erythrocytes.
Prognostic Significance of Plasma Osteopontin in Patients with Locoregionally Advanced Head and Neck Squamous Cell Carcinoma Treated on TROG 02.02 Phase III Trial
Authors: Annette M. Lim, Danny Rischin, Richard Fisher, Hongbin Cao, Kathleen Kwok, Daniel Truong, Grant A. McArthur, Richard J. Young, Amato Giaccia, Lester Peters, Quynh-Thu Le
Journal: Clinical Cancer Research (2011)

High plasma osteopontin (OPN) levels have been reported to be an adverse prognostic factor in head and neck squamous cell carcinomas (HNSCC), correlate with tumor hypoxia, and be predictive of benefit from hypoxia-targeted therapy. We sought to confirm the prognostic and predictive significance of OPN in patients treated on a large international trial.Patients with stage III/IV HNSCC were randomized to receive definitive radiotherapy concurrently with cisplatin or cisplatin plus the hypoxic cell cytotoxin, tirapazamine (TPZ). Eligibility criteria for this prospective substudy included plasma sample availability for OPN assay by ELISA and absence of major radiation therapy deviations (N = 578). OPN concentrations were analyzed for overall survival (OS) and time to locoregional failure (TTLRF), adjusting for known prognostic factors. Additional analysis was carried out in patients with available tumor p16(INK4A) staining status.The median OPN level was 544 ng/mL (range: 7-2,640). High OPN levels were not associated with worse OS (relative HR, 1.03 for highest tertile) or TTLRF (relative HR 0.91 for highest tertile). There was no interaction between OPN and treatment arm for OS or TTLRF (P = 0.93 for OS; P = 0.87 for TTLRF). For the highest tertile the 2-year OS was 66% on control arm and 67% on TPZ arm (HR = 1.11, P = 0.67). Similarly for p16(INK4A) negative patients in the highest tertile, the 2-year OS was 61% on control arm and 63% on TPZ arm (HR = 1.05, P = 0.86).We found no evidence that high plasma OPN levels were associated with an adverse prognosis in HNSCC, or were predictive of benefit with hypoxia targeting therapy.