tbuckley/cabot-search huggingface dataset:
Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration.
Authors: T W Kuijpers, E P Mul, M Blom, N L Kovach, F C Gaeta, V Tollefson, M J Elices, J M Harlan
Journal: The Journal of Experimental Medicine (1993)

Leukocyte extravasation is mediated by multiple interactions of adhesive surface structures with ligands on endothelial cells and matrix components. The functional role of beta 1 (CD29) integrins (or very late antigen [VLA] proteins) in eosinophil migration across polycarbonate filters was examined under several in vitro conditions. Eosinophil migration induced by the chemoattractant C5a or platelet-activating factor was fully inhibited by monoclonal antibody (mAb) 8A2, a recently characterized "activating" CD29 mAb. However, inhibition by mAb 8A2 was observed only under filter conditions that best reflected the in vivo situation, i.e., when the eosinophils migrated over filters preincubated with the extracellular matrix (ECM) protein fibronectin (FN), or when the filters were covered with confluent monolayers of cultured human umbilical vein endothelial cells (HUVEC). When bare untreated filters were used, mAb 8A2 had no effect, whereas the C5a-directed movement was prevented by CD18 mAb. Studies with alpha-subunit (CD49)-specific mAbs indicated that the integrins VLA-4 and -5 mediated migration across FN-preincubated filters, and VLA-2, -4, -5, and -6 were involved in eosinophil migration through filters covered with HUVEC. In contrast with the activating CD29 mAb 8A2, a combination of blocking CD49 mAbs or the nonactivating but blocking CD29 mAb AIIB2 failed to inhibit completely eosinophil migration over FN-preincubated or HUVEC-covered filters. mAb 8A2 stimulated binding to FN but not to HUVEC. Moreover, eosinophil migration over FN-preincubated or HUVEC-covered filters was significantly inhibited by anti-connecting segment 1 (CS-1) mAbs, as well as the soluble CS-1 peptide (unlike migration across bare untreated filters). Thus, inhibition of eosinophil migration by mAb 8A2 depended upon the presence of ECM proteins and not upon the presence of HUVEC per se. In conclusion, "freezing" adhesion receptors of the beta 1 integrin family into their high-avidity binding state by the activating CD29 mAb 8A2 results in a complete inhibition of eosinophil migration under physiological conditions. Hence, activation of beta 1 integrin-mediated cell adhesion may represent a new approach to prevent influx of inflammatory cells.
Activation of the classical complement pathway in spontaneous bacterial peritonitis.
Authors: G Bird, G Senaldi, M Panos, N Rolando, G Alexander, D Vergani, R Williams
Journal: Gut (1992)

<h3>Objective:</h3> To determine if Nuedexta(20mg dextromethorphan/10mg quinidine; Avanir Corporation) can improve frontal lobe pseudobulbar irritability in adult autistic patients. A double blind, placebo controlled crossover study was designed to see if there would be statistically significant difference from placebo. <h3>Background:</h3> Autism is occurring in 1:68 children, is a lifelong condition, and has no cure. Comorbid irritability is a major problem. Theoretical excessive glutaminergic activation receptor activity in frontal cortex in autistic brain has been described. Nuedexta acts as an NMDA antagonist blocking excessive glutaminergic effect. It is approved for adults with frontal lobe irritability of pseudobulbar type, and many autistic adults may have similar irritability. <h3>Design/Methods:</h3> Thirteen autistic adults (ADOS confirmed diagnossi, 11 male, 2 female, average age 21 years) completed a double blinded, placebo-controlled crossover study with interim washout period of 4 weeks separating each treatment vs. placebo arm. Primary outcome measure was the Aberrabt Behavioral Checklist-Irritability (ABC-I), and secondary outocome measures were Overt Aggression Scale (OAS) and total ABC. Clinical Global Impression Scales were also used assessing speech and social behaviors and irritability. Statistical analysis of mean values using a paired-t test was done. <h3>Results:</h3> All primary and secondary standardized scales were statistically significant for improvement of irritability and function with Nuedexta over placebo. ABC-I (p=0.021), total ABC (p=0.043) and OAS (p=0.023), and CGI social was significant (p=0.022) and receptive and expressive language CGI showed strong trends (p=0.057 and 0.47 respectively). Washout baseline and initial baseline showed no statistically significant difference in scores, adding to the significance of the above outcomes. Only 1 patient dropped out for side effects in worsened behaviors possibly do to interaction with comedicat, and 1 con-compliant patient dropped out leaving 13/15 completing the 21 week study. <h3>Conclusions:</h3> This study shows significant improvement if irritability and improved social function in adult autistic patients in treatment with Nuedexta over placebo. Further studies are warranted with Nuedexta or similar agents in this population. <b>Study Supported by:</b> This study was supported by an investigator initiated grant from Avanir Corporation that manufactures Nuedexta. The sponsor provided medication and placebo for the study and patients received this free of charge. Informed consent was obtained from the Sutter Sacramento Institutional Review Board. <b>Disclosure:</b> Dr. Chez has received research support for activities with UCB, Eisai, and Lundbeck. Dr. Chez has received research support from GW and Marinus. Dr. Kile has received research support from Octapharma.
Does HIV/AIDS Have a Biological Impact on the Risk of Human Papillomavirus–Related Cancers?
Authors: Howard D. Strickler
Journal: JNCI Journal of the National Cancer Institute (2009)

HIV-related immunosuppression is a well-accepted, strong biological risk factor for two virus-associated cancers: Kaposi’s sarcoma, which is associated with Kaposi’s sarcoma – associated herpesvirus, and non-Hodgkin lymphoma, which is associated with Epstein – Barr virus. In fact, recognition of an extraordinarily high rate of Kaposi’s sarcoma among men who have sex with men in New York and California during the early 1980s was one of the first indications of the existence of a human immunodeficiency virus ( 1 – 3 ). Soon thereafter, high rates of non-Hodgkin lymphoma in men who have sex with men were also recognized ( 4 , 5 ), and both Kaposi’s sarcoma and non-Hodgkin lymphoma became designated as AIDS-defining malignancies in HIV-positive patients ( 6 – 8 ). It was not until the 1990s though that formal linkages between population-based AIDS registries and cancer registries were initiated ( 9 , 10 ). The AIDS – cancer match registry study in the United States ( 11 , 12 ), and similar studies in other countries ( 13 – 15 ), found that the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma were increased by at least 100-fold in persons who developed AIDS compared with the general population ( 11 , 12 ). Furthermore, there were indications of a biological gradient—one of several criteria used to assess a possible causal relationship. Specifically, the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma increased, and with lower CD4 T-cell count at time of AIDS onset ( 16 ) with increasing time after AIDS diagnosis (which is thought to be a surrogate indicator
An assessment of methods of treating viral warts by comparative treatment trials based on a standard design
Authors: MARY H. BUNNEY, MARGARET W. NOLAN, DAVID A. WILLIAMS
Journal: British Journal of Dermatology (1976)

Journal Article An assessment of methods of treating viral warts by comparative treatment trials based on a standard design Get access MARY H. BUNNEY, MARY H. BUNNEY Department of Dermatology, Royal Infirmary, Edinburgh Dr Mary H. Bunney, Department of Dermatology, Royal Infirmary, Lauriston Place, Edin‐burgh EH3 9YW. Search for other works by this author on: Oxford Academic Google Scholar MARGARET W. NOLAN, MARGARET W. NOLAN Department of Dermatology, Royal Infirmary, Edinburgh Search for other works by this author on: Oxford Academic Google Scholar DAVID A. WILLIAMS DAVID A. WILLIAMS Department of Statistics, University of Edinburgh Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 6, 1 June 1976, Pages 667–679, https://doi.org/10.1111/j.1365-2133.1976.tb05167.x Published: 01 June 1976
Effect of Endotoxin on Ventilation and Breath Variability
Authors: HUGH L. PREAS, AMAL JUBRAN, R. WILLIAM VANDIVIER, DEBRA REDA, PAUL J. GODIN, STEVEN M. BANKS, MARTIN J. TOBIN, ANTHONY F. SUFFREDINI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also received ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration of endotoxin produced fever, increased respiratory frequency, decreased inspiratory time, and widened alveolar–arterial oxygen tension gradient (all p ⩽ 0.001); these responses were blocked by ibuprofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increased fractional inspiratory time, minute ventilation, and mean inspiratory flow (all p ⩽ 0.025). Endotoxin altered the autocorrelative behavior of respiratory frequency by increasing its autocorrelation coefficient at a lag of one breath, the number of breath lags with significant serial correlations, and its correlated fraction (all p < 0.05); these responses were blocked by ibuprofen. Changes in correlated behavior of respiratory frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and dyspnea independent of fever and symptoms, and it curtailed the freedom to vary respiratory timing—a response that appears to be mediated by the cyclooxygenase pathway.Keywords: endotoxemia; respiratory center; Fourier analysis; sepsis; respiratory muscles
Safety and efficacy of colonic EMR in a district general hospital
Authors: J. Subhani, D. Lindo, D. Gertner, R. Warburton, N. Alsanjari, A. Abdullah
Journal: Gut (2011)

<h3>Introduction</h3> Virtually all published data on colonic endoscopic mucosal resection (EMR) comes from expert centres and yet it is likely that the majority of these procedures are performed outside these hospitals. At our centre, like many others, a single endoscopist (JMS) provides an EMR service that the other eight colonoscopists have referred to over the last 5+ years. We evaluated its use, efficacy and safety. <h3>Methods</h3> Sessile and flat colonic polyps &gt;10 mm assessed for resection were identified prospectively and follow-up data collection started. These would include referrals to the EMR service as well as lesions resected by JMS at the index endoscopy. Multi-session resections were done within 3 months. Standard endoscopic follow-up was at 3 months for piecemeal resections. For en-bloc resections follow-up was at a minimum as per BSG guidelines but additional surveillance procedures may have been undertaken due to patient and histological factors. All initial resections were performed by JMS with Olympus equipment the majority by lift and cut method. Argon was used after piecemeal resections as appropriate. <h3>Results</h3> 340 lesions were assessed in 303 patients. 31 did not undergo resection (21 judged T2+ stage, 3 due to position, 4 due to size and 3 due to non-adenomatous pathology). 296 required one session, 11 two sessions and 2 three sessions. Clearance was achieved at the initial session in 93% of polyps &gt; = 20 mm. <h3>Safety</h3> The following complication rates were calculated for all polyps or (polyps &gt; = 20 mm). Perforation and surgery 0.3% (0.5%), Admission post procedure 1.2% (1.9%), Late bleed requiring endoscopy +/− admission 2.4% (3.8%), Late bleed requiring transfusion 0.3% (0.5%), Post-polypectomy syndrome requiring admission 0.3% (0.5%) and Stricture 0.3% (0.5%). <h3>Conclusion</h3> The safety and efficacy in this study is similar to that in other published series from western expert centres. The complications rates seem acceptable and provide data to consent with. The higher recurrence rates with lesions &gt;4 cm may be reduced with newer techniques such as endoscopic submucosal dissection. The model of a single endoscopist initially providing an EMR service has worked in our centre and in addition provided a focus for new consultant and senior SpR training.
Ankylosing spondylitis: introductory comments on its diagnosis and treatment
Authors: M A Khan
Journal: Annals of the Rheumatic Diseases (2002)

A nkylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disorder of uncertain aetiology that primarily affects the axial skeleton (sacroiliac joints and spine). Sacroiliac joint involvement (sacroiliitis) is its hallmark.1 The course of AS is highly variable and can be characterised by spontaneous remissions and exacerbation, particularly in early disease. The disease activity, however, generally persists for many decades, rarely entering a long term remission. The disease in some patients may be relatively mild or stay limited to the sacroiliac joints and the lumbar spine. Many patients may not seek medical help, which combined with the insidious nature of AS, may preclude an early diagnosis. There is currently no cure for AS, nor is there any medical intervention which can prevent or retard its progression.

Only a doctor who is fully cognisant of the clinical nature of AS might consider the possibility of a spondyloarthropathy (SpA), much less AS, when presented with a young individual in their teens or early to mid-20s with chronic back pain.1,2 Yet, this is a typical initial presentation of AS. Unfortunately, the presence of inflammatory back pain during the clinically unrecognised “pre-spondylitic” phase, which on average might last 5–10 years or longer, is accompanied by progressive structural damage that may take place inconspicuously.1–8 Diagnosis is often established when AS reaches the stage where structural damage has led to easily recognisable abnormal physical findings or readily apparent radiographic abnormalities of the sacroiliac joints and spine, or both.1–4

Figure 1, which represents data collected by a 78 item professional survey of patients with AS conducted by the German AS society in 1996, illustrates well the protracted time delay between onset of AS and its diagnosis.5 A total of 1614 patients with AS responded to the questionnaire. The average …
Long-Term Follow-Up of High-Dose Methotrexate-Based Therapy With and Without Whole Brain Irradiation for Newly Diagnosed Primary CNS Lymphoma
Authors: Igor T. Gavrilovic, Adília Hormigo, Joachim Yahalom, Lisa M. DeAngelis, Lauren E. Abrey
Journal: Journal of Clinical Oncology (2006)

Purpose We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. Patients and Methods Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. Results The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. Conclusion Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.
Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-α
Authors: Christian C. Yost, Melvin M. Denis, Stephan Lindemann, Frederick J. Rubner, Gopal K. Marathe, Michael Buerke, Thomas M. McIntyre, Andrew S. Weyrich, Guy A. Zimmerman
Journal: The Journal of Experimental Medicine (2004)

In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that regulate messenger RNA (mRNA) translation. HL-60 myelocytic cells differentiated to surrogate PMNs respond to activation by platelet activating factor by initiating translation and with appearance of specific mRNA transcripts in polyribosomes. cDNA array analysis of the polyribosome fraction demonstrated that retinoic acid receptor (RAR)-α, a transcription factor that controls the expression of multiple genes, is one of the polyribosome-associated transcripts. Quiescent surrogate HL60 PMNs and primary human PMNs contain constitutive message for RAR-α but little or no protein. RAR-α protein is rapidly synthesized in response to platelet activating factor under the control of a specialized translational regulator, mammalian target of rapamycin, and is blocked by the therapeutic macrolide rapamycin, events consistent with features of the 5′ untranslated region of the transcript. Newly synthesized RAR-α modulates production of interleukin-8. Rapid expression of a transcription factor under translational control is a previously unrecognized mechanism in human PMNs that indicates unexpected diversity in gene regulation in this critical innate immune effector cell.
New Developments in Tyrosine Kinase Inhibitor Therapy for Newly Diagnosed Chronic Myeloid Leukemia
Authors: Philipp le Coutre, Michaela Schwarz, Theo D. Kim
Journal: Clinical Cancer Research (2010)

Abstract The biology of chronic myeloid leukemia (CML) has enabled pioneering studies with targeted therapies. BCR-ABL inhibition with imatinib results in high levels of efficacy in patients with newly diagnosed CML in chronic phase (CP), but an estimated 35% of patients could benefit from more effective treatment. Several novel treatment strategies are being investigated in newly diagnosed CML-CP. These strategies include upfront treatment with next-generation tyrosine kinase inhibitors, such as dasatinib, nilotinib, or bosutinib, which also target BCR-ABL but with increased in vitro potency compared with imatinib, and possibly a reduced potential for resistance. Recent in vitro studies have shown that short-term exposure to dasatinib or continuous exposure to imatinib result in equivalent levels of apoptosis, indicating that potent intermittent inhibition is a successful strategy for improving dasatinib tolerability. Modified imatinib regimens are also being investigated in newly diagnosed CML-CP, including higher doses and combination with alternative classes of agents, such as interferon. Existing data suggest that both newer agents and combination approaches can improve treatment responses compared with standard imatinib treatment, although further data are needed, particularly from ongoing phase 3 trials, before the standard of care is revised. Clin Cancer Res; 16(6); 1771–80
The Solute Carrier Families Have a Remarkably Long Evolutionary History with the Majority of the Human Families Present before Divergence of Bilaterian Species
Authors: P. J. Hoglund, K. J. V. Nordstrom, H. B. Schioth, R. Fredriksson
Journal: Molecular Biology and Evolution (2010)

The Solute Carriers (SLCs) are membrane proteins that regulate transport of many types of substances over the cell membrane. The SLCs are found in at least 46 gene families in the human genome. Here, we performed the first evolutionary analysis of the entire SLC family based on whole genome sequences. We systematically mined and analyzed the genomes of 17 species to identify SLC genes. In all, we identified 4,813 SLC sequences in these genomes, and we delineated the evolutionary history of each of the subgroups. Moreover, we also identified ten new human sequences not previously classified as SLCs, which most likely belong to the SLC family. We found that 43 of the 46 SLC families found in Homo sapiens were also found in Caenorhabditis elegans, whereas 42 of them were also found in insects. Mammals have a higher number of SLC genes in most families, perhaps reflecting important roles for these in central nervous system functions. This study provides a systematic analysis of the evolutionary history of the SLC families in Eukaryotes showing that the SLC superfamily is ancient with multiple branches that were present before early divergence of Bilateria. The results provide foundation for overall classification of SLC genes and are valuable for annotation and prediction of substrates for the many SLCs that have not been tested in experimental transport assays.
Statistical Analysis of Array Expression Data as Applied to the Problem of Tamoxifen Resistance
Authors: S. G. Hilsenbeck, W. E. Friedrichs, R. Schiff, P. O'Connell, R. K. Hansen, C. K. Osborne, S. A. W. Fuqua
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Although the emerging complementary DNA (cDNA) array technology holds great promise to discern complex patterns of gene expression, its novelty means that there are no well-established standards to guide analysis and interpretation of the data that it produces. We have used preliminary data generated with the CLONTECH Atlas™ human cDNA array to develop a practical approach to the statistical analysis of these data by studying changes in gene expression during the development of acquired tamoxifen resistance in breast cancer. METHODS: For hybridization to the array, we prepared RNA from MCF-7 human breast cell tumors, isolated from our athymic nude mouse xenograft model of acquired tamoxifen resistance during estrogen-stimulated, tamoxifen-sensitive, and tamoxifen-resistant growth. Principal components analysis was used to identify genes with altered expression. RESULTS AND CONCLUSIONS: Principal components analysis yielded three principal components that are interpreted as 1) the average level of gene expression, 2) the difference between estrogen-stimulated gene expression and the average of tamoxifen-sensitive and tamoxifen-resistant gene expression, and 3) the difference between tamoxifen-sensitive and tamoxifen-resistant gene expression. A bivariate (second and third principal components) 99% prediction region was used to identify outlier genes that exhibit altered expression. Two representative outlier genes, erk-2 and HSF-1 (heat shock transcription factor-1), were chosen for confirmatory study, and their predicted relative expression levels were confirmed in western blot analysis, suggesting that semiquantitative estimates are possible with array technology. IMPLICATIONS: Principal components analysis provides a useful and practical method to analyze gene expression data from a cDNA array. The method can identify broad patterns of expression alteration and, based on a small simulation study, will likely provide reasonable power to detect moderate-sized alterations in clinically relevant genes.