tbuckley/cabot-search huggingface dataset:
Health Outcomes of Continuous Positive Airway Pressure versus Oral Appliance Treatment for Obstructive Sleep Apnea
Authors: Craig L. Phillips, Ronald R. Grunstein, M. Ali Darendeliler, Anastasia S. Mihailidou, Vasantha K. Srinivasan, Brendon J. Yee, Guy B. Marks, Peter A. Cistulli
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) therapy are commonly used to treat obstructive sleep apnea (OSA). Differences in efficacy and compliance of these treatments are likely to influence improvements in health outcomes.Objectives: To compare health effects after 1 month of optimal CPAP and MAD therapy in OSA.Methods: In this randomized crossover trial, we compared the effects of 1 month each of CPAP and MAD treatment on cardiovascular and neurobehavioral outcomes.Measurements and Main Results: Cardiovascular (24-h blood pressure, arterial stiffness), neurobehavioral (subjective sleepiness, driving simulator performance), and quality of life (Functional Outcomes of Sleep Questionnaire, Short Form-36) were compared between treatments. Our primary outcome was 24-hour mean arterial pressure. A total of 126 patients with moderate-severe OSA (apnea hypopnea index [AHI], 25.6 [SD 12.3]) were randomly assigned to a treatment order and 108 completed the trial with both devices. CPAP was more efficacious than MAD in reducing AHI (CPAP AHI, 4.5 ± 6.6/h; MAD AHI, 11.1 ± 12.1/h; P < 0.01) but reported compliance was higher on MAD (MAD, 6.50 ± 1.3 h per night vs. CPAP, 5.20 ± 2 h per night; P < 0.00001). The 24-hour mean arterial pressure was not inferior on treatment with MAD compared with CPAP (CPAP-MAD difference, 0.2 mm Hg [95% confidence interval, −0.7 to 1.1]); however, overall, neither treatment improved blood pressure. In contrast, sleepiness, driving simulator performance, and disease-specific quality of life improved on both treatments by similar amounts, although MAD was superior to CPAP for improving four general quality-of-life domains.Conclusions: Important health outcomes were similar after 1 month of optimal MAD and CPAP treatment in patients with moderate-severe OSA. The results may be explained by greater efficacy of CPAP being offset by inferior compliance relative to MAD, resulting in similar effectiveness.Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415).
Replacement of Pre-T Cell Receptor Signaling Functions by the CD4 Coreceptor
Authors: Anne M. Norment, Katherine A. Forbush, Nhan Nguyen, Marie Malissen, Roger M. Perlmutter
Journal: The Journal of Experimental Medicine (1997)

An important checkpoint in early thymocyte development ensures that only thymocytes with an in-frame T cell receptor for antigen β (TCR-β) gene rearrangement will continue to mature. Proper assembly of the TCR-β chain into the pre-TCR complex delivers signals through the src-family protein tyrosine kinase p56lck that stimulate thymocyte proliferation and differentiation to the CD4+CD8+ stage. However, the biochemical mechanisms governing p56lck activation remain poorly understood. In more mature thymocytes, p56lck is associated with the cytoplasmic domain of the TCR coreceptors CD4 and CD8, and cross-linking of CD4 leads to p56lck activation. To study the effect of synchronously inducing p56lck activation in immature CD4−CD8− thymocytes, we generated mice expressing a CD4 transgene in Rag2−/− thymocytes. Remarkably, without further experimental manipulation, the CD4 transgene drives maturation of Rag2−/− thymocytes in vivo. We show that this process is dependent upon the ability of the CD4 transgene to bind Lck and on the expression of MHC class II molecules. Together these results indicate that binding of MHC class II molecules to CD4 can deliver a biologically relevant, Lck-dependent activation signal to thymocytes in the absence of the TCR-α or -β chain.
PROGNOSIS IN CRITICAL CARE
Authors: Lucila Ohno-Machado, Frederic S. Resnic, Michael E. Matheny
Journal: Annual Review of Biomedical Engineering (2006)

Prognostic risk prediction models have been employed in the intensive care unit (ICU) setting since the 1980s and provide health care providers with important information to help inform decisions related to treatment and prognosis, as well as to compare outcomes across institutions. Prognostic models for critical care are among the most widely utilized and tested predictive models in healthcare. In this article, we review and compare mortality prediction models, including the APACHE (1981), SAPS (1984), APACHE-II (1985), MPM (1987), APACHE-III (1991), SAPS-II (1993), and MPM-II (1993). We emphasize the importance of model calibration in this domain. In addition, we present a brief review of the statistical methodology, multiple logistic regression, which underlies most of the models currently used in critical care.
Antibiotics can improve outcomes in heart patients
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Antibiotic treatment improves outcomes in patients with acute coronary syndrome, a British study team reports.

The team's report, to be published in Circulation (but already available at www.circulationaha.org), says that antibiotic treatment improves outcomes in patients with acute coronary syndrome, even if they do not have signs of infection with Helicobacter pylori or Chlamydia pneumoniae .

Meanwhile, in a separate but related study to be published in the same issue, researchers from the Framingham heart study in Massachusetts report that concentrations of C …
Anti-self receptors. I. Direct detection of H-2L region-restricted receptors on murine thymocytes.
Authors: D Y Sia, C R Parish
Journal: The Journal of Experimental Medicine (1980)

A high proportion (20--50%) of murine thymocytes form rosettes with either syngeneic or allogeneic erythrocytes. The specificity of this interaction was investigated by measuring the ability of different erythrocyte sonicates to inhibit rosette formation. With erythrocyte sonicates from recombinant mouse strains it was demonstrated that rosetting with syngeneic erythrocytes was mediated by H-2L and/or H-2D region-restricted receptors. The specificity of autorosetting was directly mapped to the H-2L region by the inability of erythrocyte sonicates from the BALB/c-H-2dm2 mutant, an H-2L-deletion mutant, to inhibit the rosetting of wild-type (BALB/c) thymocytes. The B10,2D2-H-2dm1 mutant, which has substantially modified H-2L and H-2D antigens, supported this conclusion. Furthermore, anti-H-2L sera were able to specifically block the inhibition of rosetting by erythrocyte sonicates. The above procedures clearly implicated the H-2L region in the thymocyte rosetting of d and k haplotypes. With the s haplotype the rosetting receptor was mapped to the H-2L/H-2D region, whereas with the b and q haplotypes rosetting was only mapped to the D end of the H-2 complex. This study also suggested complete cross-reaction between the thymocyte receptors carried by the k and d haplotypes, whereas the receptors of b, q, and s haplotypes were haplotype specific. In addition, the inhibition assay indicated that the rosetting of thymocytes with allogeneic and xenogeneic (rat) erythrocytes was mediated by a receptor primarily directed against self-H-2L. Finally, the critical role played by the H-2L region in this rosetting phenomenon was demonstrated by the inability of thymocytes from the H-2L-deletion mutant (H-2dm2) to rosette with syngeneic, allogeneic (rat) erythrocytes.
Cardiac calmodulin-stimulated protein phosphatase: purification and identification of specific sarcolemmal substrates.
Authors: A S Manalan, D K Werth
Journal: Circulation Research (1987)

A calmodulin-stimulated protein phosphatase has been purified from bovine myocardium. The purification procedure involves sequential DEAE-Sephacel ion exchange chromatography, calmodulin-Sepharose affinity chromatography, and high performance liquid chromatography using a Spherogel TSK DEAE 5PW column. By SDS polyacrylamide gel electrophoresis, the purified cardiac phosphatase consists of two subunits of Mr 61,000 and 19,000, similar to the brain enzyme, calcineurin. Protein phosphatase activity of the cardiac enzyme is stimulated by Ca2+-calmodulin and inhibited by the calmodulin antagonist drug, calmidazolium. Effects of a series of divalent cations on catalytic activity of the cardiac calmodulin-stimulated protein phosphatase are similar to those observed with calcineurin, when the two enzymes are assayed under identical conditions. Highly enriched preparations of bovine cardiac sarcolemma contain substrates of cAMP-dependent protein kinase of Mr 166 K, 133 K, 108 K, 79 K, 39 K, and 14 K, which are specifically dephosphorylated by the calmodulin-stimulated phosphatase with pseudofirst-order rate constants of 0.23, 0.46, 0.69, 0.35, 0.69, and 0.115 min-1, respectively. These substrates are not present in purified preparations of cardiac sarcoplasmic reticulum. These results support a role of the calmodulin-stimulated phosphatase in the Ca2+-regulation of specific sarcolemmal processes by protein dephosphorylation.
Induced Pluripotent Stem Cells from Human Kidney
Authors: Ian Rogers
Journal: Journal of the American Society of Nephrology (2011)

Kidney disease is a growing health issue for modern society,[1][1][][2]–[3][3] and there are a number of causes, including prematurity, genetic abnormalities, inflammation, hypertension, and diabetes. Current treatments for ESRD include dialysis and transplantation, but both are expensive, rely on
Aberrant Expression of the Tyrosine Kinase Receptor EphA4 and the Transcription Factor Twist in Sézary Syndrome Identified by Gene Expression Analysis
Authors: Remco van Doorn, Remco Dijkman, Maarten H. Vermeer, Jacoba J. Out-Luiting, Elisabeth M. H. van der Raaij-Helmer, Rein Willemze, Cornelis P. Tensen
Journal: Cancer Research (2004)

Abstract Sézary syndrome (Sz) is a malignancy of CD4+ memory skin-homing T cells and presents with erythroderma, lymphadenopathy, and peripheral blood involvement. To gain more insight into the molecular features of Sz, oligonucleotide array analysis was performed comparing gene expression patterns of CD4+ T cells from peripheral blood of patients with Sz with those of patients with erythroderma secondary to dermatitis and healthy controls. Using unsupervised hierarchical clustering gene, expression patterns of T cells from patients with Sz were classified separately from those of benign T cells. One hundred twenty-three genes were identified as significantly differentially expressed and had an average fold change exceeding 2. T cells from patients with Sz demonstrated decreased expression of the following hematopoietic malignancy-linked tumor suppressor genes: TGF-β receptor II, Mxi1, Riz1, CREB-binding protein, BCL11a, STAT4, and Forkhead Box O1A. Moreover, the tyrosine kinase receptor EphA4 and the potentially oncogenic transcription factor Twist were highly and selectively expressed in T cells of patients with Sz. High expression of EphA4 and Twist was also observed in lesional skin biopsy specimens of a subset of patients with cutaneous T cell lymphomas related to Sz, whereas their expression was nearly undetectable in benign T cells or in skin lesions of patients with inflammatory dermatoses. Detection of EphA4 and Twist may be used in the molecular diagnosis of Sz and related cutaneous T-cell lymphomas. Furthermore, the membrane-bound EphA4 receptor may serve as a target for directed therapeutic intervention.
Endoscopic management of postoperative biliary complications in donors for living donor liver transplantation
Authors: Kazunori Hasegawa, Shujiro Yazumi, Hiroto Egawa, Hiroyuki Tamaki, Masanori Asada, Yuzo Kodama, Hiroshi Hisatsune, Kazuichi Okazaki, Koichi Tanaka, Tsutomu Chiba
Journal: Clinical Gastroenterology and Hepatology (2003)
<i>BRCA2</i> Deep Intronic Mutation Causing Activation of a Cryptic Exon: Opening toward a New Preventive Therapeutic Strategy
Authors: Olga Anczuków, Monique Buisson, Mélanie Léoné, Christine Coutanson, Christine Lasset, Alain Calender, Olga M. Sinilnikova, Sylvie Mazoyer
Journal: Clinical Cancer Research (2012)

Diagnostic screening of the BRCA1/2 genes in breast cancer families is mostly done on genomic DNA. For families with a very strong family history and no mutation identified in the coding sequences or the exon-intron boundaries, BRCA1/2 transcripts' analysis is an efficient approach to uncover gene inversion and pre-mRNA splicing defaults missed by conventional DNA-based protocols.We analyzed RNA from patients of negative BRCA families by reverse transcriptase PCR and identified an insertion in one family that we characterized by sequencing and by using a minigene splicing assay. More than 2,000 additional BRCA1/2 negative families were subsequently screened for this mutation using a dedicated PCR approach.Nine families were found to harbor a BRCA2 mutant transcript containing a 95-nucleotide cryptic exon between exons 12 and 13. This cryptic exon results from a new mutation located deep into intron 12, c.6937+594T > G, which reinforces the strength of a preexisting 5' splice site, turning it into a perfect consensus sequence. It is systematically included in transcripts produced by the mutant allele in cells from mutation carriers or produced by a mutant splicing reporter minigene. The inclusion of the cryptic exon was prevented when we cotransfected the minigene with antisense oligonucleotides complementary to the 3' or mutated 5' splice sites.This first deep intronic BRCA mutation emphasizes the importance of analyzing RNA to provide comprehensive BRCA1/2 diagnostic tests and opens the possibility of using antisense therapy in the future as an alternative strategy for cancer prevention.
Pancreatic function testing: serum PABA measurement is a reliable and accurate measurement of exocrine function.
Authors: A R Tanner, D P Robinson
Journal: Gut (1988)

A comparison between the NBT-PABA/14C-PABA test (NBT-PABA, n-benzoyl-tyrosyl para-aminobenzoic acid) using the PABA excretion index (PEI) and serum PABA estimation at 90 minutes has been made in 42 consecutive subjects attending for investigation of possible pancreatic disease to a District General Hospital (DGH). The PEI was unobtainable or incorrect on 38% of occasions compared with 9% for the serum test. Sensitivity, specificity, and efficiency for the PEI (n = 33 valid results) were 71%, 88%, and 79% respectively and for the serum PABA (n = 41 valid results), 95%, 90%, and 93% respectively. These results confirm that measurement of serum PABA is a simpler, more reliable, and a more accurate method of assessing pancreatic function.
Polymerase chain reaction based human leucocyte antigen genotyping for the investigation of suspected gastrointestinal biopsy contamination
Authors: A C Bateman, S J Turner, J M Theaker, B F Warren, W M Howell
Journal: Gut (1999)

BACKGROUND Mislabelling or contamination of surgical specimens may lead to diagnostic inaccuracy, particularly within gastrointestinal pathology when multiple small mucosal biopsy specimens are commonly taken, and where a tiny fragment of foreign tissue may be indistinguishable from true biopsy material using histological assessment alone. AIMS To assess the utility of polymerase chain reaction (PCR) based human leucocyte antigen (HLA) genotyping techniques for the investigation of potentially mislabelled or contaminated gastrointestinal biopsy specimens. PATIENTS Ten cases (28 samples) in which mislabelling or contamination was suspected, comprising four upper gastrointestinal tract biopsies and six colonoscopic biopsy series. METHODS Direct and nested PCR-sequence specific primer (SSP) based HLA class II genotyping was performed on DNA extracted from formalin fixed and paraffin wax embedded tissue (23 samples) or peripheral blood leucocytes (five samples). RESULTS A full HLA-DRB1 genotype was determined in all 28 samples. In seven cases the HLA-DRB1 genotype of the putative contaminant was different to that of the corresponding reference tissue, confirming different individual origins for the contaminant and reference material. In one case the contaminant tissue was shown to possess the same HLA-DRB1 alleles as a second patient (probable source). In the remaining three cases the same HLA-DRB1 alleles were detected within the potential contaminant and reference tissues. CONCLUSIONS PCR based HLA class II genotyping is a valuable tool for investigating potential contamination or mislabelling within gastrointestinal biopsy specimens and this report has confirmed contamination in seven of ten cases studied.
Spirometric findings in asbestos-exposed subjects with pleural plaques missed by chest radiography but detected by HRCT
Authors: Ericson Bagatin, Mario Terra-Filho, Lara Maris Nápolis, José Alberto Neder, Gustavo de Souza Portes Meirelles, Reynaldo Tavares Rodrigues, Luiz Eduardo Nery
Journal: European Respiratory Journal (2012)

Introduction:  High-resolution computed tomography (HRCT) is recognizably more sensitive than chest X-ray (CXR) in detecting small-to-moderately large pleural plaques (PP) in asbestos-exposed subjects.  Objectives:  We reasoned that if the PP missed on CXR are associated with decreased lung function, this would lend support to a wider use of HRCT in these subjects.  Methods:  HRCT and spirometry were obtained in 1075 miners and millers who have been exposed to progressively lower airborne concentrations of asbestos over time (Groups I to III) and were free of PP or asbestosis on CXR.  Results:  We found that 100/1075 (9.3%) of the subjects had PP only on HRCT 44/90 (48.8%) in Group I, 44/537 (8.2%) in Group II and 12/448 (2.7%) in Group III. As shown in the Table, subjects with PP on HRCT but not CXR had consistently lower spirometric values than those deemed as normal by both methods (p   Conclusions:  We conclude that the lack of sensitivity of CXR in detecting PP in asbestos-exposed subjects is a matter of concern, as subjects with these abnormalities only on HRCT had decreased lung function values. This seems of special relevance among more exposed subjects.
Inhibition of Chk1 by CEP-3891 Accelerates Mitotic Nuclear Fragmentation in Response to Ionizing Radiation
Authors: Randi G. Syljuåsen, Claus Storgaard Sørensen, Jesper Nylandsted, Claudia Lukas, Jiri Lukas, Jiri Bartek
Journal: Cancer Research (2004)

Abstract The human checkpoint kinase Chk1 has been suggested as a target for cancer treatment. Here, we show that a new inhibitor of Chk1 kinase, CEP-3891, efficiently abrogates both the ionizing radiation (IR)-induced S and G2 checkpoints. When the checkpoints were abrogated by CEP-3891, the majority (64%) of cells showed fragmented nuclei at 24 hours after IR (6 Gy). The formation of nuclear fragmentation in IR-treated human cancer cells was directly visualized by time-lapse video microscopy of U2-OS cells expressing a green fluorescent protein-tagged histone H2B protein. Nuclear fragmentation occurred as a result of defective chromosome segregation when irradiated cells entered their first mitosis, either prematurely without S and G2 checkpoint arrest in the presence of CEP-3891 or after a prolonged S and G2 checkpoint arrest in the absence of CEP-3891. The nuclear fragmentation was clearly distinguishable from apoptosis because caspase activity and nuclear condensation were not induced. Finally, CEP-3891 not only accelerated IR-induced nuclear fragmentation, it also increased the overall cell killing after IR as measured in clonogenic survival assays. These results demonstrate that transient Chk1 inhibition by CEP-3891 allows premature mitotic entry of irradiated cells, thereby leading to accelerated onset of mitotic nuclear fragmentation and increased cell death.
Physician-attributable Differences in Intensive Care Unit Costs
Authors: Allan Garland, Ziad Shaman, John Baron, Alfred F. Connors
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Variation in practice and outcomes, not explained by patient or illness characteristics, is common in health care, including in intensive care units (ICUs).To quantify within-ICU, between-physician variation in resource use in a single medical ICU.This was a prospective, noninterventional study in a medical ICU where nine intensivists provide care in 14-d rotations. Consecutive sample consisted of 1,184 initial patient admissions whose care was provided by a single intensivist. Multivariate models were constructed for average daily discretionary costs, ICU length of stay, and hospital mortality, adjusting for patient and illness characteristics, and workload.The identity of the intensivist was a significant predictor for average daily discretionary costs (p < 0.0001), but not ICU length of stay (p = 0.33) or hospital mortality (p = 0.83). The intensivists had more influence on costs than all other variables except the severity and type of acute illness. Average daily discretionary costs varied by 43% across the different intensivists, equating to a mean difference of 1,003 dollars per admission between the highest and lowest terciles of intensivists.There are large differences among intensivists in the amount of resources they use to manage critically ill patients. Higher resource use was not associated with lower length of stay or mortality.
Primary Analysis of the Phase II Component of a Phase I/II Dose Intensification Study Using Three-Dimensional Conformal Radiation Therapy and Concurrent Chemotherapy for Patients With Inoperable Non–Small-Cell Lung Cancer: RTOG 0117
Authors: Jeffrey D. Bradley, Kyounghwa Bae, Mary V. Graham, Roger Byhardt, Ramaswamy Govindan, Jack Fowler, James A. Purdy, Jeff M. Michalski, Elizabeth Gore, Hak Choy
Journal: Journal of Clinical Oncology (2010)

Phase I of Radiation Therapy Oncology Group (RTOG) 0117 determined that 74 Gy was the maximum-tolerated dose with concurrent weekly carboplatin/paclitaxel chemotherapy for inoperable non-small-cell lung cancer (NSCLC). Phase II results are reported here. PATIENTS AND METHODS Patients with unresectable stages I-III NSCLC were eligible. Chemotherapy consisted of weekly paclitaxel at 50 mg/m(2) and carboplatin at area under the curve 2 mg/m(2). The radiation dose was 74 Gy given in 37 fractions. Radiation therapy volumes included those of the gross tumor and involved nodes. The volume of lung at or exceeding 20 Gy (V20) was mandated to be <or= 30%.
Sweat-gland necrosis after beta-adrenergic antagonist treatment in a patient with pheochromocytoma
Authors: J.M. NAEYAERT, E. DEROM, S. SANTOSA, R. RUBENS
Journal: British Journal of Dermatology (1987)

Journal Article Sweat‐gland necrosis after beta‐adrenergic antagonist treatment in a patient with pheochromocytoma Get access J.M. NAEYAERT, J.M. NAEYAERT Department of Dermatology, State University of Ghent, Ghent, Belgium Dr J.M.Naeyaert, Department of Dermatology, Slate University of Ghent, De Pintelaan 185, B‐9000 Ghent, Belgium. Search for other works by this author on: Oxford Academic Google Scholar E. DEROM, E. DEROM Endocrinology Section, Department of Internal Medicine, State University of Ghent, Ghent, Belgium Search for other works by this author on: Oxford Academic Google Scholar S. SANTOSA, S. SANTOSA Department of Dermatology, State University of Ghent, Ghent, Belgium Search for other works by this author on: Oxford Academic Google Scholar R. RUBENS R. RUBENS Endocrinology Section, Department of Internal Medicine, State University of Ghent, Ghent, Belgium Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 3, 1 September 1987, Pages 371–376, https://doi.org/10.1111/j.1365-2133.1987.tb04145.x Published: 01 September 1987