tbuckley/cabot-search huggingface dataset:
Long-term survival of influenza virus infected club cells drives immunopathology
Authors: Nicholas S. Heaton, Ryan A. Langlois, David Sachs, Jean K. Lim, Peter Palese, Benjamin R. tenOever
Journal: The Journal of Experimental Medicine (2014)

Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influenza virus infection. We demonstrate that these cells, known as club cells, elicit a robust transcriptional response to virus infection, show increased interferon stimulation, and induce high levels of proinflammatory cytokines after successful viral clearance. Specific depletion of these surviving cells leads to a reduction in lung tissue damage associated with IAV infection. We propose a model in which infected, surviving club cells establish a proinflammatory environment aimed at controlling virus levels, but at the same time contribute to lung pathology.
Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc
Authors: Shih-Hwa Chiou, Bo-Hwa Jiang, Yung-Luen Yu, Shih-Jie Chou, Ping-Hsing Tsai, Wei-Chao Chang, Liang-Kung Chen, Li-Hsin Chen, Yueh Chien, Guang-Yuh Chiou
Journal: The Journal of Experimental Medicine (2012)

Poly(ADP-ribose) polymerase 1 (Parp1) catalyzes poly(ADP-ribosylation) (PARylation) and induces replication networks involved in multiple nuclear events. Using mass spectrometry and Western blotting, Parp1 and PARylation activity were intensively detected in induced pluripotent stem cells (iPSCs) and embryonic stem cells, but they were lower in mouse embryonic fibroblasts (MEFs) and differentiated cells. We show that knockdown of Parp1 and pharmacological inhibition of PARylation both reduced the efficiency of iPSC generation induced by Oct4/Sox2/Klf4/c-Myc. Furthermore, Parp1 is able to replace Klf4 or c-Myc to enhance the efficiency of iPSC generation. In addition, mouse iPSCs generated from Oct4/Sox2/Parp1-overexpressing MEFs formed chimeric offspring. Notably, the endogenous Parp1 and PARylation activity was enhanced by overexpression of c-Myc and repressed by c-Myc knockdown. A chromatin immunoprecipitation assay revealed a direct interaction of c-Myc with the Parp1 promoter. PAR-resin pulldown, followed by proteomic analysis, demonstrated high levels of PARylated Chd1L, DNA ligase III, SSrp1, Xrcc-6/Ku70, and Parp2 in pluripotent cells, which decreased during the differentiation process. These data show that the activation of Parp1, partly regulated by endogenous c-Myc, effectively promotes iPSC production and helps to maintain a pluripotent state by posttranslationally modulating protein PARylation.
A<i>BTB/POZ</i>Gene,<i>NAC-1</i>, a Tumor Recurrence–Associated Gene, as a Potential Target for Taxol Resistance in Ovarian Cancer
Authors: Masako Ishibashi, Kentaro Nakayama, Shamima Yeasmin, Atsuko Katagiri, Kouji Iida, Naomi Nakayama, Manabu Fukumoto, Kohji Miyazaki
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We previously determined that NAC-1, a transcription factor and member of the BTB/POZ gene family, is associated with recurrent ovarian carcinomas. In the current study, we investigated further the relationship between NAC-1 expression and ovarian cancer. Experimental Design: NAC-1 expression was assessed by immunohistochemistry, and clinical variables were collected by retrospective chart review. SiRNA system and NAC-1 gene transfection were used to asses NAC-1 function in Taxol resistance in vivo. Results: Overexpression of NAC-1 correlated with shorter relapse-free survival in patients with advanced stage (stage III/IV) ovarian carcinoma treated with platinum and taxane chemotherapy. Furthermore, overexpression of NAC-1 in primary tumors predicted recurrence within 6 months after primary cytoreductive surgery followed by standard platinum and taxane chemotherapy. NAC-1 expression levels were measured and compared among the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel. Overexpression of NAC-1 was observed in only the Taxol-resistant KF28TX and KFr13 TX cells but not in KF28 or cisplatin-resistant KFr13 cells. To confirm that NAC-1 expression was related to Taxol resistance, we used two independent but complementary approaches. NAC-1 gene knockdown in both KF28TX and KFr13TX rescued paclitaxel sensitivity. Additionally, engineered expression of NAC-1 in RK3E cells induced paclitaxel resistance. Conclusions: These results suggest that NAC-1 regulates Taxol resistance in ovarian cancer and may provide an effective target for chemotherapeutic intervention in Taxol-resistant tumors.
DIFFICULT MIDWIFERY IN GENERAL PRACTICE
Authors: S. G. Luker
Journal: BMJ (1923)

TMEDICALfJOtI3and olfactory lobes presented a dark brown greenish staining.The cortex of the cerebrum, pons, and cerebellum under the pia mater exhibited numorous black nodules and spots.There were melanotic Lumours in thoi base of the left lung, in the liver, in the retro- peritoneal tissue, and adherent to the outside of both suprarenal capsules, the substance of these organs being unaltered.Melanotic Cancer in the Olfactory Mucous Membrane.I have already stated that melanin pigment is of regular occurrence in the olfactory epitlhelium and in that of the labyrinth.Mr. de Santi has recently removed a melanotic cancer growing high up on the nasal septum, and the patient so far has no recurrence.The case is an extremely rare onie.Mr. Arthur Cheatle has informed me that the Dccurrence of a melanotic growth in the labyrinth is not known to him.CONCLUSION.Experience incident to the removal of a large number of melanomas is similar to that in connexion with other varieties of new growths.Free and early excision is not followed by recurrence in situ except in malignant cases where the disease has already spread widely.Simultaneously with the change from melanoma to melanotic cancer there is a detachment and degeneration of cells pro- ducing metastasis which exhibits itself later on.The general bearing of recent observations suggests the hope that further chemical research may arrive at a means of controlling the disease by therapeutic measures.RErsEREcEs.
DETERMINATION OF HÆMOGLOBIN II. THE HALDANE HÆMOGLOBIN STANDARD COMPARED WITH IRON AND GASOMETRIC ESTIMATIONS
Authors: E.J. King, M. Gilchrist, I.D.P. Wootton, R. Donaldson, R.B. Sisson, R.G. Macfarlane, H.M. Jope, J.R.P. O'Bbien, J.M. Peterson, D.H. Strangeways
Journal: The Lancet (1947)
p53 negatively regulates intestinal immunity by delaying mucosal T cell cycling
Authors: Andreas Sturm, Jugoh Itoh, James W. Jacobberger, Claudio Fiocchi
Journal: Journal of Clinical Investigation (2002)

To mount an effective immune response, T cells must divide in response to antigen contact. To maintain tolerance, mucosal lamina propria T cells (LPTs) may adapt their cycling to an antigen-rich gut stimulatory environment. Here, we compared the cell cycle kinetics of LPTs and peripheral blood T cells (PBTs) before and after CD3- and CD2-mediated activation. While CD3-activated naive (CD45RA+) and memory (CD45RO+) PBTs peaked in the S and G2/M phase at 2–3 days, CD3-activated LPTs peaked at 4–6 days. In contrast, CD2 activation induced modest PBT but vigorous LPT cycling. The doubling time of CD3-activated PBTs was 1 day, while that of CD3- or CD2-activated LPTs was 2 days. LPTs failed to upregulate cyclin-dependent kinase 4 and cyclin D3, but Rb phosphorylation and cyclin A and B1 upregulation were induced by CD2 engagement. The extents of clonal expansion in LPT and PBT were comparable, indicating that LPTs’ slow replication delays but does not hinder cell division. CD2-activated LPTs displayed a striking upregulation of p53, whose blockade by antisense oligonucleotides accelerated their S phase transit time to that of CD3-activated PBTs. By slowing LPT cycling, p53 may act as a negative regulator of mucosal immunity, promoting immunological tolerance by preventing excessive T cell replication.
An Improved Likelihood Ratio Test for Detecting Site-Specific Functional Divergence among Clades of Protein-Coding Genes
Authors: Cameron J. Weadick, Belinda S.W. Chang
Journal: Molecular Biology and Evolution (2011)

Maximum likelihood codon substitution models have proven useful for studying when and how protein function evolves, but they have recently been criticized on a number of fronts. The strengths and weaknesses of such methods must therefore be identified and improved upon. Here, using simulations, we show that the Clade model C versus M1a test for functional divergence among clades is prone to false positives under simple evolutionary conditions. We then propose a new null model (M2a_rel) that better accounts for among-site variation in selective constraint. We show that the revised test has an improved false-positive rate and good power. Applying this test to previously analyzed data sets of primate ribonucleases and mammalian rhodopsins reveals that some conclusions may have been misled by the original method. The improved test should prove useful for identifying patterns of divergence in selective constraint among paralogous gene families and among orthologs from ecologically divergent species.
The Role of Cytidine Deaminase and GATA1 Mutations in the Increased Cytosine Arabinoside Sensitivity of Down Syndrome Myeloblasts and Leukemia Cell Lines
Authors: Yubin Ge, Tanya L. Jensen, Mark L. Stout, Robin M. Flatley, Patrick J. Grohar, Yaddanapudi Ravindranath, Larry H. Matherly, Jeffrey W. Taub
Journal: Cancer Research (2004)

Abstract Myeloblasts from Down syndrome (DS) children with acute myeloid leukemia (AML) are significantly more sensitive in vitro to 1-β-d-arabinofuranosylcytosine (ara-C) and generate higher 1-β-d-arabinofuranosylcytosine 5′-triphosphate (ara-CTP) than non-DS AML myeloblasts. Semiquantitative reverse transcription-PCR analyses demonstrated that transcripts for cytidine deaminase (CDA) were 2.7-fold lower in DS than for non-DS myeloblasts. In contrast, transcripts of cystathionine-β-synthase and deoxycytidine kinase were a median 12.5- and 2.6-fold higher in DS compared with non-DS myeloblasts. The ratio of deoxycytidine kinase/CDA transcripts significantly correlated with ara-C sensitivities and ara-CTP generation. In clinically relevant AML cell line models, high cystathionine-β-synthase transcripts in DS CMK cells were accompanied by 10-fold greater ara-C sensitivity and 2.4-fold higher levels of ara-CTP compared with non-DS CMS cells. Overexpression of CDA in non-DS THP-1 cells was associated with a 100-fold decreased ara-C sensitivity and 40-fold decreased ara-CTP generation. THP-1 cells secreted CDA into the incubation media and converted extracellular ara-C completely to 1-β-d-arabinofuranosyluracil within 30 min. Rapid amplification of 5′-cDNA ends (5′-RACE) and reverse transcription-PCR assays identified short- (sf) and long-form (lf) CDA transcripts in THP-1 cells with different 5′ untranslated regions and translational start sites; however, only the latter resulted in the active CDA. Although 5′ flanking sequences for both CDA transcripts exhibited promoter activity in reporter gene assays, activity for the CDAlf was low. The presence of several GATA1 binding sites in the CDAsf promoter and the uniform detection of GATA1 mutations in DS megakaryocytic leukemia suggested the potential role of GATA1 in regulating CDA transcription and the CDAsf promoter acting as an enhancer. Transfection of GATA1 into Drosophila Mel-2 cells stimulated the CDAlf promoter in a dose-dependent fashion. Additional identification of the mechanisms of differential expression of genes encoding enzymes involved in ara-C metabolism between DS and non-DS myeloblasts may lead to improvements in AML therapy.
Exertional Leg Pain in Patients With and Without Peripheral Arterial Disease
Authors: Jimmy C. Wang, Michael H. Criqui, Julie O. Denenberg, Mary M. McDermott, Beatrice A. Golomb, Arnost Fronek
Journal: Circulation (2005)

Background— Although exertional leg pain is a hallmark of peripheral arterial disease (PAD) and can occur in persons without PAD, symptom variation has received inadequate attention. Methods and Results— Three cohort studies were combined for cross-sectional analysis. The San Diego Claudication Questionnaire assessed exertional leg pain. PAD was defined as ankle brachial index (ABI) ≤0.90 or history of lower-extremity revascularization. Of 3658 subjects, 3629 were analyzed after exclusions. Of these, 24.1% had PAD in 1 or both legs. There was a stepwise decrease in average ABI, from no pain to pain on exertion and rest, noncalf pain, atypical calf pain, and classic claudication ( P =0.002). When stratified by PAD, this trend was no longer significant. Legs with ABIs &gt;0.90 and revascularization had pain distributions intermediate between that of normal legs (ABI, 1.00 to 1.39) and legs with ABIs ≤0.90. Compared with normal legs, legs with low-normal (0.91 to 0.99) and high-normal (≥1.40) ABIs had higher pain rates, suggesting borderline disease and vascular stiffness, respectively. Multivariable logistic regression models showed that ABI was a strong correlate of pain category throughout the ABI range. Independently of ABI, age, male sex, diabetes, smoking history, high body mass index, myocardial infarction, and previous revascularization were all significant correlates of exertional leg pain. Conclusions— No category of exertional leg pain was sufficiently sensitive or specific for routine PAD diagnosis. Legs with low-normal and high-normal ABIs appeared to have ischemic leg pain; thus, a “normal ABI” is likely to range from 1.00 to 1.39. In addition to ABI, several risk variables were independent correlates of exertional leg pain.
Drug combinations and all cause mortality in heart disease: Use of statins is not supported by study
Authors: Eddie Vos
Journal: BMJ (2005)

Drug combinations and all cause mortality in heart disease No new insights were gainedEditor-Hippisley-Cox and Coupland conclude that the addition of angiotensin converting enzyme (ACE) inhibitors to combinations of drugs conferred no additional benefit in their study of patients in primary care with ischaemic heart disease. 1 However, such a conclusion should be reached with caution.The drugs were given to the patients with the highest risk of death.A higher percentage of patients who died were treated with ACE inhibitors, and the greatest improvement in risk of death after adjustment for risk factors was seen in the patients treated with these drugs.ACE inhibitors might thus have been given to the patients with the most severe disease in each comorbidity group-for example, to diabetic patients with kidney disease and to patients with the most severe heart failure.Therefore the study can give no indication of the crucial question whether the outcome would have been equally good for the group of 463 patients who probably had the most severe disease and received statins, aspirin, blockers, and ACE inhibitors if they had not been given ACE inhibitors.Replacement of yes or no for comorbidity factors with more discriminating variables, such as presence of microalbuminuria and a severity measure for heart disease, would probably have improved the study.However, this cannot replace the quality of a randomised, placebo controlled study comparing the effect of adding ACE inhibitors to the other study drugs.Therefore the study by Hippisley-Cox and Coupland adds no new knowledge to how patients with ischaemic heart disease in primary care should be treated.
Aberrant Face and Gaze Habituation in Fragile X Syndrome
Authors: Jennifer Lynn Bruno, Amy S. Garrett, Eve-Marie Quintin, Paul K. Mazaika, Allan L. Reiss
Journal: American Journal of Psychiatry (2014)

The authors sought to investigate neural system habituation to face and eye gaze in fragile X syndrome, a disorder characterized by eye-gaze aversion, among other social and cognitive deficits.
Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia
Authors: Marina Konopleva, Twee Tsao, Peter Ruvolo, Irina Stiouf, Zeev Estrov, Clinton E. Leysath, Shourong Zhao, David Harris, Shirong Chang, C. Ellen Jackson, Mark Munsell, Nanjoo Suh, Gordon Gribble, Tadashi Honda, W. Stratford May, Michael B. Sporn, Michael Andreeff
Journal: Blood (2002)
BILAG-2004 index captures systemic lupus erythematosus disease activity better than SLEDAI-2000
Authors: C-S Yee, D A Isenberg, A Prabu, K Sokoll, L-S Teh, A Rahman, I N Bruce, B Griffiths, M Akil, N McHugh, D D'Cruz, M A Khamashta, P Maddison, A Zoma, C Gordon
Journal: Annals of the Rheumatic Diseases (2007)

To assess the reliability of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture disease activity as compared with the British Isles Lupus Assessment Group (BILAG)-2004 index.Patients with systemic lupus erythematosus from 11 centres were assessed separately by two raters in routine practice. Disease activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of agreement for items was used to assess the reliability of SLEDAI-2000. The ability to detect disease activity was assessed by determining the number of patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI-2000 score (<6) and number of patients with low activity on BILAG-2004 (overall score C, D or E) but high SLEDAI-2000 score (>or=6). Treatment of these patients was analysed, and the increase in treatment was used as the gold standard for active disease.93 patients (90.3% women, 69.9% Caucasian) were studied: mean age was 43.8 years, mean disease duration 10 years. There were 43 patients (46.2%) with a difference in SLEDAI-2000 score between the two raters and this difference was >or=4 in 19 patients (20.4%). Agreement for each of the items in SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased. There were only five patients (5.4%) with low activity on BILAG-2004 but a high SLEDAI-2000 score.SLEDAI-2000 is a reliable index to assess systemic lupus erythematosus disease activity but it is less able than the BILAG-2004 index to detect active disease requiring increased treatment.
Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated Phenotype
Authors: Wilma C.G. van Staveren, David Weiss Solís, Laurent Delys, Laurence Duprez, Guy Andry, Brigitte Franc, Gerry Thomas, Frédérick Libert, Jacques E. Dumont, Vincent Detours, Carine Maenhaut
Journal: Cancer Research (2007)

Cell lines are crucial to elucidate mechanisms of tumorigenesis and serve as tools for cancer treatment screenings. Therefore, careful validation of whether these models have conserved properties of in vivo tumors is highly important. Thyrocyte-derived tumors are very interesting for cancer biology studies because from one cell type, at least five histologically characterized different benign and malignant tumor types can arise. To investigate whether thyroid tumor-derived cell lines are representative in vitro models, characteristics of eight of those cell lines were investigated with microarrays, differentiation markers, and karyotyping. Our results indicate that these cell lines derived from differentiated and undifferentiated tumor types have evolved in vitro into similar phenotypes with gene expression profiles the closest to in vivo undifferentiated tumors. Accordingly, the absence of expression of most thyrocyte-specific genes, the nonresponsiveness to thyrotropin, as well as their large number of chromosomal abnormalities, suggest that these cell lines have acquired characteristics of fully dedifferentiated cells. They represent the outcome of an adaptation and evolution in vitro, which questions the reliability of these cell lines as models for differentiated tumors. However, they may represent useful models for undifferentiated cancers, and by their comparison with differentiated cells, can help to define the genes involved in the differentiation/dedifferentiation process. The use of any cell line as a model for a cancer therefore requires prior careful and thorough validation for the investigated property.
Visits to the country pose biggest risk of E coli infection
Authors: B. Christie
Journal: BMJ (2001)

Camping trips and visits to the countryside pose a greater risk of E coli 0157 infection than contaminated food, an expert task force set up in Scotland to investigate the problem has concluded.

It says that the highest risk comes from contact with fresh animal faeces and recommends that precautions be taken to keep farm animals away from land to be used for recreational purposes.

The United Kingdom has one of the highest rates of E coli 0157 poisoning in the world, and Scotland is the worst …
Bioinformatic Analysis of the Urine Proteome of Acute Allograft Rejection
Authors: Edmond O’Riordan, Tatyana N. Orlova, Jianfeng Mei J, Khalid Butt, Praveen M. Chander, Shafiq Rahman, Muong Mya, Rena Hu, Jahangir Momin, Elizabeth W. Eng, Dierk J. Hampel, Bertram Hartman, Matthias Kretzler, Veronica Delaney, Michael S. Goligorsky
Journal: Journal of the American Society of Nephrology (2004)

The urinary proteome in health and disease attracts increasing attention because of the potential diagnostic and pathophysiologic biomarker information carried by specific excreted proteins or their constellations. This cross-sectional study aimed to analyze the urinary proteome in patients with biopsy-proven acute rejection (<i>n</i> = 23) compared with transplant recipients with stable graft function (<i>n</i> = 22) and healthy volunteers (<i>n</i> = 20) and to correlate this with clinical, morphologic, and laboratory data. Urine samples were preadsorbed on four different protein chip surfaces, and the protein composition was analyzed using a surface-enhanced laser desorption/ionization time-of-flight mass spectrometer platform. The data were analyzed using two independent approaches to sample classification. Patients who experienced acute rejection could be distinguished from stable patients with a sensitivity of 90.5 to 91.3% and a specificity of 77.2 to 83.3%, depending on the classifier used. Protein masses that were important in constructing the classification algorithms included those of mass 2003.0, 2802.6, 4756.3, 5872.4, 6990.6, 19,018.8, and 25,665.7 Da. Normal urine was distinguished from transplant urine using a protein marker of mass 78,531.2 Da with both a sensitivity and a specificity of 100%. In conclusion, (<i>1</i>) urine proteome in transplant recipients with stable graft function was significantly different from healthy control subjects, and (<i>2</i>) acute rejections were characterized by a constellation of excreted proteins. Analysis of the urinary proteome may expedite the noninvasive prediction of acute graft rejection, thus importantly assisting in establishing the diagnosis.