tbuckley/cabot-search huggingface dataset:
An antiinflammatory role for IKKβ through the inhibition of “classical” macrophage activation
Authors: Carol Ho Yan Fong, Magali Bebien, Arnaud Didierlaurent, Ruth Nebauer, Tracy Hussell, David Broide, Michael Karin, Toby Lawrence
Journal: The Journal of Experimental Medicine (2008)

The nuclear factor kappaB (NF-kappaB) pathway plays a central role in inflammation and immunity. In response to proinflammatory cytokines and pathogen-associated molecular patterns, NF-kappaB activation is controlled by IkappaB kinase (IKK)beta. Using Cre/lox-mediated gene targeting of IKKbeta, we have uncovered a tissue-specific role for IKKbeta during infection with group B streptococcus. Although deletion of IKKbeta in airway epithelial cells had the predicted effect of inhibiting inflammation and reducing innate immunity, deletion of IKKbeta in the myeloid lineage unexpectedly conferred resistance to infection that was associated with increased expression of interleukin (IL)-12, inducible nitric oxide synthase (NOS2), and major histocompatibility complex (MHC) class II by macrophages. We also describe a previously unknown role for IKKbeta in the inhibition of signal transducer and activator of transcription (Stat)1 signaling in macrophages, which is critical for IL-12, NOS2, and MHC class II expression. These studies suggest that IKKbeta inhibits the "classically" activated or M1 macrophage phenotype during infection through negative cross talk with the Stat1 pathway. This may represent a mechanism to prevent the over-exuberant activation of macrophages during infection and contribute to the resolution of inflammation. This establishes a new role for IKKbeta in the regulation of macrophage activation with important implications in chronic inflammatory disease, infection, and cancer.
Pulmonary Manifestations of Gaucher Disease
Authors: FRANCESCA SANTAMARIA, GIANCARLO PARENTI, GUIDO GUIDI, MIRELLA FILOCAMO, PIETRO STRISCIUGLIO, GIACOMO GRILLO, VINCENZO FARINA, PAOLA SARNELLI, MARIA GRAZIA RIZZOLO, ANTONIO ROTONDO, GENEROSO ANDRIA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Pulmonary disease is a complication of Gaucher disease (GD), a lysosomal disorder due to the deficiency of glucocerebrosidase. Lung involvement was investigated through chest radiography, high-resolution computed tomography of the chest, pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13 Italian GD patients, six homoallelic for the L444P mutation (Group A), seven with various genotypes (Group B). Echocardiography and transcutaneous oxygen tension measurement at room air and after breathing 100% oxygen were performed to exclude pulmonary hypertension and/or intrapulmonary shunts. A score index (SI) including lung involvement evaluated the severity of GD. In three Group A patients with respiratory symptoms and in an asymptomatic male interstitial involvement was demonstrated; one child died of aspiration pneumonia. Group B patients had no signs of lung damage; PFT were normal in all cases but one. SaO2 was normal in both groups. Pulmonary vascular disease was ruled out in three cases with respiratory symptoms. In Groups A and B the median SI were 22 and 13, respectively (p < 0.01). L444P homozygotes appear at major risk for developing pulmonary disease, even at earlier ages. A comprehensive evaluation of lung involvement is recommended primarily in these subjects.
Topical ketoprofen TDS patch versus diclofenac gel: efficacy and tolerability in benign sport related soft-tissue injuries * COMMENTARY * COMMENTARY
Authors: Francisco Esparza, César Cobián, José Fernando Jiménez, Juan José García-Cota, Carlos Sánchez, Antonio Maestro
Journal: British Journal of Sports Medicine (2006)

To compare the ketoprofen TDS patch with diclofenac gel in the treatment of traumatic acute pain in benign sport-related soft-tissue injuries.7-14 treatment days, prospective, randomised, open study.Outpatients aged 18-70 years diagnosed for painful benign sport-related soft-tissue injury (sprains, strains and contusions within the prior 48 h), randomised to either ketoprofen patch 100 mg once daily (n = 114) or diclofenac gel 2-4 g three times daily (n = 109).7-14 days of topical non-steroidal anti-inflammatory drugs treatment to assess the pain intensity changes (daily activities and spontaneous at rest) in a daily diary (100-mm Visual Analogue Scale (VAS)).Pain intensity (VAS).The ketoprofen patch was not inferior to diclofenac gel in reducing the baseline pain during daily activities (difference of -1.17 mm in favour of ketoprofen patch, 95% CI (-5.86 to 3.52), reducing to the baseline VAS 79%. Ketoprofen patch presented also a higher cure rate (64%) than diclofenac gel (46%) at day 7 (p = 0.004). Patient opinions about the treatment comfort (pharmaceutical shape, application and dosage) were also statistically higher for the ketoprofen patch (>80% of the patients rated as good or excellent the patch removal and skin adherence).Ketoprofen patches are effective and safe pain relievers for the treatment of sports injury pain with advantages compared with diclofenac gel.
EVIDENCE THAT THE <scp>L</scp>-ASPARAGINASE OF GUINEA PIG SERUM IS RESPONSIBLE FOR ITS ANTILYMPHOMA EFFECTS
Authors: J. D. Broome
Journal: The Journal of Experimental Medicine (1963)

Cells of the original line of lymphoma 6C3HED, which regularly prove susceptible to the effects of guinea pig serum in vivo, were cultured in Eagle's medium devoid of L-asparagine; after a latent period of 2 or more weeks, during which time the cell population declined markedly, some of the cells began to proliferate, and thereafter continued vigorous growth. On implantation into mice the proliferating cells were found, however, to have completely and permanently lost their susceptibility to the effects of guinea pig serum. By contrast, when cultures of the original line of 6C3HED cells were prepared in Eagle's medium to which L-asparagine was added in a concentration of 20.0 mg/liter or more, they proliferated vigorously from the beginning; after long periods of growth in the enriched medium in vitro they remained susceptible to the effects of guinea pig serum upon test in vivo. Other amino acids, purines, and pyrimidines were unable to substitute for L-asparagine in this relation. Furthermore, a variant subline of 6C3HED cells which had become insensitive to guinea pig serum under in vivo conditions did not require L-asparagine for growth in tissue culture. It seems plain from the findings as a whole, that in 6C3HED cells, L-asparagine dependence in vitro is associated with the in vivo character of guinea pig serum sensitivity, and conversely L-asparagine independent variants are insusceptible to the effects of guinea pig serum. The implications of the findings complement those of a companion paper in which direct evidence is provided that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects.
2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling
Authors: Xudong Fu, Randall M. Chin, Laurent Vergnes, Heejun Hwang, Gang Deng, Yanpeng Xing, Melody Y. Pai, Sichen Li, Lisa Ta, Farbod Fazlollahi, Chuo Chen, Robert M. Prins, Michael A. Teitell, David A. Nathanson, Albert Lai, Kym F. Faull, Meisheng Jiang, Steven G. Clarke, Timothy F. Cloughesy, Thomas G. Graeber, Daniel Braas, Heather R. Christofk, Michael E. Jung, Karen Reue, Jing Huang
Journal: Cell Metabolism (2015)
Aberrant Expression and Potency as a Cancer Immunotherapy Target of Inhibitor of Apoptosis Protein Family, Livin/ML-IAP in Lung Cancer
Authors: Hiroyuki Hariu, Yoshihiko Hirohashi, Toshihiko Torigoe, Hiroko Asanuma, Midori Hariu, Yasuaki Tamura, Katsuyuki Aketa, Chika Nabeta, Katsuya Nakanishi, Kenjiro Kamiguchi, Yoshinori Mano, Hiroshi Kitamura, Junichi Kobayashi, Tomohide Tsukahara, Noriharu Shijubo, Noriyuki Sato
Journal: Clinical Cancer Research (2005)

CD8(+) CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP(+) lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.
Development of severe hypoxaemia in chronic obstructive pulmonary disease patients at 2,438 m (8,000 ft) altitude
Authors: CC Christensen, M Ryg, OK Refvem, OH Skjonsberg
Journal: European Respiratory Journal (2000)

The arterial oxygen tensions (Pa,02) in chronic obstructive pulmonary disease (COPD) patients travelling by air, should, according to two different guidelines, not be lower than 7.3 kPa (55 mmHg) and 6.7 kPa (50 mmHg), respectively, at a cabin pressure altitude of 2,438 m (8,000 ft). These minimum in-flight Pa,O2 values are claimed to correspond to a minimum Pa,O2 of 9.3 kPa (70 mmHg) at sea-level. The authors have tested whether this limit is a safe criterion for predicting severe in-flight hypoxaemia. The authors measured arterial blood gases at sea-level, at 2,438 m and at 3,048 m (10,000 ft) in an altitude chamber at rest and during light exercise in 15 COPD patients with forced expiratory volume in one second (FEV1) &lt;50% of predicted, and with sea-level Pa,O2 &gt;9.3 kPa. Resting Pa,O2 decreased below 7.3 kPa and 6.7 kPa in 53% and 33% of the patients, respectively, at 2,438 m, and in 86% and 66% of the patients at 3,048 m. During light exercise, Pa,O2 dropped below 6.7 kPa in 86% of the patients at 2,438 m, and in 100% of the patients at 3,048 m. There was no correlation between Pa,O2 at 2,438 m and pre-flight values of Pa,O2, FEV1 or transfer factor of the lung for carbon monoxide. In contrast to current medical guidelines, it has been found that resting arterial oxygen tension &gt;9.3 kPa at sea-level does not exclude development of severe hypoxaemia in chronic obstructive pulmonary disease patients travelling by air. Light exercise, equivalent to slow walking along the aisle, may provoke a pronounced aggravation of the hypoxaemia.
Identification of conserved gene structures and carboxy-terminal motifs in the Myb gene family of Arabidopsis and Oryza sativa L. ssp. indica
Authors: Cizhong Jiang, Xun Gu, Thomas Peterson
Journal: Genome biology (2004)

Myb proteins contain a conserved DNA-binding domain composed of one to four repeat motifs (referred to as R0R1R2R3); each repeat is approximately 50 amino acids in length, with regularly spaced tryptophan residues. Although the Myb proteins comprise one of the largest families of transcription factors in plants, little is known about the functions of most Myb genes. Here we use computational techniques to classify Myb genes on the basis of sequence similarity and gene structure, and to identify possible functional relationships among subgroups of Myb genes from Arabidopsis and rice (Oryza sativa L. ssp. indica).This study analyzed 130 Myb genes from Arabidopsis and 85 from rice. The collected Myb proteins were clustered into subgroups based on sequence similarity and phylogeny. Interestingly, the exon-intron structure differed between subgroups, but was conserved in the same subgroup. Moreover, the Myb domains contained a significant excess of phase 1 and 2 introns, as well as an excess of nonsymmetric exons. Conserved motifs were detected in carboxy-terminal coding regions of Myb genes within subgroups. In contrast, no common regulatory motifs were identified in the noncoding regions. Additionally, some Myb genes with similar functions were clustered in the same subgroups.The distribution of introns in the phylogenetic tree suggests that Myb domains originally were compact in size; introns were inserted and the splicing sites conserved during evolution. Conserved motifs identified in the carboxy-terminal regions are specific for Myb genes, and the identified Myb gene subgroups may reflect functional conservation.
Risk of suicide in twins: 51 year follow up study
Authors: Cecilia Tomassini, Knud Juel, Niels V Holm, Axel Skytthe, Kaare Christensen
Journal: BMJ (2003)

the question with an existing scale and not a semistructured interview. 4 5Such a subjective question requires further rigorous evaluation before we advocate its widespread application to screen for depression in patients with advanced cancer.
Clinicians' offer to help monitor public health responsibility deal is ignored by government
Authors: A. O'Dowd
Journal: BMJ (2011)

An offer by clinicians to help monitor and evaluate the effects of the government’s responsibility deal with the food and drinks industry on public health has been ignored so far, MPs have been told.

The national responsibility deal agreement between the government and the food and drinks industry, which was launched in March, contains a series of voluntary pledges aimed at improving public health, including improved labelling on calorie and alcohol contents of food and drink and efforts to improve promote physical activity and health through the workplace ( BMJ 2011;342:d1702; doi:10.1136/bmj.d1702). 

Many health bodies and charities refused to sign up to it, including the BMA, Alcohol Concern, and the UK Alcohol Health Alliance, which comprises 32 health organisations …
Validity of a Simple ST-Elevation Acute Myocardial Infarction Risk Index
Authors: Saif S. Rathore, Kevin P. Weinfurt, Cary P. Gross, Harlan M. Krumholz
Journal: Circulation (2003)

Risk-stratification scores derived from randomized clinical trial (RCT) data should be evaluated in community-based populations. A simple risk-stratification index for patients with ST-segment elevation myocardial infarction derived from an RCT population was recently proposed, but it has not been validated in a community-based cohort.We evaluated the simple risk index using data from 49 711 patients > or =65 years of age hospitalized with ST-elevation myocardial infarction. We evaluated the distribution of patients in the 5 simple risk index groups, compared observed and published 30-day mortality rates, and assessed the score's discrimination and calibration. The simple risk index provided poor discrimination (c=0.62) and calibration (goodness of fit P<0.001) for survival at 30 days. Risk score distribution was skewed, because two thirds (66.1%) of all patients were classified in the highest-risk group, whereas fewer than 11.0% were classified in the 3 lowest-risk groups. Thirty-day mortality estimates were lower than those observed in the cohort (risk group 2 to 5: 1.9% to 17.4% versus 5.3% to 27.9%). Risk index discrimination, calibration, score distribution, and mortality estimates were worse among patients who did not receive acute reperfusion therapy than among those who did.The limited performance of the simple risk index highlights the limitations of applying prognostic models derived in RCT populations to the general population of patients 65 years and older. Prognostic scores must be validated in community-based cohorts before integration into clinical practice.
Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors
Authors: Widya Mulyasasmita, Lei Cai, Ruby E. Dewi, Arshi Jha, Sabrina D. Ullmann, Richard H. Luong, Ngan F. Huang, Sarah C. Heilshorn
Journal: Journal of Controlled Release (2014)
Long-term oxygen therapy
Authors: T. L. Petty
Journal: European Respiratory Journal (2005)

To the Editors: 

The topic of long term oxygen therapy (LTOT) has been a great interest to our group, beginning with our first report in 1967 1. Here, we showed a marked increase in exercise capability with use of ambulatory oxygen (AO) in selected patients with advanced chronic obstructive pulmonary disease (COPD). By contrast, the carefully carried out, randomised, controlled study of AO in oxygen-dependent patients, recently published in the European Respiratory Journal , concludes that AO is not associated with increased walk tolerance or improved quality of life …
Effect of intra-abdominal volume increment on kidneys in minipigs with intra-abdominal hypertension after hemorrhagic shock and resuscitation
Authors: Zheng-gang Wang, Hao Tan, Lian-yang Zhang, Dao-cheng Liu, Hua-liang Xiao, Wen-hua Du
Journal: Military Medical Research (2014)

To investigate the effect of intra-abdominal volume increment (IAVI) on intra-abdominal hypertension (IAH) in the kidneys. Eight minipigs were successfully established as IAH models and were randomly divided into two groups: the IAVI group and the sham-operated group. The intravesicular pressure, inferior vena cava pressure and urine volume were measured before shock, 2 h after IAH, and 22 h after surgery, respectively. The following indices were measured: serum creatinine, urea nitrogen, renal cortical thickness, ratio of abdominal anteroposterior diameter/transverse diameter, renal thickness, diameter of the renal sinus and the wet/dry ratio of renal tissues. The intravesicular pressure (IVP) of the 8 minipig IAH models was calculated to be 21.16 ± 4.63 mmHg. There was a significant increase in the abdominal anteroposterior diameter/transverse diameter ratio. The minipigs in the IAVI group survived during the observational period, whereas 2 minipigs died at 18 h and 20 h in the sham-operated group. Twenty-two hours after surgery, the animals in the IAVI group displayed increased urinary volume (UV) and decreased Cr and Ur and remarkable decreases of VP and IVCP. After IAH, the renal cortical thickness and the renal thickness increased significantly. The renal wet/dry ratio in the sham-operated group was higher than that in the IAVI group. IAVI helps to control renal dysfunction after IAH, which may be related to lowering the intra-abdominal pressure, thus alleviating renal edema and blood stasis.
Can We Predict Who's at Risk for Developing Bone Metastases in Breast Cancer?
Authors: Larissa A. Korde, Julie R. Gralow
Journal: Journal of Clinical Oncology (2011)

Bone metastases are common in patients with advanced breast cancer.Bone is the first site of distant disease in 25% to 40% of patients with metastatic breast cancer, and up to 60% to 80% of patients with recurrent breast cancer eventually show evidence of skeletal involvement. 1 The process of breast cancer metastasis, including tumor cell seeding, tumor dormancy, and metastatic growth, is only partly
Histocompatibility antigens in plaque psoriasis and palmoplantar pustulosis
Authors: D. Kemmett, Irene M. Leigh, H.A. Baker, D. McCloskey, A. Alonso, J. Awad, H. Festenstein
Journal: British Journal of Dermatology (1985)

The inheritance of susceptibility to psoriasis is thought to be multifactorial; expression of the disorder being influenced by environmental factors. Studies of histocompatibility antigens (HLA) help our understanding of the genetic inheritance of susceptibility to the disease. Early HLA studies in chronic plaque psoriasis (CPP) have shown an increased incidence of B13 and B17. More recently the antigens CW6 and DR7 have also been shown to be increased. No statistical increase has been shown in patients with persistent pustular psoriasis of the palms and soles (PPP). However there are limited data on class II antigens in this group. No previous study has compared the two groups of patients in the same population or compared clinical subsets of CPP. Eighty‐five British Caucasian patients with CPP and 45 with PPP were typed for antigens of the HLA A, B, C and DR loci. Our results confirm the increased frequencies of B13, BW57 (B17), Cw6 and DR7 in CPP patients compared with controls, and we have also found a previously unreported decrease in the frequency of BW44 (B12). In contrast the PPP patient group had increased frequencies of B8, Cw7 and DR3. HLA associations of subsets of patients related with family history, age of onset, severity of disease, the presence of arthritis and nail changes have also been assessed.
ERKs in Cancer: Friends or Foes?
Authors: Xavier Deschênes-Simard, Filippos Kottakis, Sylvain Meloche, Gerardo Ferbeyre
Journal: Cancer Research (2014)

Abstract The extracellular signal–regulated kinase ERK1 and ERK2 (ERK1/2) cascade regulates a variety of cellular processes by phosphorylating multiple target proteins. The outcome of its activation ranges from stimulation of cell survival and proliferation to triggering tumor suppressor responses such as cell differentiation, cell senescence, and apoptosis. This pathway is intimately linked to cancer as several of its upstream activators are frequently mutated in human disease and are shown to accelerate tumorigenesis when engineered in the mouse genome. However, measurement of activated ERKs in human cancers or mouse models does not always support a role in tumorigenesis, and data consistent with a role in tumor suppression have been reported as well. The intensity of ERK signaling, negative feedback loops that regulate the pathway, and cross-talks with other signaling pathways, seem to be of primary importance in determining the final cellular outcome. Cell senescence, a putative tumor-suppression mechanism, depends on high-intensity ERK signals that trigger phosphorylation-dependent protein degradation of multiple proteins required for cell-cycle progression. This response may be circumvented during carcinogenesis by a variety of mechanisms, some of them yet to be discovered, which in essence turn ERK functions from tumor suppression to tumor promotion. The use of pharmacologic inhibitors targeting this pathway must be carefully evaluated so they are applied to cases in which ERKs are mainly oncogenic. Cancer Res; 74(2); 412–9. ©2014 AACR.