tbuckley/cabot-search huggingface dataset:
Role of tumor necrosis factor-alpha on mesangial cell MCP-1 expression and monocyte migration
Authors: R Pai, H Ha, M A Kirschenbaum, V S Kamanna
Journal: Journal of the American Society of Nephrology (1996)

Monocyte chemotactic protein-1 (MCP-1), a specific chemoattractant for monocytes, has been thought to play an important role in the recruitment and accumulation of monocytes within the glomerulus seen in glomerular diseases. This study examined the role of tumor necrosis factor (TNF)-alpha-mediated cellular signal transduction pathways on mesangial cell MCP-1 gene expression and monocyte migration. Incubation of mesangial cells with TNF-alpha stimulated MCP-1 mRNA expression in a dose- and time-dependent manner. Phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, increased MCP-1 message by mesangial cells while depleting PKC decreased MCP-1 gene expression to control levels. Activation of PKC-depleted mesangial cells with PMA but not with TNF-alpha inhibited MCP-1 mRNA expression. Similarly, calphostin C, a PKC inhibitor, failed to inhibit TNF-alpha-induced MCP-1 expression. The incubation of mesangial cells with various protein tyrosine kinase inhibitors (PTK, e.g., herbimycin, tyrphostin, genistein) blocked TNF-alpha-induced MCP-1 mRNA message. Additional experiments examining the role of cAMP on MCP-1 expression indicated that the preincubation of mesangial cells with various cAMP generating substances (pertussis toxin, isoproterenol, dbcAMP) did not induce mesangial cell MCP-1 mRNA transcripts. However, the coincubation of mesangial cells with TNF-alpha and dbcAMP completely inhibited TNF-alpha-induced MCP-1 gene expression. Finally, TNF-alpha-activated mesangial cell media increased monocyte transmigration that could be blocked by neutralizing anti-MCP-1. These studies indicate that TNF-alpha facilitates monocyte transmigration into the glomerulus mediated by the increased expression of MCP-1 by mesangial cells. TNF-alpha-induced mesangial cell MCP-1 expression is regulated by signal transduction pathways involving PTK but not those dependent on PKC or cAMP.
Longitudinal Study of the Relationship Between Chemoradiation Therapy for Non–Small-Cell Lung Cancer and Patient Symptoms
Authors: Xin Shelley Wang, Diane L. Fairclough, Zhongxing Liao, Ritsuko Komaki, Joe Y. Chang, Gary M. Mobley, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2006)

Cancer patients undergoing aggressive therapy suffer from multiple nonspecific treatment-related symptoms. The goal of this prospective study was to establish a profile of the development of different symptoms over the time of therapy and to examine symptom-related functional interference in patients with non-small-cell lung cancer (NSCLC) undergoing concurrent chemoradiation therapy (CXRT).Patients with locally advanced unresectable (stage II-IIIB) NSCLC were recruited for the study (N = 64). The M.D. Anderson Symptom Inventory (MDASI) was used to measure multiple symptoms before and weekly for 12 weeks after the start of CXRT. Mixed-effect growth curve models were used to estimate symptom development during CXRT.Approximately 63% of patients suffered from moderate to severe levels of multiple symptoms by the end of CXRT. Symptom clusters with four development patterns appeared over the time of CXRT. With some variation between patients, all symptoms had a significant impact on the level of interference (all P < .001). Fatigue, distress, and sadness were the single strongest predictors of total symptom interference (each R2 > or = 0.49). Physical symptoms had greater impact on interference with function when they were moderate to severe, whereas affective symptoms had the largest effect on interference when they were mild to moderate.Longitudinal analysis identified symptom clusters that have different development patterns in NSCLC patients receiving CXRT, providing a base for more accurate symptom management and suggesting the need for further study to identify potential mechanisms that might lead to better symptom control or prevention.
Chikungunya Outbreaks — The Globalization of Vectorborne Diseases
Authors: Rémi N. Charrel, Xavier de Lamballerie, Didier Raoult
Journal: New England Journal of Medicine (2007)

In 2006, an outbreak of chikungunya fever — an arthralgic disease caused by a mosquito-borne alphavirus — swept over a number of islands in the Indian Ocean (the Comoros, Mauritius, the Seychelles, Madagascar, Mayotte, and Reunion). In Reunion, which has a population of 770,000, there were 265,000 clinical cases (an incidence of 34%), and the disease was implicated in 237 deaths (about 1 per 1000 clinical cases); a recent report by Reunion health authorities indicated that the seroprevalence was 35%, with very few asymptomatic cases. The epidemic had started with outbreaks in Kenya in 2004 and the Comoros early in . . .
Integrated, Genome-Wide Screening for Hypomethylated Oncogenes in Salivary Gland Adenoid Cystic Carcinoma
Authors: Chunbo Shao, Wenyue Sun, Marietta Tan, Chad A. Glazer, Sheetal Bhan, Xiaoli Zhong, Carole Fakhry, Rajni Sharma, William H. Westra, Mohammad O. Hoque, Christopher A. Moskaluk, David Sidransky, Joseph A. Califano, Patrick K. Ha
Journal: Clinical Cancer Research (2011)

Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy that is poorly understood. To look for relevant oncogene candidates under the control of promoter methylation, an integrated, genome-wide screen was conducted.Global demethylation of normal salivary gland cell strains using 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A (TSA), followed by expression array analysis was conducted. ACC-specific expression profiling was generated using expression microarray analysis of primary ACC and normal samples. Next, the two profiles were integrated to identify a subset of genes for further validation of promoter demethylation in ACC versus normal. Finally, promising candidates were further validated for mRNA, protein, and promoter methylation levels in larger ACC cohorts. Functional validation was then conducted in cancer cell lines.We found 159 genes that were significantly re-expressed after 5-aza-dC/TSA treatment and overexpressed in ACC. After initial validation, eight candidates showed hypomethylation in ACC: AQP1, CECR1, C1QR1, CTAG2, P53AIP1, TDRD12, BEX1, and DYNLT3. Aquaporin 1 (AQP1) showed the most significant hypomethylation and was further validated. AQP1 hypomethylation in ACC was confirmed with two independent cohorts. Of note, there was significant overexpression of AQP1 in both mRNA and protein in the paraffin-embedded ACC cohort. Furthermore, AQP1 was upregulated in 5-aza-dC/TSA-treated SACC83. Finally, AQP1 promoted cell proliferation and colony formation in SACC83.Our integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC. AQP1 is a promising oncogene candidate for ACC and is transcriptionally regulated by promoter hypomethylation.
Bilirubin Is Negatively Associated With A1C Independently of Fasting Plasma Glucose, Age, Obesity, Inflammation, Hemoglobin, and Iron in Apparently Healthy Japanese Men and Women
Authors: Eiji Oda
Journal: Diabetes Care (2010)

It has been reported that fasting plasma glucose (FPG) is not significantly associated with risks of cardiovascular disease (CVD) and death from any cause adjusting for A1C, but A1C was significantly associated with risks of CVD and death from any cause adjusting for FPG in nondiabetic adults (1). A1C levels appear to increase with age, and any condition that changes red cell turnover, such as hemolytic anemia, chronic malaria, major blood loss, or blood transfusions, will influence A1C levels (2). Other than age and iron deficiency, some cardiovascular risk factors related with inflammation and oxidant stress may have independent associations with …
ACUTE HAEMORRHAGIC PANCREATITIS: LAPAROTOMY: RECOVERY
Authors: G. W. K. Crosland
Journal: BMJ (1917)

Struthers, who founid nio redness, swelling, or fluctuation in the region of the hip, and a(lvised againist interference at that time.On February 4tlh it was noted that the temperaiture was still risinig each eveninig.Fluctuation was evidenit over the right ilium, anid ani inicision evacuate(d pus wlicil on culture vielded the Staphylococcus aureus.A drainage tube was in;serted.Pus was dailY evacuated oni washinig througlh the jugular bulb.The temperature colntinued to swing, and the patient still complainied of pain in the right hip.On February 7th he complained of pain in the right knee.Professor Lorraini Smith waas consultedl regarding the intra- venous injection of eusol, anid at 5 p.m. blood was withdrawn from anl arm veini, and thereafter 50 c.cm. of eusol and normal saline were injected.(On culture the blood yielded a Gram- positive staphlylococcus and a Gram-positive bacillus.)Third Operation.On February 11th it was noted that the temperature wvas still swinging, that the wou-nds slhowed little reaction, and the patienit still complained of severe pain in. the right lip, aind kept the right hi) and( knee joilnts flexed.Mr. Struthers made an incisioin over the right ilitum, anid exposed the boine freely.'When the gouge was iniserted pus oozed out of the bone.Tihe ilium was accordingly pierced, andl a free flow of pus obtainied from a large abscess between thie anterior surface of the ilium alnd the.iliacus muscle.Tlle hole in the bonie was enlarged, and the abscess cavity washed out with eusol.Two drainiage
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: L. Joe Berry, Dorothy S. Smythe
Journal: The Journal of Experimental Medicine (1961)

There exists an inverse proportionality between number of heat-killed cells of Salmonella typhimurium injected intraperitoneally into mice and the quantity of urinary nitrogen the animals excrete during a 17 hour period following the subcutaneous administration of 2 units of ACTH. This relationship has been developed into an assay for bacterial endotoxin. Mice immunized against S. typhimurium require 10 to 20 times the number of cells needed by control animals to suppress urinary nitrogen excretion to the same extent. Intravenous saccharated iron oxide sensitizes animals so that fewer heat-killed salmonellae can be detected. Heat-killed cells of Staphylococcus aureus are without effect in the assay. Several lipopolysaccharides derived from Gram-negative bacteria are effective in preventing the rise of urinary nitrogen excreted in response to ACTH and the amount required, compared to the LD(50), is in the same ratio for all of them. Citrated mouse serum partially inactivates the endotoxin during in vitro incubation for 1 hour at 37 degrees C. while normal serum does not. Dichloroisoproterenol protects mice against the lethal effects of lipopolysaccharide and it lowers its effectiveness in the assay. The minimum amount of endotoxin reliably determined by the test is 0.25 microg. of an E. coli preparation that was given intravenously in mice in which the reticuloendothelial system had been "blocked" with saccharated iron oxide.
Survivin gene expression and prognosis in recurrent colorectal cancer Reply
Authors: M MILLER
Journal: Gut (2001)

Editor,—Sarela and colleagues ( Gut 2000 >46: 645–50 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]) report on the association of Survivin gene expression and prognosis in recurrent colorectal cancer. The methods described for detecting Survivin mRNA relied on reverse transcription-polymerase chain reaction (RT-PCR), an exquisitely sensitive technique that has not previously been validated for this gene. We wish to point out three areas of technical difficulty in the methodology. (A) The fidelity of mRNA extraction and RT was tested using oligonucleotide primers for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a “housekeeping” gene. However, this may give rise to false positives by amplification of pseudogenes from contaminating genomic DNA.1 The β-actin primers (as described by Raff and colleagues1) do not amplify genomic DNA and therefore provide absolute evidence that RT has been successful. Alternatively, this problem could be corrected either by DNase digestion of RNA before RT or by having negative RT controls for each sample. (B) The process of RT using an oligo dT nucleotide as the RT primer results in the creation of … Professor P J Guillou, Professional Surgical Unit, Level 8, Clinical Sciences Building, St James's University Hospital, Leeds LS9 7TF, UK.p.j.guillou{at}leeds.ac.uk [1]: {openurl}?query=rft.jtitle%253DBioTechniques%26rft.stitle%253DBiotechniques%26rft.aulast%253DRaff%26rft.auinit1%253DT.%26rft.volume%253D23%26rft.issue%253D3%26rft.spage%253D456%26rft.epage%253D460%26rft.atitle%253DDesign%2Band%2Btesting%2Bof%2Bbeta-actin%2Bprimers%2Bfor%2BRT-PCR%2Bthat%2Bdo%2Bnot%2Bco-amplify%2Bprocessed%2Bpseudogenes.%26rft_id%253Dinfo%253Adoi%252F10.2144%252F97233st02%26rft_id%253Dinfo%253Apmid%252F9298216%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.2144/97233st02&link_type=DOI [3]: /lookup/external-ref?access_num=9298216&link_type=MED&atom=%2Fgutjnl%2F48%2F1%2F137.atom [4]: /lookup/external-ref?access_num=A1997XW10200022&link_type=ISI
Analysis of the CD4<sup>+</sup> T cell responses to house dust mite allergoid
Authors: P. Kalinski, M. C. Lebre, D. Kramer, E. C. De Jong, J. W. P. M. Van Schijndel, M. L. Kapsenberg
Journal: Allergy (2003)

Background: Modified allergen extracts (allergoids) with reduced IgE‐binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T‐cell stimulatory capacity is less well studied and is a subject of the present study. Methods: We compared the ability of native house dust mite extract ( Dermatophagoides pteronyssinus ; HDM) and the glutaraldehyde‐modified allergoid (HDM‐GA) to induce the proliferation and cytokine production by fresh PBMC and by DC‐stimulated polyclonal Th cells and HDM‐specific Th cell clones. Results: Freshly isolated T cells showed a partially reduced responsiveness to HDM‐GA, differentially pronounced in different donors. HDM‐specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM‐GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor‐dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM‐specific T cell clones. Conclusions: The reduced stimulatory potential of HDM‐GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid‐nonreactive HDM‐specific Th cells may result in differential responses of individual patients to immunotherapy.
Molecular Imaging of <i>N</i>-linked Glycosylation Suggests Glycan Biosynthesis Is a Novel Target for Cancer Therapy
Authors: Joseph N. Contessa, Mahaveer S. Bhojani, Hudson H. Freeze, Brian D. Ross, Alnawaz Rehemtulla, Theodore S. Lawrence
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Redundant receptor tyrosine kinase (RTK) signaling is a mechanism for therapeutic resistance to epidermal growth factor receptor (EGFR) inhibition. A strategy to reduce parallel signaling by coexpressed RTKs is inhibition of N-linked glycosylation (NLG), an endoplasmic reticulum (ER) cotranslational protein modification required for receptor maturation and cell surface expression. We therefore investigated the feasibility of blocking NLG in vivo to reduce overexpression of RTKs. Experimental Design: We developed a model system to dynamically monitor NLG in vitro and in vivo using bioluminescent imaging techniques. Functional imaging of NLG is accomplished with a luciferase reporter (ER-LucT) modified for endoplasmic reticulum translation and glycosylation. After in vitro validation, this reporter was integrated with D54 glioma xenografts to do noninvasive imaging of tumors, and inhibition of NLG was correlated with RTK protein levels and tumor growth. Results: The ER-LucT reporter shows the ability to sensitively and specifically detect NLG inhibition. Using this molecular imaging approach we carried out serial imaging studies to determine safe and efficacious in vivo dosing of the GlcNAc-1-phosphotransferase inhibitor tunicamycin, which blocks N-glycan precursor biosynthesis. Molecular analyses of tunicamycin-treated tumors showed reduced levels of EGFR and Met, two RTKs overexpressed in gliomas. Furthermore, D54 and U87MG glioma xenograft tumor experiments showed significant reductions in tumor growth following NLG inhibition and radiation therapy, consistent with an enhancement in tumor radiosensitivity. Conclusions: This study suggests that NLG inhibition is a novel therapeutic strategy for targeting EGFR and RTK signaling in both gliomas and other malignant tumors. Clin Cancer Res; 16(12); 3205–14. ©2010 AACR.
VX-770, a CFTR potentiator, may have a potential clinical benefit in a subgroup of people with cystic fibrosis
Authors: S. Shah
Journal: Thorax (2011)

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CFTR (CF transmembrane conductance regulator) protein, an epithelial ion channel. Some mutations, of which the G551D mutation is the most common (occurring in approximately 5% of people with CF), permit the defective CFTR protein to reach the epithelial …
Exhaled Nitric Oxide in High-Altitude Pulmonary Edema
Authors: HERVÉ DUPLAIN, CLAUDIO SARTORI, MATTIA LEPORI, MARC EGLI, YVES ALLEMANN, PASCAL NICOD, URS SCHERRER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m. It is not clear whether, in addition to hemodynamic factors and defective alveolar fluid clearance, inflammation plays a pathogenic role in HAPE. We therefore made serial measurements of exhaled pulmonary nitric oxide (NO), a marker of airway inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude exposure (4,559 m). To examine the relationship between pulmonary NO synthesis and pulmonary vascular tone, we also measured systolic pulmonary artery pressure (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any tendency to increase during the development of lung edema. Throughout the entire sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE-prone than in control subjects, and there existed an inverse relationship between Ppa and exhaled NO (r = − 0.51, p < 0.001). These findings suggest that HAPE is not preceded by airway inflammation. Reduced exhaled NO may be related to altered pulmonary NO synthesis and/or transport and clearance, and the data in our study could be consistent with the novel concept that in HAPE-prone subjects, a defect in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and in turn to pulmonary edema.
Total skin examination during screening for malignant melanoma does not increase the detection rate
Authors: M.J.M. DE ROOIJ, F.H.J. RAMPEN, L.J. SCHOUTEN, H.A.M. NEUMANN
Journal: British Journal of Dermatology (1996)

Total skin examination during public screening for malignant melanoma is often advocated, but the benefit of this approach has not been established properly. We assessed the yield of examination of the entire skin, in addition to examination of intentionally shown skin lesions, in people attending melanoma screening clinics in southern Limburg, the Netherlands, in 1993. Of the 4146 attenders, 2910 (70%) showed a specific skin spot. Additional examination of the entire skin was offered to 1385 people. There were 1221 evaluable cases. Fourteen presumptive diagnoses of malignancies were encountered: seven malignant melanomas, all with low clinical suspicion, and seven basal cell carcinomas. Histology revealed three basal cell carcinomas. No malignant melanomas were confirmed by histology. It is concluded that additional total skin examination during screening for malignant melanoma is not worthwhile, except perhaps for persons presenting lesions that are suspicious of melanoma or dysplastic naevi.
Cooperation between integrin α5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity
Authors: Suyong Choi, Sin-Ae Lee, Tae Kyoung Kwak, Hyeon Jung Kim, Mi Ji Lee, Sang-Kyu Ye, Sung-Hoon Kim, Semi Kim, Jung Weon Lee
Journal: Blood (2008)
Differential regulation of transforming growth factor beta and interleukin 2 genes in human T cells: demonstration by usage of novel competitor DNA constructs in the quantitative polymerase chain reaction.
Authors: B Li, P K Sehajpal, A Khanna, H Vlassara, A Cerami, K H Stenzel, M Suthanthiran
Journal: The Journal of Experimental Medicine (1991)

The regulation of mRNA encoding transforming growth factor beta (TGF-beta) and interleukin 2 (IL-2) in normal human T cells was explored using novel competitor DNA constructs in the quantitative polymerase chain reaction and accessory cell-independent T cell activation models. Our experimental design revealed the following: (a) TGF-beta mRNA and IL-2 mRNA are regulated differentially in normal human T cells, quiescent or signaled with the synergistic combinations of: sn-1,2-dioctanoylglycerol and ionomycin or anti-CD3 monoclonal antibody (mAb) and anti-CD2 mAb; (b) the steady-state level of TGF-beta mRNA in the stimulated T cells, in contrast to that of IL-2 mRNA, is increased by the immunosuppressant cyclosporine (CsA); and (c) the paradoxical effect of CsA on TGF-beta mRNA levels is also appreciable at the level of production of functionally active TGF-beta protein. Our findings, in addition to demonstrating the utility of the competitor DNA constructs for the precise quantification of immunoregulatory cytokines, suggest a novel and unifying mechanistic basis for the immunosuppression and some of the complications (e.g., renal fibrosis) associated with CsA usage.
Levels of emotion and levels of consciousness
Authors: Carroll Izard
Journal: Behavioral and Brain Sciences (2007)

Merker makes a strong case for the upper brain stem as being the neural home of primary or phenomenal consciousness. Though less emphasized, he makes an equally strong and empirically supported argument for the critical role of the mesodiencephalon in basic emotion processes. His evidence and argument on the functions of brainstem systems in primary consciousness and basic emotion processes present a strong challenge to prevailing assumptions about the primacy of cognition in emotion-cognition-behavior relations.
A suspicious clot
Authors: P Lee, F-K Cheah, J Huang, D Poon, C-M Loo
Journal: Thorax (2009)

A suspicious clotA 72-year-old man presented with right-sided pleuritic chest pain, chronic cough and weight loss.Chest x ray revealed a moderate sized pleural effusion.Chest CT showed thromboembolism of the right main pulmonary artery, and pleural effusion with compression atelactasis of the right lower lobe of the lung (fig 1).As the thrombus appeared suspicious, being unilateral, central and occupying the entire lumen of the pulmonary artery without abnormality in the contralateral lung, magnetic resonance arteriography was performed which showed heterogeneous enhancement (fig 2).Positron emission tomography (PET)/CT confirmed increased [ 18 F]fluorodeoxyglucose (FDG) uptake by the mass in the right main pulmonary artery, pleura, right clavicle, L1 vertebral body and both adrenal glands (fig 3).He underwent CT-guided biopsy of the L1 vertebral body, and histology was compatible with intimal sarcoma of the pulmonary artery.He was treated with gemcitabine but developed acute dyspnoea with hypotension, and died of heart failure from tumour embolism.Primary pulmonary artery sarcomas are often misdiagnosed as emboli and suspected when patients do not improve with anticoagulation therapy, which accounts for the advanced stage at diagnosis. 1 As magnetic resonance imaging, PET and PET/CT are used more frequently in the evaluation of pulmonary malignancy, it is possible that diagnosis of this rare disease can be made earlier in the clinical course.