tbuckley/cabot-search huggingface dataset:
Sinusoidal dilatation: a rare side effect of azathioprine
Authors: A M Jacobi
Journal: Annals of the Rheumatic Diseases (2004)

Hepatotoxicity is an often reported side effect of azathioprine treatment, which requires monitoring of serum transaminases and γ-glutamyltransferase (γ-GT), especially during the first 6 months of treatment. This case report, however, illustrates that side effects of azathioprine can also occur after a longer period of treatment. We report a case of sinusoidal dilatation as a rare side effect of azathioprine treatment in a patient with systemic sclerosis.

A 50 year old female patient with systemic sclerosis presented with a rapid increase of body weight (approximately 5 kg within 3 days) and abdominal circumference, diffuse abdominal pain, oedema of the lower extremities, dyspnoea, tachycardia, and low blood pressure (90/60 mm Hg). Because systemic sclerosis with pulmonary involvement had been diagnosed 1½ years previously, the patient received azathioprine (2 mg/kg) and prednisone (5 mg) daily. The patient tested positive …
Brain "ouabain" mediates the sympathoexcitatory and hypertensive effects of high sodium intake in Dahl salt-sensitive rats.
Authors: B S Huang, F H Leenen
Journal: Circulation Research (1994)

To assess whether brain ouabain-like activity (OLA) mediates the hypertensive effects of high sodium intake in Dahl salt-sensitive (Dahl S) rats, the effects of blockade of brain OLA on mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were evaluated in conscious Dahl salt-resistant (Dahl R) and Dahl S rats on a regular (120 mumol/g) or high sodium (1370 mumol/g) diet from 4 to 7 weeks of age. Dahl S rats given high sodium showed higher basal MAP and augmented responses of MAP and RSNA to air stress and to intracerebroventricular injection of the alpha 2-adrenergic receptor agonist guanabenz as compared with Dahl R rats or Dahl S rats given regular sodium. In contrast, the sympathoexcitatory and pressor responses to intracerebroventricular injection of ouabain (0.3 and 1.0 microgram) were markedly attenuated in Dahl S rats given high sodium. Intracerebroventricular preinjection of 0.3 microgram ouabain significantly enhanced blood pressure and RSNA responses to air stress and intracerebroventricular guanabenz in Dahl S rats given regular sodium to the levels observed in Dahl S rats given high sodium. Intracerebroventricular digoxin-specific antibody Fab (DAF) fragments (132 micrograms/8 microL for 5 minutes) did not change basal MAP and RSNA during the first 4 hours after administration in Dahl S rats on a high sodium diet for 3 weeks. However, 18 hours after the injection of DAF fragments, basal MAP and RSNA were significantly decreased, reaching values for Dahl S rats on a regular sodium diet. The magnitude of increases or decreases in MAP and RSNA to air stress or intracerebroventricular guanabenz were significantly attenuated by the DAF fragments in Dahl S rats on a high sodium but not regular sodium diet. Concomitant intracerebroventricular infusion of DAF fragments (200 micrograms per day) prevented the development of hypertension after a high sodium diet in Dahl S rats and prevented an augmentation in pressor and sympathoexcitatory responses to air stress. After discontinuing the infusion of DAF fragments, resting MAP gradually increased to the high levels found in Dahl S rats given high sodium treated with gamma-globulins. These results support the concept that high sodium intake may cause hypertension in Dahl S rats by increasing endogenous brain OLA, thereby enhancing sympathetic outflow and basal blood pressure as well as sympathoexcitatory and pressor responses to stress.
Clinical assessment for identifying causes of acute respiratory failure in cancer patients
Authors: David Schnell, Julien Mayaux, Jérôme Lambert, Antoine Roux, Anne-Sophie Moreau, Lara Zafrani, Emmanuel Canet, Virginie Lemiale, Michael Darmon, Élie Azoulay
Journal: European Respiratory Journal (2012)

In cancer patients with acute respiratory failure (ARF), early adequate therapy is associated with better outcomes. We investigated the performance of the DIRECT approach, which uses criteria available at the bedside at admission to the intensive care unit (ICU), to identify causes of ARF in cancer patients. This cohort study included cancer patients with ARF of determined aetiology. Associations of aetiological groups with the selected criteria were evaluated using correspondence analysis. 424 cancer patients were included: 201 (47%) with bacterial pneumonia, 131 (31%) with opportunistic infections and 92 (22%) with noninfectious disorders. Mechanical ventilation (both invasive and noninvasive) was needed in 328 (77%) patients, treatment for shock in 217 (51%) patients and dialysis in 82 (19%) patients. 142 (34%) patients died in the ICU. Correspondence plots showed that bacterial pneumonia was associated with neutropenia, solid tumour, multiple myeloma, <3 days since symptom onset, shock, unilateral crackles and unilateral radiographic pattern. Opportunistic infections were associated with steroids, lymphoproliferative disorders and haematopoietic stem-cell transplantation, whereas noninfectious disorders were associated with acute leukaemia The selected criteria are strongly associated with causes of ARF in cancer patients and could be used to develop an algorithm for selecting first-line diagnostic investigations and empirical treatments.
CD4+CD25+ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer
Authors: Stephan Roux, Lionel Apetoh, Fanny Chalmin, Sylvain Ladoire, Grégoire Mignot, Pierre-Emmanuel Puig, Gregoire Lauvau, Laurence Zitvogel, François Martin, Bruno Chauffert, Hideo Yagita, Eric Solary, François Ghiringhelli
Journal: Journal of Clinical Investigation (2008)

Tumors that progress do so via their ability to escape the antitumor immune response through several mechanisms, including developing ways to induce the differentiation and/or recruitment of CD4(+)CD25(+) Tregs. The Tregs, in turn, inhibit the cytotoxic function of T cells and NK cells, but whether they have an effect on the cytotoxic function of tumor-infiltrating DCs (TIDCs) has not been determined. Here we have shown, in 2 rodent models of colon cancer, that CD4(+)CD25(+) Tregs inhibit the ability of CD11b(+) TIDCs to mediate TNF-related apoptosis-inducing ligand-induced (TRAIL-induced) tumor cell death. In both models of cancer, combination treatment with Mycobacterium bovis Bacillus Calmette-Guérin (BCG), which activates the innate immune system via TLR2, TLR4, and TLR9, and cyclophosphamide (CTX), which depletes Tregs, eradicated the tumors. Further analysis revealed that the treatment led to a marked increase in the number of CD11b(+) TIDCs that killed the tumor cells via a TRAIL-dependent mechanism. Furthermore, acquisition of TRAIL expression by the CD11b(+) TIDCs was induced by BCG and dependent on signaling through TLR2, TLR4, and TLR9. In vivo transfer of Tregs abrogated the ability of BCG to induce CD11b(+) TIDCs to express TRAIL and thereby nullified the efficacy of the CTX-BCG treatment. Our data have therefore delineated what we believe to be a novel mechanism by which Tregs inhibit the antitumor immune response.
Prediagnostic Serum Levels of Cytokines and Other Immune Markers and Risk of Non-Hodgkin Lymphoma
Authors: Mark P. Purdue, Qing Lan, Rachel Bagni, William G. Hocking, Dalsu Baris, Douglas J. Reding, Nathaniel Rothman
Journal: Cancer Research (2011)

Abstract Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case–control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-α] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR = 1.7, 95% CI: 1.1–2.8; Ptrend = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9–9.4; Ptrend &amp;lt; 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0–4.0, Ptrend = 0.01; sCD27: OR = 4.1, 95% CI: 1.9–8.5, Ptrend = 0.0001). Elevated levels of IL-10, TNF-α and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis. Cancer Res; 71(14); 4898–907. ©2011 AACR.
Perception versus Reality of the Burden of Chronic Kidney Disease in the United States
Authors: Joseph Coladonato, Preston Klassen, William F. Owen
Journal: Journal of the American Society of Nephrology (2002)

In the May issue of the Journal of the American Society of Nephrology , Clase et al. ([1][1]) applied four calculated measures of renal function to data from the National Health And Nutrition Examination Survey (NHANES) III to quantitate the burden of kidney disease in nondiabetic adults in the
Scalp Involvement in Dermatomyositis
Authors: J S Kasteler, J P Callen
Journal: JAMA (1994)

To characterize scalp involvement in patients with dermatomyositis.Case series.All patients with dermatomyositis seen in our office between 1988 and mid 1993. Patient inclusion in this study required fulfillment of three or more of Bohan and Peter's criteria for dermatomyositis.Of 17 patients with the diagnosis of dermatomyositis, scalp involvement was present in 14. Five of the 14 patients with scalp involvement were diagnosed as having scalp psoriasis or seborrheic dermatitis before progression of their disease or tissue examination revealed the diagnosis of dermatomyositis. In all patients, the scalp involvement was manifested as atrophic, erythematous, scaly plaques. In addition, alopecia was noted in six of the 14 patients. Treatment of cutaneous involvement included sun avoidance, topical corticosteroids and/or antimalarials, and/or methotrexate.Recognition of this process is important because scalp involvement is often overlooked, may be misdiagnosed initially, and can be the presenting complaint in some patients with dermatomyositis.
Allorestricted cytotoxic T cells. Large numbers of allo-H-2Kb-restricted antihapten and antiviral cytotoxic T cell populations clonally develop in vitro from murine splenic precursor T cells.
Authors: J Reimann, D Kabelitz, K Heeg, H Wagner
Journal: The Journal of Experimental Medicine (1985)

Cytotoxic T lymphocyte (CTL) responses of splenic T cells from C57BL/6 B6) mice and mutant H-2Kbm1 (bm1) mice to haptenic (trinitrophenyl [TNP] ) and herpes simplex virus (HSV) determinants in the context of an allogenic (wild-type or mutant) H-2Kb molecule were analyzed in a modified limiting dilution system. In the B6-anti-bm1TNP mixed leukocyte reaction (MLR), estimated frequencies for precursors of CTL clones that lysed bm1TNP targets ranged from 1/120 to 1/400; in the bm1-anti-B6TNP MLR, estimated frequencies of precursors of CTL clones that lysed B6TNP targets ranged from 1/500 to 1/1,300. Estimated frequencies for precursors of CTL clones that lysed the respective unmodified and TNP-modified allogeneic targets were two- to three-fold lower. Lytic specificity patterns determined by split-well analysis showed that at least 20-30% of the generated CTL populations (selected for a high probability of clonality) in both MLR displayed allorestricted lysis of TNP-modified concanavalin A blast targets. In the B6-anti-bm1HSV MLR, estimated frequencies for precursors of CTL clones that lysed bm1HSV targets ranged from 1/70 to 1/300; in the bm1-anti-B6HSV MLR, estimated frequencies for precursors of CTL clones that lysed B6HSV targets ranged from 1/300 to 1/1,200. Again, estimated frequencies for precursors of CTL clones that lysed the respective noninfected and virus-infected allogeneic targets were two- to fourfold lower. Of the CTL populations selected for a high probability of clonality at least 30-60% displayed allorestricted lysis of virus-infected lipopolysaccharide blast targets in both MLR. It is concluded that a large fraction of clonally developing CTL populations stimulated with TNP-modified or HSV-infected allo-H-2Kb-bearing cells displayed an allorestricted pattern of recognition. It was further evident that the estimated frequencies of splenic precursors that generated allorestricted CTL clones was two- to threefold higher than the estimated frequencies of precursors that gave rise to the respective alloreactive CTL populations.
Pulmonary structural changes in neonatal hyaline membrane disease treated with high pressure artificial respiration
Authors: M. J. Becker, J. G. Koppe
Journal: Thorax (1969)

Fourteen babies with hyaline membrane disease were treated with artificial respiration using intermittent positive pressure. At present six children are in good health; four still show alterations on the chest radiograph. Eight babies died; in these, high pressures (50 cm. H<sub>2</sub>O on the average) were used with high concentrations of oxygen (up to 100%). Severe pulmonary changes were found. The lungs were heavy and non-aerated. There was emphysema only in the child treated for six weeks. Bronchi and bronchioli showed a marked epithelial hyperplasia as well as squamous-cell metaplasia, whereas at other sites epithelial necrosis was apparent. The muscular layer was hypertrophic and mucous glands appeared hyperplastic. Hyaline membranes containing bilirubin pigment were found in six of the eight cases. The alveolar epithelium was extremely atypical. The interstitium showed a proliferation of fibroblasts which resulted in a pronounced interstitial fibrosis in the child treated for six weeks. It is suggested that this treatment may aggravate the pathological changes caused by the hyaline membrane disease itself. Therefore, artificial positive pressure respiration should be used only when other measures fail to help the infant during the period when spontaneous recovery is possible.
Comprehensive Molecular Analysis of Mismatch Repair Gene Defects in Suspected Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Cases
Authors: James Mueller, Isabella Gazzoli, Prathap Bandipalliam, Judy E. Garber, Sapna Syngal, Richard D. Kolodner
Journal: Cancer Research (2009)

An accurate algorithm is essential for effective molecular diagnosis of hereditary colorectal cancer (CRC). Here, we have extended the analysis of 71 CRC cases suspected to be Lynch syndrome cases for MSH2, MLH1, MSH6, and PMS2 gene defects. All cases were screened for mutations in MSH2, MLH1, and MSH6, and all cases where tumors were available were screened for microsatellite instability (MSI) and expression of MSH2 and MLH1. Subsequently, mutation-negative cases were screened for MLH1 methylation and mutations in PMS2. Of the MSI-high (MSI-H) cases, 96% had a mismatch repair (MMR) gene defect, mostly involving MSH2 or MLH1; one PMS2 mutation, one MLH1 epimutation, and no MSH6 mutations were found. Four of the 28 MSI-H cases, including one Amsterdam criteria case, had biallelic tumor MLH1 methylation, indicating that sporadic cases can be admixed in with Lynch syndrome cases, even those meeting the strongest criteria for Lynch syndrome. MMR gene defects were found in similar frequency in cases where tumors were and were not available. One MLH1 and one MSH2 deletion mutation were found in MSI-stable/low cases, indicating that MSI testing can exclude cases with pathogenic mutations. Our analysis supports a diagnostic algorithm where cases are selected for analysis based on clinical criteria or prediction models; isolated sporadic young-onset cases can be prescreened by tumor testing, whereas familial cases may be directly subjected to molecular analysis for mutations in MMR genes followed by MSI, protein expression, and DNA methylation analysis to aid in the resolution of mutation-negative cases.
Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease
Authors: AM Saunders, C Hulette, KA Welsh-Bohmer, DE Schmechel, B Crain, JR Burke, MJ Alberts, WJ Strittmatter, JCS Breitner, C Rosenberg, SV Scott, PC Gaskell, MA Pericak-Vance, AD Roses
Journal: The Lancet (1996)
The relation between hyperinflation and daily activity in COPD patients
Authors: S. Dijkhuis, F.H.C. de Jongh, P.D.L.P.M. van der Valk, M. Tabak, M.G. Brusse-Keizer
Journal: European Respiratory Journal (2014)

Although we did not find any relation between DH and PA, SH could be a useful marker to indicate reduced PA. Many patients used a decreased tidal volume and pursed-lips breathing to counteract DH. Different correlations between SH and PA were found to be present between subjects who either were or were not engaged in an exercise-training program. Therefore, this stratification should also be investigated in future studies.
Human Papillomavirus E7 Enhances Hypoxia-Inducible Factor 1–Mediated Transcription by Inhibiting Binding of Histone Deacetylases
Authors: Jason M. Bodily, Kavi P.M. Mehta, Laimonis A. Laimins
Journal: Cancer Research (2010)

Infection by human papillomaviruses (HPV) leads to the formation of benign lesions, warts, and in some cases, cervical cancer. The formation of these lesions is dependent upon increased expression of proangiogenic factors. Angiogenesis is linked to tissue hypoxia through the activity of the oxygen-sensitive hypoxia-inducible factor 1α (HIF-1α). Our studies indicate that the HPV E7 protein enhances HIF-1 transcriptional activity whereas E6 functions to counteract the repressive effects of p53. Both high- and low-risk HPV E7 proteins were found to bind to HIF-1α through a domain located in the N-terminus. Importantly, the ability of E7 to enhance HIF-1 activity mapped to the C-terminus and correlated with the displacement of the histone deacetylases HDAC1, HDAC4, and HDAC7 from HIF-1α by E7. Our findings describe a novel role of the E7 oncoprotein in activating the function of a key transcription factor mediating hypoxic responses by blocking the binding of HDACs.
Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance
Authors: Martin Aichinger, Chunyan Wu, Jelena Nedjic, Ludger Klein
Journal: The Journal of Experimental Medicine (2013)

Macroautophagy serves cellular housekeeping and metabolic functions through delivery of cytoplasmic constituents for lysosomal degradation. In addition, it may mediate the unconventional presentation of intracellular antigens to CD4(+) T cells; however, the physiological relevance of this endogenous MHC class II loading pathway remains poorly defined. Here, we characterize the role of macroautophagy in thymic epithelial cells (TECs) for negative selection. Direct presentation for clonal deletion of MHC class II-restricted thymocytes required macroautophagy for a mitochondrial version of a neo-antigen, but was autophagy-independent for a membrane-bound form. A model antigen specifically expressed in Aire(+) medullary TECs (mTECs) induced efficient deletion via direct presentation when targeted to autophagosomes, whereas interference with autophagosomal routing of this antigen through exchange of a single amino acid or ablation of an essential autophagy gene abolished direct presentation for negative selection. Furthermore, when this autophagy substrate was expressed by mTECs in high amounts, endogenous presentation and indirect presentation by DCs operated in a redundant manner, whereas macroautophagy-dependent endogenous loading was essential for clonal deletion at limiting antigen doses. Our findings suggest that macroautophagy supports central CD4(+) T cell tolerance through facilitating the direct presentation of endogenous self-antigens by mTECs.
1041-94 Noninvasive evaluation of coronary artery flow using transthoracic color doppler echocardiograpy in patients with acute myocardial infarction in the emergency room
Authors: Eiichi Nagashima, Takahiro Ota, Michihiko Hirayama, Hitomi Kawano, Kenji Shimeno, Keiji Nagae, Shiro Yanagi, Kazuyoshi Hirota, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2004)
What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study
Authors: W Hamilton
Journal: Thorax (2005)

<b>Background:</b> Over 38 000 new cases of lung cancer occur each year in the UK. Most are diagnosed after initial presentation to primary care, but the relative importance of the various clinical features is largely unknown. <b>Methods:</b> A population based case-control study was undertaken in all 21 general practices in Exeter, Devon, UK (population 128 700). 247 primary lung cancers were studied in subjects aged over 40 years diagnosed between 1998 and 2002 and 1235 controls matched by age, sex and general practice. The entire primary care record for 2 years before diagnosis was coded using the International Classification of Primary Care-2. Univariable and multivariable conditional logistic regression analyses were used to identify and quantify clinical features independently associated with lung cancer. The main outcome measures were odds ratios and positive predictive values for these variables. <b>Results:</b> Seven symptoms (haemoptysis, loss of weight, loss of appetite, dyspnoea, thoracic pain, fatigue and cough), one physical sign (finger clubbing), and two abnormal investigation results (thrombocytosis and abnormal spirometry) were associated with lung cancer in multivariable analyses, as was cigarette smoking. After excluding variables reported in the final 180 days before diagnosis, haemoptysis, dyspnoea and abnormal spirometry remained independently associated with cancer. <b>Conclusions:</b> This study provides an evidence base for selection of patients for investigation of possible lung cancer, both for clinicians and for developers of guidelines.