tbuckley/cabot-search huggingface dataset:
Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation
Authors: Didier Ducloux, Cécile Courivaud, Jamal Bamoulid, Bérengère Vivet, Aline Chabroux, Marina Deschamps, Jean-Michel Rebibou, Christophe Ferrand, Jean-Marc Chalopin, Pierre Tiberghien, Philippe Saas
Journal: Journal of the American Society of Nephrology (2010)

Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts <300/mm3 and 36 (12%) died during follow-up. We observed a higher death rate in patients with CD4 T cell lymphopenia persisting for >1 year (24.1 versus 7.6%; P < 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P = 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3+ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P = 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P = 0.013). In summary, prolonged polyclonal anti-thymocyte globulin–induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections.
WIP Regulates Signaling via the High Affinity Receptor for Immunoglobulin E in Mast Cells
Authors: Alexander Kettner, Lalit Kumar, Inés M. Antón, Yoji Sasahara, Miguel de la Fuente, Vadim I. Pivniouk, Hervé Falet, John H. Hartwig, Raif S. Geha
Journal: The Journal of Experimental Medicine (2004)

Wiskott-Aldrich syndrome protein–interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcϵRI) in mast cells. WIP-deficient bone marrow–derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcϵRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcϵRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcϵRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcϵRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.
Science of assessment
Authors: N Bellamy
Journal: Annals of the Rheumatic Diseases (2005)

Psoriatic arthritis is a multisystem disorder which, from a measurement standpoint, demands consideration of its cutaneous manifestations and both axial and peripheral musculoskeletal involvement. Measurements of various aspects of impairment, ability/disability, and participation/handicap are feasible using existing measurement techniques, which are for the most part valid, reliable, and responsive. Nevertheless, there remain opportunities for the further development of consensus around core set measures and responder criteria, as well as for instrument development and refinement, standardised assessor training, cross-cultural adaptation of health status questionnaires, electronic data capture, and the introduction of standardised quantitative measurement into routine clinical care.
Role of nitric oxide in rat nephrotoxic nephritis
Authors: V Bremer, A Tojo, K Kimura, Y Hirata, A Goto, T Nagamatsu, Y Suzuki, M Omata
Journal: Journal of the American Society of Nephrology (1997)

Nitric oxide (NO), generated by inducible NO synthase (iNOS) in migrating macrophages, is increased in glomerulonephritis. This study investigates the effect of NO inhibition on rat nephrotoxic nephritis (NTN) to clarify the role of NO production in glomerular damage. NTN was induced in Sprague Dawley rats by an injection of an anti-glomerular basement membrane (GBM) antibody. Urinary nitrite excretion and nitrite release from kidney slices (5.47 +/- 1.19 versus 2.15 +/- 0.73 nmol/mg protein, NTN versus Control, P < 0.05) were increased in NTN on day 2. Glomerular macrophage infiltration and intercellular adhesion molecule (ICAM)-1 expression increased from day 2. iNOS expression was increased in interstitial macrophages. Glomerular endothelial cell NOS (ecNOS) expression evaluated by counting immunogold particles along GBM was suppressed (0.06 +/- 0.02 versus 0.35 +/- 0.04 gold/micron GBM, P < 0.0001). Glomerular damage developed progressively. NG-nitro-L-arginine methyl ester (L-NAME), which inhibits both iNOS and ecNOS and aminoguanidine (AG), a relatively selective inhibitor for iNOS, equally suppressed nitrite in urine and renal tissue. Glomerular ICAM-1 expression and macrophage infiltration were reduced by L-NAME, but not by AG. Expression of ecNOS was significantly increased by L-NAME (0.91 +/- 0.08, P < 0.0001 versus NTN), but slightly by AG (0.18 +/- 0.04). AG significantly and L-NAME slightly attenuated the glomerular damage at day 4. In conclusion, suppression of iNOS prevents glomerular damage in the early stage of NTN. Treatment by L-NAME reduces macrophage infiltration by suppression of ICAM-1 expression, which may be explained by an increase in ecNOS expression.
Absolute lymphocyte count is a novel prognostic indicator in extranodal natural killer/T-cell lymphoma, nasal type
Authors: J.J. Huang, W.Q. Jiang, T.Y. Lin, Y. Huang, R.H. Xu, H.Q. Huang, Z.M. Li
Journal: Annals of Oncology (2010)

extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a heterogeneous entity with poor survival, requiring risk stratification in affected patients. We proposed absolute lymphocyte count (ALC) as a new prognostic factor in ENKL.we retrospectively analyzed 128 patients newly diagnosed with ENKL. Independent prognostic factors of survival were determined by Cox regression analysis.patients with low ALC (<1.0 × 10(9)/l) at diagnosis tended to have more adverse clinical features. Patients with high ALC (≥1.0 × 10(9)/l) at diagnosis had better overall survival (OS; P < 0.0001) and progression-free survival (PFS; P<0.0001), and achieved higher complete remission rates (P=0.001). Multivariate analysis with known prognostic factors showed that ALC, B symptoms and advanced stage were independent predictors for OS and PFS. Using the International Prognostic Index, Prognostic Index for Peripheral T-cell lymphoma unspecified, or Korean Prognostic Index for nasal NK/T-cell lymphoma, the majority of patients were in the low-risk category (with no or one adverse factor). ALC was helpful to differentiate the low-risk patients with different survival outcomes (P < 0.0001).our data suggest that ALC at diagnosis is a novel, powerful predictor of prognosis in ENKL. Immune status at diagnosis might have an important influence on survival in patients with ENKL.
HCN4 Dynamically Marks the First Heart Field and Conduction System Precursors
Authors: Xingqun Liang, Gang Wang, Lizhu Lin, Jennifer Lowe, Qingquan Zhang, Lei Bu, Yihan Chen, Ju Chen, Yunfu Sun, Sylvia M. Evans
Journal: Circulation Research (2013)

Rationale: To date, there has been no specific marker of the first heart field to facilitate understanding of contributions of the first heart field to cardiac lineages. Cardiac arrhythmia is a leading cause of death, often resulting from abnormalities in the cardiac conduction system (CCS). Understanding origins and identifying markers of CCS lineages are essential steps toward modeling diseases of the CCS and for development of biological pacemakers. Objective: To investigate HCN4 as a marker for the first heart field and for precursors of distinct components of the CCS, and to gain insight into contributions of first and second heart lineages to the CCS. Methods and Results: HCN4CreERT2, -nuclear LacZ, and -H2BGFP mouse lines were generated. HCN4 expression was examined by means of immunostaining with HCN4 antibody and reporter gene expression. Lineage studies were performed using HCN4CreERT2, Isl1Cre, Nkx2.5Cre, and Tbx18Cre, coupled to coimmunostaining with CCS markers. Results demonstrated that, at cardiac crescent stages, HCN4 marks the first heart field, with HCN4CreERT2 allowing assessment of cell fates adopted by first heart field myocytes. Throughout embryonic development, HCN4 expression marked distinct CCS precursors at distinct stages, marking the entire CCS by late fetal stages. We also noted expression of HCN4 in distinct subsets of endothelium at specific developmental stages. Conclusions: This study provides insight into contributions of first and second heart lineages to the CCS and highlights the potential use of HCN4 in conjunction with other markers for optimization of protocols for generation and isolation of specific conduction system precursors.
Severe Toxoplasmosis in Immunocompetent Hosts: Be Aware of Atypical Strains
Authors: Vincent Sobanski, Daniel Ajzenberg, Laurence Delhaes, Nathalie Bautin, Nicolas Just
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Toxoplasma gondii is an intracellular protozoan parasite with a worldwide distribution.Humans are generally infected by consumption of undercooked meat or vegetables and water soiled by cat feces (1).Usually asymptomatic in healthy hosts, the pri-mary infection leads to mononucleosis-like illness with cervical lymphadenopathy in 10% of subjects (2).Severe toxoplasmosis can be found in the immunocompromised population, particularly in patients with AIDS (3).In healthy individuals, this condition is rare in Europe and the United States but seems to be more common in tropical areas (4).We present the case of a 47-year-old man referred to our institution for a flu-like syndrome with dyspnea that had not responded to oseltamivir and then ceftriaxone.Night sweats, nausea, and vomiting appeared after admission.Physical examination revealed evening fever of 38-39 8 C, thoracic macular rash, and enlarged supraclavicular and axillary and inguinal supracentimetric lymph nodes.Blood pressure was 115/75 mm Hg, mean heart rate was 90 beats per minute, respiratory rate was 20 breaths per minute, and transcutaneous oxygen saturation was 92% breathing ambient air.The pulmonary auscultation was normal.A chest radiograph showed subtle, diffuse, interstitial infiltrates (Figure 1A).Initial laboratory tests revealed a normal blood cell count.The arterial blood gas results on room air were: pH 7.52, Pa O 2
Involvement of Myoendothelial Gap Junctions in the Actions of Endothelium-Derived Hyperpolarizing Factor
Authors: Shaun L. Sandow, Marianne Tare, Harold A. Coleman, Caryl E. Hill, Helena C. Parkington
Journal: Circulation Research (2002)

Abstract — The nature of the vasodilator endothelium-derived hyperpolarizing factor (EDHF) is controversial, putatively involving diffusible factors and/or electrotonic spread of hyperpolarization generated in the endothelium via myoendothelial gap junctions (MEGJs). In this study, we investigated the relationship between the existence of MEGJs, endothelial cell (EC) hyperpolarization, and EDHF-attributed smooth muscle cell (SMC) hyperpolarization in two different arteries: the rat mesenteric artery, where EDHF-mediated vasodilation is prominent, and the femoral artery, where there is no EDHF-dependent relaxation. In the rat mesenteric artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization of both ECs and SMCs, and characteristic pentalaminar MEGJs were found connecting the two cell layers. In contrast, in the femoral artery, ACh evoked hyperpolarization in only ECs but not in SMCs, and no MEGJs were present. Selective hyperpolarization of ECs or SMCs evoked hyperpolarization in the other cell type in the mesenteric artery but not in the femoral artery. Disruption of gap junctional coupling using the peptide Gap 27 markedly reduced the ACh-induced hyperpolarization in SMCs, but not in ECs, of the mesenteric artery. These results show that transfer of EC hyperpolarization or of a small molecule to SMCs through MEGJs is essential and sufficient to explain EDHF.
Thymic Dependency of Tumor-Induced Immunodepression2
Authors: G. F. Rowland, A. J. Edwards, M. R. Sumner, C. M. Hurd
Journal: JNCI Journal of the National Cancer Institute (1973)

With hemolytic pleque techniques, splenic immune responses of varying degrees of thymic dependency were determined during mammary tumor growth in C3H/He mice, and histologic and gravimetric changes in lymphoid organs were described. After immunization with horse red blood cells, Escherichia coli lipopolysaccharide (LPS), or the hapten 4-hydroxy-3-iodo-5-nitrophenylacetic acid coupled to bovine γ-globulin, both 19s and 7s plaque-forming cells were measured. The effects of the adjuvant Bordetella pertussis were also examined. Depression during tumor growth increased with the degree of thymic dependency of the immune responses. The thymic-independent LPS response was not depressed, but strongly thymic-dependent responses were markedly reduced. We concluded that the immunodepressive effects of tumor growth were mediated through someaspect of T-cell function.
Perioperative β-Blockers Revisited
Authors: Seamus P. Whelton, Sandeep Bansal
Journal: JAMA Internal Medicine (2013)

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M11 Adequacy of 22 and 21 Gauge EBUS-TBNA histology samples for genotyping of primary lung adenocarcinoma
Authors: A Jeyabalan, ARL Medford
Journal: Thorax (2013)

<h3>Introduction</h3> Epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer have been shown to confer improved responsiveness to tyrosine kinase inhibitors. NICE recommends tyrosine kinase inhibitors as first line therapy in patients with locally advanced or metastatic tumours with EGFR gene mutations. Evidence from a multicentre retrospective study of 119 patients undergoing EBUS-TBNA to obtain cell block samples showed that EGFR mutation analysis was possible in 89.9% (107/119)<sup>1</sup>. Similar results 32/36 (88.8%) have been observed in a smaller more recent study<sup>2</sup>. The aim of this single centre prospective study was to evaluate the adequacy of EBUS-TBNA histology specimens using both 21G and 22G needles in confirmed primary lung adenocarcinoma. <h3>Methods</h3> A prospective analysis was performed on 250 consecutive patients undergoing EBUS-TBNA between 2009 and 2013. 21G or 22G needles (Olympus ViziShot, NA-201SX-4021 and NA-201SX-4022) were used by operator discretion. A minimum of 2 passes were carried out per nodal station. Samples were fixed in formalin and prepared for histopathological analysis. The proportion of confirmed primary lung adenocarcinoma samples in which EGFR mutation testing was feasible was determined. <h3>Results</h3> Primary lung adenocarcinoma was confirmed in 45 patients (18%). EGFR mutation analysis was attempted in 35 of these patients and was possible in 34 (97.1%). EGFR mutation was present in 3 patients (8.8%). <h3>Conclusions</h3> This single centre study demonstrates both 22G and 21G EBUS-TBNA samples are adequate for EGFR mutation analysis with no clear superiority in contrast to recent data suggesting disease phenotyping may be superior using a 21G needle when analysed by histopathology. We speculate that higher sample usability rates for mutation analysis may have been facilitated by the use of histological specimens however further larger studies are required to confirm this hypothesis. <h3>References</h3> Navani N, Brown JM, Nankivell M <i>et al</i>. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicentre study of 774 patients. <i>AJRCCM</i> (2012); 185(12): 1316–22 Esterbrook G, Anathhanam S, Plant PK. Adequacy of endobronchial ultrasound transbronchial needle aspiration samples in the subtyping of non-small cell lung cancer. <i>Lung Cancer</i> (2013); 80(1): 30–4.
A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.
Authors: I Inoue, T Nakajima, C S Williams, J Quackenbush, R Puryear, M Powers, T Cheng, E H Ludwig, A M Sharma, A Hata, X Jeunemaitre, J M Lalouel
Journal: Journal of Clinical Investigation (1997)

In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications.
Antigen-specific T cell-mediated suppression. V. H-2-linked genetic control of distinct antigen-specific defects in the production and activity of L-glutamic acid50-L-tyrosine50 suppressor factor.
Authors: R N Germain, C Waltenbaugh, B Benacerraf
Journal: The Journal of Experimental Medicine (1980)

The occurrence of distinct genetic defects affecting the generation of T cell-derived suppressor factor (TsF) or the suppressive activity of such TsF was investigated. For the synthetic polypeptide L-glutamic acid50-L-tyrosine50 (GT), it could be shown that the nonsuppressor strain A/J fails to produce suppressor T cells (Ts1) capable of GT-TsF generation upon challenge with GT. Conversely, B6, another nonsuppressor strain, produces GT-TsF active on other allogeneic strains such as A/J, but itself fails to be suppressed by this material. (B6A)F1 mice both make GT-TsF, and are suppressed by it. Further experiments revealed that the production of GT-TsF and the ability to be suppressed by GT-TsF are under the control of H-2-linked genes. Finally, the defect in GT-TsF activity in B6 mice was shown to be exquisitely antigen specific, in that this strain can be suppressed by a closely related TsF specific for L-glutamic acid60-L-alanine30-L-tyrosine10. It is suggested that H-2 (I) control of suppressor T cell (Ts) activity may reflect the involvement of I-A and I-C gene products in antigen presentation to Ts in analog with other T cell subsets, and that TsF function might also involve such presentation, in this case of the idiotypic structures of the TsF-combining site. Predictions deriving from this hypothesis are discussed, including the possibility that H-2 linked immune response genes regulate auto-anti-idiotypic responses in immune networks.
Don't let radiation scare trump patient care: 10 ways you can harm your patients by fear of radiation-induced cancer from diagnostic imaging
Authors: Alan S Brody, R Paul Guillerman
Journal: Thorax (2014)

For many people, the term radiation is linked to atomic bombs, cancer and death. Even without these associations, ionising radiation in the form of X-rays is frightening. Acute exposure to X-rays cannot be sensed in any way, yet can be lethal within days or weeks if received at a high enough dose. There is clearly good reason to be concerned about unnecessary exposure to X-rays. In diagnostic imaging, balancing this danger is the benefit that can be realised from the use of these X-rays. When a group of leading general internists was asked to rank 30 medical innovations by the most adverse effect on their patients if the innovation were unavailable, the most important innovation ‘by a considerable margin’ was MRI and CT scanning.1 MRI does not use ionising radiation, but CT scanning is more widely available, can be completed in under 10 s compared with 20–30 min for MRI, and is the imaging modality of choice for acute trauma to the head or abdomen and for evaluation of the lungs.

How can your concern about radiation risk hurt your patient? Simply put, by not doing an imaging study that could benefit the patient more, or by unduly compromising image quality in an effort to reduce radiation dose. The following are 10 common ways that a medical caregiver can wrongly assess the risk : benefit of imaging to the detriment of his or her patients.

### Overweighting the risk of radiation

The risk is very, very low. The lifetime attributable risk of cancer mortality to a 10-year-old from a 3 mGy average organ dose (similar to that from a body CT scan) is approximately 1/3000 for a girl and1/4700 for a boy, using the Biological Effects of Ionising Radiation VII estimates.2 This compares to the 1/5 probability, without additional radiation exposure, of dying of cancer for a typical person …
The nonexpression of CD36 on reticulocytes and mature red blood cells does not modify the clinical course of patients with sickle cell anemia
Authors: Ketty Lee, Pierre Gane, Françoise Roudot-Thoraval, Bertand Godeau, Dora Bachir, Françoise Bernaudin, Jean-Pierre Cartron, Frédéric Galactéros, Philippe Bierling
Journal: Blood (2001)