tbuckley/cabot-search huggingface dataset:
Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents.
Authors: G D Martich, R L Danner, M Ceska, A F Suffredini
Journal: The Journal of Experimental Medicine (1991)

Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.
THE HISTOGENESIS OF CHRONIC URANIUM NEPHRITIS WITH ESPECIAL REFERENCE TO EPITHELIAL REGENERATION
Authors: Jean Oliver
Journal: The Journal of Experimental Medicine (1915)

1. Proliferation of connective tissue in chronic uranium nephritis is early and progressive and due to a direct stimulation on the part of the uranium. 2. The hydronephrotic theory fails to explain the phenomena observed in the progress of the chronic nephritis. 3. Carmine is deposited, as shown by Suzuki, in the proximal convoluted tubule only, and in different amounts in different levels of this segment of the tubule, so that subdivisions may be made. 4. Regeneration begins about the fourth day, but varies in proportion to the dose of renal irritant given. 5. The first cells to appear are large vesicular elements, and there is a gradual development of syncytium-like masses and giant-cells. These last are due to the rapidity of cell division. 6. Small, deeply staining nuclei, which are morphologically identical with the newly regenerated cells described by Thorel and others, are present from the first day of the acute nephritis and are persisting renal cells which have been slightly affected by the toxic agent.
The feasibility of awake thoracic epidural anesthesia in patients requiring VATS wedge resection
Authors: Serkan Bayram, Çagatay Tezel, Ezgi Cesur, Serda Kanbur, Hakan Kiral, Senol Urek
Journal: European Respiratory Journal (2013)

Background:Video-assisted thoracic surgery (VATS) is usually performed with general anesthesia and single lung ventilation. However, performing thoracic surgery under awake anesthesia has several potential advantages including avoidance of airway trauma associated with endotracheal intubation and single lung ventilation.  Objectives:The study was aimed to analyze the feasibility, safety, and early results of awake thoracic surgery in patients who underwent videothoracoscopic pulmonary resection.  Methods:In 2012, four patients underwent VATS wedge resection via thoracic epidural anesthesia for both diagnostic and therapeutic indications.  Results:listed  Conclusions: In our study, awake pulmonary videothoracoscopic wedge resection was easily accepted and well tolerated by patients resulted in shorter ICU stay. Large scale randomized controlled studies are needed in order to refine our findings.
Paroxysmal Ventricular Tachycardia with Second Degree V-A Block and Reciprocal Rhythm
Authors: SIDNEY GRAU, JAMES L. GOUAUX
Journal: Circulation (1950)

An instance of paroxysmal ventricular tachycardia with retrograde conduction is presented. This occurred in a patient in the terminal stage of arteriosclerotic heart disease. The electrocardiograms obtained during this period, representative portions of which are illustrated, were unique in that reciprocal beats and fusion beats were noted; the latter being unusual because of the origin and site of fusion of the impulses. A hitherto unreported abnormality of the retrograde P wave is also described and illustrated.
Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase Fyn
Authors: Coralie Bloch-Queyrat, Marie-Claude Fondanèche, Riyan Chen, Luo Yin, Francis Relouzat, André Veillette, Alain Fischer, Sylvain Latour
Journal: The Journal of Experimental Medicine (2005)

SAP is an adaptor protein that is expressed in NK and T cells. It is mutated in humans who have X-linked lymphoproliferative (XLP) disease. By interacting with SLAM family receptors, SAP enables tyrosine phosphorylation signaling of these receptors by its ability to recruit the Src-related kinase, Fyn. Here, we analyzed the role of SAP in NK cell functions using the SAP-deficient mouse model. Our results showed that SAP was required for the ability of NK cells to eliminate tumor cells in vitro and in vivo. This effect strongly correlated with expression of CD48 on tumor cells, the ligand of 2B4, a SLAM-related receptor expressed in NK cells. In keeping with earlier reports that studied human NK cells, we showed that SAP was necessary for the ability of 2B4 to trigger cytotoxicity and IFN-γ secretion. In the absence of SAP, 2B4 function was shifted toward inhibition of NK cell–mediated cytotoxicity. By analyzing mice lacking Fyn, we showed that similarly to SAP, Fyn was strictly required for 2B4 function. Taken together, these results provide evidence that the 2B4-SAP-Fyn cascade defines a potent activating pathway of natural cytotoxicity. They also could help to explain the high propensity of patients who have XLP disease to develop lymphoproliferative disorders.
Predictors of health care seeking for irritable bowel syndrome: a population based study
Authors: N J Talley, P M Boyce, M Jones
Journal: Gut (1997)

Background —It has been suggested that psychological factors rather than symptoms drive subjects with irritable bowel syndrome (IBS) to seek medical care, but this issue has not been tackled in a population based study. Aim —To identify whether psychological factors or abuse explain health care seeking for IBS. Methods —A sample of residents of Penrith (a Sydney suburb representative of the Australian population) selected randomly from the electoral rolls (that by law include the entire population ⩾18 years) was mailed a validated self-report questionnaire. Measured were gastrointestinal symptoms including the Manning (and Rome) criteria for IBS, health care seeking, neuroticism (Eysenck Personality Questionnaire), psychological morbidity (General Health Questionnaire: GHQ) and sexual, physical and emotional abuse (including the standardised Drossman questions). Results —Among 730 subjects, 96 (13%, 95% confidence interval (CI) 11–16%) had IBS by the Manning criteria. Of those with IBS, 73% (95% CI 63–81%) had sought medical care for abdominal pain or discomfort. Only increasing pain severity (odds ratio (OR) = 2.10, 95% CI 1.11–3.95) and duration of pain (OR=1.53, 95% CI 1.10–2.13) were independently associated with seeking health care for IBS. Pain severity was also predictive of recent care seeking (OR=1.74, 95% CI 1.12–1.96). Neuroticism, psychological morbidity and abuse history were not significant predictors. Conclusion —Psychological factors do not seem to explain health care seeking among community subjects with IBS.
Tsunami Lung Accompanied by Multiple Disorders
Authors: Takahiro Hiruma, Kensuke Nakamura, Ryota Inokuchi, Hideaki Kurata, Masataka Gunshin, Takehiro Matsubara, Takeshi Ishii, Susumu Nakajima, Naoki Yahagi, Kazuaki Shinohara
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Mechanical determinants of maximum isotonic lengthening rate in rat left ventricular myocardium.
Authors: M R Zile, W H Gaasch, A W Wiegner, K G Robinson, O H Bing
Journal: Circulation Research (1987)

The effects of changing loading conditions and inotropic state on maximum isotonic lengthening rate (+dL/dt, muscle lengths/sec) were examined in isolated rat myocardium. Physiologically sequenced contractions were studied in 18 left ventricular papillary muscle preparations (stimulation rate, 12/min). To study the effects of changing loading conditions, only one loading variable (preload, total load, or late load) was changed during each contraction, while the others were held constant. To study the effects of isoproterenol (10(-6) M) and temperature (28 vs. 33 degrees C) on maximum isotonic lengthening rate, preload and late load were held constant and +dL/dt was examined at a common total load. When preload was increased from 0.7 +/- 0.1 to 1.4 +/- 0.1 g/mm2, muscle length increased from 0.98 +/- 0.003 to 1.01 +/- 0.002 muscle lengths, the extent of shortening increased from 0.05 +/- 0.003 to 0.08 +/- 0.003 muscle lengths, but minimum length (0.93 +/- 0.01 muscle lengths) and +dL/dt (1.1 +/- 0.1 muscle lengths/sec) were unchanged. When total load was increased from 1.5 to 4.5 g/mm2, minimum length increased from 0.91 +/- 0.05 to 0.97 +/- 0.05 muscle lengths and +dL/dt fell from 1.4 +/- 0.1 to 0.5 +/- 0.1 muscle lengths/sec. Late load (the load borne by or applied to the muscle during isotonic lengthening) was altered by changing its magnitude (g/mm2) or time (milliseconds after stimulation) of application. As late load was increased from 1.4 +/- 0.02 to 2.1 +/- 0.3 g/mm2, +dL/dt increased from 1.3 +/- 0.2 to 2.1 +/- 0.3 muscle lengths/sec.(ABSTRACT TRUNCATED AT 250 WORDS)
Iodothyronine Release from the Perfused Canine Thyroid following Cessation of Stimulation
Authors: Peter Laurberg
Journal: Journal of Clinical Investigation (1980)

The kinetics of thyroid secretion after termination of stimulation by 100 μU/ml bovine thyroid stimulating hormone (TSH) or 5 mM cyclic AMP (cAMP) were studied using perfused canine thyroid lobes. All experiments were performed as paired comparisons, one thyroid lobe acting as a control continuing to receive infusion of the stimulator. 2.5 h after termination of TSH infusion, the secretion of thyroxine (T4), 3,5,3′-triiodothyronine (T3), and 3,3′,5′-triiodothyronine (rT3) was not significantly different from that of the control lobes. After cessation of cAMP infusion, the secretion of T4 continued unaffected for ∼40 min. Then a gradual decline in T4 release occurred. The secretion of T3 and rT3 decreased somewhat earlier leading to a transient phase with increases in the T4:T3 and T4:rT3 ratios in the thyroid effluent.
An Antibody Targeting the Type I Insulin-like Growth Factor Receptor Enhances the Castration-Induced Response in Androgen-Dependent Prostate Cancer
Authors: Stephen R. Plymate, Kathy Haugk, Ilsa Coleman, Lillie Woodke, Robert Vessella, Peter Nelson, R. Bruce Montgomery, Dale L. Ludwig, Jennifer D. Wu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To determine the effect of inhibition of insulin-like growth factor-IR (IGF-IR) signaling with an antibody to the IGF-IR, A12, in conjunction with androgen withdrawal on prostate cancer progression in a human prostate xenograft model, LuCaP 35. Experimental Design: LuCaP 35 was implanted s.c. in severe combined immunodeficient mice. At the time of castration, mice were randomized to one of three groups. Group 1 was castrate only; group 2 received A12 40 mg/kg i.p. for 2 weeks beginning 1 week after castration; and group 3 received A12 40 mg/kg i.p. for 2 weeks beginning 2 weeks after castration. Results: In group 1, tumor volume decreased to 60% of the starting volume 4 weeks post-castration. In groups 2 and 3, tumor volumes nadired 6 weeks after castration at &amp;lt;10% of the volume at time of castration (P &amp;lt; 0.01). Tumor regrowth was not seen in groups 2 or 3 until 15 weeks after castration. Androgen receptor (AR) localization in tumors showed a decrease in nuclear staining in groups 2 and 3 compared with group 1 (P &amp;lt; 0.001). Tumor volume correlated with nuclear AR intensity. AR-regulated genes increased early in group 1, but did not increase in groups 2 and 3. Thus, tumor-specific survival was prolonged by the addition of A12 to castration. Conclusions: This study shows that the inhibition of IGF-IR enhances the effects of castration in prostate cancer. These effects are associated with a decrease in AR signaling and nuclear AR localization, and recurrence is associated with an increase in AR-regulated gene expression.
First-line temozolomide chemotherapy in progressive low-grade astrocytomas after radiotherapy: molecular characteristics in relation to response
Authors: W. Taal, H. J. Dubbink, C. B. L. Zonnenberg, B. A. Zonnenberg, T. J. Postma, J. M. M. Gijtenbeek, W. Boogerd, F. H. Groenendijk, J. M. Kros, M. C. M. Kouwenhoven, R. van Marion, I. van Heuvel, B. van der Holt, J. E. C. Bromberg, P. A. E. Sillevis Smitt, W. N. M. Dinjens, M. J. van den Bent
Journal: Neuro-Oncology (2010)

Only a few studies examined the effect of temozolomide (TMZ) in recurrent low-grade astrocytoma (LGA) after surgery, none of which included a homogeneous and sufficiently sized group of patients with progression after radiotherapy (RT). We evaluated a cohort of 58 patients treated with TMZ for progression after RT of a previous LGA and investigated the relation between outcome and mutations in the IDH1, IDH2, and TP53 genes, O⁶-methylguanine-methyltransferase (MGMT) promoter methylation, trisomy of chromosome 7, and loss of chromosomes 1p and 19q. All patients received first-line TMZ 200 mg/m²/day on days 1-5 every 4 weeks for a progressive LGA with a contrast-enhancing lesion on MRI after RT. Six months progression-free survival (PFS) was 67%, and the median overall survival was 14 months. An objective response was obtained in 54%. TP53 mutations and loss of chromosome 19q showed a borderline association with PFS, but none of the other molecular characteristics were correlated with the outcome to TMZ. Both a methylated MGMT promoter gene and IDH1 mutations were found in 86% of the tumor samples. A correlation was found between IDH1 mutations and MGMT promoter methylation (P < .001). Neither MGMT promoter methylation nor IDH1 mutations correlated with PFS, but the interval between the very first symptom of the LGA and the start of the TMZ was significantly longer in the patients with IDH1 mutations (P = .01) and a methylated MGMT promoter (P = .02). We conclude that MGMT promoter methylation and IDH1 mutations seem to predict survival from the time of diagnosis, but not PFS to TMZ.
IL-6 and Serum Amyloid A Synergy Mediates Angiotensin II–Induced Muscle Wasting
Authors: Liping Zhang, Jie Du, Zhaoyong Hu, Guofeng Han, Patrice Delafontaine, Gabriela Garcia, William E. Mitch
Journal: Journal of the American Society of Nephrology (2009)

Animal studies suggest that increased levels of circulating angiotensin II (AngII) could contribute to the loss of lean body mass in chronic kidney disease, but the mechanism by which this occurs is unclear. Here, AngII infusion increased circulating IL-6 and its hepatic production in wild-type mice, suggesting that AngII-induced inflammation may trigger muscle loss. AngII infusion also stimulated the suppressor of cytokine signaling (SOCS3) in muscle, which led to loss of insulin receptor substrate 1 (IRS-1), thereby impairing insulin/IGF-1 signaling and enhancing protein degradation. All of these responses to AngII were suppressed in IL-6-deficient mice. Recombinant human IL-6 (rhIL-6) treatment of cultured myotubes only minimally increased SOCS3, however, suggesting the contribution of other mediators. Because AngII increases hepatic serum amyloid A (SAA) expression in an IL-6-dependent manner, we treated wild-type mice with rhIL-6 and an SAA1-overexpressing adenovirus; the combination led to a significantly greater increase in SOCS3 and decrease in IRS-1 compared with either rhIL-6 or SAA1 alone. We observed similar effects on SOCS3 and IRS-1 when we treated cultured muscle myotubes with rhIL-6 and SAA1. Taken together, these results suggest an interorgan response to high levels of AngII: Hepatic production of IL-6 and SAA increases, and these mediators act synergistically to impair insulin/IGF-1 signaling, which promotes muscle proteolysis. Targeting the high levels of IL-6 and SAA in catabolic disorders might be a therapeutic approach to prevent muscle wasting.
A fuzzy gene expression-based computational approach improves breast cancer prognostication
Authors: Benjamin Haibe-Kains, Christine Desmedt, Françoise Rothé, Martine Piccart, Christos Sotiriou, Gianluca Bontempi
Journal: Genome biology (2010)

Early gene expression studies classified breast tumors into at least three clinically relevant subtypes. Although most current gene signatures are prognostic for estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancers, few are informative for ER negative/HER2 negative and HER2 positive subtypes. Here we present Gene Expression Prognostic Index Using Subtypes (GENIUS), a fuzzy approach for prognostication that takes into account the molecular heterogeneity of breast cancer. In systematic evaluations, GENIUS significantly outperformed current gene signatures and clinical indices in the global population of patients.
Another major win for physiotherapy -- curing patellofemoral pain
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2009)

Thanks for the positive feedback about BJSM ’s recent articles – particularly the January (http://bjsm.bmj.com/content/vol43/issue1) and February (http://bjsm.bmj.com/content/vol43/issue2) issues edited by Professor Steven Blair. Many emails supported the claims that physical activity is the most powerful single medical intervention.1 The downside is that Neville Owen has made me feel guilty if I sit for a mere 12 hours.2 The result? Ageing BJSM editor shuffling around the streets of Vancouver at 10 pm getting his “fix” in 3°C temperatures. The voices of Steven Blair and Art Kramer in my head3 penetrating the usual cacophony, “30–60 minutes a day keeps dementia at bay”. “Too late!” you say?

Coincidentally with this month’s cover story, we learn that Jenny McConnell received Australia’s highest honour — the Order of Australia Medal (OAM) — for her “service to physiotherapy as a practitioner and researcher, particularly through …
Initiation of Signal Transduction through the T Cell Receptor Requires the Multivalent Engagement of Peptide/MHC Ligands
Authors: J.Jay Boniface, Joshua D Rabinowitz, Christoph Wülfing, Johannes Hampl, Ziv Reich, John D Altman, Ronald M Kantor, Craig Beeson, Harden M McConnell, Mark M Davis
Journal: Immunity (1998)

While much is known about intracellular signaling events in T cells when T cell receptors (TCRs) are engaged, the mechanism by which signaling is initiated is unclear. We have constructed defined oligomers of soluble antigen-major histocompatibility complex (MHC) molecules, the natural ligands for the TCR. Using these to stimulate specific T cells in vitro, we find that agonist peptide/MHC ligands are nonstimulatory as monomers and minimally stimulatory as dimers. Similarly, a partial-agonist ligand is very weakly active as a tetramer. In contrast, trimeric or tetrameric agonist ligands that engage multiple TCRs for a sustained duration are potent stimuli. Ligand-driven formation of TCR clusters seems required for effective activation and helps to explain the specificity and sensitivity of T cells.
Unaltered respiratory-related evoked potentials after acute diaphragm dysfunction in humans
Authors: M. Bezzi, C. Donzel-Raynaud, C. Straus, C. Tantucci, M. Zelter, J-P. Derenne, T. Similowski
Journal: European Respiratory Journal (2003)

Respiratory muscles play an important role in the origin of respiratory sensations. Data dissecting the role of the diaphragm and other inspiratory muscles are scarce. This study aimed to determine the impact of diaphragm dysfunction following inspiratory resistive loading on respiratory-related evoked potentials considered as a neurophysiological substrate of certain types of respiratory sensations. Altogether, nine subjects aged 25–50 yrs (six females) participated in the study. Transdiaphragmatic pressure output of cervical magnetic stimulation (with subdivision in oesophageal and gastric component), and respiratory-related evoked potentials (C3 and C4 derivations in the international 10–20 system) following mid-inspiratory occlusions were studied before and after an inspiratory-resistive loading challenge. Predominant diaphragm dysfunction was observed in seven subjects (average 28% reduction in transdiaphragmatic pressure, from 27.25–19.91 cmH 2 0, with increased oesophageal-to-gastric pressure ratio). The latencies and amplitudes of all the components of the respiratory-related evoked potentials were unchanged. The study concluded that predominant diaphragm fatigue does not affect respiratory-related evoked potentials.
No evidence of parvovirus B19 in tissue samples from patients with polyarteritis nodosa and microscopic polyangiitis as assessed by the polymerase chain reaction
Authors: Z Sachetto
Journal: Annals of the Rheumatic Diseases (2006)

Parvovirus B19 (B19) has been implicated in the aetiopathogenesis of some cases of systemic vasculitis, mainly giant cell arteritis.1 A positive serological test for B19 has been reported in a few patients with polyarteritis nodosa (PAN).2–4

As far as we know no studies of B19 DNA in tissue samples of patients with PAN have been published, so we used a nested polymerase chain reaction (PCR) approach to screen for B19 DNA in fixed paraffin embedded tissue samples from patients with PAN and microscopic polyangiitis (MPA). The diagnosis was based on the Chapell-Hill Consensus Conference guidelines.5 Only tissue samples from patients with vasculitis were used for DNA preparations.

DNA was extracted using a commercial kit (DNeasy tissue kit, Quiagen). A nested PCR for B19 was carried out using a previously published set …