tbuckley/cabot-search huggingface dataset:
Atherosclerosis in Takayasu arteritis
Authors: E Seyahi, S Ugurlu, R Cumali, H Balci, N Seyahi, S Yurdakul, H Yazici
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> Chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis. We hypothesised that atherosclerosis may also be increased in Takayasu arteritis. <b>Methods:</b> The frequency of atherosclerotic plaques and the intima–media thickness (IMT) were investigated in 30 female patients with Takayasu arteritis (mean age (standard deviation), 35.4 (8.0) years), along with 45 sex-matched and age-matched patients with SLE (37.4 (6.8)) and 50 healthy controls (38.2 (5.7)). Plaques were scanned and IMT was measured at both sides of the common carotids, carotid bulb, and internal and external carotid arteries by B-mode ultrasonography. Traditional risk factors for atherosclerosis were also assessed. <b>Results:</b> Most of the atherosclerotic risk factors were comparable between patients with Takayasu arteritis and SLE. More atherosclerotic plaques were observed among patients with Takayasu arteritis (8/30; 27%) and those with SLE (8/45; 18%) than among the healthy controls (1/50; 2%; p = 0.005). Logistic regression analyses showed that the presence of a plaque was associated only with age in both Takayasu arteritis and SLE (p = 0.04 and 0.02, respectively). The mean overall IMT was significantly higher among patients with Takayasu arteritis (0.95±0.31 mm) than among the patients with SLE (0.58±0.10 mm) and the healthy controls (0.59±0.08 mm; p&lt;0.001). <b>Conclusion:</b> Patients with Takayasu arteritis have a high rate of atherosclerotic plaques, at least as frequent as that observed among patients with SLE.
S37 Matrix metalloproteinases drive collagen degradation and leukocyte migration in human tuberculosis: clinical and cellular studies
Authors: T Sathyamoorthy, JS Friedland, L Tezera, PT Elkington
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Tuberculosis (TB) causes disease worldwide and multi-drug resistance is rising. Matrix metalloproteinases (MMPs) cause immunopathological lung matrix destruction, which results in transmission, morbidity and mortality. We specifically investigated collagenases in TB, studying secreted MMP-1 and MMP-8, and membrane bound MMP-14. <h3>Methods</h3> Plasma was prospectively collected from TB patients (n = 151), respiratory symptomatics (n = 109) and controls (n = 120). Plasma MMP concentrations were measured by Luminex bead array. Induced sputum MMP-14 mRNA from TB patients and controls was quantified by RT-PCR. MMP-14 expression in TB patient biopsies was studied by immunohistochemistry. Human monocytes were stimulated with Mycobacterium tuberculosis (Mtb) H37Rv or Conditioned Media from Mtb infected monocytes (CoMTb) and MMP-14 measured using flow cytometry. Fluorescent microscopy detected MMP-14 and monocyte driven fluorescent collagen degradation. Monocyte migration was measured by the agarose spot assay. <h3>Results</h3> Plasma MMP-1 was elevated in TB (median 229pcg/ml) compared to controls (median 2pcg/ml; p&lt;0.001). MMP-8 was increased in TB (median 8359pcg/ml) compared to both respiratory symptomatics (median 3547pcg/ml; p&lt;0.001) and controls (median 3236pcg/ml; p&lt;0.001), and discriminated TB from respiratory symptomatics with moderate predictive ability, with an area under the curve of 0.79 by receiver operating characteristic analysis. In induced sputum, MMP-14 mRNA (normalised to β-actin) was increased 3.3-fold in TB compared to controls (p&lt;0.05) and mRNA levels positively correlated with the extent of lung infiltration on chest radiograph (r = 0.483; p&lt;0.05). Macrophages of TB granulomas in patient biopsies stained strongly positive for MMP-14. Mtb increased monocyte MMP-14 surface expression 31.7-fold (p&lt;0.05) and CoMTb 17.5-fold (p&lt;0.01), secondary to increased mRNA. Mtb-infected monocytes degraded collagen, with co-localised MMP-14 surface expression. Monocytes migrated to the edge of CoMTb-impregnated agarose drops, expressing MMP-14 on migration. Inhibition of MMP-14 activity with a neutralising antibody, decreased Mtb driven collagen degradation by 73% (p&lt; 0.001) and CoMTb driven monocyte migration by 44% (p&lt;0.001). Inhibition of chemokine signalling using pertussis toxin reduced CoMTb driven MMP-14 surface expression by 35% (p&lt;0.05). <h3>Discussion</h3> Collagen destruction is critical to pathogenesis in pulmonary TB, and these data implicate three collagenases, MMP-1, -8 and -14, in causing immunopathology and regulating leukocyte migration. MMPs may represent novel diagnostic and therapeutic targets.
Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases
Authors: Ian F. Robey, Brenda K. Baggett, Nathaniel D. Kirkpatrick, Denise J. Roe, Julie Dosescu, Bonnie F. Sloane, Arig Ibrahim Hashim, David L. Morse, Natarajan Raghunand, Robert A. Gatenby, Robert J. Gillies
Journal: Cancer Research (2009)

Abstract The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases. Here, we show that oral NaHCO3 selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by 31P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO3 therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO3 therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease. [Cancer Res 2009;69(6):2260–8]
Overexpression of Ref-1 Inhibits Hypoxia and Tumor Necrosis Factor–Induced Endothelial Cell Apoptosis Through Nuclear Factor-κB–Independent and –Dependent Pathways
Authors: Jennifer L. Hall, Xiaohong Wang, None Van Adamson, Ying Zhao, Gary H. Gibbons
Journal: Circulation Research (2001)

We hypothesized that a redox-sensitive transcription factor, redox factor-1 (Ref-1) (HAP1, APE, and APEX), was critical in the regulation of endothelial cell survival in response to hypoxia and cytokines, including tumor necrosis factor (TNF)-alpha. Hypoxia resulted in a significant decrease in Ref-1 protein expression in both human umbilical vein endothelial cells and calf pulmonary artery endothelial cells. The hypoxia-induced decrease in Ref-1 expression was followed by a significant induction of apoptosis as measured by caspase 3 activity and nuclear morphology. Transient upregulation of Ref-1 significantly inhibited hypoxia-induced apoptosis. However, deletion of the redox-sensitive domain of Ref-1 abolished the antiapoptotic effect. We postulated that the antiapoptotic effects of Ref-1 were mediated through nuclear factor-kappaB (NF-kappaB). However, blockade of NF-kappaB with a dominant-negative IkappaB (S32A/S36A) expression vector had no effect on Ref-1-mediated survival under hypoxic conditions. The second aim of this study was to test the cytoprotective ability of Ref-1 upregulation in response to TNF-induced apoptosis. Ref-1 inhibition of TNF-induced death was associated with a significant potentiation of NF-kappaB activity. Deletion of the redox-sensitive domain of Ref-1 significantly inhibited TNF-induced NF-kappaB activation. Moreover, loss of the redox-sensitive domain also abolished the antiapoptotic effect of Ref-1 in response to TNF. To test whether Ref-1 induced activation of NF-kappaB was necessary to promote survival, we blocked NF-kappaB activity with a dominant-negative IkappaB (S32A/S36A). Indeed, blockade of NF-kappaB activity abolished the ability of Ref-1 to rescue TNF-induced apoptosis. In conclusion, upregulation of Ref-1 promotes endothelial cell survival in response to hypoxia and TNF through NF-kappaB-independent and NF-kappaB-dependent signaling cascades, respectively. Moreover, it seems that Ref-1 may act as a critical cofactor, mediating the TNF-induced NF-kappaB response in the vascular endothelium.
The axes of social differentiation and the evidence base on health equity
Authors: Michael P Kelly
Journal: Journal of the Royal Society of Medicine (2010)

The term health gradient is widely used to describe the ways in which mortality and morbidity are related to social position; the higher the social status the better the health, and conversely, the lower the social status the worse the health. This population level pattern has been noted since modern records began.1 This paper considers some of the theoretical, conceptual and methodological issues which are attached to the health gradient and the implications of these for the methods of evidence accumulation and synthesis and evidence-based medicine more generally.
Pulmonary Squamous Cell Carcinoma following Head and Neck Squamous Cell Carcinoma: Metastasis or Second Primary?
Authors: Tom W. Geurts, Petra M. Nederlof, Michiel W.M. van den Brekel, Laura J. van't Veer, Daphne de Jong, August A.M. Hart, Nico van Zandwijk, Houke Klomp, Alfons J.M. Balm, Marie-Louise F. van Velthuysen
Journal: Clinical Cancer Research (2005)

To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma.For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a squamous cell carcinoma of the lung, clinical data, histology, and analysis of loss of heterozygosity (LOH) were used to differentiate metastases from second primary tumors.Clinical evaluation suggested 38 patients with metastases and 6 with second primaries. We developed a novel interpretation strategy based on biological insight and on our observation that multiple LOH on different chromosome arms are not independent. LOH analysis indicated metastatic disease in 19 cases and second primary squamous cell carcinoma in 24 cases. In one case, LOH analysis was inconclusive. For 25 patients, LOH supported the clinical scoring, and in 18 cases, it did not. These 18 discordant cases were all considered to be second primary tumors by LOH analysis.A considerable number of squamous cell lung lesions (50% in this study), clinically interpreted as metastases, are suggested to be second primaries by LOH analysis. For these patients, a surgical approach with curative intent may be justified.
Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats
Authors: Ludmilla Le Berre, Yann Godfrin, Eberhard Günther, Françoise Buzelin, Sabine Perretto, Helga Smit, Dontscho Kerjaschki, Claire Usal, Cristina Cuturi, Jean-Paul Soulillou, Jacques Dantal
Journal: Journal of Clinical Investigation (2002)

Buffalo/Mna rats spontaneously develop a focal segmental glomerulosclerosis with a histological pattern similar to the human disease. In this study, we investigated the potential of recurrence of the disease by transplantation of normal kidneys into Buffalo/Mna recipients. Kidneys from healthy LEW.1W rats were grafted into proteinuric 6-month-old Buffalo/Mna rats without or with specific tolerance induction following donor-specific transfusion (DST) aimed at controlling host anti-donor immune responses. The inverse combination was carried out to determine whether a proteinuric Buffalo/Mna kidney can recover its permselectivity in a normal environment. As a control, LEW.1W kidneys were grafted into Wistar Furth recipients. After transplantation without DST, recurrence of proteinuria in LEW.1W kidneys appeared at approximately 10 days, possibly associated with rejection of the graft. In the same combination with DST, proteinuria occurred after 20 days, and the attendant glomerular damage suggested that the initial kidney disease had recurred. Transplanted control animals remained free of proteinuria. In the opposite combination, the proteinuria and the lesions of Buffalo/Mna kidneys regressed after transplantation into healthy LEW.1W rats. The recurrence of proteinuria after transplantation in Buffalo/Mna and the remission of lesions in Buffalo/Mna kidneys transplanted into normal hosts suggests that Buffalo/Mna rats express circulating albuminuric factors, which may be relevant to the relapse of idiopathic nephrotic syndrome in humans.
Sleepwalking, night terrors, and consciousness.
Authors: A H Crisp, B M Matthews, M Oakey, M Crutchfield
Journal: BMJ (1990)

OBJECTIVE--To determine some personality and psychoneurotic characteristics of adults who have the sleepwalking-night terrors syndrome. DESIGN--Prospective assessment of two groups of consecutive patients with a firm diagnosis of either of two specific sleep disorders as established clinically and by polysomnography. SETTING--Outpatient sleep disorders clinic and sleep laboratory in a tertiary referral centre. PATIENTS--12 Patients referred consecutively to the clinic in whom a diagnosis of sleepwalking (six) or night terrors (six) was confirmed. MAIN OUTCOME MEASURES--Psychological characteristics as measured at the time of clinical assessment by means of the Eysenck personality questionnaire, the hostility and direction of hostility questionnaire, and the Crown-Crisp experiential index. RESULTS--Both groups scored exceptionally highly on the hysteria scale of the Crown-Crisp experiential index and the night terrors group also scored highly on the anxiety scale. The patients with sleepwalking also scored highly on a measure of externally directed hostility. CONCLUSIONS--The physiological and psychological features identified in these patients, possibly reflecting different expressions of a constitutional cerebral characteristic, may be explored in terms of hysterical dissociation. The findings contribute to the debate concerning the nature of sleepwalking, in particular with and without the forensic aspects.
Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations
Authors: Katja Gehmlich, Petros Syrris, Emma Peskett, Alison Evans, Elisabeth Ehler, Angeliki Asimaki, Aris Anastasakis, Adalena Tsatsopoulou, Apostolos-Ilias Vouliotis, Christodoulos Stefanadis, Jeffrey E. Saffitz, Nikos Protonotarios, William J. McKenna
Journal: Cardiovascular Research (2010)

AimsRecent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood.
Vasopressin Compared with Norepinephrine Augments the Decline of Plasma Cytokine Levels in Septic Shock
Authors: James A. Russell, Chris Fjell, Joseph L. Hsu, Terry Lee, John Boyd, Simone Thair, Joel Singer, Andrew J. Patterson, Keith R. Walley
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock.Objectives: Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock.Methods: We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours.Measurements and Main Results: A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony–stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony–stimulating factor in patients who had more severe shock.Conclusions: Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock.Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).
Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment
Authors: Viviane Hess, Roger A'Hern, Nazar Nasiri, D. Michael King, Peter R. Blake, Desmond P.J. Barton, John H. Shepherd, T. Ind, J. Bridges, K. Harrington, Stanley B. Kaye, Martin E. Gore
Journal: Journal of Clinical Oncology (2004)

Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate.Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study.Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls.Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.
The childhood asthma epidemic
Authors: G Russell
Journal: Thorax (2006)

Ward based patients may have even more variable glucose levels due to the intermittent nature of their caloric intake, in contrast to the continuous feeding that occurs commonly in critical care.The compounding effects of glucocorticoid treatment, frequently used in patients with COPD, have already been highlighted.Insulin infusions carry a risk of inadvertent hypoglycaemia which increases as blood glucose targets become more stringent.Indeed, in a major study of insulin therapy which aimed for blood glucose levels between 4.4 and 6.0 mmol/l, a 4.2% increase in the incidence of blood glucose levels of ,2.2 mmol/l was identified, although these episodes apparently had no adverse sequelae. 4Finally, the implica- tions for nursing workload are considerable; the development of computerised infusion control systems may help.If the benefits of tight glycaemic control on mortality in patients with acute exacerbations of COPD are proved, the potential impact on the health care of patients with such a common disease is enormous.It will be revealing if the outcome is significantly influenced by what many would consider to be routine medical care that should be undertaken in all patients.
Analysis of the <i>In Vivo</i> and <i>In Vitro</i> Effects of Photodynamic Therapy on Breast Cancer by Using a Sensitizer, Sinoporphyrin Sodium
Authors: Xiaobing Wang, Jianmin Hu, Pan Wang, Shaoliang Zhang, Yichen Liu, Wenli Xiong, Quanhong Liu
Journal: Theranostics (2015)

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. Photosensitizers are critical components for PDT. Sinoporphyrin sodium, referred to as DVDMS, is a newly identified photosensitizer that was isolated from Photofrin. Here, we evaluated the effects of DVDMS-mediated PDT (DVDMS-PDT) on tumor cell proliferation and metastasis in the highly metastatic 4T1 cell line and a mouse xenograft model. DVDMS-PDT elicited a potent phototoxic effect in vitro, which was abolished using the reactive oxygen species (ROS) scavenger N-acetylcysteine. In addition, DVDMS-PDT effectively inhibited the migration of 4T1 cells in scratch wound-healing and transwell assays. Using an in vivo mouse model, DVDMS-PDT greatly prolonged the survival time of tumor-bearing mice and inhibited tumor growth and lung metastasis, consistent with in vitro findings. PDT with DVDMS had a greater anti-tumor efficacy than clinically used Photofrin. Moreover, preliminary toxicological results indicate that DVDMS is relatively safe. These results suggest that DVDMS is a promising sensitizer that warrants further development for use in cancer treatment with PDT or other sensitizing agent-based therapies.