tbuckley/cabot-search huggingface dataset:
Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases.
Authors: D A Arenberg, S L Kunkel, P J Polverini, S B Morris, M D Burdick, M C Glass, D T Taub, M D Iannettoni, R I Whyte, R M Strieter
Journal: The Journal of Experimental Medicine (1996)

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.
Tyndalising the pill
Authors: J O Drife
Journal: BMJ (1994)

William Tyndale, the first person to translate the Bible into English, was strangled and burnt in 1536. He had become unpopular with an establishment which wished to keep knowledge away from the common people. In 1994 Tyndale would no doubt be a computer buff using the internet. I wonder if he would turn his attention to drug advertising.

American magazines like the New Yorker sometimes carry ads for prescription only medicines: the drug's benefits are described, and the reader is advised to ask a physician about it. I doubt if this is popular with American doctors but the US Food and …
Reliability of SMA-12 Profile
Authors: Thomas A. Marciniak
Journal: JAMA (1976)

To the Editor.—  I believe that Dr Burdick (234:1019, 1975) erred in his criticism of Dr Barnett's discussion of the 12-factor automated chemical analysis (SMA-12) profile (233:911, 1975). Using 95% confidence limits and screening a presumably healthy population, one would not expect that most panels will have at least one value outside the normal range. Assuming independence of channels, one can easily calculate the expected percentage of panels with at least one abnormal value: (1—0.95 12 )× 100% = 46%.  However, the assumption of independence may not be valid for the SMA-12 profile. For example, serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin determinations may reasonably be expected to be interdependent. Interdependencies will tend to reduce the percentage in question. Although an expected value cannot be calculated because mathematical descriptions of the interdependencies are not available, the published data of Cunnick et al 1 are relevant. In their analysis of 1,000
P5-14-06: Interaction between Stoma and Tumor Characteristics as a New Prognostic and Predictive Marker in Breast Carcinomas.
Authors: E Tagliabue, M Sandri, P Casalini, P Aiello, SM Pupa, R Orlandi, A Balsari, T Triulzi
Journal: Cancer Research (2011)

Abstract Background. We recently demonstrated that primary breast tumors can be classified based upon extracellular matrix composition (ECM) (Bergamaschi et al.) suggesting stroma characteristics could influence tumor progression. Aim of this study is to further investigate the robustness of this classification and its impact in tumor progression and response to therapy. Methods. The expression profile of ECM-related genes was analyzed by unsupervised hierarchical clustering in 10 independent datasets of breast tumors, counting more than 1000 samples and the prognostic and predictive value of this signature were evaluated in two datasets of not treated patients and in one dataset of neo-adjuvant treated patients, respectively. Results. Only one of ECM subsets (ECM3) showed a homogeneous gene pattern that consistently allowed the classification of an independent group of tumors in all tested datasets. ECM3 is characterized by highly correlated over expression of 34 ECM genes encoding mainly structural proteins. From 24 to 38% of cases were ECM3-enriched and were mainly estrogen receptor-positive and low grade (p&amp;lt;0.0001). The ECM3 showed inconsistent association with DMFS in the two data sets of not treated patients, whereas the interaction between ECM3 and grade showed strongly and significant association with DMFS (HR=5.35, p=0.0012). In particular, multivariate analysis of covariates available (size, ER, age and ECM) indicated that ECM3 is significantly associated with worse DMFS in grade III patients (HR=2.5, p=0.0386), whereas it is slightly correlated with better DMFS in grade I-II patients (HR=0.6, p=0.088). It is noteworthy that the probability of 10-year DMFS was 90% in ECM3 versus 74% in non-ECM3 patients in differentiated tumors, and 75% in non-ECM3 versus 41 % in ECM3 grade III tumors. The interaction between ECM3 and grade remained significantly associated with DMFS also in ER negative (HR=14.2, p=0.03) and ER positive (HR=3.34, p=0.079) subgroups. ECM3, indeed, was correlated with good and bad prognosis in differentiated and grade III tumors, respectively. Moreover analysis of a data set of patients treated neoadjuvantly with chemotherapy revealed that, among the grade III tumors, pathological complete response was reached by 9% of ECM3 versus 74% of non-ECM3 tumors (p=0.04). In differentiated tumors no response difference was observed according to ECM. Conclusions. Our results provide evidence that breast carcinoma progression and response to therapy are influenced by the interaction between tumor and stromal characteristics. (Partially supported by AIRC). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-06.
Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?
Authors: A Vannini, K Cheung, M Fusconi, J Stammen-Vogelzangs, J P H Drenth, A C Dall'Aglio, F B Bianchi, L E Bakker-Jonges, W J van Venrooij, G J M Pruijn, A J W Zendman
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored. <b>Objectives:</b> To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases). <b>Methods:</b> Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control). <b>Results:</b> The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87–93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42–50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples. <b>Conclusions:</b> In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.
Early expression of toll-like receptor-4 in vein graft atherosclerosis in ApoE(-l-) mice suggests a potential role for activation of innate immunity in accelerated atherosclerosis
Authors: Xiao Jun Li, Juliana Yano, Kuang-Yuh Chyu, Xiaoning Zhao, Paul C. Dimayuga, Bojan Cercek, Prediman K. Shah
Journal: Journal of the American College of Cardiology (2003)
Heat stress-induced resistance to myocardial infarction in the isolated heart from transgenic [(mREN-2)27] hypertensive rats
Authors: M Joyeux
Journal: Cardiovascular Research (1998)

Objective: Heat stress (HS) is known to confer protection against ischaemia–reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated rat heart and on the myocardial heat stress protein (HSP) 72 synthesis, in transgenic [(mREN-2)27] hypertensive (TGH) rats or normotensive (NT) controls. Methods: TGH or NT rats were either heat stressed (42°C for 15 min) or sham anaesthetised. After 24 h, their hearts were isolated, perfused using the Langengorff technique, and subjected to a 35-min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using electrophoresis coupled with Western blot analysis. Results: Infarct-to-risk (I/R) ratio was significantly reduced in HS (15.5±1.2%) compared to sham (42.2±2.1%) hearts of NT rats. This reduction in infarct size was maintained in TGH hearts (I/R: 20.0±1.0 vs. 48.0±3.8%). Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the four experimental groups. Western blot analysis of the myocardial HSP72 content showed a heat stress-induced increase of this protein, in both TGH and NT animals. Conclusion: These results demonstrate that the myocardial protective effect induced by heat stress could extend to a pathological animal model like the transgenic [(mREN-2)27] hypertensive rat and is correlated with a myocardial HSP72 induction.
Scavenging new insights into atherogenesis
Authors: Menno P.J. de Winther, Marten H. Hofker
Journal: Journal of Clinical Investigation (2000)

According to current hypotheses, atherosclerosis begins to develop when lipoproteins accumulate in the arterial intima and become chemically modified, thus initiating local vessel wall inflammation and attracting monocytes from the circulation. Modified lipoproteins are taken up avidly by monocyte-derived macrophages, and the resulting fat-laden macrophages (now known as foam cells) reside in the vessel wall and exacerbate the local inflammatory response. Since LDL receptor–deficient (LDLR-deficient) macrophages are not attenuated in their ability to develop into foam cells, it has long been known that foam cell formation requires receptors distinct from the LDLR. Moreover, macrophages do not readily take up native plasma lipoproteins in large amounts and will only become foam cells when exposed to oxidized, acetylated, or otherwise covalently modified lipoproteins. Hence, the discovery of the “scavenger” receptors for modified lipoproteins and the elucidation of lipid-modification processes are of crucial importance in our understanding of atherogenesis.
Needle Diagnosis of Pneumonitis
Authors: Paul D. Bandt
Journal: JAMA (1972)

Twenty-five percutaneous needle aspiration biopsies were performed with fluoroscopic guidance in 21 patients with pulmonary infectious lesions. All patients were immunologically compromised due to immunosuppressive therapy or malignant disease. In none of the patients was the etiologic diagnosis of the pneumonitis established by routine methods, including transtracheal aspirates. In 16 patients the causative organism was recovered from the needle aspirations. No serious complications developed in these debilitated patients when an 18-gauge thin-walled needle was used. However, the use of a cutting needle (Franklin-Silverman) had an unacceptable complication rate in patients with thrombocytopenia.
443 INTRAHEPATIC EXPRESSION OF CCL17 AND CCL22 CHEMOKINES IN HEPATITIS C VIRUS INFECTED PATIENTS MAY PROMOTE THE RECRUITMENT OF T REGULATORY CELLS AND CHRONICITY OF INFECTION
Authors: J.-I. Riezu-Boj, E. Larrea, R. Aldabe, L. Guembe, E. Galeano, I. Echeverria, P. Sarobe, J. Prieto, J.-J. Lasarte
Journal: Journal of Hepatology (2010)
Abstract B44: The microRNA-200/Zeb1 axis regulates ECM-dependent Src signaling, cytoskeletal changes and cancer cell invasion
Authors: Christin Ungewiss, Jonathon D. Roybal, David H. Peng, Don L. Gibbons
Journal: Cancer Research (2015)

Abstract The microRNA-200 family (miR-200) has been shown to be a master regulator of epithelial-to-mesenchymal transition (EMT), partially through a double-negative feedback loop with the transcription repressor Zeb1, allowing cells to acquire an invasive and metastatic phenotype. Using our mutant Kras and p53 murine model of metastatic lung adenocarcinoma, we are investigating the role of the Zeb1/miR-200 axis in regulating cytoskeletal reorganization, a characteristic requirement of cell motility and invasion. Functional assays demonstrated differential actin reorganization within cell lines with different miR-200 levels based upon the extracellular matrix composition, leading us to hypothesize that miR-200 regulates the activation of signaling pathways that mediate a pro-invasive cytoskeletal reorganization. Based upon the importance of cell-matrix interactions in producing cellular activation we identified the Src pathway as a critical mediator of invasion upon miR-200 repression in murine and human lung cancer cell lines. Pharmacologic inhibition of Src significantly reduces in vitro cell migration and invasion in Boyden chamber assays and in 3D cell cultures, which can be mimicked using Integrin β1 blockade. Biochemical analysis of this Src inhibition reveals a significant reduction in the phosphorylated FAK and cortactin levels, two downstream targets of Src. TGFβ stimulation is a strong EMT inducer, producing miR-200 repression and Src activation in our models, which can be blocked biochemically using Src inhibitors, with associated phenotypic changes in 2D and 3D cultures. This data suggests that miR-200 regulates the cell-matrix contact (e.g. integrins), acting through the Src pathway and modulating central players in actin dynamics to promote actin reorganization and invasion. Citation Format: Christin Ungewiss, Jonathon D. Roybal, David H. Peng, Don L. Gibbons. The microRNA-200/Zeb1 axis regulates ECM-dependent Src signaling, cytoskeletal changes and cancer cell invasion. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B44. doi:10.1158/1538-7445.CHTME14-B44
Bullous pemphigoid and primary biliary cirrhosis
Authors: D.V. HAMILTON, A.W. McKENZIE
Journal: British Journal of Dermatology (1978)

Journal Article Bullous pemphigoid and primary biliary cirrhosis Get access D.V. HAMILTON, D.V. HAMILTON Dermatology Department, Norfolk and Norwich Hospital, Norwich Search for other works by this author on: Oxford Academic Google Scholar A.W. McKENZIE A.W. McKENZIE Dermatology Department, Norfolk and Norwich Hospital, Norwich Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue 4, 1 October 1978, Pages 447–450, https://doi.org/10.1111/j.1365-2133.1978.tb06186.x Published: 01 October 1978
Consortium looks to NHS Direct to handle all GP calls
Authors: H. Mooney
Journal: BMJ (2011)

Staff at NHS Direct call centres may have to book GP appointments for thousands of patients across the country as the service attempts to expand its role and build new links with the new GP commissioning consortiums.

The proposal, put forward in NHS Direct board papers last month, suggests that the government’s new 111 number will become the number that patients will call for all primary care services, rather than just for urgent care, as is currently proposed. 

The 111 telephone number is currently being piloted for urgent (non-emergency) calls in three areas through NHS Direct, the NHS’s telephone and internet service, on behalf of the Department of Health. If the pilot is successful the government hopes to expand the number nationally, and NHS Direct will be in the bidding to provide and service the 111 number. …
Jaccoud's arthritis. A case report.
Authors: E Beausang, E V Barnett, S Goldstein
Journal: Annals of the Rheumatic Diseases (1967)

A woman admitted for cardiac catheterization was found to have chronic arthritis of both hands.She gave a history of many recurrent attacks of rheumatic fever with gradual development of her joint defor- mity.On further study, these changes were found to consist of marked ulnar deviation of the fingers at the matacarpophalangeal joints and hyperextension of the proximal interphalangeal joints of the 2nd, 3rd, 4th, and 5th digits unaccompanied by clinical evidence of bone destruction.Serological tests for rheumatoid factors were negative and the patient had a normal erythrocyte sedimentation rate.Her catheterization data showed severe aortic stenosis.The above results conform to the criteria outlined by Jaccoud (1869) as necessary for the diagnosis of chronic post rheumatic fever arthritis.The relationship of chronic deforming arthritis and valvular heart disease is complex and has been the source of a large number of investigations both clinical and pathological.It is now apparent that rheumatic fever is a late non-suppurative complication of Group A streptococcal infection manifested clinically by many symptoms (Master, 1944; Massell and Jones, 1944; Hubble, 1943), the most typical of which is migratory polyarthritis.Per- manent joint deformity is not one of the criteria used in the diagnosis of rheumatic fever (Duckett Jones, 1944).Rheumatoid arthritis may also present as an acute febrile polyarthritis but is not usually associated with streptococcal infection.A distinction between the two varieties of arthritis may be made
Shear Stress Regulates Angiotensin Type 1 Receptor Expression in Endothelial Cells
Authors: Bhama Ramkhelawon, Jose Vilar, Daniel Rivas, Barend Mees, Rini de Crom, Alain Tedgui, Stéphanie Lehoux
Journal: Circulation Research (2009)

Rationale : Shear stress (SS) has an established role in atherosclerotic plaque localization, but how it exerts its protective effect is not fully understood. Objective : To test the hypothesis that SS may downregulate angiotensin type 1 receptors (AT 1 Rs). Angiotensin II has been shown to be proinflammatory and to promote atherosclerosis. Methods and Results : Using immunohistochemistry, we found a pronounced expression of AT 1 R in the inner, atheroprone regions of the aortic arch of C57BL/6 and endothelial NO synthase–deficient (eNOS −/− ) mice but not eNOS-overexpressing mice. In human umbilical vein endothelial cells (HUVECs), laminar SS (15 dyn/cm 2 ) induced a biphasic decrease in AT 1 R protein expression characterized by a first reduction at 1 hour (31±4% of static control, P &lt;0.01), partial recovery at 3 hours (65±9%), and a second more prolonged decline at 6, 12, and 24 hours (48±9%, 36±9%, 33±5%, respectively, P &lt;0.05). One and 24 hours of SS significantly reduced fluorescent angiotensin binding compared to static HUVECs. Shear-induced downregulation of AT 1 R was abolished by treatment with protein kinase A and G inhibitors or N G -nitro- l -arginine methyl ester (L-NAME). Fittingly, stimulating static HUVECs with an NO donor decreased AT 1 R protein levels. RT-PCR revealed a significant ( P &lt;0.05) decrease of AT 1 R mRNA in HUVECs exposed to SS during 3 (6±2% of static control), 6 (4±1%), 12 (4±1%), and 24 hours (15±4%), suggesting a transcriptional downregulation of AT 1 R at length. Finally, angiotensin-induced vascular cell adhesion molecule was abated in HUVECs exposed to SS and in the outer aortic arch of mice. Conclusions : Our results demonstrate that SS may convey some of its atheroprotective effects through downregulation of AT 1 R in endothelial cells.
Altered membrane sodium transport in Bartter's syndrome
Authors: Jerry D. Gardner, Artemis P. Simopoulos, Allen Lapey, Shlomo Shibolet
Journal: Journal of Clinical Investigation (1972)

To explore the possibility that Bartter's syndrome is the manifestation of an inherited abnormality of sodium transport, we have measured various parameters of sodium transport in erythrocytes from patients with Bartter's syndrome, their siblings, and their parents. Sodium transport in six of the eight patients with Bartter's syndrome differed significantly from that in the other two patients. On the basis of this difference, the patients were divided into two groups (type I and type II). In the six type I patients, fractional sodium outflux (0.38+/-0.05/hr [SD]) was significantly less than normal (0.50+/-0.07) and erythrocyte sodium concentration (9.48+/-0.84 mmoles/liter cells per hr) was significantly greater than normal (5.24+/-0.66). In the two type II patients, none of the measured parameters of sodium transport differed significantly from normal. Erythrocyte sodium transport in the relatives of three type I patients was altered in a way similar to that in the type I patients and was significantly different from that in the relatives of a type II patient. These findings indicate the presence of inherited alterations of erythrocyte sodium transport in certain patients with Bartter's syndrome.
Nuclear Magnetic Resonance Techniques in Medicine
Authors: E. MORTON BRADBURY
Journal: Annals of Internal Medicine (1983)

Nuclear magnetic resonance (NMR) techniques are now finding exciting new noninvasive applications in medicine. There are two major approaches. The first is as an analytical technique using 31P NMR spectroscopy for the identification and quantitation of the more abundant phosphate metabolites in various tissues. Changes in the levels of these metabolites and in intracellular cytoplasmic pH can be followed in various ischemic and hypoxic conditions to monitor metabolic response to stress situations and to diagnose inborn errors of metabolism. The second major approach is an entirely different application of NMR techniques and uses 1H, the nucleus most abundant in biological tissues, largely in water and fats, to produce NMR images of any section of the body. By applying non-uniform magnetic fields across a section of the body, hydrogen nuclei in different elemental volumes in the section are tagged with different frequencies and their signals can be processed to give an image of the section. In contrast to computed tomographic scanning, NMR has particularly powerful application in the imaging of soft tissues.