tbuckley/cabot-search huggingface dataset:
Abstract 5326: CCL2 is critical for immunoresistance in association with cancer EMT
Authors: Chie Kudo-Saito, Yutaka Kawakami
Journal: Cancer Research (2010)

Abstract Purpose: Epitherial-to-mesenchymal transition (EMT) is a key step toward cancer metastasis, which is still a critical issue in cancer therapy. We previously reported that Snail-induced EMT accelerates cancer metastasis through multiple immunosuppressions using murine and human melanoma cells. However, the molecular mechanism is not completely understood. In this study, we confirmed the Snail-induced immunosuppressions using various human cancer cell lines, and further elucidated the mechanisms by identifying the specific mediators. Results: We first established human pancreatic cancer cell line Panc-1 cells showing typical EMT features such as reduced adhesion and enhanced invasion after transduction with snail gene, which is a transcription factor governing EMT. When human PBMCs were cocultured with the Snail transfectants, CD11c+ cell differentiation was significantly inhibited, and immunosuppressive CD4+FOXP3+ Treg cells were increased as similarly observed using Snail+ melanoma, suggesting the general features of the Snail-induced immunosuppressive mechanisms. We next conducted GeneChip analysis to identify other possible mechanisms by comparing gene profiles between the Snail transfectant and the parental cells. CCL2 was significantly upregulated in various Snail+ tumor cells after transduction with snail or treatment with TGFβ, a potent EMT inducer. CCL2 not only enhanced tumor invasion but also caused immunosuppressions through induction of Lipocalin 2 (LCN2), which was reported to induce apoptosis in various cells. CCL2 also increased LCN2 receptor Megalin and immunosuppressive molecules IDO and PD-L1 in DCs; in turn, LCN2 increased CCR2 in DCs. Utilizing the cooperative mechanism induced by CCL2 and LCN2, Snail+ cancer cells severely hampered APC function through induction of apoptosis and PD-L1/IDO expressions followed by Treg generation and then CTL attenuation. CCL2 blockade utilizing the specific siRNA or antibody significantly inhibited both tumor invasion and those immunosuppressions in vitro. Intratumoral injection with these anti-CCL2 reagents significantly inhibited tumor growth and metastasis by enhancing anti-tumor response systemically in vivo. Conclusion: These results demonstrate that CCL2 plays a vital role in the Snail-induced immunosuppressions. CCL2 blockade in tumor microenvironment may be an attractive strategy to overcome metastasis and immunoresistance of Snail+ cancers by restoring immunocompetence in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5326.
New drug combination for execution in US leaves hospitals in short supply
Authors: C. Dyer
Journal: BMJ (2014)

<h3>Objective</h3> Inhaled particulate matter (PM) in secondhand smoke (SHS) is deleterious for smokers and non-smokers. Different additives in cigarettes might effect the amount of PM. This study aimed to assess the influence of additives on the PM emissions from different cigarette types in SHS. <h3>Design</h3> An experimental study of PM measuring in SHS of cigarettes without exposition of any person. <h3>Method</h3> The concentrations of PM (PM<sub>10</sub>, PM<sub>2.5</sub> and PM<sub>1</sub>) in SHS of four different types of cigarettes of the brand Lucky Strike, two types with additives (Original Red, Original Blue) and two types without additives (Straight Red, Straight Blue), in comparison to the reference cigarette 3R4F were analysed. An automatic environmental tobacco smoke emitter generated SHS in an enclosed space with a volume of 2.88 m<sup>3</sup>. PM was measured with a laser aerosol spectrometer (Grimm model 1.109). Afterwards, the measuring values of the four Lucky Strike brands and the reference cigarette were statistically evaluated and visualised. <h3>Results</h3> Lucky Strike Straight Blue, a cigarette type without additives and lower tar amount, showed 10% to 25% lower PM mean values compared with the other tested Lucky Strike products, but 21% (PM<sub>1</sub>) respectively 27% (PM<sub>2.5</sub>,PM<sub>10</sub>) higher mean values than the reference cigarette. The PM mean of all measured smoke-free baseline values (clean air) was 1.6 µg/m³. It increased up to about 1800 µg/m³ for the reference cigarette and up to about 3070 µg/m³ for the Lucky Strike Original Blue. <h3>Conclusions</h3> The findings of this study show the massive increase of PM amount by smoking cigarettes in enclosed spaces and suggest that additives in tobacco products increase the PM amount in SHS. For validation, further comparative studies are necessary focusing on the comparison of the PM concentration of cigarettes with and without additives. <h3>Implications</h3> Due to the exposure to SHS, 890 000 people die each year worldwide. PM in SHS endangers the health of both non-smokers and smokers. This study considers the effect of additives like aromatics and humectant agents in cigarettes on PM in SHS. Do additives in tobacco products increase the amount of PM?
Pancreatic β-Cell Function and Immune Responses to Insulin After Administration of Intranasal Insulin to Humans At Risk for Type 1 Diabetes
Authors: Leonard C. Harrison, Margo C. Honeyman, Cheryl E. Steele, Natalie L. Stone, Elena Sarugeri, Ezio Bonifacio, Jennifer J. Couper, Peter G. Colman
Journal: Diabetes Care (2004)

OBJECTIVE—Mucosal administration of insulin retards development of autoimmune diabetes in the nonobese diabetic mouse model. We conducted a double-blind crossover study in humans at risk for type 1 diabetes to determine if intranasal insulin was safe, in particular did not accelerate β-cell destruction, and could induce immune effects consistent with mucosal tolerance. RESEARCH DESIGN AND METHODS—A total of 38 individuals, median age 10.8 years, with antibodies to one or more pancreatic islet antigens (insulin, GAD65, or tyrosine phosphatase-like insulinoma antigen 2) were randomized to treatment with intranasal insulin (1.6 mg) or a carrier solution, daily for 10 days and then 2 days a week for 6 months, before crossover. The primary outcome was β-cell function measured as first-phase insulin response (FPIR) to intravenous glucose at 0, 6, and 12 months and then yearly; the secondary outcome was immunity to islet antigens, measured monthly for 12 months. RESULTS—No local or systemic adverse effects were observed. Diabetes developed in 12 participants with negligible β-cell function at entry after a median of 1.1 year. Of the remaining 26, the majority had antibodies to two or three islet antigens and FPIR greater than the first percentile at entry, as well as β-cell function that generally remained stable over a median follow-up of 3.0 years. Intranasal insulin was associated with an increase in antibody and a decrease in T-cell responses to insulin. CONCLUSIONS—Results from this pilot study suggest that intranasal insulin does not accelerate loss of β-cell function in individuals at risk for type 1 diabetes and induces immune changes consistent with mucosal tolerance to insulin. These findings justify a formal trial to determine if intranasal insulin is immunotherapeutic and retards progression to clinical diabetes.
Potential coeliac disease in type 1 diabetes mellitus: does a positive antibody lead to increased complications?
Authors: J. S. Leeds, A. D. Hopper, M. Hadjivassiliou, S. Tesfaye, D. S. Sanders
Journal: Gut (2011)

<h3>Introduction</h3> Coeliac disease (CD) is more common in people with type 1 diabetes than in the general population. We have previously shown that patients with type 1 diabetes and newly identified CD have worse glycaemic control, lipid profile, renal involvement and retinal disease. Patients with positive antibodies but a normal duodenal biopsy may also have gluten related complications but this has not been investigated in patients with coexisting type 1 diabetes. <h3>Methods</h3> 1000 patients with type 1 diabetes were recruited and 14 new cases CD were identified. Patients with positive EMA and/or tissue transglutaminase but a normal duodenal biopsy were compared to the newly diagnosed CD and a matched cohort of patients with negative antibodies. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined. <h3>Results</h3> 51 patients were included in the study (14 CD/diabetes, 22 potential CD and 14 diabetes only). There were no differences in age, gender, BMI and diabetes duration between the groups. Median HbA1c, total cholesterol, HDL cholesterol and cholesterol:HDL ratio was not significantly different in those with potential CD compared to diabetes only controls unlike those with CD/diabetes. There were no significant differences in quality of life scores between any of the groups. The prevalence of retinopathy was not significantly different between the groups but the prevalence of advanced lesions was higher in those with CD/diabetes (p=0.02). The prevalence of nephropathy was not significantly different between groups but patients with CD/diabetes had a higher prevalence of advanced renal disease (p=0.009). There was no difference in the prevalence of neuropathy between the groups. <h3>Conclusion</h3> In type 1 diabetes, enteropathy as well as antibody positivity is required to increase diabetes related complications whereas antibody positivity alone does not. The numbers in this study are small and therefore confirmation in a larger study would be desirable.
Letter: Septic abortion and the Dalkon Shield.
Authors: D F Hawkins
Journal: BMJ (1974)

recommnended by the Halsbury Committee would inflate these mind-boggling sums to 12p and 9p respectively.This, surely is the form in which doctors and the public at large should have N.H.S. expenditure presented to them.It would then be plain to all that for the medical profession to help the D.H.S.S. to wallow a little less deeply in the financial mire in which it now flounders is not only super- erogatery but iirrelevant.More important, this way of looking at the costs of the care of acute illness also offers a way of meeting those costs.If every patient in hospital, except perhaps the very young and the very old, contributed lOp a day to that hospital he could rest secure in the knowledge that this trivial premium-the cost of five cigarettes, a can of coke, a bar of chocolate, or 1pints of petrol-would ensure that whatever illness he had, whatever urgent service he might need, whatever unforseen comnplication or reverse he might suffer, cover would be provided at any houir of the day or night.Doubling the levy to a mere 2Op a day would, moreover, underwrite the de.spe,rately needed increase of salaries for nurses and ancillaries.Politicians of all colours have long lacked the courage to tell their electors that this kind of service must be paid for.Perhaps, after all, the D.H.S.S.
An independent effect of osmolality on urea transport in rat terminal inner medullary collecting ducts.
Authors: J M Sands, D C Schrader
Journal: Journal of Clinical Investigation (1991)

We have shown that urea transport across the terminal inner medullary collecting duct (terminal IMCD) is mediated by a vasopressin-stimulated, facilitated diffusion process exhibiting properties consistent with a transporter. To investigate whether hypertonic NaCl, as exists in vivo in the inner medulla, affects urea permeability, we studied isolated perfused rat terminal IMCD segments. Perfusate and bath osmolality were varied symmetrically by adding or removing NaCl or mannitol. Urea permeability rose progressively when osmolality was increased with NaCl or mannitol from 290 to 690 mOsm/kg H2O in the absence of vasopressin; there was no further increase at 890 mOsm/kg H2O. In the presence of 10(-8) M arginine vasopressin, urea permeability increased when NaCl was added to raise osmolality from 290 to 490 mOsm/kg H2O but there was no further increase at 690 mOsm/kg H2O. When 1 mM 8-bromo cyclic AMP was added to the bath, raising NaCl still increased urea permeability. These results suggest that urea transport across the rat terminal IMCD is regulated both by vasopressin and by osmolality at values present in the renal inner medulla. Osmolality seems to activate urea transport across the rat terminal IMCD by mechanisms distinct from those of vasopressin or cyclic AMP.
The Relationship of Sodium Retention and Venous Pressures to Edema Formation
Authors: RALPH GOLDMAN, SAMUEL H. BASSETT
Journal: Circulation (1955)

Two patients with congestive cardiac failure were placed on a metabolic balance regimen and supplemental sodium chloride was administered. Weight changes in these patients could be closely correlated with the amount of sodium retention and appeared to be initially independent of brachial venous pressure thus supporting the concept that edema in congestive failure results from prinmary sodium retention rather than primary elevation in venous pressure.
Osgood-Schlatter Disease
Authors: Meyer Alpert
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In the Questions and Answers section ofThe Journal(<b>178</b>:1124 [Dec 16] 1961) the following statement by Dr. J. C. Ivins appears: "The so-called Osgood-Schlatter's disease is a growth disturbance seen during adolescence." The concept of an underlying "growth disturbance" in Osgood-Schlatter's disease has not been accepted by most modern students of this disorder. This condition is now considered to be basically related to trauma involving the distal portion of the patellar tendon, the tibial tubercle, and the adjacent soft tissues. It is essentially a clinical diagnosis, but radiographs will often show one or more of the following changes: (1) avulsion of an osseous fragment from the tibial tubercle apophysis; (2) a small osseous body in the distal patellar tendon; (3) thickening of the patellar tendon; (4) thickening of the soft tissues anterior to the tibial tubercle. On pathologic examination there will often be an avulsed
Efficacy of Glimepiride for the Treatment of Diabetes Occurring During Glucocorticoid Therapy
Authors: Soji Kasayama, Toshio Tanaka, Kunihiko Hashimoto, Masafumi Koga, Ichiro Kawase
Journal: Diabetes Care (2002)

Approximately 5–25% of patients receiving glucocorticoids exhibit overt diabetes (1). Glucocorticoids may precipitate diabetes in individuals with impaired insulin secretion by reducing insulin sensitivity (2). The relative importance of β-cell dysfunction and insulin resistance for the pathophysiology of the glucocorticoid-induced diabetes is not well defined. Therefore, there is no consensus treatment for glucocorticoid-induced diabetes. Glimepiride is a sulfonylurea that lowers blood glucose levels by stimulating insulin secretion from pancreatic β-cells and secondarily by increasing glucose uptake in peripheral tissues (3). Such action mechanisms might be suitable for the treatment of glucocorticoid-induced diabetes. Here we examined the effects of glimepiride on patients with newly diagnosed …
Erythrapheresis in polycythemia.
Authors: R J Gregory
Journal: BMJ (1983)

<h3>Background</h3> Female patients with chest pain pose unique problems to clinicians. Traditionally, epidemiological evidence has demonstrated low sensitivity and specificity in physiologic stress testing leading to poor accuracy in the ability of these tests to predict coronary artery disease (CAD) among women with chest pain We evaluated the accuracy of clinical symptoms, dobutamine stress echo (DSE) and nuclear stress testing (NST) in predicting presence of CAD among women presenting with chest pain in a large, tertiary referral center. <h3>Methods</h3> We evaluated 30 female patients that have undergone cardiac catheterization within the past two years. These patients proceeded to cath after having a positive DSE, NST or due to strong clinical suspicion. Patients with acute myocardial infarction, planned valvular surgery or coronary bypass were excluded from statistical analyses. Presence of CAD was defined as any stenotic lesions greater than 50% of coronary luminal diameter. Differences among groups were analyzed by ANOVA, paired and unpaired Student9s t tests for significance. Data reported as percent accuracy. <h3>Results</h3> All patients underwent cardiac catherization as a result of strong clinical suspicion, positive DSE or nuclear stress myocardial imaging. The accuracy of DSE in predicting presence of CAD is 67%, significantly (P≤ 0.05) higher than nuclear stress myocardial imaging (accuracy = 18%). There was a trend towards a significant difference between DSE and clinical suspicion in predicting presence of CAD, (67% vs. 42%, P = NS). Clinical suspicion is more accurate than nuclear stress imaging in predicting CAD (42% vs. 18%, P ≤ 0.05). <h3>Conclusions</h3> Female patients with chest pain pose unique problems to clinicians. From our single center study, the data demonstrate that DSE is superior to clinical suspicion and nuclear stress imaging in accurately predicting presence of CAD among women presenting with chest pain.
Mycosis fungoides mimicking granuloma annulare
Authors: T. Jouary, M. Beylot-Barry, B. Vergier *, J. Paroissien +, M.S. Doutre, C. Beylot
Journal: British Journal of Dermatology (2002)

Journal Article Mycosis fungoides mimicking granuloma annulare Get access T. Jouary, T. Jouary Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar M. Beylot‐Barry, M. Beylot‐Barry Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Correspondence: Marie Beylot‐Barry MD PhD. Search for other works by this author on: Oxford Academic Google Scholar B. Vergier, B. Vergier Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar J. Paroissien, J. Paroissien Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar M.S. Doutre, M.S. Doutre Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar C. Beylot C. Beylot Departments of Dermatology and *Pathology, Hôpital Haut‐Lévêque, 33600 Pessac, France †CHU de Bordeaux, 11 rue Montalembert, 16000 Angoulème, France E‐mail: Marie.Beylot‐Barry@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 6, 1 June 2002, Pages 1102–1103, https://doi.org/10.1046/j.1365-2133.2002.47321.x Published: 01 June 2002
High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-α2b for 60 weeks
Authors: Olle Reichard, Ulla Foberg, Aril Frydén, Lars Mattsson, Gunnar Norkrans, Anders Sönnerborg, Rune Wejstål, Zhi-Bing Yun, Ola Weiland
Journal: Hepatology (1994)

To evaluate the effect of prolonged interferon-alpha treatment on serum aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with chronic hepatitis C virus infection were treated with 3 MU interferon-alpha 2b thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT levels for at least 1 yr, antibodies to HCV by second-generation tests and liver histological findings consistent with chronic hepatitis C. Before treatment hepatitis C virus RNA was found in serum in 39 of 40 (97.5%) patients. Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60%) patients, of whom 15 of 24 (62.5%) had sustained ALT responses up to 24 wk after treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared from serum in 17 of 40 (42.5%) patients, including all sustained responders, one nonsustained responder and one nonresponder. We conclude that 60 wk of treatment with interferon-alpha 2b seems to induce a high percentage of sustained response, which coincides with cessation of viral replication.
THE DIFFERENT FORMS OF MEDIASTINAL PLEURISY WITH REPORT OF THREE CASES
Authors: ANDERS FRICK
Journal: JAMA (1910)

<h3>DEFINITION</h3> By mediastinal pleurisy, anatomically speaking, we understand, of course, an inflammation of the part of the parietal pleura which covers the mediastinum, the anterior as well as the posterior. But when we speak of mediastinal pleurisy as a clinical entity we differentiate it as a particular form of pleurisy, not merely because the mediastinal pleura happens to be inflamed, but because in certain clinical aspects it differs radically from ordinary pleurisy. This difference is, however, present only in those cases in which the inflammation of the mediastinal pleura leads to the formation of an encysted gathering of exudate between the mediastinum and the internal surface of the lung. In the following description I shall therefore confine myself to cases of this kind, with exclusion, for instance, of cases in which the inflammation of the mediastinal pleura is a pleuritis sicca, or, if exudative, occurs in conjunction with inflammatory changes in the rest of the pleura with free communication
The 'Growth Disease' in American Institutional Medicine
Authors: D. F. McLaughlin
Journal: JAMA (1982)

To the Editor.—  In a recent COMMENTARY (1982;247:469) entitled The 'Growth Disease' in American Institutional Medicine, Albert J. Miller, MD, bewails the circumstances in which governing boards have abdicated their oversight responsibilities. He goes on to say that aggressive growth-oriented administrators have seized power by default, but are unable to escape financial deficits.  While this may indeed be true in some instances, there are other pertinent aspects. For example, hospital board members may pursue hospital contracts for firms in which they have a vested interest. Areas involved may include food services, laundries, office supplies, financial services, or construction. Such conflicts of interest do arise from time to time. They may represent undue pressure brought to bear on the administrator hoping to curry favor and establish a coterie of sympathetic board members (after all, the board hires and fires the administrator, as well as setting his salary). Institutions should establish clear-cut
Cooperation between Mononuclear Phagocytes and Lymphocytes in Immunity
Authors: Emil R. Unanue
Journal: New England Journal of Medicine (1980)

THE immune response is initiated by the introduction of a foreign molecule, an antigen, into an organism. The manner in which an antigen stimulates immunity is immensely complex — a reflection, no doubt, of the multiplicity of effector functions that must be generated and of the fine balance that must develop between what is prophylactic (and hence beneficial to the organism) and what is harmful. More specifically, the immune cells must first identify the antigen as foreign and precisely discriminate this foreign molecule from the organism's own molecules. Biochemically, the foreign antigen may be similar to autogenous antigens. Subsequently, a . . .