tbuckley/cabot-search huggingface dataset:
Osteoprotegerin in Prostate Cancer Bone Metastasis
Authors: Eva Corey, Lisha G. Brown, Jeffrey A. Kiefer, Janna E. Quinn, Tiffany E.M. Pitts, Julie M. Blair, Robert L. Vessella
Journal: Cancer Research (2005)

Abstract Osteoprotegerin (OPG), a critical regulator of osteoclastogenesis, is expressed by prostate cancer cells, and OPG levels are increased in patients with prostate cancer bone metastases. The objective of this study was to investigate the effects of OPG overexpression on prostate cancer cells and prostate cancer/bone cell interactions in vitro and in vivo. OPG-transfected C4-2 cells expressed 8.0 ng OPG per mL per 106 cells, whereas no OPG was detected in the media of C4-2 cells transfected with a control plasmid. OPG overexpressed by C4-2 cells protected these cells from tumor necrosis factor-related apoptosis-inducing ligand–induced apoptosis and decreased osteoclast formation. Subcutaneous OPG-C4-2 and pcDNA-C4-2 tumors exhibited similar growth and take-rate characteristics. However, when grown in bone, tumor volume was decreased in OPG-C4-2 versus pcDNA-C4-2 (P = 0.0017). OPG expressed by C4-2 cells caused increases in bone mineral density (P = 0.0074) and percentage of trabecular bone volume (P = 0.007), and decreases in numbers of osteoblasts and osteoclasts when compared with intratibial pcDNA-C4-2 tumors (P = 0.003 and P = 0.019, respectively). In summary, our data show that increased expression of OPG in C4-2 cells does not directly affect proliferation of prostate cancer cells but indirectly decreases growth of C4-2 tumors in the bone environment. Our data also show that OPG expressed by C4-2 cells inhibits bone lysis associated with C4-2 bone metastasis, which results in net increases in bone volume. We therefore hypothesize that OPG expressed in prostate cancer patient bone metastases may be at least partially responsible for the osteoblastic character of most prostate cancer bone lesions.
Targeted Ablation of Osteocytes Induces Osteoporosis with Defective Mechanotransduction
Authors: Sawako Tatsumi, Kiyoaki Ishii, Norio Amizuka, Minqi Li, Toshihiro Kobayashi, Kenji Kohno, Masako Ito, Sunao Takeshita, Kyoji Ikeda
Journal: Cell Metabolism (2007)
Climate Change and Human Health: Risks and Responses
Authors: Cathy Read
Journal: BMJ (2004)

The UK government's chief scientist, David King, has said that “climate change is the most severe problem we are facing today—more serious even than the threat of terrorism.” Yet terrorism continues to dominate the world's news media and preoccupy the thoughts of many people. James Wolfensohn, president of the World Bank, recently told an audience of representatives of business and civil society groups that the environment was on the back burner of international discussions on development. Eds A J McMichael, D H Campbell-Lendrum, C F Corvalän, K L Ebi, A K Githeko, J D Scheraga, A Woodward World Health Organization, SFr20 (SFr14 in developing countries)/$18, pp 322 ISBN 92 4 156248X publications@who.int Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> It is perhaps time to be reminded of Hippocrates, suggests Tony McMichael, one … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): Comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children
Authors: S ROWNTREE, T PLATTSMILLS, J COGSWELL, E MITCHELL
Journal: Journal of Allergy and Clinical Immunology (1987)
Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury
Authors: Ciro Indolfi, Angelo Cioppa, Eugenio Stabile, Emilio Di Lorenzo, Giovanni Esposito, Alfonso Pisani, Antonio Leccia, Luigi Cavuto, Angela Maria Stingone, Alaide Chieffo, Claudia Capozzolo, Massimo Chiariello
Journal: Journal of the American College of Cardiology (2000)
Organization and management I
Authors: R. G. Hulsebos, F. W. Bellman, D. Reis Miranda, J. Ruiz, L. García, Y. González, A. Boix, M. A. Asenjo, F. Saulnier, J. M. Descamps, G. De Pouvourville, A. Durocher, B. Blettery, J. Carlet, F. Fraisse, F. Nicolas, Ph. Lardet, H. Hubert, S. Loyez, D. Sion, D. J. Cook
Journal: Intensive Care Medicine (1992)
Excision Margins for Melanoma in Awkward Places Like the Eyelid
Authors: David M. Reifler
Journal: JAMA (1993)

<h3>To the Editor.</h3> —I read with interest a recently published National Institutes of Health (NIH) consensus statement that identified several clinical directions for future research on the diagnosis and treatment of early melanoma of the skin.<sup>1</sup>These included the determination of optimal margins for primary melanomas deeper than 1 mm and the investigation of alternative therapies for primary melanomas in which normal tissue conservation is critical. One of these (unmentioned) special locations is the eyelid, where consensus panel recommendations of excision margins (0.5 cm for melanoma in situ and 1 cm for thin invasive melanoma) represent radical sacrifices of eyelid tissue. From the few reported series in the ophthalmologic literature,<sup>2</sup>it appears that cutaneous melanoma of the eyelid is rare but carries a relatively favorable prognosis in comparison with cutaneous melanomas of other sites. These differences in prognosis and unique aspects of eyelid anatomy may have important treatment
Prognosis of colonic Crohn's disease.
Authors: P R Elliott, J K Ritchie, J E Lennard-Jones
Journal: BMJ (1985)

end of 12 hours the patient received 18 ampoules of antivenom if in group 1 and 10 ampoules if in group 2. Lyophilised polyvalent antivenom (Haffkine Biopharmaceutical Corporation, Bombay) was used throughout.The dose of antivenom was dissolved in distilled water and then added to 100-300 ml 5%o glucose for infusion.Children and adults were given the same dose.Comparison of the two groups was based on the interval between adminis- tration of the first dose of antivenom and the first normal clotting time and on the number of patients developing complications.For the purpose of the study acute renal failure was defined as oliguria for 24 hours (urine output below 400 ml) or more with raised blood urea or serum creatinine concentrations.The study was conducted between July 1982 and June 1983 and included 53 patients.The interval between the patient being bitten and treatment being started, the period for the clotting time to become normal, and the number of patients who developed acute renal failure and other complications were not appreciably different between the two groups (table).None of the patients had any neurological deficit attributable to envenomation by cobra or krait.None were sensitive to antivenom on skin testing, and serum reactions to antivenom were transient and did not necessitate treatment being stopped.
Abstract 4641: Distinctive expression of polycomb group proteins Bmi1 and EZH2 in non-small cell lung cancers and their clinical and clinicopathological significance
Authors: Junko Kikuchi, Ichiro Kinoshita, Eiki Kikuchi, Jun Konishi, Yasushi Shimizu, Satoshi Oizumi, Masaharu Nishimura, Hirotoshi Dosaka-Akita
Journal: Cancer Research (2010)

Abstract Background: The polycomb group genes, Bmi1 and EZH2, function as transcriptional repressors involved in gene silencing. They are involved in the malignant transformation and biological aggressiveness of several human carcinomas. In the present study, we evaluated Bmi1 and EZH2 protein expression in specimens of human non-small cell lung cancers (NSCLCs). Methods: We conducted an immunohistochemical assessment of 157 surgically resected NSCLCs to evaluate the correlation between Bmi1 and EZH2 expression and various features, including clinical, clinicopathological and biological characteristics. Results: Normal bronchial epithelia showed abundant expression of Bmi1 and sporadic expression of EZH2. NSCLC patients with high EZH2 expression in tumor cells showed poorer prognosis than those with low EZH2 expression in all pStages (p = 0.001) and in pStage I (p = 0.006). Multivariate analysis showed that high EZH2 expression was a independent unfavorable prognostic factor in pStage I patients (p = 0.048). High EZH2 expression was significantly correlated with non-adenocarcinoma histology (p = 0.001), moderate and poor differentiation (p = 0.001), advanced pT stage (p = 0.02), and high Ki-67 and cyclin E labeling index (p &amp;lt; 0.001). Bmi1 expression, in contrast, was not a significant prognostic factor, and was not correlated with any clinicopathological factors other than early pT stage. Conclusion: Bmi1 and EZH2 show characteristic and distinctive expression in NSCLCs. High EZH2 expression is correlated with tumor aggressiveness, and may provide a novel prognostic marker for NSCLCs. 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 4641.
538Profilin-1 plasma levels are modulated by LPS induced disseminate intravascular coagulation
Authors: I Ramaiola, E Pena, L Badimon
Journal: Cardiovascular Research (2014)

Purpose: Disseminated intravascular coagulation (DIC) is a pathological condition derived from an excessive activation and stimulation of the coagulation system in which an excess of thrombin and fibrin deposition contribute to platelet aggregation provoking thrombotic microangiopaty. The objective of the present study was to determine whether profilin-1, a platelet protein secreted to plasma that we have found in STEMI patients is also released during DIC, a mayor platelet activator process.
Adventitial Myofibroblasts Contribute to Neointimal Formation in Injured Porcine Coronary Arteries
Authors: Yi Shi, James E. O'Brien, Ali Fard, John D. Mannion, Dian Wang, Andrew Zalewski
Journal: Circulation (1996)

Background The adventitia undergoes remodeling changes after a deep medial coronary injury. Because this process is associated with the formation of adventitial myofibroblasts, which resemble medial smooth muscle (SM) cells, we have examined myofibroblast involvement in the development of neointima. Methods and Results In a porcine model, severe endoluminal coronary injury resulted in fibroblast proliferation and adventitial remodeling. Significant adventitial responses were associated with increased neointimal formation ( P &lt;.01). To examine the contribution of adventitial cells to the development of neointima, proliferating cells were labeled with bromodeoxyuridine (BrdU) at 12 and 24 hours after injury, and their subsequent localization was determined by immunohistochemistry (n=24). At 2 to 3 days after severe injury, the adventitia contained numerous BrdU-labeled cells (37±4%), whereas the media demonstrated infrequent labeled cells (4±1%). Adventitial cells lacked α-SM actin and desmin, which distinguished them from medial SM cells. At 7 to 8 days, some labeled cells acquired characteristics of myofibroblasts expressing α-SM actin. They were found to translocate to the gap between dissected media and contributed to the formation of neointima (76±19%). At 18 to 35 days, labeled cells were abundant in the neointima (86±5%). They showed uniform immunostaining for α-SM actin but not for desmin, thereby differing from medial SM cells and blood-borne cells. Conclusions This study demonstrates translocation of adventitial fibroblasts to neointima, their phenotypic modulation to myofibroblasts, and distinct characteristics of myofibroblasts within neointima after severe endoluminal coronary injury. These findings suggest the significance of vascular fibroblasts in the process of arterial repair.
A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis C
Authors: Stefan Zeuzem, Uwe Hopf, Vicente Carreno, Moisés Diago, Mitchell Shiffman, Stefan Grüne, Francis J. Dudley, Ashok Rakhit, Karen Rittweger, Sing Hiem Yap, Raymond S. Koff, Howard C. Thomas
Journal: Hepatology (1999)

Interleukin–12 (IL–12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The present open–label, multicenter, dose–escalation phase I/II study was designed to assess tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin–12 (rHuIL–12) in the treatment of chronic hepatitis C. Sixty patients (42 men, 18 women, aged 24–60) were treated with 0.03 μg/kg (n = 16), 0.1 μg/kg (n = 14), 0.25 μg/kg (n = 15), or 0.5 μg/kg rHuIL–12 (n = 15) for 10 consecutive weeks. rHuIL–12 was generally well tolerated, with 2 patients (3.3%) being withdrawn from treatment for adverse events. Treatment was associated with temporary decreases in neutrophils and lymphocyte counts and with elevations in serum transaminases and bilirubin. Serum IL–12 levels observed were higher at 0.5 μg/kg compared with 0.25 μg/kg doses, suggesting a dose–related increase in systemic exposure of IL–12. Measurable levels of interferon gamma (IFN–γ) were also observed at the highest dose of 0.5 μg/kg. At the end of treatment hepatitis C virus (HCV) RNA was detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3 of 16 patients of the 0.03–μg/kg dose group, in 3 of 14 of the 0.10–μg/kg dose group, in 6 of 15 of the 0.25–μg/kg dose group, and in 8 of 15 patients of the 0.5–μg/kg dose group. Although in several cases serum alanine transaminase (ALT) levels decreased either during or after treatment, ALT normalization was observed in only 4 patients at the end of treatment and in 5 patients at the end of follow–up. Significant anti-rHuIL–12 antibody titers were not detectable in any patient. In conclusion, antiviral activity of rHuIL–12 in patients with chronic hepatitis C does not appear advantageous in comparison with other currently available treatments.
<i>Helicobacter pylori</i>directs tolerogenic programming of dendritic cells
Authors: Min Zhang, Maochang Liu, Jay Luther, John Y. Kao
Journal: Gut Microbes (2010)

Our laboratory has shown that Helicobacter pylori infection in mice triggers an increase in the number of subepithelial lamina propria CD11c+ dendritic cells with luminal projections. The physical characteristic of these cells is consistent with their ability to traverse epithelial tight junctions as reported by Maria Recigno (Recigno et al. Nature Immunology 2001; 2:361-7). Gastric CD103+ dendritic cells, which are known to induce mucosal regulatory T cells, were also increased in number, raising the question whether H. pylori infection induces a regulatory T cell-skewed response by way of a bacteria-dendritic cell interaction. In fact, bone marrow-derived dendritic cells underwent tolerogenic programming, skewing the balance between effector and regulatory T cell responses towards regulatory T cell differentiation in a transforming growth factor-β- and interleukin-10-dependent manner. Depletion of regulatory T cell numbers augmented H. pylori-specific effector helper T cell responses, which correlated with a lower degree of H. pylori colonization. These results suggest H. pylori is capable of inducing a regulatory T cell-skewed response that limits the host's ability to eradicate the bacteria, allowing the H. pylori infection to persist. To better understand the mechanism of H. pylori tolerogenic programming we compared the differential expressions of 34 genes critical for dendritic cell function in bone marrow-derived dendritic cells pulsed with live H. pylori or other gram-negative bacteria (e.g., Escherichia coli, Acinetobacter lwoffii). Our data imply that H. pylori targets the Toll-like receptor 2 pathway to induce a regulatory T cell-skewed response. In addition, we show that H. pylori-pulsed dendritic cells are capable of inducing the conversion of naïve T cells to regulatory T cells. These observations are evidence of a unique tolerogenic program in dendritic cells that involves active editing of the immune response by H. pylori, favoring its persistence in the gastric mucosa.
Low cell binding ability of HCV is closely related to interferon treatment especially in patients with HCV genotype 2a/2b A large series prospective study on Japanese patients with chronic hepatitis C
Authors: Yoichi Kimura, Kazuhiro Hayashida, Yusuke Yanagi, Hiromi Ishibashi, Kouhei Akazawa, Yoshiyuki Niho
Journal: Journal of Hepatology (2000)
No reflow and extent of infarction during maximal vasodilation in the porcine heart.
Authors: W B Johnson, S A Malone, G A Pantely, C G Anselone, J D Bristow
Journal: Circulation (1988)

To explore the relation between myocardial and vascular injury in the generation of the no-reflow phenomenon, the pressure-flow relation during maximal vasodilation after coronary artery reperfusion was studied in the open-chest porcine model. During both endogenous and maximal vasodilation with intracoronary adenosine, pressure-flow (P/Q) plots were constructed before and after 20-minute (n = 9) or 40-minute (n = 17) circumflex artery occlusions. Decreases in circumflex vascular bed conductance were represented by downward shifts in P/Q plot regression lines. No significant change occurred in P/Q line slope or pressure at zero flow 30 minutes after release of the 20-minute occlusion, and no infarction was found. After release of the 40-minute occlusion, a small but insignificant decrease in P/Q line slope occurred during endogenous vasodilation. However, during maximal vasodilation, a significant (p less than 0.01) decrease in P/Q line slope was present during reperfusion compared with preocclusion corresponding to a decrease in vasodilatory reserve (P/Q line slope = 1.52 +/- 0.14 ml/min/mm Hg preocclusion vs. 1.03 +/- 0.13 at 15 minutes reperfusion). Pretreatment with aspirin did not prevent this decrease in vascular conductance during maximal vasodilation. Total circumflex, as well as subendocardial, midmyocardial, and subepicardial blood flows, was measured with radioactive microspheres. There was a good correlation between the extent of infarction measured by triphenyltetrazolium chloride staining and the decrease in vascular conductance during maximal vasodilation for all three myocardial layers as well as for the total circumflex vascular bed. Hence, the degree of no-reflow correlates closely with the extent of infarction during maximal vasodilation (but not during endogenous vasodilation) and is not altered by aspirin therapy.
Altered transcriptional regulation of phosphoenolpyruvate carboxykinase in rats following endotoxin treatment.
Authors: M Hill, R McCallum
Journal: Journal of Clinical Investigation (1991)

The molecular mechanism involved in altered regulation of the rate-limiting enzyme in hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), during endotoxemia is not completely understood. We examined, therefore, the effect of a nonlethal dose of Escherichia coli endotoxin on PEPCK gene expression in fasted rats. 5 h after endotoxin treatment, the PEPCK transcription rate and the amount of mRNA(PEPCK) were significantly decreased at a time when the insulin/glucagon (I/G) molar ratio and plasma corticosterone levels were significantly increased. Similar results were observed in a time course study, in which altered cAMP induction of PEPCK gene expression paralleled changes in the I/G molar ratio. In diabetic rats treated with endotoxin, PEPCK gene expression was decreased in the absence, however, of an increased I/G molar ratio. This finding indicates that other factors, such as inflammatory mediators or cytokines, alter PEPCK gene transcription during endotoxemia. IL-6, a putative mediator of endotoxin action in the liver, had no effect on PEPCK gene expression in fasted rats, but did decrease cAMP induction of PEPCK gene expression. These results indicate that, during endotoxemia, regulation of PEPCK gene expression is influenced by inflammatory mediators in addition to the classical endocrine hormones. IL-6, however, does not appear to be involved directly in the altered regulation of the PEPCK gene during endotoxemia.
Web tool indicates the most effective health measures in deprived areas
Authors: Lynn Eaton
Journal: BMJ (2007)

Primary care trusts in some of England's poorest areas have a new web based management tool to assess how they can improve mortality in their local population.

The programme, devised by the London Health Observatory and the Yorkshire and Humber Public Health Observatory for the Department of Health, allows trusts in deprived areas to see what measures would help save the most lives. It looks at four specific interventions known to have a major effect on mortality: smoking cessation; reducing infant …
Communicating With Spanish-Speaking Patients—Reply
Authors: Lisa C. Diamond
Journal: JAMA (2009)

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Chronic gastritis, alcohol, and non-ulcer dyspepsia
Authors: D. M. Roberts
Journal: Gut (1972)

An investigation of 102 men comprising alcoholics, patients with non-ulcer dyspepsia, and healthy controls is reported. It demonstrates that alcohol is a cause of chronic gastritis and the severity of the mucosal lesion is directly related to the duration of excess drinking. Contrary to popular belief, chronic gastritis does not give rise to symptoms. The effect of alcohol on the gastric mucosa is a direct one and is not mediated by malnutrition, hepatic damage, intestinal malabsorption, anaemia, ascorbic acid deficiency, or any disturbance in immune tolerance. The natural history of chronic gastritis is described, involving an initial hypertrophy and hyperfunction of the gastric mucosa, followed by atrophy and hypofunction. Cigarette smoking is confirmed as another cause of chronic gastritis. The non-ulcer dyspepsia syndrome is unrelated to chronic gastritis.