tbuckley/cabot-search huggingface dataset:
TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTS
Authors: J. Skeens, C. Semba, M. Dake
Journal: Annual Review of Medicine (1995)

Management of bleeding esophageal varices due to portal hypertension has traditionally relied on endoscopic sclerotherapy and operative intervention with placement of a portosystemic shunt. Although percutaneous decompression of portal hypertension was investigated 25 years ago, it was not clinically feasible until recently. With the advent of intravascular stents, the technique of creating a transjugular intrahepatic portosystemic shunt (TIPS) can now be effectively applied to treat the complications of portal hypertension, including variceal hemorrhage and refractory ascites. Since its introduction in 1989, TIPS has enjoyed widespread clinical application. The initial results with this procedure are encouraging and suggest that it is an effective means of reducing the frequency of variceal hemorrhage in patients with portal hypertension. The long-term patency rate and frequency of complications, however, have not been clearly defined. Similarly, the role of TIPS in the treatment of refractory ascites, Budd-Chiari syndrome, and hepatorenal syndrome remains unclear because sufficient data do not yet exist to support its general use in these settings.
The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity
Authors: Gillian J. Wilson, Mohlopheni J. Marakalala, Jennifer C. Hoving, Arjan van Laarhoven, Rebecca A. Drummond, Bernhard Kerscher, Roanne Keeton, Esther van de Vosse, Tom H.M. Ottenhoff, Theo S. Plantinga, Bachti Alisjahbana, Dhirendra Govender, Gurdyal S. Besra, Mihai G. Netea, Delyth M. Reid, Janet A. Willment, Muazzam Jacobs, Sho Yamasaki, Reinout van Crevel, Gordon D. Brown
Journal: Cell Host & Microbe (2015)

The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8−/− mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8−/− mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man.
Radical Prostatectomy Versus Watchful Waiting in Localized Prostate Cancer: the Scandinavian Prostate Cancer Group-4 Randomized Trial
Authors: A. Bill-Axelson, L. Holmberg, F. Filen, M. Ruutu, H. Garmo, C. Busch, S. Nordling, M. Haggman, S.-O. Andersson, S. Bratell, A. Spangberg, J. Palmgren, H.-O. Adami, J.-E. Johansson
Journal: JNCI Journal of the National Cancer Institute (2008)

The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
Deficiency in the Repair of DNA Damage by Homologous Recombination and Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition
Authors: Nuala McCabe, Nicholas C. Turner, Christopher J. Lord, Katarzyna Kluzek, Aneta Białkowska, Sally Swift, Sabrina Giavara, Mark J. O'Connor, Andrew N. Tutt, Małgorzata Z. Zdzienicka, Graeme C.M. Smith, Alan Ashworth
Journal: Cancer Research (2006)

Abstract Deficiency in either of the breast cancer susceptibility proteins BRCA1 or BRCA2 induces profound cellular sensitivity to the inhibition of poly(ADP-ribose) polymerase (PARP) activity. We hypothesized that the critical role of BRCA1 and BRCA2 in the repair of double-strand breaks by homologous recombination (HR) was the underlying reason for this sensitivity. Here, we examine the effects of deficiency of several proteins involved in HR on sensitivity to PARP inhibition. We show that deficiency of RAD51, RAD54, DSS1, RPA1, NBS1, ATR, ATM, CHK1, CHK2, FANCD2, FANCA, or FANCC induces such sensitivity. This suggests that BRCA-deficient cells are, at least in part, sensitive to PARP inhibition because of HR deficiency. These results indicate that PARP inhibition might be a useful therapeutic strategy not only for the treatment of BRCA mutation-associated tumors but also for the treatment of a wider range of tumors bearing a variety of deficiencies in the HR pathway or displaying properties of ‘BRCAness.’ (Cancer Res 2006; 66(16): 8109-15)
Visualization of early events in tumor formation of eGFP-transfected rat colon cancer cells in liver
Authors: Olaf R.F. Mook, Jan Van Marle, Heleen Vreeling-Sindelárová, Remmet Jonges, Wilma M. Frederiks, Cornelius J.F. Van Noorden
Journal: Hepatology (2003)

Colon cancer preferentially metastasizes to the liver. To determine cellular backgrounds of this preference, we generated an enhanced green fluorescent protein (eGFP)-expressing rat adenocarcinoma cell line (CC531s) that forms metastases in rat liver after administration to the portal vein. Intravital videomicroscopy (IVVM) was used to visualize early events in the development of tumors in livers of live animals from the time of injection of the cancer cells up to 4 days afterward. Based on information obtained with IVVM, tissue areas were selected for further analysis using confocal laser scanning microscopy (CLSM), electron microscopy (EM), and electron tomography. It was shown that initial arrest of colon cancer cells in sinusoids of the liver was due to size restriction. Adhesion of cancer cells to endothelial cells was never found. Instead, endothelial cells retracted rapidly and interactions were observed only between cancer cells and hepatocytes. Tumors developed exclusively intravascularly during the first 4 days. In conclusion, initial steps in the classic metastatic cascade such as adhesion to endothelium and extravasation are not essential for colon cancer metastasis in liver.
Lessons on Tumour Response: Imaging during Therapy with <sup>177</sup>Lu-DOTA-octreotate. A Case Report on a Patient with a Large Volume of Poorly Differentiated Neuroendocrine Carcinoma
Authors: Ulrike Garske, Mattias Sandström, Silvia Johansson, Dan Granberg, Hans Lundqvist, Mark Lubberink, Anders Sundin, Barbro Eriksson
Journal: Theranostics (2012)

Favourable outcomes of peptide receptor radiotherapy (PRRT) of neuroendocrine tumours have been reported during the last years. Still, there are uncertainties on the radionuclides to be used, the treatment planning, and the indication in patients with a high proliferation rate.This case report describes a patient with a high tumour burden of poorly differentiated neuroendocrine carcinoma of unknown primary with a proliferation rate in liver metastases up to 50%, undergoing fractionated treatment with 7 cycles of (177)Lu-DOTA-octreotate (7.4 GBq each) after disease progression on two different chemotherapy regiments. Based on initial staging scintigraphy, somatostatin receptor expression was very high.Longitudinal dosimetry studies during therapy indicated ongoing increases in tumour-to-organ ratios that coincided with an objective response.We conclude that fractionated therapy with (177)Lu-DOTA-octreotate should be considered a treatment option also for those patients with large tumours, high proliferation, and high receptor expression.
Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI11
Authors: Tiziana Piepoli, Cemile Jakupoglu, Wenli Gu, Elena Lualdi, Blanca Suarez-Merino, Pietro L. Poliani, Maria Grazia Cattaneo, Barbara Ortino, Dorota Goplen, Jian Wang, Rosa Mola, Francesca Inverardi, Carolina Frassoni, Rolf Bjerkvig, Ortrud Steinlein, Lucia M. Vicentini, Oliver Brüstle, Gaetano Finocchiaro
Journal: Neuro-Oncology (2006)

Disruptions of LGI1 in glioblastoma (GBM) cell lines and LGI1 mutations in families with autosomal dominant epilepsy imply a role for LGI1 in glial cells as well as in neurons. Although we and others could not find LGI1 mutations in malignant gliomas, our initial studies appeared to support the idea that LGI1 is poorly expressed or absent in these tumors. Microarray data suggested that LGI1 could be involved in the control of matrix metalloproteinases, and we found that tumors derived from U87 glioblastoma cells overexpressing LGI1 were less aggressive than U87 control tumors. To our surprise, we observed that LGI1 expression after differentiation of murine neural stem cells was robust in neurons but negligible in glial cells, in agreement with immunohistochemistry studies on rodent brain. This observation could suggest that the variable levels of LGI1 expression in gliomas reflect the presence of neurons entrapped within the tumor. To test this hypothesis, we investigated LGI1 expression in parallel with expression of the neuronal marker NEF3 by real-time PCR on 30 malignant gliomas. Results showed a strong, positive correlation between the expression levels of these two genes (P < 0.0001). Thus, our data confirm that LGI1 is involved in cell-matrix interactions but suggest that its expression is not relevant in glial cells, implying that its role as a tumor suppressor in gliomas should be reconsidered.
Mitigation of stress-induced suppression of contact hypersensitivity by odorant inhalation
Authors: J. Hosoi, M. Tanida, T. Tsuchiya
Journal: British Journal of Dermatology (2001)

Various skin functions are affected by stress. We have previously shown that odorant inhalation can regulate skin immune reactions.To test the hypothesis that certain odorants can mitigate the effects of stress on skin immune reactions.Contact hypersensitivity (CH) reactions were elicited in C57BL/6 mice. Mice were subjected to immobilization stress and were exposed to odorants for 2 days. Epidermal sheets were stained for I-A antigens and analysed by confocal laser scanning microscopy. Serum corticosterone levels were assayed by radioimmunoassay.Exposure of mice to 1,3-dimethoxy-5-methylbenzene (DMMB) had no effect on the intact CH reaction, but it upregulated the reaction suppressed by immobilization stress. Other odorants, including terpinyl acetate and valerian oil, had minor effects on the CH reaction. Suppression of I-A-positive cells was prevented by DMMB inhalation. Valerian oil, but not DMMB, downregulated stress-induced plasma corticosterone levels.Results suggest that odorant inhalation modulates various physiological pathways, some of which result in regulation of skin function.
Socioeconomic Status and Health: Mediating and Moderating Factors
Authors: Edith Chen, Gregory E. Miller
Journal: Annual Review of Clinical Psychology (2012)

Health disparities (differences in health by socioeconomic groups) are a pressing issue in our society. This article provides an overview of a multilevel approach that seeks to understand the mechanisms underlying health disparities by considering factors at the individual, family, and neighborhood levels. In addition, we describe an approach to connecting these factors to various levels of biological processes (systemic inflammation, cellular processes, and genomic pathways) that drive disease pathophysiology. In the second half of the article, we address the question of why some low-socioeconomic-status (low-SES) individuals manage to maintain good physical health. We identify naturally occurring psychosocial factors that help buffer these individuals from adverse physiological responses and pathogenic processes leading to chronic disease. What is protective for low-SES individuals is not the same as what is protective for high-SES individuals, and this needs to be taken into account in interventions aimed at reducing health disparities.
Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper
Authors: M. Aapro, C. Bernard-Marty, E.G.C. Brain, G. Batist, F. Erdkamp, K. Krzemieniecki, R. Leonard, A. Lluch, S. Monfardini, M. Ryberg, P. Soubeyran, U. Wedding
Journal: Annals of Oncology (2010)

Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered.A committee of experts in breast cancer and NHL met under the auspices of the International Society for Geriatric Oncology to review the literature and make recommendations, based on level of evidence, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines.Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening for risk factors, rigorous monitoring of cardiac function and early intervention. Use of liposomal anthracycline formulations, prolonging the infusion time for conventional anthracyclines and cardioprotective measures should be considered. However, when treatment is being given with curative intent, care should be taken to ensure reduced cardiotoxicity is not achieved at the expense of efficacy.
Radiographic patterns and response to corticosteroid hip injection
Authors: M J Plant, A A Borg, K Dziedzic, J Saklatvala, P T Dawes
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> A prospective, open study of corticosteroid hip injection (CHI) was performed to determine if different radiological patterns of arthritis vary in their response. <h3>METHODS</h3> Forty five patients (15 with rheumatoid arthritis, 27 with osteoarthritis, and three with anklyosing spondylitis) underwent hip injection with 80 mg methyl- prednisolone and lignocaine under <i>x</i> ray control. Outcome was assessed at two, 12, and 26 weeks for pain, range of hip movement, and graded functional questionnaire. Patients estimated their pain in four components, night pain, rest pain, weight bearing, and referred pain, each measured by 10 cm visual analogue score and summed to give a total score out of 40 cm. Hip radiographs were evaluated blindly for pattern and severity of arthritis, as well as for progression between 0 and 26 weeks. <h3>RESULTS</h3> Median total pain score decreased from 29 cm at baseline to 22 cm at two weeks (p=0.0001), 24 cm at 12 weeks (p=0.03), but had returned nearly to baseline by 26 weeks (25 cm, p=0.3). Greatest improvement was seen for night pain. Mean range of internal rotation increased from 16 to 28 degrees at two weeks (p=0.03) and 23 degrees at 12 weeks (p=0.06). Functional ability did not change. Hips with an atrophic pattern of arthritis on plain radiography gained negligible pain relief at two weeks compared with hips with a hypertrophic or mixed bone response (p=0.04). The degree of pain relief was similar in patients with OA and RA, and was not influenced by radiographic severity or by the direction of migration of the femoral head. <h3>CONCLUSION</h3> Pain and internal rotation improve for up to 12 weeks after CHI. CHI offers a useful and safe therapeutic option for patients with hip arthritis, with the exception of those with a purely atrophic radiological pattern.
α11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy
Authors: Ilana Talior-Volodarsky, Kim A. Connelly, Pamma D. Arora, Donald Gullberg, Christopher A. McCulloch
Journal: Cardiovascular Research (2012)

Diabetic cardiomyopathy is characterized by the production of a disorganized fibrotic matrix in the absence of coronary atherosclerosis and hypertension. We examined whether adhesion of cardiac fibroblasts to glycated collagens mediates the differentiation of pro-fibrotic myofibroblasts, which may contribute to cardiac fibrosis. By microarray, we found that methylglyoxal-treated collagen selectively enhanced α11 integrin expression in human cardiac fibroblasts, while levels of other collagen-binding integrins (α1, α2, and α10) were unchanged. Similar increases in α11 integrin mRNA and protein expression were observed in cardiac fibroblasts from streptozotocin (STZ)-treated Sprague–Dawley rats. In human cardiac fibroblasts plated on methyglyoxal-treated collagen and in cardiac fibroblasts from diabetic rats, transforming growth factor (TGF)-β2 but not TGF-β1 or TGF-β3 was increased compared with controls. Knock-down of α11 integrin and TGF-β receptors with small-interfering RNA blocked the increased expression of TGF-β2, α-smooth muscle actin (α-SMA), and α11 integrin that were induced in cells plated on methylglyoxal-treated collagen. Further, inhibition of Smad3 signalling blocked methylglyoxal-collagen up-regulation of α11 integrin and α-SMA expression. Rats with STZ-induced diabetes exhibited increased phosphorylation of Smad3 in cardiac tissues compared with control rats. Interactions between α11 integrins and the Smad-dependent TGF-β2 signalling may contribute to the formation of pro-fibrotic myofibroblasts and the development of a fibrotic interstitium in diabetic cardiomyopathy.
The SOD Mimetic Tempol Ameliorates Glomerular Injury and Reduces Mitogen-Activated Protein Kinase Activity in Dahl Salt-Sensitive Rats
Authors: Akira Nishiyama, Masanori Yoshizumi, Hirofumi Hitomi, Shoji Kagami, Shuji Kondo, Akira Miyatake, Megumu Fukunaga, Toshiaki Tamaki, Hideyasu Kiyomoto, Masakazu Kohno, Takatomi Shokoji, Shoji Kimura, Youichi Abe
Journal: Journal of the American Society of Nephrology (2004)

It was shown recently that renal injury in Dahl salt-sensitive (DS) hypertensive rats is accompanied by mitogen-activated protein kinase (MAPK) activation. The present study was conducted to elucidate the contribution of reactive oxygen species to MAPK activities and renal injury in DS rats. DS rats were maintained on high salt (H; 8.0% NaCl; n = 7) or low salt (L; 0.3% NaCl; n = 6) diets; H + a superoxide dismutase mimetic, tempol (3 mmol/L in drinking water; n = 8); or H + hydralazine (0.5 mmol/L in drinking water; n = 8) for 4 wk. Mean BP (MBP) in DS/H and DS/L rats was 185 +/- 7 and 113 +/- 3 mmHg, respectively. DS/H rats showed a higher ratio of urinary protein excretion and creatinine (U(protein)V/U(cr)V; 20.3 +/- 1.1) and a higher cortical collagen content (22 +/- 1 micro g/mg) than in DS/L rats (2.4 +/- 0.1 and 13 +/- 1 micro g/mg, respectively). The expression of p22-phox and Nox-1, essential components of NAD(P)H oxidase, in renal cortical tissue was approximately threefold higher in DS/H rats than in DS/L rats. Increased activities of renal cortical MAPK, including extracellular signal-regulated kinases (ERK) 1/ERK2 and c-Jun NH(2)-terminal kinases (JNK) were also observed in DS/H rats by 7.0 +/- 0.7- and 4.3 +/- 0.2-fold, respectively. Tempol treatment significantly decreased MBP (128 +/- 3 mmHg), U(protein)V/U(cr)V (4.8 +/- 0.4), and cortical collagen content (14 +/- 1 micro g/mg) and normalized ERK1/ERK2 and JNK activities in DS/H rats. Histologically, tempol markedly ameliorated progressive sclerotic and proliferative glomerular changes in DS/H rats. Hydralazine-treated DS/H rats showed similar MBP (127 +/- 5 mmHg) to tempol-treated DS/H rats. Hydralazine also decreased U(protein)V/U(cr)V (16.2 +/- 1.5) and cortical collagen content (19 +/- 1 micro g/mg) in DS/H rats. However, these values were significantly higher than those of tempol-treated rats. Furthermore, although hydralazine significantly reduced JNK activity (-56 +/- 3%), ERK1/ERK2 activities were unaffected. These data suggest that reactive oxygen species, generated by NAD(P)H oxidase, contribute to the progression of renal injury through ERK1/ERK2 activation in DS/H hypertensive rats.