tbuckley/cabot-search huggingface dataset:
Involvement of Toll-Like Receptor 4 Signaling in Interferon- Production and Antitumor Effect by Streptococcal Agent OK-432
Authors: M. Okamoto, T. Oshikawa, T. Tano, G. Ohe, S. Furuichi, H. Nishikawa, S. U. Ahmed, S. Akashi, K. Miyake, O. Takeuchi, S. Akira, Y. Moriya, S. Matsubara, Y. Ryoma, M. Saito, M. Sato
Journal: JNCI Journal of the National Cancer Institute (2003)

The streptococcal agent OK-432 has been used for immunotherapy of head and neck cancer, among other malignancies, but its mechanism of action is unknown. Because the Toll-like receptor 4 (TLR4)/MD-2 complex is important in enabling the mammalian immune system to recognize bacterial components, we investigated whether expression of the TLR4 and MD-2 genes is associated with OK-432-induced anticancer immunity.Peripheral blood mononuclear cells (PBMCs) from 28 patients with head and neck cancer were analyzed for TLR4 and MD-2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis. PBMCs were treated in vitro with OK-432 or with OK-PSA (a lipoteichoic-acid-related molecule that is an active component of OK-432), and interferon-gamma (IFN-gamma) mRNA expression, an immune response measure, was analyzed by RT-PCR. Patient sera collected 24 hours after OK-432 administration were examined for IFN-gamma protein using an enzyme-linked immunosorbent assay. Lewis lung carcinoma-bearing wild-type C57BL/6 and TLR4-deficient mice (four mice per group) received intraperitoneal injections of OK-432, and tumor volumes and sera IFN-gamma levels were measured over time. All statistical tests were two-sided.Twenty patients expressed both TLR4 and MD-2. Expression of TLR4 and MD-2 genes was associated with the in vivo IFN-gamma induction in 19 patients administered OK-432 (Fisher's exact test P<.001). Although both OK-432 and OK-PSA induced IFN-gamma expression from PBMCs in vitro, expression of TLR4 and MD-2 was associated only with IFN-gamma expression induced by OK-PSA (P<.001). In vivo intraperitoneal administration of OK-432 resulted in an increase of IFN-gamma in sera from wild-type mice but not in sera from TLR4-deficient mice. Tumors in wild-type mice treated with OK-432 were statistically significantly smaller than those in mice treated with saline (P =.007). By contrast, in TLR4-deficient mice, there was no difference in tumor volume between the two treatment groups.TLR4 and MD-2 may mediate OK-432-induced anticancer immunity.
Prognostic Impact of the Indexation of Left Ventricular Mass in Patients Undergoing Dialysis
Authors: Carmine Zoccali, Francesco Antonio Benedetto, Francesca Mallamaci, Giovanni Tripepi, Giuseppe Giacone, Alessandro Cataliotti, Giuseppe Seminara, Benedetta Stancanelli, Lorenzo Salvatore Malatino
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Left ventricular hypertrophy (LVH) is exceedingly frequent in patients undergoing dialysis. Cardiac mass is proportional to body size, but the influence of various indexing methods has not been studied in patients with end-stage renal disease. The issue is important because malnutrition and volume expansion would both tend to distort the estimate of LV mass (LVM) in these patients. In a cohort of 254 patients, the prognostic impact on all-cause mortality and cardiovascular outcomes of LVH values, calculated according to two established methods of indexing, either body surface area (BSA) or height2.7, was assessed prospectively. When LVM was analyzed as a categorical variable, the height2.7-based method identified a larger number of patients with LVH than the corresponding BSA-based method. One hundred and thirty-seven fatal and nonfatal cardiovascular events occurred during the follow-up period. Overall, 90 patients died, 51 of cardiovascular causes. In separate Cox models, both the LVM/height2.7 and the LVM/BSA index independently predicted total and cardiovascular mortality (P < 0.001). However, the height2.7-based method coherently produced a closer-fitting model (P ≤ 0.02) than did the BSA-based method. The height2.7 index was also important for the subcategorization of patients according to the presence of concentric or eccentric LVH because the prognostic value of such subcategorization was apparent only when the height2.7-based criterion was applied. In conclusion, LVM is a strong and independent predictor of survival and cardiovascular events in patients undergoing dialysis. The indexing of LVM by height2.7 provides more powerful prediction of mortality and cardiovascular outcomes than the BSA-based method, and the use of this index appears to be appropriate in patients undergoing dialysis.
Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium
Authors: Nathaniel Rothman, Christine F Skibola, Sophia S Wang, Gareth Morgan, Qing Lan, Martyn T Smith, John J Spinelli, Eleanor Willett, Silvia De Sanjose, Pierluigi Cocco, Sonja I Berndt, Paul Brennan, Angela Brooks-Wilson, Sholom Wacholder, Nikolaus Becker, Patricia Hartge, Tongzhang Zheng, Eve Roman, Elizabeth A Holly, Paolo Boffetta, Bruce Armstrong, Wendy Cozen, Martha Linet, F Xavier Bosch, Maria Grazia Ennas, Theodore R Holford, Richard P Gallagher, Sara Rollinson, Paige M Bracci, James R Cerhan, Denise Whitby, Patrick S Moore, Brian Leaderer, Agnes Lai, Charlotte Spink, Scott Davis, Ramon Bosch, Aldo Scarpa, Yawei Zhang, Richard K Severson, Meredith Yeager, Stephen Chanock, Alexandra Nieters
Journal: The Lancet Oncology (2005)
A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours
Authors: M Miyaki
Journal: Gut (2003)

During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.
Interleukin-9 Is Required for Allergic Airway Inflammation Mediated by the Cytokine TSLP
Authors: Weiguo Yao, Yanlu Zhang, Rukhsana Jabeen, Evelyn T. Nguyen, David S. Wilkes, Robert S. Tepper, Mark H. Kaplan, Baohua Zhou
Journal: Immunity (2013)
Circulating testosterone, sex hormone binding globulin and prolactin in women with late onset or persistent acne vulgaris
Authors: C.R. DARLEY, J.D. KIRBY, G.M. BESSER, D.D. MUNRO, C.R.W. EDWARDS, L.H. REES
Journal: British Journal of Dermatology (1982)

Serum testosterone, sex hormone binding globulin (SHBG) and prolactin were measured in thirty-eight women with acne which persisted or started after the age of 18 years. One or more of these levels were abnormal in 76% of patients. Increased testosterone or low SHBG were present alone or in combination in 60% of patients. This group was presumed to have a raised level of non-protein bound, metabolically-available testosterone. Hyperprolactinaemia, which was present in 45% of patients, may be important in view of the reported association with increased adrenal androgens. The hormonal abnormalities may be causally related to the acne and a greater understanding of them may lead to better treatment.
The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts
Authors: Kerstin Klein, Pawel A Kabala, Aleksander M Grabiec, Renate E Gay, Christoph Kolling, Lih-Ling Lin, Steffen Gay, Paul P Tak, Rab K Prinjha, Caroline Ospelt, Kris A Reedquist
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To investigate the effects of BET bromodomain protein inhibition on inflammatory activation and functional properties of rheumatoid arthritis synovial fibroblasts (RASF). <h3>Methods</h3> The expression of the BET bromodomain proteins BRD2, BRD3 and BRD4 was analysed in synovial tissue by immunohistochemistry. RASF were stimulated with tumour necrosis factor (TNF)-α, interleukin (IL)-1β and toll-like receptor (TLR) ligands (Pam3, pIC and lipopolysaccharide (LPS)) in the presence or absence of the BET inhibitor I-BET151, or siRNA targeting BRD2, BRD3 and BRD4. RASF expression of inflammatory mediators, including MMP1, MMP3, IL-6 and IL-8, was measured by q-PCR, q-PCR array and ELISA. Cellular viability, apoptosis, proliferation and chemoattractive properties of RASF were investigated using MTT, cell apoptosis ELISA, BrdU-based proliferation and transwell migration assays. <h3>Results</h3> BRD2, BRD3 and BRD4 proteins were detected in rheumatoid arthritis (RA) synovial tissue, expressed in both RASF and macrophages. I-BET151 suppressed cytokine and TLR ligand-induced secretion of MMP1, MMP3, IL-6 and IL-8, and mRNA expression of more than 70% of genes induced by TNF-α and IL-1β. Combined silencing of BRD2, BRD3 and BRD4 significantly reduced cytokine and TLR ligand-induced expression of a subset of gene products targeted by I-BET151, including MMP1, CXCL10 and CXCL11. I-BET151 treatment of RASF reduced RASF proliferation, and the chemotactic potential for peripheral blood leucocytes of RASF conditioned medium. <h3>Conclusions</h3> Inhibition of BET family proteins suppresses the inflammatory, matrix-degrading, proliferative and chemoattractive properties of RASF and suggests a therapeutic potential in the targeting of epigenetic reader proteins in RA.
Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma
Authors: Frederic Garban, Michel Attal, Mauricette Michallet, Cyrille Hulin, Jean H. Bourhis, Ibrahim Yakoub-Agha, Thierry Lamy, Gerald Marit, Frederic Maloisel, Christian Berthou, Mamoun Dib, Denis Caillot, Bernard dePrijck, Nicolas Ketterer, Jean-Luc Harousseau, Jean-Jacques Sotto, Philippe Moreau
Journal: Blood (2006)
Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis
Authors: J.M. Sowden, B.R. Allen, J. Berth-Jones, R.A.C. Graham-Brown, R.J. Motley, A.Y. Finlay, M. Salek, R. Marks, J.S. Ross, R.D.R. Camp
Journal: The Lancet (1991)
The Chemiluminescence Response of Human Platelets
Authors: Elaine L. Mills, Jonathan M. Gerrard, Dana Filipovich, James D. White, Paul G. Quie
Journal: Journal of Clinical Investigation (1978)

Human platelets and platelet particulate fractions were found to emit a burst of chemiluminescence during incubation with arachidonic acid. The magnitude of light emission was directly related to the number of platelets in the reaction mixture and varied little for the same individual from day to day. The chemiluminescence response of platelets was localized to the particulate fraction and was almost totally oxygen dependent. In addition to arachidonate, seven other polyunsaturated fatty acids, including several that are not prostaglandin precursors, also induced platelet chemiluminescence.
Influence of P53 on the radiotherapy response of hepatocellular carcinoma
Authors: Ana R. Gomes, Ana M. Abrantes, Ana F. Brito, Mafalda Laranjo, João E. Casalta-Lopes, Ana C. Gonçalves, Ana B. Sarmento-Ribeiro, Maria F. Botelho, José G. Tralhão
Journal: Clinical and Molecular Hepatology (2015)

See the commentary-article "P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma" on page 230.
Use of medical resources and quality of life of patients with chronic heart failure: a prospective survey in a large Italian community hospital
Authors: Maria C. Albanese, Michal Plewka, Dario Gregori, Claudio Fresco, Giorgio Avon, Donato Caliandro, Libero Grassi, Paolo Rossi, Paolo Udina, Alessandro Bulfoni, Roberto Colle, Anna Linda Cuzzato, Paolo M. Fioretti
Journal: European Journal of Heart Failure (1999)
Organic Cation Transporters Are Determinants of Oxaliplatin Cytotoxicity
Authors: Shuzhong Zhang, Katherine S. Lovejoy, James E. Shima, Leah L. Lagpacan, Yan Shu, Anna Lapuk, Ying Chen, Takafumi Komori, Joe W. Gray, Xin Chen, Stephen J. Lippard, Kathleen M. Giacomini
Journal: Cancer Research (2006)

Abstract Although the platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin have similar DNA-binding properties, only oxaliplatin is active against colorectal tumors. The mechanisms for this tumor specificity of platinum-based compounds are poorly understood but could be related to differences in uptake. This study shows that the human organic cation transporters (OCT) 1 and 2 (SLC22A1 and SLC22A2) markedly increase oxaliplatin, but not cisplatin or carboplatin, accumulation and cytotoxicity in transfected cells, indicating that oxaliplatin is an excellent substrate of these transporters. The cytotoxicity of oxaliplatin was greater than that of cisplatin in six colon cancer cell lines [mean ± SE of IC50 in the six cell lines, 3.9 ± 1.4 μmol/L (oxaliplatin) versus 11 ± 2.0 μmol/L (cisplatin)] but was reduced by an OCT inhibitor, cimetidine, to a level similar to, or even lower than that of, cisplatin (29 ± 11 μmol/L for oxaliplatin versus 19 ± 4.3 μmol/L for cisplatin). Structure-activity studies indicated that organic functionalities on nonleaving groups coordinated to platinum are critical for selective uptake by OCTs. These results indicate that OCT1 and OCT2 are major determinants of the anticancer activity of oxaliplatin and may contribute to its antitumor specificity. They also strongly suggest that expression of OCTs in tumors should be investigated as markers for selecting specific platinum-based therapies in individual patients. The development of new anticancer drugs, specifically targeted to OCTs, represents a novel strategy for targeted drug therapy. The results of the present structure-activity studies indicate specific tactics for realizing this goal. (Cancer Res 2006; 66(17): 8847-57)
South London Ophthalmic Hospital
Authors: J. Z. Laurence
Journal: BMJ (1859)

Hewent to bed one night in his usual health, and on rising in the nmorning, he found to his great surprise " that he could scarcely see."On trying his eyes further, he found that in attempting to take something off the mantelpiece, he altogether missed his distance.Being obliged to go into the country that morning, he with great difficulty walked to the railway station,
Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema
Authors: Markku Lähteenvuo, Krista Honkonen, Tomi Tervala, Tuomas Tammela, Erkki Suominen, Johanna Lähteenvuo, Ivana Kholová, Kari Alitalo, Seppo Ylä-Herttuala, Anne Saaristo
Journal: Circulation (2011)

Background— Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods and Results— The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (β-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D–treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C–treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions— These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.
Prevalence of pulmonary hypertension in patients undergo hemodialysis
Authors: Abbas Fadaii, Fateme HamidImmani, Bahar Taherkhanchi, Bahador Bagheri
Journal: European Respiratory Journal (2012)

Introduction

Pulmonary hypertension (PH) is one of most important untoward effects of hemodialysis in end stage renal disease (ESRD) patients. Prevelance of hemodialysis-induced pulmonary hypertension is still a subject of debate. The goal of the present work was to determine prevalence of PH in patients who undergo hemodialysis.

Methods

This study was done in hemodialysis ward of Tehran Labbafi Nejad hospital. During 2010, 400 ESRD patients who underwent hemodialysis for at least six months were studied. The exclusion criteria were as follows: cardiac disease with effect on pulmonary artery pressure, pulmonary disease (e.g. COPD), smoking and using calcium channel blockers. Baseline and clinical characteristics of subjects were recorded. Pulmonary pressure was measured by cardiologist using echo cardiography. Pulmonary artery pressure (PAP) higher than 35 mmHg was considered pulmonary hypertension.

Results

Results are presented in mean ± SD. 53% of patients were male and mean was 59 ± 18 yr. The most common cause of ESRD was diabetes mellitus (35%). Duration of hemodialysis was 24 ± 17 months. None of the patients had previous history of kidney transplantation. Mean of Ejection fraction and PAP were 57 ± 5% (44-73) and 39 ± 9 (25-70) mmHg, respectively. 66% patients had pulmonary hypertension. All of them had long duration of dialysis and low EF (56 ± 5%) (P<0.008). They were older than other subjects (63 ± 16). No significant difference was observed about causes of renal diseases, gender and drugs.

Conclusion: Our findings show that PAP is associated with duration of dialysis, age and EF. Due to high prevalence of pulmonary hypertension, it is necessary to screen this disorder and diminish its untoward effects.
Interleukin 7 is produced by murine and human keratinocytes.
Authors: C Heufler, G Topar, A Grasseger, U Stanzl, F Koch, N Romani, A E Namen, G Schuler
Journal: The Journal of Experimental Medicine (1993)

Interleukin 7 (IL-7) was originally identified as a growth factor for B cell progenitors, and subsequently has been shown to exert proliferative effects on T cell progenitors and mature peripheral T cells as well. Constitutive IL-7 mRNA expression so far had been demonstrated in bone marrow stromal cell lines, thymus, spleen, and among nonlymphoid tissues in liver and kidney. Here we show that both murine and human keratinocytes express IL-7 mRNA and release IL-7 protein in biologically relevant amounts. The physiological or pathological relevance of keratinocyte-derived IL-7 is presently unknown. Our finding that keratinocytes can produce IL-7 in concert with reports that IL-7 is a growth factor for in vivo primed antigen-specific T cells, as well as for T lymphoma cells suggests, however, that keratinocyte-derived IL-7 is important in the pathogenesis of inflammatory skin diseases and cutaneous T cell lymphoma.
Long-term clinical outcome of gastric MALT lymphoma after eradication of<i>Helicobacter pylori</i>: a multicentre cohort follow-up study of 420 patients in Japan
Authors: Shotaro Nakamura, Toshiro Sugiyama, Takayuki Matsumoto, Katsunori Iijima, Shouko Ono, Masahiro Tajika, Akira Tari, Yasuhiko Kitadai, Hiroshi Matsumoto, Tadanobu Nagaya, Toshiro Kamoshida, Norihiko Watanabe, Toshimi Chiba, Hideki Origasa, Masahiro Asaka
Journal: Gut (2011)

<h3>Objective</h3> A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after <i>Helicobacter pylori</i> eradication. <h3>Methods</h3> 420 patients with gastric low-grade MALT lymphoma who had undergone successful <i>H pylori</i> eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. <h3>Results</h3> 323 patients (77%) responded to <i>H pylori</i> eradication. A logistic regression analysis showed that absence of <i>H pylori</i>, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/<i>API2-MALT1</i> were independent predictors of resistance to <i>H pylori</i> eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a ‘watch and wait’ strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. <h3>Conclusions</h3> The excellent long-term outcome of gastric MALT lymphoma after <i>H pylori</i> eradication was confirmed by this large-scale follow-up study.