tbuckley/cabot-search huggingface dataset:
Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana
Authors: Daniel Chandramohan, Seth Owusu-Agyei, Ilona Carneiro, Timothy Awine, Kwame Amponsa-Achiano, Nathan Mensah, Shabbar Jaffar, Rita Baiden, Abraham Hodgson, Fred Binka, Brian Greenwood
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effects of intermittent preventive treatment for malaria in infants (IPTi) with sulfadoxine-pyrimethamine in an area of intense, seasonal transmission. <b>Design</b> Cluster randomised placebo controlled trial, with 96 clusters allocated randomly to sulfadoxine-pyrimethamine or placebo in blocks of eight. <b>Interventions</b> Children received sulfadoxine-pyrimethamine or placebo and one month of iron supplementation when they received DPT-2, DPT-3, or measles vaccinations and at 12 months of age. <b>Main outcome measures</b> Incidence of malaria and of anaemia determined through passive case detection. <b>Results</b> 89% (1103/1242) of children in the placebo group and 88% (1088/1243) in the IPTi group completed follow-up to 24 months of age. The protective efficacy of IPTi against all episodes of malaria was 24.8% (95% confidence interval 14.3% to 34.0%) up to 15 months of age. IPTi had no protective effect against malaria between 16 and 24 months of age (protective efficacy −4.9%, −21.3% to 9.3%). The incidence of high parasite density malaria (≥ 5000 parasites/μl) was higher in the IPTi group than in the placebo group between 16 and 24 months of age (protective efficacy −19.5%, −39.8% to −2.2%). IPTi reduced hospital admissions with anaemia by 35.1% (10.5% to 52.9%) up to 15 months of age. IPTi had no significant effect on anaemia between 16 and 24 months of age (protective efficacy −6.4%, −76.8% to 35.9%). The relative risk of death up to 15 months of age in the IPTi group was 1.26 (95% confidence interval 0.81 to 1.96; P =0.31), and from 16 to 24 months it was 1.28 (0.77 to 2.14; P =0.35). <b>Conclusions</b> Intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine can reduce malaria and anaemia in infants even in seasonal, high transmission areas, but concern exists about possible rebound in the incidence of malaria in the second year of life.
Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report
Authors: Yu Ri Seo, Se Hyung Kim, Hyun Jung Kim, Chan Kyu Kim, Seong Kyu Park, Eun Suk Koh, Dae Sik Hong
Journal: Journal of Hematology & Oncology (2010)

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted.
Lymphotoxin-β Receptor Signaling through NF-κB2-RelB Pathway Reprograms Adipocyte Precursors as Lymph Node Stromal Cells
Authors: Cécile Bénézech, Emma Mader, Guillaume Desanti, Mahmood Khan, Kyoko Nakamura, Andrea White, Carl F. Ware, Graham Anderson, Jorge H. Caamaño
Journal: Immunity (2012)
Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women
Authors: Ming-Whei Yu, Yu-Ching Yang, Shi-Yi Yang, Hung-Chuen Chang, Yun-Fan Liaw, Shi-Ming Lin, Chun-Jen Liu, Shou-Dong Lee, Chih-Lin Lin, Pei-Jer Chen, Shee-Chan Lin, Chien-Jen Chen
Journal: Hepatology (2002)

The androgen receptor (AR) gene is localized on chromosome X, and shorter CAG repeats in exon 1 of the AR gene were recently suggested to increase hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk among men. To examine whether the relationship between the AR-CAG repeats and HCC was also evident among women, we conducted a case-control study in Taiwan. The number of AR-CAG repeats was determined for 238 women with HCC and 354 unrelated control subjects (comprising 188 first-degree and 166 nonbiological relatives) selected from female relatives of patients with HCC. Women harboring 2 AR alleles with more than 23 CAG repeats had an increased risk of HCC (age-adjusted odds ratio [OR], 1.82; 95% CI, 1.06-3.14), compared with women with only short alleles or a single long allele. The association between harboring 2 AR alleles containing longer CAG repeats and HCC was more striking among HBV carriers (age-adjusted OR for more than 22 repeats, 2.23; 95% CI, 1.14-4.34) and particularly prominent among HBV carriers under age 53 years (age-adjusted OR, 3.16; 95% CI, 1.13-8.82). When CAG repeats were analyzed as a continuous variable, the increase in HCC risk associated with each incremental repeat in the shorter of 2 alleles in a given genotype was statistically significant among women with a first-degree relative with HCC (age-adjusted OR, 1.18; 95% CI, 1.01-1.37). No such relationship was detected among women without the family history. In conclusion, our observations suggest that the AR-CAG alleles may contribute to HCC predisposition among women through a mechanism different from that for men.
Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats
Authors: Koji Tomiyama, Atsushi Ikeda, Shinya Ueki, Atsunori Nakao, Donna B. Stolz, Yasushi Koike, Amin Afrazi, Chandrashekhar Gandhi, Daisuke Tokita, David A. Geller, Noriko Murase
Journal: Hepatology (2008)

Abstract Proinflammatory responses play critical roles in hepatic ischemia/reperfusion (I/R) injury associating with liver transplantation (LTx), and carbon monoxide (CO) can effectively down-regulate them. Using wild-type (WT) to enhanced green fluorescent protein (EGFP)-transgenic rat LTx with 18-hour cold preservation in University of Wisconsin solution, this study analyzed the relative contribution of donor and host cells during early posttransplantation period and elucidated the mechanism of hepatic protection by CO. CO inhibited hepatic I/R injury and reduced peak alanine aminotransferase levels at 24 hours and hepatic necrosis at 48 hours. Abundant EGFP+ host cells were found in untreated WT liver grafts at 1 hour and included nucleated CD45+ leukocytes (myeloid, T, B, and natural killer cells) and EGFP+ platelet-like depositions in the sinusoids. However, reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated graft nonparenchymal cells (NPCs) revealed that I/R injury-induced proinflammatory mediators [for example, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS)] were not up-regulated in purified CD45+ cells of donor or host origin. Instead, TNF-α and IL-6 messenger RNA (mRNA) elevation was exclusively seen in isolated CD68+ cells, whereas iNOS mRNA up-regulation was seen in hepatocytes. Nearly all CD68+ cells at 1 hour after LTx were EGFP− donor Kupffer cells, and CO efficiently inhibited TNF-α and IL-6 up-regulation in the CD68+ Kupffer cell fraction. When graft Kupffer cells were inactivated with gadolinium chloride, activation of inflammatory mediators in liver grafts was significantly inhibited. Furthermore, in vitro rat primary Kupffer cell culture also showed significant down-regulation of lipopolysaccharide (LPS)-induced inflammatory responses by CO. Conclusion: These results indicate that CO ameliorates hepatic I/R injury by down-regulating graft Kupffer cells in early postreperfusion period. The study also suggests that different cell populations play diverse roles by up-regulating distinctive sets of mediators in the acute phase of hepatic I/R injury. (Hepatology 2008;48:1608–1620.)
Mature Results of a Phase II Study of Rituximab Therapy for Nodular Lymphocyte–Predominant Hodgkin Lymphoma
Authors: Ranjana H. Advani, Sandra J. Horning, Richard T. Hoppe, Sarah Daadi, John Allen, Yasodha Natkunam, Nancy L. Bartlett
Journal: Journal of Clinical Oncology (2014)

Purpose Universal expression of CD20 by malignant cells in nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) led us to evaluate rituximab (R) as a therapeutic option. Patient and Methods Patients with previously treated or newly diagnosed NLPHL were treated with R (375 mg/m 2 once per week for 4 weeks) or, after a protocol amendment, with R plus R maintenance (MR; administered once every 6 months for 2 years). Primary and secondary outcome measures were progression-free survival (PFS) and overall response rate (ORR), respectively. Results A total of 39 patients were enrolled (R, n = 23; R + MR, n = 16). After four once-per-week treatments, ORR was 100% (complete response, 67%; partial response, 33%). At median follow-ups of 9.8 years for R and 5 years for R + MR, median PFS were 3 and 5.6 years (P = .26), respectively; median overall survival (OS) was not reached. Estimated 5-year PFS and OS for patients treated with R versus R + MR were 39.1% (95% CI, 23.5 to 65.1) and 95.7% (95% CI, 87.7 to 100) versus 58.9% (95% CI, 38.0 to 91.2) and 85.7% (95% CI, 69.2 to 100), respectively. Nine of 23 patients experiencing relapse had evidence of transformation to aggressive B-cell lymphoma; six of these patients had infradiaphragmatic involvement at study entry. Conclusion R is an active agent in NLPHL. Although responses are not durable in most patients, a significant minority experience remissions lasting &gt; 5 years. R + MR results in a nonsignificant increase in PFS compared with R. R may be considered in the relapsed setting for NLPHL. The potential for transformation of NLPHL to aggressive B-cell lymphoma underscores the importance of rebiopsy and long-term follow-up.
Cardiac Transplantation— A Current Appraisal
Authors: John H. Kennedy
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The recent technical achievement of five short-term successful human cardiac homotransplants by Barnard<sup>1</sup>in Cape Town, Republic of South Africa, by Kantrowitz in New York, and by Shumway in Palo Alto, Calif, culminated over seven years of experimental work by several laboratories. Lower and Shumway<sup>2</sup>in 1960 reported survival of dogs 6 to 21 days after orthotopic cardiac homotransplantation. With the addition of immuno-suppressive therapy (methotrexate), Blumenstock<sup>3</sup>was able to extend survival under the same circumstances to 42 days. Kondo et al<sup>4</sup>in 1965 reported survival of one of 40 puppies for 112 days after orthotopic cardiac homotransplantation without immuno-suppressive therapy. This animal is still alive. Thus, at best, cardiac transplantation represents clinical application of a method of treatment tested in the experimental laboratory to the one group of patients for whom contemporary cardiac surgery has little to offer—those with bad myocardium. At
A novel and translatable cell assay for the study of vascular signalling in pulmonary hypertension
Authors: Daniel M. Reed, Peter M. George, Catherine Francis, Laura B. Feyereisen, William Swain, Marc Iglarz, Amanda Wan, Benjamin Garfield, John Wort, Jane A. Mitchell
Journal: European Respiratory Journal (2013)

Pulmonary hypertension (PH) is a rare but severe disease. Endothelial and vascular smooth muscle cells are critically involved in the pathology of PH. However, pulmonary vessels are not accessible in most patients. Blood outgrowth (BO) vascular cells are derived from progenitors and are potentially valuable, highly translatable models. Here, we show for the first time that endothelial cells (BOEC) and putative smooth muscle cells can be grown out from the blood of patients with PH. BOEC from patients (n=2) aligned under complex shear conditions in a way characteristic of endothelial cells, expressed VE-cadherin and released endothelin-1. Autologous vascular smooth muscle cells were isolated from the same patients’ peripheral blood samples and displayed a typical ‘hill and valley’ morphology (Fig A). As interferon (IFN) signalling is thought to be relevant to vascular dysfunction, responses of BOEC from PH patients (n=3) to IFNα and IFNγ (30ng/ml) were compared to healthy donor cells (n=4-6). IP10 (CXCL10) was measured as a ubiquitous readout of IFN signalling. BOEC from PH patients released more IP10 in response to IFNs (Fig B). The ability to derive both endothelial and smooth muscle cells from individual patients with PH represents a key step forward in translational and personalised research in this condition.  This study was supported by an unconditional educational award from Actelion.
Inhibition of Renal Fibrosis by Gene Transfer of Inducible Smad7 Using Ultrasound-Microbubble System in Rat UUO Model
Authors: Hui Y. Lan, Wei Mu, Naruya Tomita, Xiao R. Huang, Jin H. Li, Hong-Jian Zhu, Ryuichi Morishita, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. TGF-β is a key mediator in renal fibrosis. Kidney-targeted gene therapy with anti–TGF-β strategies is expected to have therapeutic potential, but this has been hampered by concerns over the safety and practicability of viral vectors and the inefficiency of nonviral transfection techniques. The present study explored the potential role of TGF-β/Smad signaling in renal fibrosis in vivo and developed a safe and effective gene therapy to specifically block TGF-β signaling and renal fibrosis in a rat unilateral ureteral obstruction (UUO) model by transferring a doxycycline-regulated Smad7 gene or control empty vectors using an ultrasound-microbubble (Optison)-mediated system. The Smad7 transgene expression was tightly controlled by addition of doxycycline in the daily drinking water. Groups of six rats were sacrificed at day 7, and the transfection rate, Smad7 transgene expression, and tubulointerstitial fibrosis including α-smooth muscle actin and collagen matrix mRNA and protein expression were determined. Compared with the non-ultrasound treatment, the combination of ultrasound with Optison largely increased the transfection rate of FITC-ODN and Smad7 transgene expression up to a 1000-fold, and this was found in all kidney tissues. Compared with normal rats, Smad7 expression within the UUO kidney was significantly reduced, and this was associated with up to a sixfold increase in Smad2 and Smad3 activation and severe tubulointerstitial fibrosis. In contrast, treatment with inducible Smad7 resulted in a fivefold increase in Smad7 expression with complete inhibition of Smad2 and Smad3 activation and tubulointerstitial fibrosis in terms of tubulointerstitial myofibroblast accumulation (85%↓) and collagen I and III mRNA and protein expression (60 to 70%↓). In conclusion, the ultrasound-mediated inducible Smad7 gene transfer is a safe, effective, and controllable gene therapy. TGF-β–mediated renal fibrosis is regulated positively by Smad2/3, but negatively by Smad7. Target blockade of TGF-β/Smad signaling by expression of Smad7 may provide a new therapeutic potential for renal fibrosis. E-mail: [email protected]
Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603
Authors: Yue Lu, Sumio Sakamaki, Hiroyuki Kuroda, Toshiro Kusakabe, Yuichi Konuma, Takehide Akiyama, Akihito Fujimi, Naofumi Takemoto, Kyokusen Nishiie, Takuya Matsunaga, Yasuo Hirayama, Junji Kato, Shinichiro Kon, Katsuhisa Kogawa, Yoshiro Niitsu
Journal: Blood (2001)
LUPUS ERYTHEMATOSUS AND TUBERCULOSIS
Authors: H. G. BROOKE
Journal: British Journal of Dermatology (1895)

THE view that lupus erythematosus is an affection of tubercular origin has received strong support from many competent observers, from Besnier, for example, in France, and from Boeck of Christiania, but so far the idea is simply hypothetical.The lesions are, in a large number of cases, so symmetrical (and tend to become so in all as they progress), and its origin is so evidently erythematous, that the failure to discover bacilli in the lesions themselves is not surprising ; indeed, we may say, that it would be more surprising to find them in an affection which has from its outset such a tendency to exact symmetry .
Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice
Authors: M. Neovius, J. F. Simard, L. Klareskog, J. Askling
Journal: Annals of the Rheumatic Diseases (2011)

To investigate sick leave and disability pension in rheumatoid arthritis (RA) in relation to the initiation of biological and non-biological antirheumatic therapies in clinical practice.Patients aged 19-60 years initiating non-biological mono (n=2796) or combination disease-modifying antirheumatic drug (DMARD) therapy (n=973), or biological agents (n=4787) were identified in the Swedish Rheumatology Quality Register between 1999 and 2007. Sick leave and disability pension data (1995-2010) were retrieved from national registers.During the year before the start of mono DMARD, combination DMARD and biological treatment, 10%, 12% and 43% of patients received disability pension benefits, respectively. The corresponding combined annual sick leave and disability pension days were 78 (54+25), 132 (105+27) and 190 (79+111). Irrespective of treatment type, initiators were characterised by a history of increasing sick leave and disability pension. Treatment start was associated with a break in this trajectory: sick leave decreased while disability pension increased, resulting in a net stabilisation of total days. Higher levels of days on sick leave and disability pension at treatment start were observed in patients initiating biologics in 1999 (236 days/year) compared with 2007 (150 days/year; p<0.001), but the trajectory thereafter remained largely similar and contrasted markedly with the level in the general population.Sick leave and disability pension increased rapidly before the initiation of antirheumatic therapy, which was associated with a halt but not a reversal of this development. Work ability is a metric of importance for clinical practice, signalling large remaining needs in the RA population, and the need for intervention earlier in the disease process.
Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor.
Authors: R H DeKruyff, T Turner, J S Abrams, M A Palladino, D T Umetsu
Journal: The Journal of Experimental Medicine (1989)

We have analyzed in detail the precise requirements for the induction of human IgE synthesis using several experimental approaches with purified B cells and well-characterized alloantigen-specific CD4+ T cell clones expressing different profiles of lymphokine secretion. Using these clones under cognate conditions in which the B cells expressed alloantigens recognized by the cloned T cells, we have confirmed that IL-4 is required for the induction of IgE synthesis, but we have clearly demonstrated that IL-4 by itself is not sufficient. With several cloned CD4+ T cell lines, including an IL-4-producing clone that could not induce IgE synthesis, and cloned T cells pretreated with cyclosporin A to inhibit lymphokine synthesis, we showed that Th cell-B cell interactions are necessary for IgE synthesis, and that low molecular weight B cell growth factor (LMW-BCGF) and IL-4, in combination, are lymphokines of major importance in the induction of IgE synthesis. Together our results indicate that optimal induction of an IgE-specific response requires the exposure of B cells to a particular complex of signals that include (a) a signal(s) involving Th-B cell interaction that primes B cells to receive additional signals from soluble lymphokines, (b) a specific B cell proliferative signal provided by LMW-BCGF, and (c) a specific B cell differentiation signal provided by IL-4.
A Hypermethylated Phenotype Is a Better Predictor of Survival than <i>MGMT</i> Methylation in Anaplastic Oligodendroglial Brain Tumors: A Report from EORTC Study 26951
Authors: Martin J. van den Bent, Lonneke A. Gravendeel, Thierry Gorlia, Johan M. Kros, Lariesa Lapre, Pieter Wesseling, Johannes L. Teepen, Ahmed Idbaih, Marc Sanson, Peter A.E. Sillevis Smitt, Pim J. French
Journal: Clinical Cancer Research (2011)

The MGMT promoter methylation status has been suggested to be predictive for outcome to temozolomide chemotherapy in patients with glioblastoma (GBM). Subsequent studies indicated that MGMT promoter methylation is a prognostic marker even in patients treated with radiotherapy alone, both in GBMs and in grade III gliomas.To help determine the molecular mechanism behind this prognostic effect, we have conducted genome-wide methylation profiling and determined the MGMT promoter methylation status, 1p19q LOH, IDH1 mutation status, and expression profile on a series of oligodendroglial tumors [anaplastic oligodendrogliomas (AOD) and anaplastic oligoastrocytomas (AOA)] within EORTC study 26951. The series was expanded with tumors of the same histology and treatment from our own archive.Methylation profiling identified two main subgroups of oligodendroglial brain tumors of which survival in the CpG island hypermethylation phenotype (CIMP(+)) subgroup was markedly better than the survival of the unmethylated (CIMP(-)) subgroup (5.62 vs. 1.24 years; P < 0.0001). CIMP status correlated with survival, MGMT promoter methylation, 1p19q LOH, and IDH1 mutation status. CIMP status strongly increases the predictive accuracy of survival in a model including known clinical prognostic factors such as age and performance score. We validated our results on an independent data set from the Cancer Genome Atlas (TCGA).The strong association between CIMP status and MGMT promoter methylation suggests that the MGMT promoter methylation status is part of a more general, prognostically favorable genome-wide methylation profile. Methylation profiling therefore may help identify AODs and AOAs with improved prognosis.