tbuckley/cabot-search huggingface dataset:
Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats
Authors: Suguru Oyagi, Motohiro Hirose, Midori Kojima, Makiko Okuyama, Masaya Kawase, Toshikazu Nakamura, Hajime Ohgushi, Kiyohito Yagi
Journal: Journal of Hepatology (2005)
Multistate Outbreak of Fusarium Keratitis Associated With Use of a Contact Lens Solution
Authors: Douglas C. Chang, Gavin B. Grant, Kerry O’Donnell, Kathleen A. Wannemuehler, Judith Noble-Wang, Carol Y. Rao, Lara M. Jacobson, Claudia S. Crowell, Rodlescia S. Sneed, Felicia M. T. Lewis, Joshua K. Schaffzin, Marion A. Kainer, Carol A. Genese, Eduardo C. Alfonso, Dan B. Jones, Arjun Srinivasan, Scott K. Fridkin, Benjamin J. Park, for the Fusarium Keratitis Investigation Team
Journal: JAMA (2006)

Fusarium keratitis is a serious corneal infection, most commonly associated with corneal injury. Beginning in March 2006, the Centers for Disease Control and Prevention received multiple reports of Fusarium keratitis among contact lens wearers.To define the specific activities, contact lens hygiene practices, or products associated with this outbreak.Epidemiological investigation of Fusarium keratitis occurring in the United States. A confirmed case was defined as keratitis with illness onset after June 1, 2005, with no history of recent ocular trauma and a corneal culture growing Fusarium species. Data were obtained by patient and ophthalmologist interviews for case patients and neighborhood-matched controls by trained personnel. Available Fusarium isolates from patients' clinical and environmental specimens were genotyped by multilocus sequence typing. Environmental sampling for Fusarium was conducted at a contact lens solution manufacturing plant.Keratitis infection with Fusarium species.As of June 30, 2006, we identified 164 confirmed case patients in 33 states and 1 US territory. Median age was 41 years (range, 12-83 years). Corneal transplantation was required or planned in 55 (34%). One hundred fifty-four (94%) of the confirmed case patients wore soft contact lenses. Forty-five case patients and 78 controls were included in the case-control study. Case patients were significantly more likely than controls to report using a specific contact lens solution, ReNu with MoistureLoc (69% vs 15%; odds ratio, 13.3; 95% confidence interval, 3.1-119.5). The prevalence of reported use of ReNu MultiPlus solution was similar between case patients and controls (18% vs 20%; odds ratio, 0.7; 95% confidence interval, 0.2-2.8). Fusarium was not recovered from the factory, warehouse, solution filtrate, or unopened solution bottles; production of implicated lots was not clustered in time. Among 39 isolates tested, at least 10 different Fusarium species were identified, comprising 19 unique multilocus genotypes.The findings from this investigation indicate that this outbreak of Fusarium keratitis was associated with use of ReNu with MoistureLoc contact lens solution. Contact lens users should not use ReNu with MoistureLoc.
Value of <b> <i>p16</i> </b>INK4a and <b> <i>RASSF1A</i> </b> Promoter Hypermethylation in Prognosis of Patients with Resectable Non–Small Cell Lung Cancer
Authors: Jie Wang, J. Jack Lee, Luo Wang, Diane D. Liu, Charles Lu, You-Hong Fan, Waun Ki Hong, Li Mao
Journal: Clinical Cancer Research (2004)

Abstract The p16INK4a and RASSF1A are tumor suppressor genes frequently inactivated by de novo promoter hypermethylation in non-small cell lung cancer. We studied 119 patients with non-small cell lung cancer (70 stage I/II and 49 stage IIIA) who had undergone surgery with curative intent. The p16INK4a and RASSF1A promoter methylation statuses were determined by methylation-specific PCR. Statistical analyses, all two-sided, were performed to determine the prognostic effect of hypermethylation on various clinical parameters. Hypermethylation of the p16INK4a and RASSF1A promoters was found in 58 (49%) and 46 (39%) tumors, respectively, and 30 tumors (25%) exhibited hypermethylation of both gene promoters. In patients with stage I/II tumors, only p16INK4a promoter hypermethylation was associated with a poor 5-year overall survival rate (P = 0.002). In patients with stage IIIA disease, however, RASSF1A promoter hypermethylation was a stronger predictor of a poor 5-year overall survival rate (P &amp;lt; 0.0001) than p16INK4a promoter hypermethylation. Among the 49 patients with stage IIIA tumors, 16 (89%) of the 18 patients whose tumors showed RASSF1A promoter hypermethylation died within 3 years after surgery, as compared with only 12 (39%) of the 31 patients whose tumors had no RASSF1A promoter hypermethylation (P &amp;lt; 0.0001). Multivariate analysis indicated that RASSF1A promoter hypermethylation was the stronger independent predictor for survival in patients with locally advanced non-small cell lung cancer. Our results indicate that p16INK4a promoter hypermethylation predicts a poor 5-year survival rates for patients with resectable non-small cell lung cancer, particularly for those with early stage tumors, whereas RASSF1A promoter hypermethylation is a profound prognostic predictor for patients with locally advanced non-small cell lung cancer, suggesting an important role of RASSF1A in non-small cell lung cancer progression.
Targeted therapy for high-grade glioma with the TGF- 2 inhibitor trabedersen: results of a randomized and controlled phase IIb study
Authors: U. Bogdahn, P. Hau, G. Stockhammer, N. K. Venkataramana, A. K. Mahapatra, A. Suri, A. Balasubramaniam, S. Nair, V. Oliushine, V. Parfenov, I. Poverennova, M. Zaaroor, P. Jachimczak, S. Ludwig, S. Schmaus, H. Heinrichs, K.- H. Schlingensiepen
Journal: Neuro-Oncology (2010)

This randomized, open-label, active-controlled, dose-finding phase IIb study evaluated the efficacy and safety of trabedersen (AP 12009) administered intratumorally by convection-enhanced delivery compared with standard chemotherapy in patients with recurrent/refractory high-grade glioma. One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) were randomly assigned to receive trabedersen at doses of 10 or 80 µM or standard chemotherapy (temozolomide or procarbazine/lomustine/vincristine). Primary endpoint was 6-month tumor control rate, and secondary endpoints included response at further timepoints, survival, and safety. Six-month tumor control rates were not significantly different in the entire study population (AA and GBM). Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 µM trabedersen vs chemotherapy (p= .0032). The 2-year survival rate had a trend for superiority for 10 µM trabedersen vs chemotherapy (p = .10). Median survival for 10 µM trabedersen was 39.1 months compared with 35.2 months for 80 µM trabedersen and 21.7 months for chemotherapy (not significant). In GBM patients, response and survival results were comparable among the 3 arms. Exploratory analysis on GBM patients aged ≤55 years with Karnofsky performance status >80% at baseline indicated a 3-fold survival at 2 and 3 years for 10 µM trabedersen vs chemotherapy. The frequency of patients with related or possibly drug-related adverse events was higher with standard chemotherapy (64%) than with 80 µM trabedersen (43%) and 10 µM trabedersen (27%). Superior efficacy and safety for 10 µM trabedersen over 80 µM trabedersen and chemotherapy and positive risk–benefit assessment suggest it as the optimal dose for further clinical development in high-grade glioma.
Variants in Inflammation Genes Are Implicated in Risk of Lung Cancer in Never Smokers Exposed to Second-hand Smoke
Authors: Margaret R. Spitz, Ivan P. Gorlov, Christopher I. Amos, Qiong Dong, Wei Chen, Carol J. Etzel, Olga Y. Gorlova, David W. Chang, Xia Pu, Di Zhang, Liang Wang, Julie M. Cunningham, Ping Yang, Xifeng Wu
Journal: Cancer Discovery (2011)

Lung cancer in lifetime never smokers is distinct from that in smokers, but the role of separate or overlapping carcinogenic pathways has not been explored. We therefore evaluated a comprehensive panel of 11,737 single-nucleotide polymorphisms (SNP) in inflammatory-pathway genes in a discovery phase (451 lung cancer cases, 508 controls from Texas). SNPs that were significant were evaluated in a second external population (303 cases, 311 controls from the Mayo Clinic). An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance and restricted to those reporting adult exposure to environmental tobacco smoke. Another promising candidate was an SNP in NR4A1, although the replication OR did not achieve statistical significance. ACVR1B belongs to the TGFR-β superfamily, contributing to resolution of inflammation and initiation of airway remodeling. An inflammatory microenvironment (second-hand smoking, asthma, or hay fever) is necessary for risk from these gene variants to be expressed. These findings require further replication, followed by targeted resequencing, and functional validation.
Evolution of the secondary structures and compensatory mutations of the ribosomal RNAs of Drosophila melanogaster.
Authors: J M Hancock, D Tautz, G A Dover
Journal: Molecular Biology and Evolution (1988)

This paper examines the effects of DNA sequence evolution on RNA secondary structures and compensatory mutations. Models of the secondary structures of Drosophila melanogaster 18S ribosomal RNA (rRNA) and of the complex between 2S, 5.8S, and 28S rRNAs have been drawn on the basis of comparative and energetic criteria. The overall AU richness of the D. melanogaster rRNAs allows the resolution of some ambiguities in the structures of both large rRNAs. Comparison of the sequence of expansion segment V2 in D. melanogaster 18S rRNA with the same region in three other Drosophila species and the tsetse fly (Glossina morsitans morsitans) allows us to distinguish between two models for the secondary structure of this region. The secondary structures of the expansion segments of D. melanogaster 28S rRNA conform to a general pattern for all eukaryotes, despite having highly divergent sequences between D. melanogaster and vertebrates. The 70 novel compensatory mutations identified in the 28S rRNA show a strong (70%) bias toward A-U base pairs, suggesting that a process of biased mutation and/or biased fixation of A and T point mutations or AT-rich slippage-generated motifs has occurred during the evolution of D. melanogaster rDNA. This process has not occurred throughout the D. melanogaster genome. The processes by which compensatory pairs of mutations are generated and spread are discussed, and a model is suggested by which a second mutation is more likely to occur in a unit with a first mutation as such a unit begins to spread through the family and concomitantly through the population. Alternatively, mechanisms of proofreading in stem-loop structures at the DNA level, or between RNA and DNA, might be involved. The apparent tolerance of noncompensatory mutations in some stems which are otherwise strongly supported by comparative criteria within D. melanogaster 28S rRNA must be borne in mind when compensatory mutations are used as a criterion in secondary-structure modeling. Noncompensatory mutation may extend to the production of unstable structures where a stem is stabilized by RNA-protein or additional RNA-RNA interactions in the mature ribosome. Of motifs suggested to be involved in rRNA processing, one (CGAAAG) is strongly overrepresented in the 28S rRNA sequence. The data are discussed both in the context of the forces involved with the evolution of multigene families and in the context of molecular coevolution in the rDNA family in particular.
Intratunical Injection of Human Adipose Tissue–derived Stem Cells Prevents Fibrosis and Is Associated with Improved Erectile Function in a Rat Model of Peyronie's Disease
Authors: Fabio Castiglione, Petter Hedlund, Frank Van der Aa, Trinity J. Bivalacqua, Patrizio Rigatti, Hein Van Poppel, Francesco Montorsi, Dirk De Ridder, Maarten Albersen
Journal: European Urology (2012)
STUDIES ON THE ADJUVANT ACTION OF BACTERIAL ENDOTOXINS ON ANTIBODY FORMATION
Authors: Peter A. Ward, Arthur G. Johnson, Murray R. Abell
Journal: The Journal of Experimental Medicine (1959)

Histologic changes occurring in the rabbit spleen during the primary response to intravenous injection of bovine gamma globulin alone and in combination with bacterial endotoxin have been described. The predominant morphologic changes associated with antibody formation in animals that received antigen alone were confined to the follicular areas of the spleen. Only minimal changes were seen in the red pulp. No new cellular types appeared following endotoxin stimulus. Rather, a profound augmentation of events observed following a single injection of bovine gamma globulin alone appears to account for the higher levels of antibody incited by this adjuvant. The cell type important in antibody formation under these conditions appeared to be a modified reticular cell. Plasma cells were not part of the cellular reaction. A hypothesis describing the primary antibody response is presented.
Increased Prevalence of Enteroviral RNA in Blood Spots From Newborn Children Who Later Developed Type 1 Diabetes
Authors: Gisela G. Dahlquist, Jenny Forsberg, Lars Hagenfeldt, Jens Boman, Per Juto
Journal: Diabetes Care (2004)

e read with interest the article by Aso et al. (1) showing greater plasma concentrations of interleukin-18 (IL-18) in type 2 diabetic patients compared with matched control subjects.While the authors found no significant associations between fasting levels of IL-18 and homeostasis model assessment, a measure of insulin resistance, they found associations between IL-18 and C-reactive protein concentrations.Moreover, carotid intima-media thickness, a validated surrogate measure of atherosclerosis, was greater in diabetic patients with high IL-18 than in those with normal IL-18.As a whole, these data add to the mounting evidence that diabetes may be regarded as a chronic lowgrade inflammatory state.However, we disagree with the authors' conclusions that "the present study demonstrated for the first time that plasma IL-18 concentrations were significantly higher in type 2 diabetic patients than in age-matched control subjects" because we have reported similar findings in Diabetes Care (2).In that study, we demonstrated that 30 newly diagnosed, slightly overweight (BMI 26.9 Ϯ 1.2 kg/m 2 , means Ϯ SD) type 2 diabetic patients without clinical or instrumental evidence of micro-and macrovascular complications presented higher circulating concentrations of IL-18 compared with nondiabetic subjects matched for sex, age, and body weight (205 Ϯ 39 vs. 120 Ϯ 25 pg/ml, P Ͻ 0.01).It is reassuring to see that the fasting values of IL-18 in the Japanese diabetic patients studied by Aso et al. (1) were quite similar (203 Ϯ 153 pg/ml) to those of our Caucasian diabetic patients and that the relation between fasting plasma glucose and IL-18 concentrations was present in both studies (r ϭ 0.31, P Ͻ 0.05; r ϭ 0.24, P Ͻ 0.02, respectively).These results suggest that ethnicity does not to play a major role in these associations.IL-18 is a potent proinflammatory cy-tokine reported to play a role in plaque destabilization (3) and predict cardiovascular death in patients with coronary artery disease (4).Although IL-18 is produced mainly by monocyte/macrophages, a contribution from adipose tissue has recently been suggested (5).In the light of the evidence that IL-18 circulating levels are higher in type 2 diabetic patients than matched nondiabetic subjects and correlate with fasting glucose levels, it does not seem hazardous to hypothesize that IL-18 may play a role in acute coronary syndromes through plaque destabilization ( 6).This working hypothesis, which deserves further investigation, also finds support in the observation that acute hyperglycemia may increase circulation levels of IL-18 in both normal subjects and patients with impaired glucose tolerance (7).
An information system and medical record to support HIV treatment in rural Haiti
Authors: Hamish S F Fraser, Darius Jazayeri, Patrice Nevil, Yusuf Karacaoglu, Paul E Farmer, Evan Lyon, Mary Kay C Smith Fawzi, Fernet Leandre, Sharon S Choi, Joia S Mukherjee
Journal: BMJ (2004)

<i>Lack of infrastructure, including information and communication systems, is considered a barrier to successful HIV treatment programmes in resource poor areas. The authors describe how they set up a web based medical record system linking remote areas in rural Haiti and how it is used to track clinical outcomes, laboratory tests, and drug supplies and to create reports for funding agencies</i>
Circulating adrenomedullin is increased after heart transplantation
Authors: B Geny
Journal: Cardiovascular Research (1999)

Adrenomedullin (ADM), secreted by the failing human heart, is a newly discovered potent endogenous vasorelaxing and natriuretic peptide that may play a role in cardiorenal regulation. No data are available on ADM in heart-transplant recipients (Htx) and the aim of this study was to determine the short- and long-term responses of ADM after heart transplantation.Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32 +/- 16 months) after transplantation. Additionally, ADM was obtained in matched hypertensive and renal-transplant patients (n = 9 in each group).Plasma ADM, elevated in heart failure patients, further increased transiently at day 1 after transplantation (from 37.9 +/- 15.9 to 125.8 +/- 15.3 pmol/l, P < 0.01) and, although decreasing thereafter, remained elevated until the 30th day after transplantation (52.1 +/- 25.2 pmol/l). Late after transplantation. ADM concentrations were still increased compared to normal values (31.3 +/- 5.3 vs. 19.4 +/- 2.7 pmol/l, P < 0.001). ADM positively correlated with endothelin, atrial natriuretic peptide (ANP) and cyclosporine. ADM was also correlated with increased diastolic (r = 0.68, P < 0.04) and systolic (r = 0.66, P < 0.05) blood pressure in late Htx. No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine. ADM elevation was similar in hypertensive, renal-transplant patients and in Htx.Circulating ADM is increased after heart transplantation, in relation to hypertension, endothelin, cyclosporine and ANP. In view of ADM's biological properties, these results might suggest a compensatory role for ADM against further development of vasoconstriction and fluid retention states after heart transplantation.
Intracellular tracking of protamine/antisense oligonucleotide nanoparticles and their inhibitory effect on HIV-1 transactivation
Authors: Norbert Dinauer, Dirk Lochmann, Ilhan Demirhan, Abdellatif Bouazzaoui, Andreas Zimmer, Angelika Chandra, Jörg Kreuter, Hagen von Briesen
Journal: Journal of Controlled Release (2004)
An Exploratory Study of Systemic Administration of the Toll-like Receptor-7 Agonist 852A in Patients with Refractory Metastatic Melanoma
Authors: Reinhard Dummer, Axel Hauschild, Juergen C. Becker, Jean-Jacques Grob, Dirk Schadendorf, Veronica Tebbs, Jeannine Skalsky, Katharina C. Kaehler, Stephanie Moosbauer, Ruth Clark, Tze-Chiang Meng, Mirjana Urosevic
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A topical Toll-like receptor 7 (TLR7) agonist induces regression of cutaneous melanocytic neoplasms. We explored antitumor activity of a systemically administered TLR7 agonist, 852A, in patients with metastatic melanoma. Experimental Design: We undertook a phase II, multicenter, open-label study in patients with chemotherapy-refractory metastatic melanoma. Patients received i.v. 852A, starting at 0.6 mg/m2 and increasing to 0.9 mg/m2 based on tolerance, thrice per week for 12 weeks. Clinical response was determined by Response Evaluation Criteria in Solid Tumors. Immune effects of 852A were monitored by measuring serum type I IFN and IP-10 together with assessment of immune cell markers in peripheral blood. Results: Twenty-one patients were enrolled. Thirteen patients completed the initial 12-week treatment cycle, with two discontinuing for adverse events considered to be possibly related to study drug. Four (19%) patients had disease stabilization for &amp;gt;100 days. One patient had a partial remission after two treatment cycles, but progressed during the third. Dose-limiting toxicity was observed in two patients. Serum type I IFN and IP-10 increased in most patients on 852A administration. Serum type I IFN increases were greater after dosing with 852A 0.9 mg/m2 than after 0.6 mg/m2 (P = 0.009). The maximal increase in IP-10 compared with baseline correlated with the maximal increase in type I IFN (P = 0.003). In the eight patients with immune cell marker data, CD86 expression on monocytes increased significantly post-first dose (P = 0.007). Conclusion: Intravenous 852A was well tolerated and induced systemic immune activation that eventually resulted in prolonged disease stabilization in some patients with stage IV metastatic melanoma who had failed chemotherapy.
High Fas ligand expression on lymphocytes in lesions of ulcerative colitis
Authors: H Ueyama, T Kiyohara, N Sawada, K Isozaki, S Kitamura, S Kondo, J Miyagawa, S Kanayama, Y Shinomura, H Ishikawa, T Ohtani, R Nezu, S Nagata, Y Matsuzawa
Journal: Gut (1998)

The pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas.To analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis.FasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn's disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry.FasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn's disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn's disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions.FasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn's disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.