tbuckley/cabot-search huggingface dataset:
Ketorolac treatment of pseudophakic cystoid macular edema identified more than 24 months after cataract extraction
Authors: James M Weisz, Neil M Bressler, Susan B Bressler, Andrew P Schachat
Journal: Ophthalmology (1999)

To evaluate whether ketorolac ophthalmic drops prescribed four times a day can be associated with improved visual acuity and prompt resolution of edema for patients with pseudophakic cystoid macular edema identified more than 24 months after cataract surgery.Prospective, nonrandomized, comparative (subject self-controlled) trial.The records of nine patients who had pseudophakic cystoid macular edema more than 24 months after cataract surgery at the time treatment commenced were identified at the Wilmer Retinal Vascular Center from September 1, 1996, through March 1, 1997.Best-corrected visual acuities measured on a retroilluminated Bailey-Lovie chart approximately every 3 months, contact lens biomicroscopy, and fluorescein angiography following ketorolac.Commercially available ketorolac ophthalmic drops 0.5% were prescribed for the affected eye four times a day for at least 3 months and continued until edema resolved.Ten eyes of nine patients were identified more than 24 months after cataract extraction (median, 59 months). Seven eyes (70%) improved (mean, +3.2 lines; range, +1 to +13 lines), including six by 2 or more lines 3 months after treatment initiation. Two eyes (20%) were unchanged, and one eye (10%) was 1 line worse. All seven eyes that improved 1 line or more had some or complete angiographic resolution of fluorescein dye leakage. In these seven eyes, ketorolac was discontinued when dye leakage completely resolved or failed to continue to improve on periodic 3-month follow-up examinations. In all seven eyes, recurrence of edema was noted within 3 months after ketorolac was stopped.Chronic pseudophakic cystoid macular edema identified more than 24 months after cataract surgery can improve with topical ketorolac but probably requires persistent use.
A retrospective cohort study of the impact of biologic therapy initiation on medical resource use and costs in patients with moderate to severe psoriasis
Authors: A. Fonia, K. Jackson, C. LeReun, D.M. Grant, J.N.W.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2010)

Journal Article A retrospective cohort study of the impact of biologic therapy initiation on medical resource use and costs in patients with moderate to severe psoriasis Get access A. Fonia, A. Fonia St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and Division of Genetics and Molecular Medicine, King's College London, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar K. Jackson, K. Jackson St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and Division of Genetics and Molecular Medicine, King's College London, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. LeReun, C. LeReun Independent Biostatistician, Carrigaline, County Cork, Ireland Search for other works by this author on: Oxford Academic Google Scholar D.M. Grant, D.M. Grant IMS Health, Health Economics and Outcomes Research, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.N.W.N. Barker, J.N.W.N. Barker St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and Division of Genetics and Molecular Medicine, King's College London, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.H. Smith C.H. Smith St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and Division of Genetics and Molecular Medicine, King's College London, London, U.K. Correspondence: Catherine H. Smith. E‐mail: catherine.smith@gstt.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 4, 1 October 2010, Pages 807–816, https://doi.org/10.1111/j.1365-2133.2010.09944.x Published: 01 October 2010
Five major nuclear ribosomal repeats represent a large and variable fraction of the genomic DNA of Picea rubens and P. mariana.
Authors: M S Bobola, D E Smith, A S Klein
Journal: Molecular Biology and Evolution (1992)

The nuclear ribosomal repeats for the 18S, 5.8S, and 26S RNAs of two closely related Picea (spruce) species were characterized by restriction mapping and Southern blot hybridization. Restriction polymorphisms were identified in the IGS and ITS sequences; however, no polymorphism was species specific. As many as five different rDNA repeat units were observed in individual genomes. The repeat size for these gymnosperms ranged from a minimum of 32 kbp to greater than 40 kbp, two- to threefold larger than the typical angiosperm rDNA unit. Slot-blot hybridizations were used to determine the nuclear rDNA copy concentration. Among P. rubens individuals threefold variation was observed in the rDNA copy concentration, and among P. mariana individuals such variation was as much as sixfold. At a size greater than 32 kbp and at a concentration averaging 1.2-1.3 x 10(4) copies/pg, the rDNA constitutes approximately 4% of the total genome. Regression analysis revealed a significant relationship between copy concentration of the rDNA repeat unit in P. rubens and geographic origins. Differences in the rDNA content in Picea could contribute to the variation, in overall genome size, that has been observed within conifer species.
Traffic noise exposure and mortality due to respiratory diseases
Authors: Aurelio Tobias, Julio Diaz, Alberto Recio, Cristina Linares
Journal: European Respiratory Journal (2014)

Background and aim:  The city of Madrid has high noise levels, exceeding the WHO health protection values half days of the year. We quantify the short-term effects of noise levels on daily mortality due to respiratory diseases.   Methods:  A time-stratified case-crossover design was used. Daily mortality counts in Madrid city due to all respiratory diseases (ICD10: J00-J99), respiratory failure (ICD10: J12-18), chronic diseases (ICD-10: J40-J44), asthma (ICD-10: J45-J46) and pneumonia (ICD10: J96) from 2003 to 2005 were collected. Noise levels were collected as 24h-average daily equivalent noise (Leq24h). Over-dispersed Poisson regression models were adjusted to control for time trend and seasonality, weather variables and primary chemical air pollutants (PM2.5 and NO2).   Results : For an increase of 0.5 db(A) of Leq24h the percentage risk of mortality rise, at 1 day lag, 3.5% for all respiratory diseases and 8% for pneumonia, while for chronic diseases the risk rise 6% at 4-days lag. No effects were found for asthma. Estimates did not change after adjusting for PM2.5 and NO2.   Conclusions:  The association found between noise exposure levels and respiratory mortality suggests independent effects of noise exposure levels and air pollutants. This puts forward the need to seriously consider the high noise exposure levels reported as an important public health issue.
Testing the covarion hypothesis of molecular evolution.
Authors: M M Miyamoto, W M Fitch
Journal: Molecular Biology and Evolution (1995)

The covarion hypothesis of molecular evolution states that the fixation of mutations may alter the probability that any given position will fix the next change. Tests of this hypothesis using the divergence of real sequences are compromised because models of rate variation among sites (e.g., the gamma version of the one-parameter equation) predict sequence divergence values similar to those for the covarion process. This study therefore focuses on the extent to which the varied and unvaried codons of two well-diverged taxa are the same, because fewer are expected by the covarion hypothesis than by the gamma model. The data for these tests are the protein sequences of Cu, Zn superoxide dismutase (SOD) for mammals and plants. Simulation analyses show that the covarion hypothesis makes better predictions about the frequencies of varied and unhit positions in common between these two taxa than does the gamma version of the one-parameter model. Furthermore, the analysis of SOD tertiary structure demonstrates that mammal and plant variabilities are distributed differently on the protein. These results support the conclusions that the variable and invariable codons of mammal and plant SODs are different and that the covarion model explains the evolution of this protein better than the gamma version of the one-parameter process. Unlike other models, the covarion hypothesis accounts for rate fluctuations among positions over time, which is an important parameter of molecular evolution.
Phase II trial of imatinib mesylate (STI-571) in metastatic melanoma (MM)
Authors: O. Eton, L. Billings, K. Kim, V. Prieto, D. Davis, M. L. Frazier, A. H. Diwan, E. McGary, N. Papadopoulos, A. Y. Bedikian
Journal: Journal of Clinical Oncology (2004)

7528 Background: Imatinib mesylate (Gleevec™), an oral inhibitor of phosphorylation of certain tyrosine kinases (TK), is active in gastrointestinal stromal tumors which are chemotherapy resistant. Perhaps MM may respond to Gleevec, especially if the tumor cells or microenvironment express one of the known TK targets: KIT, PDGF receptors α or β, c-abl, or ARG. Methods: Tumor biopsies from MM patients (pts) were screened by immunohistochemistry (IHC) for TK expression in more than 25% of the cells, as a condition for enrollment in a Phase II trial testing Gleevec @ 400 mg bid. Results: All 31 pts screened met this criterion and 21 of them were treated with Gleevec (median age 58, male [13]; stage IV [19]; PS 0–1 [20]; prior Rx: none [8], Intron-A [8], one chemotherapy [5]). The one patient with strongest expression of KIT in over 75% of tumor cells tolerated treatment for one year and achieved near complete response in in-transit, inguinal/iliac, and lung metastases with marked PET scan improvement as early as 6 weeks. Quantitative dual immunofluorescence in baseline and 2nd week tumor specimens revealed a decrease in phosphoKIT relative to total KIT expression in the responder and also in 4 of 5 non-responders tested to-date. CD31/TUNEL assay showed an increase in both tumor and endothelial cell apoptosis in the responding tumor. Sequencing from this tumor's RNA revealed serine deletion at codon 715 of kit (Exon 15, Kinase II Domain), probably a result of alternate RNA splicing, with a short:long isoform ratio of 5:1. This alternate splicing has been seen in colon cancer but not in normal colon from the same patient and may be a tumor specific event. Sixteen pts (77%) had progressive disease within 6 weeks and 4 pts within 12 weeks, obviating accrual into the 2nd stage. Two pts bled in progressing metastases. Pts experienced nausea/vomiting, rash, fluid retention, fatigue (one each grade III) and only modest myelosuppression - all as reported at lower doses. Conclusions: Strong TK expression in a majority of tumor cells by IHC may predict Gleevec response in MM. More stringent assays to better select the rare patients likely to respond are being investigated, as are other ways to exploit the agent's biologic effects. No significant financial relationships to disclose.
Clinical Trials in a Dish: The Potential of Pluripotent Stem Cells to Develop Therapies for Neurodegenerative Diseases
Authors: Kelly M. Haston, Steven Finkbeiner
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Neurodegenerative diseases are a leading cause of death. No disease-modifying therapies are available, and preclinical animal model data have routinely failed to translate into success for therapeutics. Induced pluripotent stem cell (iPSC) biology holds great promise for human in vitro disease modeling because these cells can give rise to any cell in the human brain and display phenotypes specific to neurodegenerative diseases previously identified in postmortem and clinical samples. Here, we explore the potential and caveats of iPSC technology as a platform for drug development and screening, and the future potential to use large cohorts of disease-bearing iPSCs to perform clinical trials in a dish.
Ploidy Fluctuations of Mouse Plasma-Cell Neoplasm MSPC-1 During Serial Transplantation&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Kazuo Moriwaki, Hirotami T. Imai, Junkoh Yamashita, Tosihide H. Yosida
Journal: JNCI Journal of the National Cancer Institute (1971)

MSPC-1 plasma-cell neoplasm induced in BALB/c mice exhibited repeated tetraploidy during successive passages for 2 years. The cause for increased tetraploid frequency in this tumor was investigated. Neither pretreatment of host mice with γ rays nor double inoculation of diploids and tetraploids into a single host showed that the immunoselection mechanism of host animals directly affected the increase of tetraploid cells. Certain factors within the tumor cells seemed essential for facilitating tetraploidy. Whether repeated ploidy alteration was accompanied by cell population change was also studied. Analysis of marker chromosomes appearing additively during serial passages revealed that the cell population constituting one diploid phase is different from that of the next diploid phase, which is probably a variant of the former. Hypothetical processes of the repeated tetraploidy are proposed.
Tumor-Associated Antigen TA90 Immune Complex Assay Predicts Recurrence and Survival After Surgical Treatment of Stage I-III Melanoma
Authors: Mark C. Kelley, Rishab K. Gupta, Eddy C. Hsueh, Reynold Yee, Stacey Stern, Donald L. Morton
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Immune complexes (IC) containing the tumor-associated antigen TA90 can be identified in the sera of melanoma patients. We have shown that an enzyme-linked immunosorbent assay for TA90-IC can detect subclinical metastasis before surgical treatment of early-stage melanoma. We assayed the TA90-IC levels of postoperative sera from patients with melanoma and evaluated their relationship to recurrence and survival. PATIENTS AND METHODS: Multiple archival serum samples prospectively collected during postoperative surveillance of 166 patients with American Joint Committee on Cancer stage I, II, or III melanoma were analyzed for TA90-IC in a blinded fashion. Results were correlated with disease recurrence and survival determined by database and chart review. RESULTS: TA90-IC status in the early postoperative period was strongly correlated with survival. Five-year overall survival rates were 84% for TA90-IC–negative patients and 36% for TA90-IC–positive patients (P = .0001). Respective 5-year disease-free survival rates were 74% and 24% (P = .0001). The TA90-IC assay was a significant predictor of survival for both stage II and III patients. Multivariate analysis identified TA90-IC status as the strongest independent prognostic factor for both overall and disease-free survival. The TA90-IC assay was elevated in 54 (77%) of 78 patients who developed recurrent disease, becoming positive 19 ± 7 months before clinical evidence of recurrence. Overall, the assay detected recurrence with a sensitivity of 78% and specificity of 77%. Exclusion of patients receiving postoperative immunotherapy with a polyvalent melanoma cell vaccine increased sensitivity and specificity to 92% and 86%, respectively. CONCLUSION: The TA90-IC assay can accurately predict survival and detect the presence of subclinical disease after surgery for melanoma, which should be useful in selecting patients for adjuvant therapy. Because the TA90-IC assay detected recurrence on an average of 19 months sooner than did routine clinical and radiographic evaluation, it may allow more timely therapeutic interventions.
Abstract 2707: <i>In vitro</i> and <i>in vivo</i> evaluation of SNG1153, a synthetic modulator of ER-α36
Authors: Bo Zhang, Kun Meng, Xiao Shang, Zhaoyi Wang, Yanzhong Zhang, Fang Fang, Jing Wang, Zonghui Wang, Jun Wang, Yuming Guo, Shiyang Liu, Feng Chen, Hongxia Ding, Jiancun Zhang, Jun Bao
Journal: Cancer Research (2014)

Abstract Background: ER-α36, a novel truncated variant of estrogen receptor α, was recently discovered and extensively studied as a potential therapeutic target. ER-α36 was found to be overexpressed in many cancers including estrogen-positive and negative breast cancer, lung cancer, prostate cancer, endometrial cancer, liver cancer and other cancers. This suggests that ER-α36 is potentially a promising target for the development of novel anticancer agents with broader clinical applications. This study aims to evaluate the in vitro and in vivo performance of SNG1153, an orally available, synthetic modulator of ER-α36. Methods: the viabilities of ER-α36 overexpressed cancer cells were evaluated using a CCK-8 assay after exposure to SNG1153. Pharmacokinetic study was conducted in rat and SNG1153 was administered orally in escalated doses. In-vivo efficacies of SNG1153 were evaluated in Bcap-37 xenograft model, Ishikawa xenograft model and SPC-A-1 xenograft model. Results: SNG1153 showed significant inhibition at low micromolar concentrations in ER-α36 overexpressed cell lines including the one resistant to tamoxifen. SNG1153 exhibited a linear PK profile with a bioavailability of more than 55% in the rat PK study. In the in-vivo efficacy studies, 3 doses were investigated and SNG1153 showed dose-dependent inhibition. The tumor growth inhibition at high dose was 57% in the breast cancer Bcap-37 xenograft model, 65% in the endometrial cancer Ishikawa xenograft model and 52% in lung adenocarcinoma SPC-A-1 xenograft model. No signs of toxicity were observed in these models. Conclusion: SNG1153, as a synthetic ER-α36 modulator, showed promising activities in many in vitro and in vivo models. It is currently in preclinical development stage. Citation Format: Bo Zhang, Kun Meng, Xiao Shang, Zhaoyi Wang, Yanzhong Zhang, Fang Fang, Jing Wang, Zonghui Wang, Jun Wang, Yuming Guo, Shiyang Liu, Feng Chen, Hongxia Ding, Jiancun Zhang, Jun Bao. In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2707. doi:10.1158/1538-7445.AM2014-2707
Reduced lung function is an independent risk factor for the development of impaired glucose tolerance
Authors: Takashi Yamane, Akihito Yokoyama, Naoki Shiota, Hiroshi Ohnishi, Noboru Hattori, Nobuoki Kohno
Journal: European Respiratory Journal (2011)

Objectives: Whether reduced pulmonary function is a risk factor for the development of impaired glucose tolerance (IGT) has yet to be determined. The aim of the present study is to obtain more information on this point in Japanese males.

Methods: First, 975 men showing normal lung function without respiratory disease were recruited in cross-sectional research. All the subjects were divided into quartiles according to baseline%FVC,%FEV1, and FEV1% and analyzed the ratio of IGT and DM. Next, 511 men showing normal pattern in 75g OGTT were recruited in longitudinal research. The subjects were divided into%FVC,%FEV1, and FEV1% quartiles, we compared the cumulative incidence rates of IGT among the four groups, and analyzed the risk factors for the development of IGT.

Results: In the cross-sectional research, the rates of IGT and DM for each quartile at first examination were significantly associated with lower%FVC and%FEV1 quartile, but not significantly with lower FEV1% quartile. During the mean follow-up period of 28.4±6.0 months, 89 (17%) among 511 normal glucose tolerance (NGT) subjects developed IGT during this period. The cumulative incident rates of IGT for each quartile were significantly higher in lower%FVC and%FEV1 group, but not significantly with lower FEV1% quartile. In a Cox proportional hazards model, only lower%FVC quartile was an independent risk for development of IGT adjust for age, BMI, systolic BP, total cholesterol, CRP, and pack-year smoking.

Conclusions: Not reduced%FEV1 and FEV1% but reduced%FVC is an independent risk factor for the development of IGT in Japanese males.
Micro-RNA screening in neuroendocrine lung tumors: Differential expression of miR-29 family members
Authors: Fabian Mairinger, Saskia Ting, Robert Werner, Thomas Hager, Claudia Vollbrecht, Robert Walter, Daniel Christoph, Karl Worm, Kurt Werner Schmid, Jeremias Wohlschlaeger
Journal: European Respiratory Journal (2013)

miRNAs are a class of small, noncoding, highly conserved single- stranded RNAs with post-transcriptional regulatory features including regulation of cell proliferation, differentiation, survival and apoptosis. They are deregulated in various tumors and show a different expression pattern, e.g. in NSCLC. These profiles can be used as a diagnostic tool. TC, AC, SCLC and LCLC belong to the NELC group, whereas an accurate discrimination of these entities is still difficult. A new and promising method for distinguishing tumor entities may be the alteration of miRNA expression between subtypes.  Basis of our analyzed samples was a bio-pool including 201 patient samples with pulmonary tumors showing neuroendocrine features. This dataset is build out of atypical and typical carcinoids of the lung as well as LCLCs and SCLCs.  We conducted miRNA screening for 763 known miRNAs involved in different tumorgenetic processes by performing 384 well TaqMan low-density array real-time qPCR. Analysis was done with TaqMan Array Human MicroRNA Card A and TaqMan Array Human MicroRNA Card B v3.0, respectively.  In the overall collective comprised out of all four entities we identified 44 significantly different exprimised miRNAs, 11 of them highly significant. 7 miRNAs show an inverse correlation to aggressiveness of the tumor.  In addition, we identified 45 micro-RNAs which significantly have an impact on survival in our collective.  miRNAs turned out to be potent markers to distinguish between tumor entities. They demonstrate to be a helpful diagnostic tool, especially in discriminating between various entities of NELC. Additionally, some miRNAs are powerful markers to predict patient’s clinical outcome.