tbuckley/cabot-search huggingface dataset:
Abstract 2550: Translational study on circulating markers in advanced melanoma patients undergoing Dacarbazine and Bevacizumab treatment
Authors: Pier Francesco Ferrucci, Chiara Martinoli, Emilia Cocorocchio, Andrea Anichini, Sara Gandini
Journal: Cancer Research (2014)

Abstract Purpose: Chemotherapy (CT) with Dacarbazine (DTIC) in association with an anti-VEGF treatment could be an intriguing exploiting path, since metastatic melanoma (MM) in vitro models showed VEGF as a possible target, due to its transcription up-regulation by DTIC. The purpose of this study was to indentify modulated circulating factors which may be used as specific biomarkers in patients (pts) affected by MM undergoing DTIC plus Bevacizumab (B = Avastin) combination and to test its tolerability and efficacy. Patients and Methods: Between July 2006-September 2009, 40 untreated MM pts underwent CT with DTIC (800mg/mq q4w) + B (10mg/kg q2w). Clinical benefit, response duration, safety and feasibility were analyzed. Moreover, 13 pts participating to the clinical study agreed to provide blood for translational research. The blood samples for this study were drawn at the same time points as for regular follow-up tests and were evaluated for the following several soluble factors: vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-R1, VEGF-R2, angiopoietin (Ang)-2, E-cadherin, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, matrix metalloproteinase (MMP)-2 and -9, tissue inhibitor of metalloproteinase (TIMP)-1 and -2. Correlations with pts clinical outcome were performed as well. Results: 36/40 pts were evaluated at the analysis-time. Median age was 57yr (male 60yr; female 47yr) and 23 were male. Three pts (8.3%) experienced a complete remission (CR), 3 pts (8.3%) developed partial response (PR), 13 (36.1%) stable disease (SD); 17 (47.2%) progressive disease (PD). Clinical benefit (CR+PR+SD) was 52.7% and treatment was well tolerated. Time to progression (months) was 10.9, respectively 22.6 for PR pts, 8.2 for SD pts and 2 for PD pts. Median-survival in the whole group was 16.5 months (PR pts 22.6; SD pts 17; PD pts 4.23). DTIC/B treatment modulates not only VEGF-A, but also VEGF-C, Ang-2 VEGF-R1 and VEGF-R2. Among soluble adhesion molecules, we observed an increase of VCAM-1 in non responder pts. Conclusions: Long-lasting responses obtained in both SD and CR/PR pts and mild side effects make DTIC/B a promising combination in advanced melanoma. The companion translational study partially clarified these clinical results by molecularly characterizing and profiling responders vs non-responders pts. Citation Format: Pier Francesco Ferrucci, Chiara Martinoli, Emilia Cocorocchio, Andrea Anichini, Sara Gandini. Translational study on circulating markers in advanced melanoma patients undergoing Dacarbazine and Bevacizumab treatment. [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 2550. doi:10.1158/1538-7445.AM2014-2550
Oxidant stress mechanism of homocysteine potentiating Con A-induced proliferation in murine splenic T lymphocytes
Authors: Q Zhang
Journal: Cardiovascular Research (2002)

Objective: An elevated plasma homocysteine (Hcy) level is considered an independent risk factor for atherosclerosis. However, the mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood. The effect of Hcy on T lymphocyte proliferation and its mechanisms were examined in normal and hyperhomocysteinemia ApoE-knockout mice. Methods: The mouse splenic T-cells were treated with Hcy, related compounds and/or antioxidants in the presence or absence of Concanavalin A (Con A). DNA synthesis, cell apoptosis, interleukin-2 level and production of reactive oxygen species (ROS) were measured. Results: Hcy (0.3–3.0 mM) and related compounds with thiol (–SH), such as cysteine and glutathione significantly potentiated Con A-induced proliferation and partially inhibited apoptosis in T lymphocytes, but it had no direct effect on resting T lymphocyte. ApoE-knockout mice with hyperhomocysteinemia (the level of plasma Hcy was 20.3±2.9 vs. 2.6±0.6 μM in control group, P<0.05) had a significant promotion of T-cell proliferation in response to Con A. Hcy (0.3–3.0 mM) also increased the intracellular ROS. Radical scavengers reduced Hcy effect. Conclusions: These data indicate that ROS generated by thiol (–SH) of Hcy auto-oxidation are involved in Hcy effect on Con A-induced T lymphocyte proliferation. These findings suggest a novel mechanism may be involved in chronic inflammatory progression of atherosclerosis with hyperhomocysteinemia.
Topically applied low-dose calcitriol has no calciotropic effect in patients with stable plaque psoriasis
Authors: A.J.A.M. Sips, J.C. Netelenbos, R. Barto, C.A. Verburgh, C. Nieboer, W.J.F. van der Vijgh
Journal: Journal of the American Academy of Dermatology (1994)
Elderly patients in acute medical wards: factors predicting length of stay in hospital.
Authors: P A Maguire, I C Taylor, R W Stout
Journal: BMJ (1986)

A prospective study of 419 patients aged 70 and over admitted to acute medical wards was carried out by medical staff from a geriatric unit. Data, including presenting problem, housing, social support, mental state, continence, and degree of independence before and after admission, were recorded. Of the 419 patients, 143 remained in hospital after 14 days and 65 after 28 days. The major factors associated with prolonged stay in hospital included advanced age, stroke, confusion and falls as reasons for admission to hospital, incontinence, and loss of independence for everyday activities. Social circumstances did not predict length of stay. Although these factors are interrelated, the most important influence on length of stay was the medical reason for admission. Early contact with the geriatric medical unit in these patients may speed up the recovery or result in more appropriate placement.
University medical school accepts tobacco company funding
Authors: Lynn Eaton
Journal: BMJ (2007)

Lester Crawford, former commissioner of the US Food and Drug Administration, was last week fined $89 377 (£45 800; €67 000), sentenced to three years of supervised probation, and required to do 50 hours of community service by Judge Deborah Robinson of the US District Court for the District of Columbia.Last October Dr Crawford (below) pleaded (below) pleaded pleaded guilty to two charges: failing to report that he and his wife owned shares in companies regulated by the agency and filing false
RNA Interference-Mediated Knockdown of DNA Methyltransferase 1 Leads to Promoter Demethylation and Gene Re-Expression in Human Lung and Breast Cancer Cells
Authors: Makoto Suzuki, Noriaki Sunaga, David S. Shames, Shinichi Toyooka, Adi F. Gazdar, John D. Minna
Journal: Cancer Research (2004)

Abstract DNA methyltransferase 1 (DNMT1) is required to maintain DNA methylation patterns in mammalian cells, and is thought to be the predominant maintenance methyltransferase gene. Recent studies indicate that inhibiting DNMT1 protein expression may be a useful approach for understanding the role of DNA methylation in tumorigenesis. To this end, we used RNA interference to specifically down-regulate DNMT1 protein expression in NCI-H1299 lung cancer and HCC1954 breast cancer cells. RNA interference-mediated knockdown of DNMT1 protein expression resulted in &amp;gt;80% reduction of promoter methylation in RASSF1A, p16ink4A, and CDH1 in NCI-H1299; and RASSF1A, p16ink4A, and HPP1 in HCC1954; and re-expression of p16ink4A, CDH1, RASSF1A, and SEMA3B in NCI-H1299; and p16ink4A, RASSF1A, and HPP1 in HCC1954. By contrast, promoter methylation and lack of gene expression was maintained when these cell lines were treated with control small interfering RNAs. The small interfering RNA treatment was stopped and 17 days later, all of the sequences showed promoter methylation and gene expression was again dramatically down-regulated, indicating the tumor cells still were programmed for these epigenetic changes. We saw no effects on soft agar colony formation of H1299 cells 14 days after DNMT1 knockdown indicating that either these genes are not functioning as tumor suppressors under these conditions, or that more prolonged knockdown or other factors are also required to inhibit the malignant phenotype. These results provide direct evidence that loss of DNMT1 expression abrogates tumor-associated promoter methylation and the resultant silencing of multiple genes implicated in the pathogenesis of human lung and breast cancer.
The First Year of Life: The Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke
Authors: Paul M. Taylor
Journal: JAMA (1980)

The first step in promoting an optimal pregnancy outcome is the identification of pregnant women and newborn infants susceptible to perinatal complications that threaten the infant's life and quality of survival. The National Institutes of Health-sponsored Collaborative Perinatal Project was planned to identify such susceptibles. This massive epidemiologic investigation prospectively followed up 37,431 singletons born between 1959 and 1966 in 12 collaborating institutions. Data on the nearly 32,000 infants followed up through the first year are presented in<i>The First Year of Life</i>. This volume was preceded in 1974 by a monograph,<i>The Women and Their Pregnancies</i>, which gave voluminous data on associations between demographic variables, perinatal complications, and perinatal mortality; salient findings are abstracted in a chapter in the present work. Monographs are planned that will present further information, including follow-up results at seven to eight years. This longitudinal study of pregnancy outcome remains unique in size, scope, and
Death After Withdrawal of Meprobamate
Authors: Leonard A. Swanson
Journal: JAMA (1963)

THE PURPOSE of this paper is to report a patient who became addicted to high doses of meprobamate and, upon withdrawal of the medication, developed anxiety, hyperhidrosis, tremors, hyperpyrexia, and grand mal seizures, and died. A review of the literature and correspondence with two manufacturers have failed to reveal any reported deaths after withdrawal in humans addicted to meprobamate.  Report of Cases  Case 1.—  A 38-year-old salesman was hospitalized on Sept 28, 1961, with complaints of nervousness, sweating, and mild tremors of the upper extremities having been present for several hours. The patient admitted at that time to having taken excessive amounts of meprobamate, but was vague as to the amounts ingested and the duration of his addiction. Later it was learned that the patient had been first placed on a regimen of 400 mg of meprobamate four times a day in 1956 for nervousness. Just when the patient increased
Neurodevelopmental Outcomes in the Early CPAP and Pulse Oximetry Trial
Authors: Yvonne E. Vaucher, Myriam Peralta-Carcelen, Neil N. Finer, Waldemar A. Carlo, Marie G. Gantz, Michele C. Walsh, Abbot R. Laptook, Bradley A. Yoder, Roger G. Faix, Abhik Das, Kurt Schibler, Wade Rich, Nancy S. Newman, Betty R. Vohr, Kimberly Yolton, Roy J. Heyne, Deanne E. Wilson-Costello, Patricia W. Evans, Ricki F. Goldstein, Michael J. Acarregui, Ira Adams-Chapman, Athina Pappas, Susan R. Hintz, Brenda Poindexter, Anna M. Dusick, Elisabeth C. McGowan, Richard A. Ehrenkranz, Anna Bodnar, Charles R. Bauer, Janell Fuller, T. Michael O'Shea, Gary J. Myers, Rosemary D. Higgins
Journal: New England Journal of Medicine (2012)

Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses.
BI-18 * CELLULAR MICROPARTICLES AS BLOOD-BORNE ENDOTHELIAL BIOMARKERS IN PATIENTS WITH MALIGNANT GLIOMAS
Authors: G. Lesser, M. Harmon, I. Khan, C. Whitlow, W. Brown
Journal: Neuro-Oncology (2014)

BACKGROUND: Identification of reliable biomarkers of tumor vascularity and/or angiogenesis in the peripheral circulation would be useful for screening, diagnosis, prognosis, assessment of treatment efficacy and surveillance in patients with malignant gliomas (MG). Cellular microparticles (MP) are small blood-borne fragments shed from the cell surface after inflammatory activation, injury or apoptosis. MP from vascular endothelial cells in highly angiogenic brain tumors like MG express a specific isoform of aminopeptidase N, CD13, not found on normal endothelium. MP may also contain CD 142 or tissue factor, an initiator of the coagulation cascade, which may reflect thromboembolic risk in patients with MG. METHODS: After obtaining informed consent, serial samples of peripheral blood were obtained from 26 patients with MG prior to the initiation of therapy for newly diagnosed or recurrent disease and at each subsequent clinic visit. Blood was centrifuged and MP were extracted from the platelet-free fraction. MP were labelled with fluorescently tagged antibodies to CD13, CD142 and CD144 (a marker of all endothelial cells) and expression was quantified using established flow cytometric techniques. RESULTS: To date, 14 samples from 7 patients with MG have been analyzed. Using calibration beads, we confirmed that our MP ranged from 0.2 to 1.5 microns in size. Fluorescent antibody expression (% of total MP analyzed in each patient) was as follows: CD13 = 18.2% (range 15 - 25); CD 142 = 9.3% (range 6 - 12); CD 144 = 16.1% (range 7 - 27). CONCLUSIONS: Endothelial markers on MPs are routinely detectable at significant levels in the peripheral blood of patients with MG. When correlated with clinical, laboratory and imaging data, MP have the potential to be useful circulating biomarkers of the vascular compartment in MG.
434. Long-Term Effects on Retinal Function and Structure Using AAV-Mediated Gene Therapy in Blind RPE65 Null Mutation Dogs
Authors: Kristina Narfstrom, Greg Tullis, Ragnheidur Bragadottir, Mathias Seeliger, Elizabeth P. Rakoczy, Martin L. Katz
Journal: Molecular Therapy (2005)

We have previously reported on successful gene transfer using recombinant adeno-associated virus-mediated (rAAV) subretinal gene delivery for the dog model of human Leber's Congenital Amaurosis. Congenitally blind dogs were treated at 4-30 months of age with similar doses of the rAAV. RPE65 construct into the right eye.
Another Case of Poisoning by Hom opathic Camphor
Authors: G. Johnson
Journal: BMJ (1875)

The recent launch of numerous currency-based ETFs, and the expected launch of more, has thrown the spotlight on the potential for currencies and currency-based ETFs to enhance portfolio returns. We believe the prevalence of underfunded pension plans increases the chances of pension crises over the next few decades. This may be particularly relevant for pension funds, many of which may be underfunded and in need of better matching their assets and liabilities, possibly by using asset classes other than equities and bonds. Numerous approaches have been proposed to address the issue, including better matching of assets to liabilities by using fixed-income products, the use of derivatives and of alternative asset classes. Foreign exchange has often been viewed as an alternative asset class, rather than as a comparable asset class to bonds and equities, due in part to the absence of a widely followed benchmark and ignorance of the return characteristics of FX. We feel that foreign exchange should be viewed as an asset class similar to bonds and equities. It has exhibited long-term systematic returns or “beta” which are comparable, if not better, than both bonds and equities since 1980. It also has greater liquidity than both. Our work suggests that for global portfolios to benefit the most from foreign exchange, allocations to FX should be in the order of 20%-30%. In that way, the quality of returns can be significantly enhanced, not least by considerably reducing the duration and magnitude of phases of returns underperformance.
Serum IL-31 levels are increased in a subset of patients with mastocytosis and correlate with disease severity in adult patients
Authors: Karin Hartmann, Nicola Wagner, Anja Rabenhorst, Liselotte Pflanz, Silke Leja, Anja Förster, Manuela Gehring, Alexander Kapp, Ulrike Raap
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract 5212: Regulation of androgen receptor expression by andro-miRs in prostate cancer
Authors: Jey Sabith Ebron, Kavleen Sikand, Jagjit Singh, Girish C. Shukla
Journal: Cancer Research (2014)

Abstract Androgen receptor (AR) is a member of the steroid receptor family which plays a significant role in the regulation of both prostate cell proliferation and growth suppression. The targeting of androgen- and AR- signaling axis remains the primary therapeutic option for prostate cancer (PCa) treatment. AR mRNA has a long 3′UTR of 6.8 kb length and is predicted to be a target of many miRNAs. The existence of long 3′UTR proposes a complex mechanism of regulation of AR gene expression through miRNAs and other factors including RNA binding proteins and polyadenylation signals. Differential expression of various miRNAs has been reported to be associated with the progression of the disease to harmone-independence and castration-resistant prostact cancer (CRPC). However, the direct regulation of AR transcriptional activity through miRNAs is not clearly understood. Our lab has discovered that AR is a target of andro-miRs (miR-488*, miR-644, miR-149, miR-512-5p). These andro-miRs bind to target sequences in the 3′UTR of AR and downregulates luciferase expression in the target-validation validation experiments as well as endogeneous AR expression. Our ongoing study of andro-miRs also indicates that, in addition to downregulation of AR gene expression by the action of andro-miRs alone and synergistically, these miRNAs can regulate AR signaling leading to androgen-independence and resistance. This post transcriptional regulation of AR gene expression through andro-miRs makes them an interesting candidate for miR-based adjunctive treatment in CRPC treatment. Note: This abstract was not presented at the meeting. Citation Format: Jey Sabith Ebron, Kavleen Sikand, Jagjit Singh, Girish C. Shukla. Regulation of androgen receptor expression by andro-miRs in prostate cancer. [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 5212. doi:10.1158/1538-7445.AM2014-5212
Polymorphisms of xenobiotic-metabolizing enzymes and susceptibility to cancer.
Authors: A Hirvonen
Journal: Environmental Health Perspectives (1999)

The variation in individual responses to exogenous agents is exceptionally wide. It is because of this large diversity of responsiveness that risk factors to environmentally induced diseases have been difficult to pinpoint, particularly at low exposure levels. Opportunities now exist for studies of host factors in cancer or other diseases in which an environmental component can be presumed. Many of the studies have shown an elevated disease proneness for individuals carrying the potential at-risk alleles of metabolic genes, but a number of controversial results have also been reported. This article is an overview of the data published to date on metabolic genotypes related to individual susceptibility to cancer.
Negotiators hit the road to explain the proposed GP contract
Authors: A. Gulland
Journal: BMJ (2003)

A series of roadshows around the United Kingdom has begun this week to explain to GPs how the proposed GP contract will work. It will be followed by a ballot, which is due to be concluded by 11 April.

Two weeks ago GP leaders unveiled the headline figures, which include a potential 50% pay hike for family doctors ( BMJ 2003;326:465). The 99 page document sent out subsequently gives fuller details. If accepted, the contract will run from April this year.

The contract puts the flesh on the bones of the quality indicators that GPs will have to achieve if they want to win extra money. There are 147 …
HLA-DRB1 and DQB1 genes in anticentromere antibody positive patients with SSc and primary biliary cirrhosis
Authors: S AKIMOTO
Journal: Annals of the Rheumatic Diseases (2001)

Periarticular bone mineral density at the knee jointRecently, dual energy x ray absorptiometry (DXA) was presented by Murphy et al as a new method for assessing periarticular bone mineral density (BMD) at the knee joint. 1 Precision errors for BMD measured at the patella, femur, and tibia were reported for 14 subjects.The paper highlights the emerging importance of measurement of radiological data and attention to regional density characteristics in bone and joint diseases.Subchondral bone mineral density of the proximal tibia has previously been assessed by dual photon absorptiometry (DPA)-the precursor of DXA.Relations between subchondral BMD of the proximal tibia and age, height, weight, and BMD of the lumbar spine and femoral neck were examined by Bohr and Schaadt. 2 Petersen et al presented subchondral BMD values for a large number of healthy subjects and for patients with various orthopaedic conditions. 3Bohr and Lund and Petersen et al examined changes in BMD at the proximal tibia after knee arthroplasty. 4 5Petersen et al examined subchondral BMD after meniscectomy, 6 and Madsen et al reported data for subchondral BMD measured in several subregions of the proximal tibia in healthy subjects and in subjects with osteoarthritis of the knee. 7Moreover, Petersen et al studied relations between bone strength and BMD assessed by DPA and DXA in the proximal tibia. 8Other related studies could be mentioned.Unfortunately, none of these studies was referred to by Murphy et al.