tbuckley/cabot-search huggingface dataset:
In vitro studies on allotype suppression. III. compounds of antiallyotype serum active in release from allotype suppression.
Authors: L T Alder, F L Adler
Journal: The Journal of Experimental Medicine (1975)

Spleen cells of b4b6 rabbits, shown to be deficient in their ability to produce b4Ig due to prenatal exposure to anti-b4, formed anti-T2 antibodies marked with the b4 determinant in response to solubilized T2 phage (S-T2) only when cultured in the presence of antibodies specific for the nonsuppressed type (b6), thus confirming and extending the previously reported observation of release from b4 suppression in cultured cells of b4-suppressed b4b5 rabbits treated with anti-b5 serum. Only antiallotype sera made in b4 rabbits were active in reversing b4 suppression. Anti-b5 or anti-b6 sera from rabbits of allotypes b6 or b5, respectively, when used in concentrations which completely or partially inhibited the formation of anti-T2 antibodies marked with the corresponding nonsuppressed allotype of the spleen donor, proved to be almost completely ineffective in causing release of suppression. Exceptions were noted when spleen cells of rabbits advanced in spontaneous escape from suppression were tested with such sera. The addition of normal b4 serum to non-b4 antiallotypic sera rendered them as effective in releasing b4 suppression in vitro as were antisera from b4 rabbits. Furthermore, the capacity of a b4 antiallotype serum to cause reversal of b4 suppression could be potentiated by the addition of normal b4 serum, indicating that nonantibody b4 Ig is a limiting factor in such a serum. Thus, the release from allotype suppression observed in cultures of spleen cells from b4-suppressed heterozygous rabbits is dependent upon the presence of two components: antibodies directed against the nonsuppressed allotype of the donor and normal b4Ig. These findings are interpreted in terms of alternate hypotheses involving (a) a mechanism of b4 derepression and (b) inactivation of a suppressor cell with recognition for a b4-labeled target.
Abstract 4192: Identification of novel genetic drivers of vulvar carcinoma in a Sleeping Beauty model of spontaneous cancer
Authors: Amy Guimaraes-Young, Traci Neff, David K. Meyerholz, Adam J. Dupuy, Michael J. Goodheart
Journal: Cancer Research (2015)

Abstract Introduction: The purpose of this study was to develop a Sleeping Beauty (SB)-induced mouse model of metastatic vulvar carcinoma with which we could identify novel tumor-driving mutations. Experimental Procedures: An existing transgenic mouse model known to induce development of benign vaginal papillomas, (PrCre/+;KrasG12D), was bred to mice containing the components of the SB system to render (PrCre/+;KrasG12D;SB) mice. The SB system consists of a transposable element (transposon) and an activating enzyme (transposase) that induces excision of the transposon from one site to another in the host cell genome. Insertional mutations that enhance cell survival and proliferation are selected for, resulting in the development of cancer. We utilize the SB system to identify candidate driver mutations since the transposon is not only the mutagen but also serves as a sequence tag for localization of mutations. Mice were aged and monitored for phenotypic signs of disease. Upon necropsy, gynecologic and other grossly abnormal organs were harvested. Genomic DNA was extracted from each sample, prepared for genetic analysis, and sequenced using the Illumina platform. Candidate genes were identified using an unbiased Monte-Carlo approach in conjunction with a gene-centric Chi-Squared analysis. Paraffin-embedded human tumor samples were obtained from the University of Iowa Hospitals and Clinics for immunohistochemical labeling of protein expression for selected genes. Results: Vulvar carcinoma developed in 29 of 29 PrCre/+;KrasG12D;SB female mice with metastases by seven months of age confirmed in 13 animals. Organs within the abdominal cavity including the uterus and ovaries contained metastatic lesions in some mice. In one mouse, a distant metastasis within the subcutaneous tissue of the thoracic back was observed. Illumina sequencing of primary lesions from all mice revealed 77 candidate tumor drivers. Conclusions: To our knowledge, the PrCre/+;KrasG12D;SB mouse is the first reported metastatic model of vulvar carcinoma. Protein expression of candidate genes identified by our SB screen are being assessed in human tissue samples. Patient clinical data will be incorporated into analyses to determine whether candidate genes are correlated to patient outcomes. This work will permit insights into the pathophysiology and future treatment of vulvar cancer. Note: This abstract was not presented at the meeting. Citation Format: Amy Guimaraes-Young, Traci Neff, David K. Meyerholz, Adam J. Dupuy, Michael J. Goodheart. Identification of novel genetic drivers of vulvar carcinoma in a Sleeping Beauty model of spontaneous cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4192. doi:10.1158/1538-7445.AM2015-4192
Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RR MM).
Authors: Jacob Laubach, Noopur S. Raje, Philippe Armand, Robert L. Schlossman, Jacalyn Rosenblatt, Jeffrey Matous, Jacquelyn Ann Hedlund, Michael Gary Martin, Craig H. Reynolds, Kenneth H. Shain, Ira Zackon, Laura Stampleman, Erica Boswell, Stacey Chuma, Rebecca Liguori, Damian Handisides, Stew Kroll, Kenneth Carl Anderson, Paul G. Richardson, Irene M. Ghobrial
Journal: Journal of Clinical Oncology (2014)

8534 Background: While alkylators, IMiDs and proteasome inhibitors are current standard treatment for pts with MM, the presence of hypoxia in the diseased bone marrow (Colla, Leukemia 2010) presents a new therapeutic target for MM. TH-302 is a novel 2-nitroimidazole prodrug of the DNA alkylator bromo-isophosphoramide mustard that is selectively activated under hypoxia. Synergistic induction of apoptosis in MM cells by TH-302 and bortezomib was shown in MM models in vivo and in vitro (Hu et al, Mol Cancer Ther 2013). An ongoing Phase 1/2 study investigates TH-302 with dex in RR MM. In the dose-escalation stage of the study, the maximum tolerated dose (MTD) of biweekly TH-302 was established at 340 mg/m2 and preliminary activity was reported based on the modified IMWG guidelines (Ghobrial et al., ASH 2013). The 340 mg/m² plus dex expansion arm is ongoing. Methods: The Phase 1/2 open-label multicenter study investigates IV TH-302 (240-480 mg/m²) plus PO dex (40 mg) on Days 1, 4, 8 and 11 of a 21-day cycle. At the MTD, a Simon two-stage minimax design was implemented to pursue a regimen with ≥25% response rate or discontinue if ≤5% (90% power, 10% alpha). Results: 16 pts (11 male, 5 female) were enrolled through completion of the initial stage of the Simon design, including 9 at the MTD. Median prior therapies was 6 (3 – 11) and median age 60 years (53 – 86). All had previously received both bortezomib and lenalidomide/thalidomide containing regimens and an alkylating agent. The most common ≥Gr 3 AEs were thrombocytopenia (44%) and leukopenia (38%). Dose limiting Gr 3 stomatitis was only reported in the 480 mg/m2 cohort. 7 pts had SAEs, 6 of which were related to TH-302, including 3 pts with pneumonia. The pre-specified target for response for the initial 9-pt Simon stage at the MTD was achieved with 1 PR, 2 MRs, 4 SDs, 1 PD and 1 NA. To date, 15 of 24 pts have been enrolled to evaluate safety and efficacy at the MTD. Conclusions: TH-302 can be administered at 340 mg/m2 biweekly with dex. Preliminary clinical activity has been noted in pts with heavily pre-treated RR MM. Data from pts in the Simon two-stage treated at the MTD will be updated and presented at the meeting. Clinical trial information: NCT01522872.
A Phase I Study of the Potent Hsp90 Inhibitor STA-9090 Administered Twice Weekly In Subjects with Hematologic Malignancies
Authors: Swaminathan Padmanabhan, Kevin R Kelly, Mark Heaney, Stephanie Hodges, Suzanne Chanel, Mark Frattini, Ronan Swords, Robert Bradley, Florentina Teofilovici, Daniel J DeAngelo
Journal: Blood (2010)
Nutrition and health in women, children, and adolescent girls
Authors: Francesco Branca, Ellen Piwoz, Werner Schultink, Lucy Martinez Sullivan
Journal: BMJ (2015)

Urgent action is needed to tackle malnutrition in all forms and to help nutrition unlock the potential of investment in the health of women, children, and adolescents, say <b>Francesco Branca</b> and <b>colleagues</b>
Fibrin-targeting peptide CREKA-conjugated multi-walled carbon nanotubes for self-amplified photothermal therapy of tumor
Authors: Bo Zhang, Huafang Wang, Shun Shen, Xiaojian She, Wei Shi, Jun Chen, Qizhi Zhang, Yu Hu, Zhiqing Pang, Xinguo Jiang
Journal: Biomaterials (2015)
Molecular relationships between alcohol dehydrogenase null-activity alleles from natural populations of Drosophila melanogaster.
Authors: J B Gibson, A V Wilks, A Agrotis
Journal: Molecular Biology and Evolution (1992)

Alcohol dehydrogenase null-activity alleles extracted from a number of natural populations of Drosophila melanogaster in Tasmania were shown to be molecularly similar by probing, with an oligonucleotide specific to an inserted region in intron 2 of the gene, genomic DNA amplified by the polymerase chain reaction. This insertion had previously been shown to be the cause of the loss of activity in one of the null alleles whose DNA sequence was known. Three Adh null alleles from mainland populations did not contain the insertion. Two of these null alleles, extracted from the Coffs Harbour population in different years, were cloned, and their DNA sequences showed that they were identical and that both had a 438-bp deletion which removed most of exon 2. The third null allele, identified in a sample of flies from Chateau Tahbilk, was shown by 4-bp restriction-endonuclease mapping to contain a 320-bp insertion in intron 1, although this may not be the cause of the loss of activity. The data show that at least three different Adh null alleles have been found in Australian populations and that at least two have been maintained as heterozygotes over a period of years.
Hepatitis C drug maker puts profit ahead of patients, US Senate report charges
Authors: Michael McCarthy
Journal: BMJ (2015)

Gilead Sciences set the price of its hepatitis C treatment sofosbuvir (marketed as Sovaldi) at $1000 a pill or $84 000 (£56 000; €79 000) for a single course of treatment to maximize revenue and to make it possible for it to charge even more for its follow-on combination drug, a US Senate finance committee has concluded. It did this even though officials at the California based company knew that lowering the price would allow more patients to be treated, the committee’s investigation found.

The committee’s report said, “Over the eight months Gilead spent determining the price of Sovaldi, the company repeatedly made clear its primary focus was outmaneuvering potential competitors to ensure its drugs had the greatest share of the market, for the highest price, for the longest period of time.”1

In a press conference on 1 December announcing the investigation’s findings, Senator Ron Wyden, an Oregon Democrat and the committee’s ranking member, …
Endotoxin Exposure: Predictors and Prevalence of Associated Asthma Outcomes in the United States
Authors: Peter S. Thorne, Angelico Mendy, Nervana Metwali, Päivi Salo, Caroll Co, Renee Jaramillo, Kathryn M. Rose, Darryl C. Zeldin
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Inhaled endotoxin induces airway inflammation and is an established risk factor for asthma. The 2005-2006 National Health and Nutrition Examination Survey included measures of endotoxin and allergens in homes as well as specific IgE to inhalant allergens.
The fifth component of complement (C5) in the mouse. Analysis of the molecular basis for deficiency.
Authors: W H Wheat, R Wetsel, A Falus, B F Tack, R C Strunk
Journal: The Journal of Experimental Medicine (1987)

C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 protein, C5 mRNA, and the C5 gene. C5-deficient protein was present as decreased amounts of an unprocessed, single-chain precursor. C5-deficient mRNA was decreased in amount and present in two forms, the smaller of which was the same as the single form in normal cells. Nuclei from both normal and deficient cells contained the larger form of C5 mRNA, and C5-deficient DNA demonstrated differences from the normal pattern on Southern analysis for two restriction enzymes. These data suggest that the primary transcript of the C5-deficient gene is abnormal, retarding the processing of the C5 mRNA, and that the C5-deficient mRNA codes for an abnormal protein.
Association of Fitness in Young Adulthood With Survival and Cardiovascular Risk
Authors: Ravi V. Shah, Venkatesh L. Murthy, Laura A. Colangelo, Jared Reis, Bharath Ambale Venkatesh, Ravi Sharma, Siddique A. Abbasi, David C. Goff, J. Jeffrey Carr, Jamal S. Rana, James G. Terry, Claude Bouchard, Mark A. Sarzynski, Aaron Eisman, Tomas Neilan, Saumya Das, Michael Jerosch-Herold, Cora E. Lewis, Mercedes Carnethon, Gregory D. Lewis, Joao A. C. Lima
Journal: JAMA Internal Medicine (2015)

Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear.
Spontaneous Intracerebral Hemorrhage
Journal: New England Journal of Medicine (2023)

ONTRAUMATIC intracerebral hemorrhage is bleeding into the parenchyma of the brain that may extend into the ventricles and, in rare cases, the subarachnoid space. Each year, approximately 37,000 to 52,400 people in the United States have an intracerebral hemorrhage. 1,2 This rate is expected to double during the next 50 years as a result of the increasing age of the population and changes in racial demographics. Intracerebral hemorrhage accounts for 10 to 15 percent of all cases of stroke and is associated with the highest mortality rate, with only 38 percent of affected patients surviving the first year. 3 Depending on the underlying cause of bleeding, intracerebral hemorrhage is classified as either primary or secondary. Primary intracerebral hemorrhage, accounting for 78 to 88 percent of cases, originates from the spontaneous rupture of small vessels damaged by chronic hypertension or amyloid angiopathy. 4 Secondary intracerebral hemorrhage occurs in a minority of patients in association with vascular abnormalities (such as arteriovenous malformations and aneurysms), tumors, or impaired coagulation. Although hypertensive intracerebral hemorrhage remains the most common form of intracerebral hemorrhage, underlying vascular abnormalities should always be considered in appropriate circumstances because of the high risk of recurrent hemorrhage and available treatment options. 5-11 The causes of intracerebral hemorrhage are shown in Table 1. We will discuss primary, or spontaneous, intracerebral hemorrhage in this review. N
Enteroaggregative, Shiga toxin-producing Escherichia coli O104:H4 outbreak: new microbiological findings boost coordinated investigations by European public health laboratories
Authors: M J Struelens, D Palm, J Takkinen
Journal: Eurosurveillance (2011)

Preview this article: Enteroaggregative, Shiga toxin-producing Escherichia coli O104:H4 outbreak: new microbiological findings boost coordinated investigations by European public health laboratories, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/16/24/art19890-en-1.gif
The benefits and side effects of ramped hypertonic sodium dialysis.
Authors: A Levin, M B Goldstein
Journal: Journal of the American Society of Nephrology (1996)

The effectiveness of ramped hypertonic sodium dialysis (RHSD) is controversial because of the prevalence of side effects (weight gain and hypertension). Standard dialysis (SD) was therefore compared with RHSD in a double-blind controlled crossover trial. Eleven patients who suffered from symptoms attributable to water shifts from extracellular fluid to intracellular fluid (headaches or hangover) or extracellular-fluid volume contraction (cramps or lightheadedness) and five asymptomatic patients were enrolled in the study. RHSD was individually tailored to each patient (to minimize thirst) during a 2-wk run-in period. Patients then received RHSD and SD for a period of 3 wk in randomized sequence. Outcome measures were both objective and subjective ratings on questionnaires. Significant differences were found between the two treatments, with RHSD improving specific problems (70% of lightheadedness/cramps, 100% of headaches/hangover) versus SD. Weight gain and hypertension were not different between the two treatments despite increased thirst sensation reported by 14/16.94% of patients preferred RHSD. Long-term studies in 20 different patients demonstrated the lack of increase in blood pressure or weight gain after 3 and 6 months of therapy.
Impact of Treatment with Eribulin (Eri) or Capecitabine (Cap) for Metastatic Breast Cancer (Mbc) on Eq–5D Utility Derived from Eortc Qlq–C30
Authors: S. Hudgens, A. Briggs, G. Velikova, A. Forsythe, S. McCutcheon, P. Kind
Journal: Annals of Oncology (2014)
Patient Safety Strategies Targeted at Diagnostic Errors
Authors: Kathryn M. McDonald, Brian Matesic, Despina G. Contopoulos-Ioannidis, Julia Lonhart, Eric Schmidt, Noelle Pineda
Journal: Annals of Internal Medicine (2013)

Missed, delayed, or incorrect diagnosis can lead to inappropriate patient care, poor patient outcomes, and increased cost. This systematic review analyzed evaluations of interventions to prevent di...
Hyaluronan induces monocyte chemoattractant protein-1 expression in renal tubular epithelial cells.
Authors: B Beck-Schimmer, B Oertli, T Pasch, R P Wüthrich
Journal: Journal of the American Society of Nephrology (1998)

Hyaluronan (HA) is a nonsulfated glycosaminoglycan that accumulates in the renal interstitium in immune-mediated kidney diseases. The functional significance of such HA deposition in the kidney has not been elucidated. Several studies have suggested that HA may exhibit proinflammatory effects. Since chemokines such as monocyte chemoattractant protein-1 (MCP-1) play an important role in the recruitment of leukocytes in renal injury, this study tested whether HA and its fragments could promote MCP-1 production by renal parenchymal cells. Mouse cortical tubular cells were stimulated with fragmented HA or with high molecular weight HA (Healon) in vitro and were examined for MCP-1 expression. Fragmented HA, but not Healon, increased MCP-1 mRNA within 30 min with a peak after 2 h. In addition, a 10-fold increase of MCP-1 protein in the supernatant was found after a 6-h stimulation with fragmented HA. The enhanced MCP-1 mRNA and protein expression in response to HA was dose-dependent between 1 and 100 microg/ml. Upregulation of MCP-1 protein production could be blocked by preincubation with actinomycin D or cycloheximide, suggesting that MCP-1 mRNA and protein expression in response to HA are based on de novo synthesis. The HA-stimulated MCP-1 production was also inhibited with anti-CD44 antibodies, suggesting that MCP-1 is upregulated at least in part by signaling through CD44. In summary, fragmented HA markedly stimulates renal tubular MCP-1 production by mechanisms that involve binding to the HA receptor CD44. It is hypothesized that the accumulation of HA in immune renal injury could participate in the recruitment and activation of inflammatory cells in vivo through production of MCP-1.
New contract negotiations must be meaningful to avoid future strikes, junior doctors say
Authors: Abi Rimmer
Journal: BMJ (2015)

Restarted negotiations on changes to the junior doctors’ contract in England must be meaningful for future industrial action to be avoided, junior doctors’ representatives have said.

Junior doctors across England were set to take part in industrial action short of a strike on Tuesday 1 December. But on Monday 30 November the BMA suspended strike action after talks with the government, facilitated by Acas (Advisory, Conciliation and Arbitration Service).1

The BMA, NHS Employers, and the Department of Health agreed to restart negotiations after the government said it would temporarily suspend its …
Relationship of Lipoproteins to Cardiovascular Events
Authors: John R. Guyton, April E. Slee, Todd Anderson, Jerome L. Fleg, Ronald B. Goldberg, Moti L. Kashyap, Santica M. Marcovina, Stephen D. Nash, Kevin D. O'Brien, William S. Weintraub, Ping Xu, Xue-Qiao Zhao, William E. Boden
Journal: Journal of the American College of Cardiology (2013)
Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization
Authors: Jan Fiedler, Kaja Breckwoldt, Christian W. Remmele, Dorothee Hartmann, Marcus Dittrich, Angelika Pfanne, Annette Just, Ke Xiao, Meik Kunz, Tobias Müller, Arne Hansen, Robert Geffers, Thomas Dandekar, Thomas Eschenhagen, Thomas Thum
Journal: Journal of the American College of Cardiology (2015)

Long noncoding ribonucleic acids (lncRNAs) are a subclass of regulatory noncoding ribonucleic acids for which expression and function in human endothelial cells and angiogenic processes is not well studied.The authors discovered hypoxia-sensitive human lncRNAs via next-generation ribonucleic acid sequencing and microarray approaches. To address their functional importance in angiogenic processes, several endothelial lncRNAs were characterized for their angiogenic characteristics in vitro and ex vivo.Ribonucleic acid sequencing and microarray-derived data showed specific endothelial lncRNA expression changes after hypoxia. Validation experiments confirmed strong hypoxia-dependent activation of 2 intergenic lncRNAs: LINC00323 and MIR503HG.Silencing of these lncRNA transcripts led to angiogenic defects, including repression of growth factor signaling and/or the key endothelial transcription factor GATA2. Endothelial loss of these hypoxia-driven lncRNAs impaired cell-cycle control and inhibited capillary formation. The potential clinical importance of these endothelial lncRNAs to vascular structural integrity was demonstrated in an ex vivo model of human induced pluripotent stem cell-based engineered heart tissue.The authors report an expression atlas of human hypoxia-sensitive lncRNAs and identified 2 lncRNAs with important functions to sustain endothelial cell biology. LncRNAs hold great promise to serve as important future therapeutic targets of cardiovascular disease.
Phase II study of infusional chemotherapy with doxorubicin, vincristine and etoposide plus cyclophosphamide and prednisone (I-CHOPE) in resistant diffuse aggressive non-Hodgkin's lymphoma: CALGB 9255
Authors: S M Lichtman, D Niedzwiecki, M Barcos, T L Carlisle, M R Cooper, J L Johnson, B A Peterson
Journal: Annals of Oncology (2000)