tbuckley/cabot-search huggingface dataset:
Possible Importance of Detergent in Millipore Filter Carcinogenesis
Authors: Edwin J. Andrews
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Possible Importance of Detergent in Millipore Filter Carcinogenesis Get access Edwin J. Andrews Edwin J. Andrews Department of Comparative Medicine, College of Medicine, The Pennsylvania State University, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 4, April 1972, Pages 1251–1254, https://doi.org/10.1093/jnci/48.4.1251 Published: 01 April 1972 Article history Received: 10 January 1972 Accepted: 10 January 1972 Published: 01 April 1972
Carcinoma of the Stomach
Authors: Claude E. Welch, Arthur W. Allen
Journal: New England Journal of Medicine (1948)

SURGICAL experience with carcinoma of the stomach at the Massachusetts General Hospital has been reviewed by Parsons1 in previous papers covering the years 1922 to 1926, and the period from 1927 to 1936 by Parsons and Welch.2 This report includes all patients admitted to this hospital on whom the diagnosis was made during the ten-year period 1937 to 1946 inclusive.In the compilation of these figures, it is, of course, our hope to show that increased knowledge of the disease and its amenability to surgical attack have resulted in a steadily increasing five-year salvage rate. But it is of equal . . .
Patellofemoral pain during adolescence: much more prevalent than appreciated
Authors: M S Rathleff
Journal: British Journal of Sports Medicine (2016)

PATELLOFEMORAL PAIN IS COMMON AMONG ADOLESCENTSMusculoskeletal conditions are not unique to the adult population.From the age of 5-9 years to the age of 10-14 years there is an almost fourfold increase in the years lived with disability as a result of musculoskeletal conditions. 1 In Danish primary care, we see an eightfold increase in the number of contacts to general practice because of knee symptoms between 5-9 and 10-19 years. 2 This makes knee pain one of the most common sites of pain in adolescents. 3ur research shows that 6-7% of the adolescent population is affected (in varying severities) by patellofemoral pain (PFP). 4 5This makes PFP one of the most common knee conditions among adolescents.Depending on how you define adolescence and adulthood, more than 95% of all research on PFP is carried out on adults.This does not match the high prevalence among adolescents.It is appreciated that children are not small adultsadolescents appear to need their own attention too.
Clubbing of the Fingers
Authors: W. P. U. Jackson
Journal: BMJ (1949)

ANKYLOSING SPONDYLITISBRiTiSH in rheumatoid arthritis), together with a generalized osteo- porosis.In 11 cases osteoporosis alone was seen, and in 19 nothing abnormal was detected.The osteoporotic and other changes were associated with a severe and widespread phase of the disease, but in no case did we see changes characteristic of rheumatoid arthritis.The biochemical and haematological data are self- explanatory and agree with the findings of other workers. SummaryTwo hundred cases of ankylosing spondylitis are reviewed.Sex incidence, age of onset, associated factors, accuracy of original diagnosis, occupation, and family and past histories are enumerated.The original symptoms and type of onset are described, as are the biochemical and haematological findings.The nature of the disease process is discussed, especially in its relation to rheumatoid arthritis, and we conclude that it is a separate entity.The analysis of the x-ray findings is discussed.
Abstract 572: Large Solid Organ Perfusion Decellularization - A Start for Human-Sized Tissue Scaffolds?
Authors: Thomas S Matthiesen, Harald C Ott, Sak-Kia Goh, Doris A Taylor
Journal: Circulation (2007)

Background . Tissue engineering involves at a minimum cells and scaffold. However, reports of generating human-sized 3-dimensional scaffolds with appropriate architecture are limited. We hypothesize that perfusion decellularization of cadaveric pig solid organs will effectively remove cellular components and DNA, potentially providing a sufficient starting point for whole solid-organ tissue engineering. Methods . Adult Yorkshire swine (~60kg) were euthanized after systemic heparinization. Heart, liver, and kidneys were removed and mounted on a perfusion apparatus. Cannulation was performed using either the aorta (heart), portal vein (liver), or renal artery (kidney). Saline at 25C was perfused to remove blood, followed by Sodium Dodecyl Sulfate (SDS) detergent perfusion until tissues were translucent and white in color (heart=40 liters; liver=19 liters; kidney=31 liters). SDS was followed by 2 liters of 1% Triton-X 100 to sequester remaining detergent via micelle formation and clearance. Decellularization was evaluated by histology (H&amp;E, DAPI, IHC). Tissue DNA content post-decellularization was quantified using a Hoechst-33258 DNA assay. Results . By histology, heart, liver, and kidney lacked intracellular components and DAPI, but retained major ECM proteins (fibronectin, collagen, and laminin). DNA in decellularized tissue was &lt;2.2% of cadaveric controls by wet weight for all organs (heart=16.0 ± 2.9 vs. control=762.6 ± 48.5 ng/mg; liver=3.6 ± 0.7 vs. control=1157.6 ±91.7 ng/mg; kidney=25.2 ± 1.7 vs. control=1380.0 ± 201.2 ng/mg). Conclusion . SDS-based perfusion decellularization of large animal organs is effective at removing cellular content and DNA. The remaining whole-organ scaffold provides a platform technology for a novel construct for tissue engineering of human sized bioartificial organs.
Correlation of low dose tamoxifen and its metabolites plasma level with Cyp 2D6, and SULT polymorphism; a pharmacogenetics study within a chemoprevention trial
Authors: D. Serrano, D. Macis, S. Gandini, H. Johansson, A. Guerrieri-Gonzaga, G. Mellgren, E. A. Lien, F. Mariett, M. Sandri, A. Decensi, B. Bonanni
Journal: Journal of Clinical Oncology (2007)

503 Background: Tamoxifen (T) is one of the most widely used drug for the treatment and prevention of estrogen receptor (ER) positive breast cancer. Individual genotype can modulate treatment efficacy. T metabolism is catalyzed by multiple enzymes: CYP2D6 is the main mediator for endoxifen, one of the most potent T metabolites. SULT may also play a role in T activation and can modulate hormone levels involved in breast cancer risk. Within a chemoprevention trial, we correlated T and its main metabolite concentration with polymorphisms (SNPs) of CYP2D6 and SULT genes. Methods: Premenopausal women (n 235) were randomly assigned in a double-blind four-arm trial to receive T 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years CYP2D6 (*4–6) and SULT1A1*3 frequencies were determined using an Allelic Discrimination Assay, following a protocol for real time polymerase chain reaction. In the subjects receiving T, we measured plasma level of the drug, and its metabolites (endoxifen, 4-hydroxy-T, N-desmethyl-T, N-desdimethyl-T and Tnoxide) using a fluorescence detector at 12 and 24 months. Results: SNPs analysis was performed in 118 women; we found 65% wild type (WT), 31% heterozygous (H) and 5% mutated (M) for CYP2D6. The SNP frequency of SULT1A was A1, 61%; SULT1A2 36% and SULT1A3 3%. At one year a positive correlation was observed between CYP2D6 M and plasma level of N- desmethyl-T, the mean plasma level being 54.6, 62.4 and 108.5 ng/ml in WT, H and M, respectively, p=.001 (p=.01 at 24 months). Endoxifen was slightly increased in the WT compared to M (15.4 vs 12.9 ng/ml). SULT polymorphisms did not show any correlation with the drug and metabolite levels. Conclusions: CYP2D6 M mediates an increased level of N- desmethylT. This observation supports the role of CYP2D6 as an important enzyme in T metabolism, but more than one cytochrome P450 isoenzymes is required. to identify good or poor T metabolizers. No significant financial relationships to disclose.
Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma
Authors: Mikko Siurala, Riikka Havunen, Dipongkor Saha, Dave Lumen, Anu J. Airaksinen, Siri Tähtinen, Víctor Cervera-Carrascon, Simona Bramante, Suvi Parviainen, Markus Vähä-Koskela, Anna Kanerva, Akseli Hemminki
Journal: Molecular Therapy (2016)

Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFα, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of (111)In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies.
Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer
Authors: Petra ter Brugge, Petra Kristel, Eline van der Burg, Ute Boon, Michiel de Maaker, Esther Lips, Lennart Mulder, Julian de Ruiter, Catia Moutinho, Heidrun Gevensleben, Elisabetta Marangoni, Ian Majewski, Katarzyna Jóźwiak, Wigard Kloosterman, Markus van Roosmalen, Karen Duran, Frans Hogervorst, Nick Turner, Manel Esteller, Edwin Cuppen, Jelle Wesseling, Jos Jonkers
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Although BRCA1-deficient tumors are extremely sensitive to DNA-damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance to therapy remains a serious clinical problem. To study the underlying mechanisms, we induced therapy resistance in patient-derived xenograft (PDX) models of BRCA1-mutated and BRCA1-methylated triple-negative breast cancer. Methods: A cohort of 75 mice carrying BRCA1-deficient breast PDX tumors was treated with cisplatin, melphalan, nimustine, or olaparib, and treatment sensitivity was determined. In tumors that acquired therapy resistance, BRCA1 expression was investigated using quantitative real-time polymerase chain reaction and immunoblotting. Next-generation sequencing, methylation-specific multiplex ligation-dependent probe amplification (MLPA) and Target Locus Amplification (TLA)–based sequencing were used to determine mechanisms of BRCA1 re-expression in therapy-resistant tumors. Results: BRCA1 protein was not detected in therapy-sensitive tumors but was found in 31 out of 42 resistant cases. Apart from previously described mechanisms involving BRCA1-intragenic deletions and loss of BRCA1 promoter hypermethylation, a novel resistance mechanism was identified in four out of seven BRCA1-methylated PDX tumors that re-expressed BRCA1 but retained BRCA1 promoter hypermethylation. In these tumors, we found de novo gene fusions that placed BRCA1 under the transcriptional control of a heterologous promoter, resulting in re-expression of BRCA1 and acquisition of therapy resistance. Conclusions: In addition to previously described clinically relevant resistance mechanisms in BRCA1-deficient tumors, we describe a novel resistance mechanism in BRCA1-methylated PDX tumors involving de novo rearrangements at the BRCA1 locus, demonstrating that BRCA1-methylated breast cancers may acquire therapy resistance via both epigenetic and genetic mechanisms.
Authors’ reply: Prioritisation of infectious diseases in public health: feedback on the prioritisation methodology, 15 July 2008 to 15 January 2009
Authors: A Gilsdorf, G Krause
Journal: Eurosurveillance (2011)

Preview this article: Authors' reply: Prioritisation of infectious diseases in public health: feedback on the prioritisation methodology, 15 July 2008 to 15 January 2009, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/16/27/art19912-en-1.gif
Integrated Safety Assessment of 2′-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers
Authors: Stanley T Crooke, Brenda F Baker, T Jesse Kwoh, Wei Cheng, Dan J Schulz, Shuting Xia, Nelson Salgado, Huynh-Hoa Bui, Christopher E Hart, Sebastien A Burel, Husam S Younis, Richard S Geary, Scott P Henry, Sanjay Bhanot
Journal: Molecular Therapy (2016)

The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2'-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2'-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied.
Onset of Spermatogenesis Is Accelerated by Gestational Administration of 1,2,3,4,6,7-Hexachlorinated Naphthalene in Male Rat Offspring
Authors: Minoru Omura, Yoshito Masuda, Miyuki Hirata, Akiyo Tanaka, Yuji Makita, Rika Ogata, Naohide Inoue
Journal: Environmental Health Perspectives (2000)

We treated pregnant rats with 1 microg/kg body weight/day 1,2,3,4,6,7-hexachlorinated naphthalene (1,2,3,4,6,7-HxCN) on days 14-16 of gestation and examined the effects on the reproductive systems of their male offspring at various phases of sexual maturation. Sperm count in the cauda epididymidis did not change in 1,2,3,4,6, 7-HxCN-treated rats on postnatal day 89, the age of sexual maturity, but the sperm count in the cauda epididymidis did increase to approximately 180% of the control value on postnatal day 62. In addition, homogenization-resistant testicular spermatids increased to approximately 160% of the control value on postnatal day 48, and the percent of postmeiotic tubules increased to approximately 190% of the control value on postnatal day 31 in this group. These results indicate that the onset of spermatogenesis was accelerated in the 1,2,3,4,6,7-HxCN rats. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had already reached the maximum level on postnatal day 31 in the 1,2,3,4,6, 7-HxCN group, suggesting that the onset of LH and FSH secretions from the pituitary gland was also accelerated and that this endocrine disruption was the cause of early onset of spermatogenesis in this group. In the fat of 1,2,3,4,6,7-HxCN-treated dams, 5.75+/-2.81 ppb 1,2,3,4,6,7-HxCN was detected when offspring were weaned. This concentration was 5-10 times higher than that found in human adipose tissue.
Cardiac Pacing and Defibrillation Devices: Cost and Effectiveness
Authors: Peter W. Groeneveld, Sanjay Dixit
Journal: Annual Review of Medicine (2016)

Implantable cardiac pacing and defibrillation devices are effective and commonly used therapies for patients with cardiac rhythm disorders. Because device implantation is not easily reversible, as well as the high healthcare costs inherent in device use, a clear understanding of the clinical benefits relative to costs is essential for both appropriate clinical use and rational policy making. Cardiac implantable electronic devices (CIEDs) have been among the best-investigated therapies in medicine; these devices have been the topic of numerous clinical and economic evaluations during the past 30 years. However, many important questions remain unclarified. We review the evidence supporting the clinical benefits of CIEDs, including effectiveness in extending survival as well as improving quality of life. We also summarize the economic studies that have investigated costs associated with these devices and their overall cost effectiveness, and we highlight important potential areas for future research.
Ribosomal Proteins Are Overexpressed in Hyperdiploid Multiple Myeloma.
Authors: Niels Weinhold, John DeVos, Dirk Hose, Jean-Francois Rossi, Benner Axel, Karène Mahtouk, Marc S. Raab, Thierry X. Rème, Anna Jauch, Jerome Moreaux, Veronique Pantesco, Hartmut Goldschmidt, Eric Jourdan, Friedrich W. Cremer, Bernard Klein, Marion Moos
Journal: Blood (2007)
CD3/8 T-Cell Responses to CMV Reactivation in Patients Undergoing Haploidentical Transplants: A Retrospective Analysis
Authors: Mahasweta Gooptu, Benjamin Leiby, Onder Alpdogan, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, Thomas R. Klumpp, Ubaldo Martinez, Barbara Pro, Manish Sharma, John L. Wagner, Mark Weiss, Neal Flomenberg, Dolores Grosso
Journal: Blood (2014)
Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists
Authors: Mackenzie J. Pearson, Roger H. Unger, William L. Holland
Journal: Diabetes Care (2016)

Since the discovery of glucagon’s opposing actions to insulin, drugs targeting the inhibition of glucagon action have been pondered. In recent years, several attempts to generate small molecules or antibodies that impair glucagon action have been pursued as potential therapeutics for type 2 diabetes. In the current issue of Diabetes Care , Kazda et al. (1) summarize the outcomes of the phase 2a and phase 2b clinical trials of LY2409021, a small-molecule glucagon receptor antagonist (GRA). This is the largest and longest trial for safety and efficacy of a GRA ever performed. Importantly, LY2409021 does not produce side effects on cholesterol homeostasis that have impeded the progress of other small-molecule GRAs. Here, we place their success in perspective and discuss the advantages and concerns relating to glucagon-based therapeutics as this line of drugs comes closer than ever to achieving their clinical potential.

In 1922, the first children with type 1 diabetes were treated with an insulin-containing pancreatic extract, preventing ketoacidosis and an insidious death. In addition to the discovery of insulin, the crew of Banting, Best, and Collip observed glucagon action, as they had noticed in their preclinical studies in canines that some of their crude insulin preparations would raise glucose levels in the dog briefly before glucose was lowered (2,3). This glucose-raising peptide was termed “glucagon” (4) and subsequently purified and identified as a 29–amino acid peptide (5). In 1959, the development of the radioimmunoassay made it possible to quantify the two major glucoregulatory hormones, insulin (6) and glucagon (7). It was quickly established that glucagon was in fact a true hormone responsible for maintaining the glucose supply to the brain via increased glycogenolysis and gluconeogenesis.

It has since been demonstrated that every form of diabetes is associated with hyperglucagonemia, the suppression of which eliminates hyperglycemia (8 …
The Toxic Touch—Cutaneous Poisoning in Classics and Shakespeare
Authors: Kimberly F. Faldetta, Scott A. Norton
Journal: JAMA Dermatology (2016)

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Abstract 1138: The Oxidized Disulphide Cystine Predicts Adverse Long Term Cardiovascular Outcomes
Authors: Riyaz S Patel, Emir Veledar, Ronak B Patel, Salman Sher, Shawn Arshad, Stephen Clements, John Douglas, Douglas Morris, S. Tanveer Rab, Habib Samady, R. Wayne Alexander, Viola Vaccarino, A. Maziar Zafari, Dean P Jones, Arshed A Quyyumi
Journal: Circulation (2009)

Introduction: Plasma levels of major amnio-thiol compounds provide a means of quantifying systemic oxidative stress. High levels of the oxidized disulphide cystine have been associated with endothelial dysfunction and risk factor burden in cross sectional studies. We hypothesized that plasma cystine levels would be predictive of adverse long term cardiovascular outcomes in subjects with suspected coronary artery disease. Methods: We studied 970 patients undergoing coronary angiography, aged 64±11 years, 68.8 % male, and measured cystine levels using HPLC. Patients were followed for “major events” defined as death, MI, hospitalized unstable angina, heart failure or stroke and “all events” which included revascularization, for a mean period of 2.4±1 years. ROC analysis identified the optimal threshold for cystine levels to predict major events as 108uM (sensitivity 40%, specificity 70%). Results: Patients with high cystine levels (mean 132±21uM) had worse prognosis compared to those with lower levels (mean ...
Reactive Polyclonal Gammopathy Associated with Polyclonal Plasmacytosis Is Common in Patients with Multiple Myeloma Receiving Prolonged Lenalidomide Therapy: A Retrospective Study of 104 Patients
Authors: Dmitriy Zamarin, Sean Devlin, Maria Arcila, Sergio A. Giralt, Heather Landau, Alex Lesokhin, Nikoletta Lendvai, David Chung, Danielle Chimento, Dilip Babu, Hani Hassoun
Journal: Blood (2012)
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1978)

COMMITTEE ON MATERNAL WELFAREEclampsia and Pulmonary InsufficiencyAn unmarried 15-year-old gravida 1 completely concealed her unwanted pregnancy until found at home during a convulsive seizure at 33 weeks' gestation. On admission to the hospital, the blood pressure was 142/102 mm Hg, and proteinuria was recorded, but other laboratory data are not available. Given diazepam, magnesium sulfate, hydralazine and furosemide, the patient also received oxytocin intravenously for the induction of labor. This measure failed, and, within a few hours, a 1678.5-g infant was delivered by cesarean section and survived and did well. Abruptio placentae was found, with blood loss described . . .