tbuckley/cabot-search huggingface dataset:
Amniotic fluid phospholipid profile determined by two-dimensional thin-layer chromatography as index of fetal lung maturation.
Authors: M J Whittle, A I Wilson, C R Whitfield, R D Paton, R W Logan
Journal: BMJ (1981)

A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic.
Abstract 1984: The Ikaros tumor suppressor regulates transcription of genes involved in cell signaling in human leukemia.
Authors: Jonathon L. Payne, Justin Sloane, Rebekka M. Bamert, Elanora Dovat, Hui Li, Marie Bulathsinghala, Chandrika Gowda, Chunhua Song, Sinisa Dovat
Journal: Cancer Research (2013)

Abstract The IKZF1 gene encodes Ikaros, a DNA binding zinc finger protein that is essential for normal hematopoietic differentiation. Deletion or mutation of Ikaros has been associated with a both T and B-cell acute lymphoblastic leukemia (ALL), as well as acute and chronic myelogenous leukemias (AML and CML). Deletion of an Ikaros allele has also been identified as a poor prognostic marker in childhood B-ALL. Thus, Ikaros is established as a major tumor suppressor in hematopoietic malignancies. The Ikaros protein can activate or repress target gene expression via chromatin remodeling. The specific mechanisms by which Ikaros exerts its tumor suppressor activities are unknown. We have defined genome-wide occupancy of Ikaros in human leukemia using ChIP-SEQ and identified a large number of potential Ikaros target genes. The quantitative Chromatin Immunoprecipitation assay (qChIP) was used to identify genes whose expression is directly regulated by Ikaros. Using this technique we show that Ikaros binds to the promoter region of a gene that is part of a pro-oncogenic pathway, as well as a tumor suppressor gene. Both genes are essential components of cell signaling pathways. The promoter regions of the two novel target genes were cloned into luciferase reporter constructs and used to transiently transfect HEK 293T cells that were co-transfected with Ikaros or empty vector (as a control). Luciferase reporter assays demonstrate that Ikaros suppresses transcription of the gene that is involved in oncogenic transformation, while it positively regulates transcription of the tumor suppressor gene. In summary, we have identified two novel Ikaros target genes. Our results suggest that Ikaros exerts its tumor suppression function by regulating the expression of target genes involved in pro-oncogenic and tumor suppressor signaling in leukemia cells. These data identify mechanisms of the tumor suppressor activity of Ikaros in leukemia. Citation Format: Jonathon L. Payne, Justin Sloane, Rebekka M. Bamert, Elanora Dovat, Hui Li, Marie Bulathsinghala, Chandrika Gowda, Chunhua Song, Sinisa Dovat. The Ikaros tumor suppressor regulates transcription of genes involved in cell signaling in human leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1984. doi:10.1158/1538-7445.AM2013-1984
Inhibitor of Heat-shock Protein 90 Enhances the Antitumor Effect of DNA Vaccine Targeting Clients of Heat-shock Protein
Authors: Chi-Chen Lin, Cheng-Fen Tu, Meng-Chi Yen, Ming-Chuan Chen, Wan-Jung Hsieh, Wen-Chang Chang, Wen-Tsang Chang, Ming-Derg Lai
Journal: Molecular Therapy (2007)

Geldanamycin (GA), a heat-shock protein (HSP) 90 inhibitor, induces degradation of HSP90 client proteins, which may promote the presentation of degradation peptides with major histocompatibility complex class I on cancer cells. We hypothesized that GA may enhance the efficacy of DNA vaccination, and investigated the therapeutic effect of the combination of GA and a DNA vaccine against HSP90 clients p185neu and Met. The efficacy of various doses of GA combined with an N-terminal neu (N′-neu) DNA vaccine was investigated in a transplanted tumor constitutively overexpressing endogenous p185neu. Low-dose (2.5 μg) but not high-dose (10 μg) GA enhanced the effect of N′-neu DNA vaccination on the inhibition of murine bladder tumor-2 tumors in syngeneic C3H mice. Anti-p185neu antibody titers were similar among all treated groups. Significantly increased infiltrations of CD8+ T cells and NK cells were observed at tumor sites. GA sensitized tumor cells to the cytotoxic effects of lymphocytes. Depletion of CD8+ T cells eliminated most of the therapeutic efficacy; in contrast, depletion of CD4+ T cells enhanced the therapeutic efficacy. A similar enhancing effect was observed for the combination of GA and a DNA vaccine targeting the Met oncogene. Our results support the use of combination of GA and DNA vaccination against GA-targeted proteins. Geldanamycin (GA), a heat-shock protein (HSP) 90 inhibitor, induces degradation of HSP90 client proteins, which may promote the presentation of degradation peptides with major histocompatibility complex class I on cancer cells. We hypothesized that GA may enhance the efficacy of DNA vaccination, and investigated the therapeutic effect of the combination of GA and a DNA vaccine against HSP90 clients p185neu and Met. The efficacy of various doses of GA combined with an N-terminal neu (N′-neu) DNA vaccine was investigated in a transplanted tumor constitutively overexpressing endogenous p185neu. Low-dose (2.5 μg) but not high-dose (10 μg) GA enhanced the effect of N′-neu DNA vaccination on the inhibition of murine bladder tumor-2 tumors in syngeneic C3H mice. Anti-p185neu antibody titers were similar among all treated groups. Significantly increased infiltrations of CD8+ T cells and NK cells were observed at tumor sites. GA sensitized tumor cells to the cytotoxic effects of lymphocytes. Depletion of CD8+ T cells eliminated most of the therapeutic efficacy; in contrast, depletion of CD4+ T cells enhanced the therapeutic efficacy. A similar enhancing effect was observed for the combination of GA and a DNA vaccine targeting the Met oncogene. Our results support the use of combination of GA and DNA vaccination against GA-targeted proteins.
Abstract 494: Identification and characterization of novel kinases that regulate BRCA1 expression and function
Authors: Wenjia Wang, Lisa M. Harlan-Williams, Roy A. Jensen
Journal: Cancer Research (2010)

Abstract Transcriptional and functional regulation of breast cancer susceptibility gene 1 (BRCA1) in the pathogenesis of sporadic breast cancers is poorly understood. About 90% of all breast cancers are considered sporadic, and 30-40% of these cases exhibit decreased expression of BRCA1 in the absence of mutations at its genetic locus. Loss of BRCA1 accelerates growth of tumor cells, while expression of BRCA1 leads to growth arrest and apoptosis. These observations support further examination of regulatory pathways of BRCA1 to restore its expression and function. To identify potential regulators of BRCA1, we developed a functional assay based on the role of BRCA1 in DNA damage repair. BRCA1 acts as a central scaffold that assembles a complex of repair proteins to sites of double-strand breaks (DSBs) following exposure to ionizing radiation (IR). Immunostaining for BRCA1 reveals these repair sites as punctate ionizing radiation-induced foci (IRIF). The ability of BRCA1 to localize to DSBs depends on both its expression and phosphorylation status. We evaluated the effect of siRNAs against kinases on BRCA1 IRIF formation because 1) phosphorylation of BRCA1 regulates many of its functions, 2) bioinformatics provides BRCA1 phosphorylation sites where the kinase involved is unknown, and 3) kinases play key roles in signaling pathways to influence gene expression or phosphorylation status. A number of kinases were identified that affected the ability of BRCA1 to form IRIF. However, the mechanism of kinase influence is unclear. Secondary siRNA screening assays have validated the kinase hits and lead kinases have been selected for further characterization. We are currently determining whether the effects of the lead kinases on BRCA1 are at the transcriptional or post-translational level and how these changes affect the ability of BRCA1 to repair DSBs by homologous recombination, to regulate the G2/M cell cycle checkpoint, and to modulate expression of downstream genes. Additionally, we are elucidating the signaling pathways that explain how the lead kinases regulate BRCA1. Once completed, we will have identified and characterized the role of the lead kinases on BRCA1 expression and function. This knowledge can translate into a novel therapy for BRCA1-related sporadic breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 494.
Charcot–Marie–Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene
Authors: Kiyoshi Hayasaka, Masato Himoro, Wataru Sato, Goro Takada, Keiichi Uyemura, Nobuyoshi Shimizu, Thomas D. Bird, P. Michael Conneally, Phillip F. Chance
Journal: Nature Genetics (1993)
Inflammatory bowel disease in childhood.
Authors: I W Booth, J T Harries
Journal: Gut (1984)

Progress reportInflammatory bowel disease in childhood Infants and children are not only growing but also developing, both physically and intellectually, and these differences embody the reasons why many diseases, of which inflammatory bowel disease is a good example, produce differing symptoms and management problems compared with adults.It is the aim of this review to highlight these differences rather than to provide a totally comprehensive account of inflammatory bowel disease in childhood.The more important causes of inflammatory bowel disease in children are similar to those in adults with the exception of food allergy, which is an important and underestimated cause of colitis in infancy, and is discussed more fully later.As there is considerable controversy surrounding inflammatory bowel disease, many of the views in this study reflect our own experience and practice, which are essentially empirical and pragmatic where there are no scientifically well founded guidelines available. IncidenceThere is evidence from several centres that there has been a recent increase in the incidence of Crohn's disease. 1 2 This increase has occurred in all age groups and in the United Kingdom, in contrast with ulcerative colitis, has been associated with a growing mortality rate.Between 18-33% of patients3 4 present before the age of 20 years, and therefore these figures must have important implications for the paediatric gastroenterologist.The increase in the number of referrals of children to the Hospital for Sick Children, London with Crohn's disease over the last few years has been such that an outpatient clinic devoted entirely to patients with inflam- matory bowel disease has been established.Despite a remarkable increase in incidence, no single environmental factor has been shown to be the aetiological agent in Crohn's disease.5In contrast with Crohn's disease, the incidence of ulcerative colitis has not changed,2 so that the overall incidence of Crohn's disease and ulcerative colitis appears to be similar.As the proportion of patients with ulcerative colitis who present at under 20 years of age may be as low as half the corresponding figure for Crohn's disease, most paediatricians will probably see significantly more Crohn's disease than ulcerative colitis in the future. Clinical manifestationsCROHN S DISEASE When Crohn's disease presents abruptly with the triad of abdominal pain, diarrhoea, and weight loss the diagnosis is usually made easily.Usually
Compositae dermatitis from airborne parthenolide
Authors: E. Paulsen, L.P. Christensen, K.E. Andersen
Journal: British Journal of Dermatology (2007)

Journal Article Compositae dermatitis from airborne parthenolide Get access E. Paulsen, E. Paulsen Department of Dermatology, Odense University Hospital, Sdr. Boulevard 29, DK‐5000 Odense C, Denmark *Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK‐5792 Aarslev, Denmark Correspondence: Evy Paulsen E‐mail: evy.paulsen@ouh.fyns‐amt.dk Search for other works by this author on: Oxford Academic Google Scholar L.P. Christensen, L.P. Christensen Department of Dermatology, Odense University Hospital, Sdr. Boulevard 29, DK‐5000 Odense C, Denmark *Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK‐5792 Aarslev, Denmark Search for other works by this author on: Oxford Academic Google Scholar K.E. Andersen K.E. Andersen Department of Dermatology, Odense University Hospital, Sdr. Boulevard 29, DK‐5000 Odense C, Denmark *Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK‐5792 Aarslev, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 3, 1 March 2007, Pages 510–515, https://doi.org/10.1111/j.1365-2133.2006.07674.x Published: 01 March 2007
Too Many Words? Mozart 1, Emperor 0-Reply
Authors: Paula A. Rochon
Journal: JAMA (1995)

In Reply.  —We thank Dr Goodman for his comments on how to simplify our writing. In rewriting our two sentences, Goodman gets a bravo for brevity, but not for accuracy. When editing one must ensure that the original meaning of the work is maintained. In his attempt to simplify our work, Goodman makes two errors that obscure our message.  The original two lines in our article were written as follows: Our findings suggest that  control trials published in journal supplements are generally of inferior quality compared with articles published in the parent  The review process surrounding the publication of journal supplements should be consistent with that of the parent journal. The first error made by Goldman was that he substituted the word  for randomized control trial in his quotation of our text. These terms are not interchangeable. Compounding this error, Goodman uses the term  instead of
Abstract 3032: The effect of a tankyrase inhibitor on the small intestine tissue homeostasis
Authors: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sørlie
Journal: Cancer Research (2014)

Abstract In the small intestine the Wnt/β-catenin pathway is involved in regulation of stem cells and tissue homeostasis. Aberrant Wnt signaling is known to cause intestinal cancers. Tankyrase enzymes play crucial roles in the regulation of the Wnt signaling pathway. Inhibition of tankyrase activity is an effective way of inhibiting Wnt/β-catenin signaling. A small molecule tankyrase inhibitor, G007-LK, was developed that inhibits tumor growth in a APC-mutant colorectal cancer xenograft model. In in vivo experiments at high doses (60 mg/kg), G007-LK treatment resulted in severe necrosis and inflammation in the small intestine, possibly affecting the stem cells. Different cell populations in the small intestine have been shown to have stem cell properties, including the Lgr5+ cell population located at the bottom of the crypts and the cells residing in +4 position counting from the crypt base. Both of these cell populations can give rise to all the various cell types of the small intestine. In the current project, we have used in vivo models to address the effect of the tankyrase inhibitor, G007-LK, on small intestine tissue homeostasis. H&amp;E staining of fixed tissue sections showed no significant differences between mice treated with 10 mg/kg G007-LK or vehicle. We performed lineage tracing from the Lgr5+ stem cells of the small intestine and observed that treatment with G007-LK reduced the number of cells traced from Lgr5+ stem cells. Immunohistochemistry (IHC) staining for the proliferation marker Ki67 showed reduced number of positive cells in the small intestinal crypts of the G007-LK- compared to vehicle-treated mice. As expected, IHC staining for β-catenin showed reduced number of positive nuclei in the G007-LK- compared to vehicle-treated mice, suggesting reduced signaling via the Wnt/β-catenin pathway. Taken together, our data show that a daily dose of the tankyrase inhibitor G007-LK (10 mg/kg), is well tolerated by mice. Administration of the tankyrase inhibitor to the mice reduces the number of lineage traced cells from the Lgr5+ stem cell population in the small intestine, without altering the general histology of the tissue. Citation Format: Jens Henrik Norum, Ellen Skarpen, Andreas Brech, Raoul Kuiper, Jo Waaler, Stefan Krauss, Therese Sørlie. The effect of a tankyrase inhibitor on the small intestine tissue homeostasis. [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 3032. doi:10.1158/1538-7445.AM2014-3032
Phagocytosis in atherosclerosis: Molecular mechanisms and implications for plaque progression and stability
Authors: D SCHRIJVERS, G DEMEYER, A HERMAN, W MARTINET
Journal: Cardiovascular Research (2006)

Macrophages play a key role in atherosclerotic plaque destabilization and rupture. In this light, selective removal of macrophages may be beneficial for plaque stability. However, macrophages are phagocytic cells and thus have an important additional role in scavenging of modified lipoproteins, unwanted or dead cells and cellular debris via phagocytosis. The concept of phagocytosis as well as the underlying mechanisms is well defined but the effect of phagocytosis in terms of plaque stability remains poorly understood. Recent findings point towards a complex role of macrophage phagocytosis in atherogenesis. Macrophages are necessary for removal of apoptotic cells from plaques, but exert strong proatherogenic properties upon phagocytosis of lipoproteins, erythrocytes and platelets. Apart from heterophagy, autophagocytosis better known as autophagy may occur in advanced atherosclerotic plaques. Several lines of evidence indicate that autophagy is initiated in plaque smooth muscle cells as a result of cellular distress. Since autophagy is well recognized as a survival mechanism, autophagic smooth muscle cells in the fibrous cap may reflect an important feature underlying plaque stability. All together, phagocytosis is a crucial process involved in atherogenesis that may significantly affect the stability of the atherosclerotic plaque.
Children Are Likely to Suffer Most from Our Fossil Fuel Addiction
Authors: Frederica P. Perera
Journal: Environmental Health Perspectives (2008)

BackgroundThe periods of fetal and child development arguably represent the stages of greatest vulnerability to the dual impacts of fossil fuel combustion: the multiple toxic effects of emitted pollutants (polycyclic aromatic hydrocarbons, particles, sulfur oxides, nitrogen oxides, metals) and the broad health impacts of global climate change attributable in large part to carbon dioxide released by fossil fuel burning.ObjectivesIn this commentary I highlight current scientific evidence indicating that the fetus and young child are at heightened risk of developmental impairment, asthma, and cancer from fossil fuel pollutants and from the predicted effects of climate disruption such as heat waves, flooding, infectious disease, malnutrition, and trauma. Increased risk during early development derives from the inherently greater biologic vulnerability of the developing fetus and child and from their long future lifetime, during which early insults can potentially manifest as adult as well as childhood disease. I cite recent reports concluding that reducing dependence on fossil fuel and promoting clean and sustainable energy is economically feasible.DiscussionAlthough much has been written separately about the toxicity of fossil fuel burning emissions and the effects of climate change on health, these two faces of the problem have not been viewed together with a focus on the developing fetus and child. Adolescence and old age are also periods of vulnerability, but the potential for both immediate and long-term adverse effects is greatest when exposure occurs prenatally or in the early years.ConclusionsConsideration of the full spectrum of health risks to children from fossil fuel combustion underscores the urgent need for environmental and energy policies to reduce fossil fuel dependence and maximize the health benefits to this susceptible population. We do not have to leave our children a double legacy of ill health and ecologic disaster.
The Accelerated Approval of Oncologic Drugs
Authors: Vinay Prasad, Sham Mailankody
Journal: JAMA (2014)

On October 31, 2013, the US Food and Drug Administration (FDA) suspended marketing and sales of the BCR-ABL tyrosine kinase inhibitor ponatinib (Iclusig, Ariad Pharmaceuticals). Just 7 weeks later, on December 20, 2013, the FDA partially reversed that decision, permitting use of the drug under a narrower indication. Ponatinib was the sixth drug approved for the treatment of chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia and indicated for patients refractory or intolerant to prior tyrosine kinase inhibitor (TKI) therapy (Table).
Two cases of solitary Peutz-Jeghers-type hamartoma of the duodenum
Authors: S. Itaba, M. Namoto, S. Somada, K. Nakamura, Y. Kumashiro, N. Nakamura, T. Yao
Journal: Endoscopy (2006)

Peutz-Jeghers syndrome is a rare autosomal dominant disease that is characterized by hamartomatous gastrointestinal polyposis and mucocutaneous pigmentation [1]. One report proposed that solitary Peutz-Jeghers-type hamartomatous polyps in patients with no other features of Peutz-Jeghers syndrome were likely to represent a separate disease entity from classic Peutz-Jeghers syndrome [2]. The solitary Peutz-Jeghers-type hamartoma of the duodenum is extremely rare in comparison with Peutz-Jeghers syndrome. We describe two such cases.
Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor Regulation of Human Th2 Cell Programming
Authors: Laura L. Elo, Henna Järvenpää, Soile Tuomela, Sunil Raghav, Helena Ahlfors, Kirsti Laurila, Bhawna Gupta, Riikka J. Lund, Johanna Tahvanainen, R. David Hawkins, Matej Orešič, Harri Lähdesmäki, Omid Rasool, Kanury V. Rao, Tero Aittokallio, Riitta Lahesmaa
Journal: Immunity (2010)
Charity challenges US “anti-prostitution” restriction
Authors: Bob Roehr
Journal: BMJ (2005)

A US charity is to challenge the US government's requirement that international non-government organisations must explicitly oppose prostitution and sex trafficking if they are to receive government funds for family planning and HIV prevention activities.

DKT International, which is based in Washington, DC, filed a lawsuit against the US Agency for International Development (USAID) on 11 August. It claims that the provision is a gag order restricting its right to free speech and is therefore unconstitutional.

The law was enacted by Congress in 2003, with …