tbuckley/cabot-search huggingface dataset:
Conserved syntenic clusters of protein coding genes are missing in birds
Authors: Peter V Lovell, Morgan Wirthlin, Larry Wilhelm, Patrick Minx, Nathan H Lazar, Lucia Carbone, Wesley C Warren, Claudio V Mello
Journal: Genome biology (2014)

Abstract Background Birds are one of the most highly successful and diverse groups of vertebrates, having evolved a number of distinct characteristics, including feathers and wings, a sturdy lightweight skeleton and unique respiratory and urinary/excretion systems. However, the genetic basis of these traits is poorly understood. Results Using comparative genomics based on extensive searches of 60 avian genomes, we have found that birds lack approximately 274 protein coding genes that are present in the genomes of most vertebrate lineages and are for the most part organized in conserved syntenic clusters in non-avian sauropsids and in humans. These genes are located in regions associated with chromosomal rearrangements, and are largely present in crocodiles, suggesting that their loss occurred subsequent to the split of dinosaurs/birds from crocodilians. Many of these genes are associated with lethality in rodents, human genetic disorders, or biological functions targeting various tissues. Functional enrichment analysis combined with orthogroup analysis and paralog searches revealed enrichments that were shared by non-avian species, present only in birds, or shared between all species. Conclusions Together these results provide a clearer definition of the genetic background of extant birds, extend the findings of previous studies on missing avian genes, and provide clues about molecular events that shaped avian evolution. They also have implications for fields that largely benefit from avian studies, including development, immune system, oncogenesis, and brain function and cognition. With regards to the missing genes, birds can be considered ‘natural knockouts’ that may become invaluable model organisms for several human diseases.
Thyroid Hormone Activation in Human Vascular Smooth Muscle Cells
Authors: Haruo Mizuma, Masami Murakami, Masatomo Mori
Journal: Circulation Research (2001)

Abstract —Thyroid hormone has been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and antiatherosclerotic effects. To exert its biological activity, thyroxine, which is a major secretory product of thyroid gland, needs to be converted to 3,5,3′-triiodothyronine (T 3 ) by iodothyronine deiodinase. Type I iodothyronine deiodinase (DI) is widely distributed and maintains circulating T 3 level, whereas type II iodothyronine deiodinase (DII) is present in a limited number of tissues to provide local intracellular T 3 . In the present study, we have identified iodothyronine deiodinase in cultured human coronary artery smooth muscle cells (hCASMCs) and human aortic smooth muscle cells (hASMCs). All of the characteristics of the deiodinating activity in hCASMCs and hASMCs were compatible with DII. Northern analysis demonstrated that DII mRNA was expressed in both hCASMCs and hASMCs, and DII mRNA levels as well as DII activities were rapidly increased by dibutyryl-cAMP or forskolin. These data demonstrate, for the first time, the expression of DII in human vascular smooth muscle cells, which is regulated by a cAMP-mediated mechanism. The present results suggest a previously unrecognized role of local T 3 production by DII in the pathophysiology of human vascular smooth muscle cells.
Ultrastructure of mononuclear phagocytes developing in liquid bone marrow cultures. A study on peroxidatic activity
Authors: JWM Van Der Meer, RHJ Beelen, DM Fluitsma, R Van Furth
Journal: The Journal of Experimental Medicine (1979)

Monoblasts, promonocytes, and macrophages in in vitro cultures of murine bone marrow were studied ultrastructurally, with special attention to peroxidatic activity. Monoblasts show peroxidatic activity in the rough endoplasmic reticulum and nuclear envelope as well as in the granules. The presence of peroxidatic activity in the Golgi apparatus could not be determined. Promonocytes have peroxidase-positive rough endoplasmic reticulum, Golgi apparatus, nuclear envelope, and granules, as previously reported. During culture, cells are formed with peroxidatic activity similar to that of monocytes or exudate macrophages (positive granules; negative Golgi apparatus, RER, and nuclear envelope); we call these cells early macrophages. In addition, transitional macrophages with both positive granules and positive RER, nuclear envelope, negative Golgi apparatus (as in exudate- resident macrophages in vivo), and mature macrophages with peroxidatic activity only in the RER and nuclear envelope (as in resident macrophages in vivo) were found. A considerable number of cells without detectable peroxidatic activity were also encountered. Our finding that macrophages with the peroxidatic pattern of monocytes (early macrophages), exudate-resident macrophages (transitional macrophages), and resident macrophages (mature macrophages), develop in vitro from proliferating precursor cells deriving from the bone marrow, demonstrates once again that resident macrophages in tissues originate from precursor cells in the bone marrow. Therefore, this conclusion can no longer be challenged on the basis of a cytochemical difference between monocytes and exudate macrophages on the one hand and resident macrophages on the other.
Differentiation and Tumorigenicity of Human Malignant Melanocytes in Relation to Their Culture Conditions23
Authors: C. Aubert, F. Rougè, J.-R. Galindo
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Differentiation and Tumorigenicity of Human Malignant Melanocytes in Relation to Their Culture Conditions Get access C. Aubert, C. Aubert Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Rougè, F. Rougè Search for other works by this author on: Oxford Academic PubMed Google Scholar J.-R. Galindo J.-R. Galindo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 1, January 1984, Pages 3–12, https://doi.org/10.1093/jnci/72.1.3 Published: 01 January 1984 Article history Received: 25 June 1982 Revision received: 20 June 1983 Accepted: 19 July 1983 Published: 01 January 1984
Inhibition of Lymphogenous Metastasis Using Adeno-Associated Virus-Mediated Gene Transfer of a Soluble VEGFR-3 Decoy Receptor
Authors: JianMin Lin, Alshad S. Lalani, Thomas C. Harding, Melissa Gonzalez, Wei-Wei Wu, Bo Luan, Guang Huan Tu, Kathryn Koprivnikar, Melinda J. VanRoey, Yulong He, Kari Alitalo, Karin Jooss
Journal: Cancer Research (2005)

The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that the lymphangiogenic growth factor, vascular endothelial growth factor-C (VEGF-C), and its receptor, VEGF receptor-3 (VEGFR3), may play a pivotal role in the promotion of metastasis to regional lymph nodes. In this study, human prostate and melanoma tumor models that preferentially metastasize to the lymph nodes following s.c. tumor cell implantation were established from lymph node metastases via in vivo selection. Melanoma tumor cell sublines established from lymph node metastasis express higher amounts of VEGF-C than the parental tumor cells. The inhibition of tumor-derived VEGF-C with a soluble VEGFR3 decoy receptor, sVEGFR3-Fc, expressed via a recombinant adeno-associated viral vector, potently blocks tumor-associated lymphangiogenesis and tumor metastasis to the lymph nodes, when the treatment was initiated before the tumor implantation. In addition, sVEGFR3-Fc serum levels required for efficient blockade of lymph node metastases are strictly dependent on the VEGF-C levels generated by the primary tumor. Recombinant adeno-associated virus-mediated gene transfer of sVEGFR3-Fc may represent a feasible therapeutic strategy for blockade of lymphogenous metastasis.
Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution.
Authors: M K Pangburn, R D Schreiber, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1977)

The complement regulatory enzyme, C3b inactivator (C3bINA), has been purified from human serum by affinity chromatography on an anti-C3bINA Sepharose column. Subsequent chromatography on DEAE-cellulose and removal of IgG with anti-IgG Sepharose resulted in a product which was found to be homogeneous by polyacrylamide gel electrophoresis at pH 8.9 and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The molecule is composed of two disulfide bonded polypeptide chains with mol wt of 50,000 and 38,000 daltons. Human CobINA was found to be a glycoprotein containing at least 10.7% carbohydrate and to have a normal serum concentration of 34 +/- 7 mug/ml (mean +/- 1 SD). Highly purified C3bINA cleaved neither free C3b nor free C4b if trace amounts of contaminating beta1H were removed from these proteins with anti-beta1H Sepharose. However, in the presence of highly purified beta1H and C3bINA, both C3bIna, both C3b and C4b were cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their structure. The action of C3bINA and beta1H on C3b produced two fragments of the alpha1-chain which did not dissociate without reduction of the molecule. These fragments have mol wt of 67,000 and 40,000 daltons. The action of C3bINA and beta1H on C4b resulted in cleavage of the alpha'-chain giving rise to the 150,000-dalton C4c and the 49,000-dalton C4d fragments which dissociated without reduction. To produce from C3b the immunochemically defined C3c and C3d, fragments, the action of an additional serum enzyme appears to be required, the effect of which can be mimicked by trypsin.
[11C]Methionine Positron Emission Tomography and Survival in Patients with Bone and Soft Tissue Sarcomas Treated by Carbon Ion Radiotherapy
Authors: Hong Zhang, Kyosan Yoshikawa, Katsumi Tamura, Takashi Tomemori, Kenji Sagou, Mei Tian, Susumu Kandatsu, Tadashi Kamada, Hiroshi Tsuji, Tetsuya Suhara, Kazutoshi Suzuki, Shuji Tanada, Hirohiko Tsujii
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether l-[methyl-11C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas. Experimental Design: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. Results: The overall median survival time was 20 months. Patients with a baseline T/N ratio of ≤6 had a significant better survival than patients with a baseline T/N ratio &amp;gt;6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of ≤4.4 had a better survival than that with a post-CIRT ratio &amp;gt;4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of &amp;gt;30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. Conclusions: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.
Three Prescriptions for Habitual Constipation
Authors: J. M. Granville
Journal: BMJ (1883)

atteviptweremadet o discern small objects.The pupil was eoTh trated and irreguliw, theretwas some lymph thrown-out at its upper and inner margin, also slight turbidity of the aqueous humour, but no pain, nor any increase of tension.Vision.and she read No. 5 (Jiiger) with difficulty.She was ordered atropine drops (gr.ii to 5j) thrice daily;-forty drops of liquor hydrafgyri perchloridi three times a day, and a leech to the -temple.On the following day (November 9th), the eye looked decidedly better.The pupil wan widely, dilated; the conjunotiva not so red, and there was also less lacrymation.An entire ring of lymph could be clearly seen adherent to the anterior capsule of the lens, occupying the site of the pupil before it wasr dilated with atropine.With the ophthalmoscope, the funduis could be seen, but not very distinctly, there being some haziness of the media; the disc ap- peared a little pink in colour, and the margin slightly blurred.November 10th.Visioha -W There was slight haziness of the retinla, the rveins were full and tortuous; the details of the fundus were rather more distinct' than on the previous day.She had no
Farm exposure in utero may protect against asthma, hay fever and eczema
Authors: J. Douwes, S. Cheng, N. Travier, C. Cohet, A. Niesink, J. McKenzie, C. Cunningham, G. Le Gros, E. von Mutius, N. Pearce
Journal: European Respiratory Journal (2008)

The aim of the present study was to assess which factors contribute to the lower prevalence of allergic diseases in farmers’ children, and the importance of timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms, hay fever and eczema were assessed, as well as current, early and prenatal farm-related exposures in 1,333 farmers’ children and 566 reference children aged 5–17 yrs. Farmers’ children had a lower incidence of asthma symptoms and eczema. Current and maternal exposure during pregnancy to animals and/or grain and hay reduced the risk of asthma symptoms, hay fever and eczema. The exposure–response association for maternal exposure was nonlinear for most outcomes. After mutual adjustment, the effects of prenatal exposure remained unchanged whereas current exposure remained protective only for asthma medication, asthma ever and hay fever. Exposure during the first 2 yrs was not associated with symptoms, after controlling for prenatal exposure. A combination of prenatal and current exposure was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28–0.80), asthma medication (OR 0.50, 95% CI 0.30–0.82), asthma ever (OR 0.50, 95% CI 0.33–0.76), hay fever (OR 0.47, 95% CI 0.30–0.73) and eczema (OR 0.46, 95% CI 0.30–0.70). Prenatal exposure may contribute to the low prevalence of asthma, hay fever and eczema in farmers’ children, but continued exposure may be required to maintain optimal protection.
Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins
Authors: Hui-Hua Li, Monte S. Willis, Pamela Lockyer, Nathaniel Miller, Holly McDonough, David J. Glass, Cam Patterson
Journal: Journal of Clinical Investigation (2007)

Cardiac hypertrophy is a major cause of human morbidity and mortality. Although much is known about the pathways that promote hypertrophic responses, mechanisms that antagonize these pathways have not been as clearly defined. Atrogin-1, also known as muscle atrophy F-box, is an F-box protein that inhibits pathologic cardiac hypertrophy by participating in a ubiquitin ligase complex that triggers degradation of calcineurin, a factor involved in promotion of pathologic hypertrophy. Here we demonstrated that atrogin-1 also disrupted Akt-dependent pathways responsible for physiologic cardiac hypertrophy. Our results indicate that atrogin-1 does not affect the activity of Akt itself, but serves as a coactivator for members of the Forkhead family of transcription factors that function downstream of Akt. This coactivator function of atrogin-1 was dependent on its ubiquitin ligase activity and the deposition of polyubiquitin chains on lysine 63 of Foxo1 and Foxo3a. Transgenic mice expressing atrogin-1 in the heart displayed increased Foxo1 ubiquitylation and upregulation of known Forkhead target genes concomitant with suppression of cardiac hypertrophy, while mice lacking atrogin-1 displayed the opposite physiologic phenotype. These experiments define a role for lysine 63-linked ubiquitin chains in transcriptional coactivation and demonstrate that atrogin-1 uses this mechanism to disrupt physiologic cardiac hypertrophic signaling through its effects on Forkhead transcription factors.
Tablet induced dysphagia in oesophageal cancer
Authors: C P Selinger
Journal: Gut (2006)

We report a case of an unusual pattern of dysphagia in an 82 year old man. He first presented in January 2005 with a six month history of dysphagia and heartburn. Following the diagnosis of an adenocarcinoma of the oesophagus he declined surgery as well as chemo- and radiotherapy.

Three months later he was referred because of increasing …
Government proposes “Ofsted style” ratings for CCG services
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The government has announced plans to introduce new “Ofsted style” ratings for healthcare in England, promising patients much greater access to information on how their local NHS services are performing. Other changes announced by the government will mean that patients can rebook hospital appointments without needing another referral from their GP, thus freeing up an estimated 2.5% of all GP appointments.

Doctors’ leaders, however, have questioned whether the ratings (similar to those used by Ofsted, the Office for Standards in Education, to rate schools) will lead to an improvement in care or give an accurate picture of services locally.

The health secretary, Jeremy Hunt, announced the changes in a speech on 29 October in London, saying that from next year …
STAT3 Mediates Regorafenib-Induced Apoptosis in Hepatocellular Carcinoma
Authors: Wei-Tien Tai, Pei-Yi Chu, Chung-Wai Shiau, Yao-Li Chen, Yong-Shi Li, Man-Hsin Hung, Li-Ju Chen, Pei-Lung Chen, Jung-Chen Su, Ping-Yi Lin, Hui-Chuan Yu, Kuen-Feng Chen
Journal: Clinical Cancer Research (2014)

Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC).HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib ([Formula: see text] mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3.Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035).Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib.
High-Density Lipoprotein Cholesterol Measurements
Authors: H. Robert Superko
Journal: JAMA (1986)

Often, plasma high-density lipoprotein cholesterol (HDLC) measurements lack sufficient accuracy to be of practical use in an individual clinical setting. Recent clinical investigations have demonstrated the strong predictive value of HDLC concentration for future coronary events and rate of progression of angiographically assessed coronary atherosclerosis. Clinical demand for HDLC measurements by clinicians has increased after the announcements of these results. The ability of clinical laboratories to assess HDLC values accurately, so that they may be applied on an individual basis, may be lacking, and enhanced accuracy should be encouraged. (JAMA 1986;256:2714-2717)
The del22q11.2 Candidate Gene <i>Tbx1</i> Controls Regional Outflow Tract Identity and Coronary Artery Patterning
Authors: Magali Théveniau-Ruissy, Mathieu Dandonneau, Karim Mesbah, Olivier Ghez, Marie-Geneviève Mattei, Lucile Miquerol, Robert G. Kelly
Journal: Circulation Research (2008)

TBX1, encoding a T-box containing transcription factor, is the major candidate gene for del22q11.2 or DiGeorge syndrome, characterized by craniofacial and cardiovascular defects including tetralogy of Fallot and common arterial trunk. Mice lacking Tbx1 have severe defects in the development of pharyngeal derivatives including cardiac progenitor cells of the second heart field that contribute to the arterial pole of the heart. The outflow tract of Tbx1 mutant embryos is short and narrow resulting in common arterial trunk. Here we show by a series of genetic crosses using transgene markers of second heart field derived myocardium and coronary endothelial cells that a subdomain of myocardium normally observed at the base of the pulmonary trunk is reduced and malpositioned in Tbx1 mutant hearts. This defect is associated with anomalous coronary artery patterning. Both right and left coronary ostia form predominantly at the right/ventral sinus in mutant hearts, proximal coronary arteries coursing across the normally coronary free ventral region of the heart. We have identified Semaphorin3c as a Tbx1-dependent gene expressed in subpulmonary myocardium. Our results implicate second heart field development in coronary artery patterning and provide new insights into the association between conotruncal defects and coronary artery anomalies.
Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22
Authors: Nandita A. Quaderi, Susann Schweiger, Karin Gaudenz, Brunella Franco, Elena I. Rugarli, Wolfgang Berger, George J. Feldman, Manuela Volta, Grazia Andolfi, S. Gilgenkrantz, Robert W. Marion, Raoul C.M. Hennekam, John M. Opitz, Maximilian Muenke, Hilger H. Ropers, Andrea Ballabio
Journal: Nature Genetics (1997)