tbuckley/cabot-search huggingface dataset:
Knockdown of the Transforming Growth Factor-β Type III Receptor Impairs Motility and Invasion of Metastatic Cancer Cells
Authors: Tracy L. Criswell, Nancy Dumont, Joey V. Barnett, Carlos L. Arteaga
Journal: Cancer Research (2008)

Abstract The transforming growth factor-β (TGF-β) signaling pathway plays dual roles in epithelial cell tumorigenesis. TGF-β is initially growth inhibitory, but as tumorigenesis progresses, TGF-β becomes prometastatic. Although the role of the types I and II TGF-β receptors is fairly well established, the role of the ubiquitously expressed TGF-β type III receptor (TβRIII) in tumorigenesis is less defined. To examine the role of TβRIII in breast cancer cells, we stably expressed short hairpin RNAs specific to TβRIII in MDA-231 human breast cancer cells and mouse mammary carcinoma cells expressing the polyomavirus middle T oncogene (PMTLuc). MDA-231 and PMTLuc cells with down-regulated TβRIII expression (231-kd; PMTLuc-kd) exhibited decreased growth rate, motility, and invasion into Matrigel, as well as an increase in apoptosis, compared with control cells. MDA-231 xenografts established in nude mice metastasized, whereas tumors made by 231-kd cells did not. Nuclear factor-κB (NF-κB) activity, which is known to regulate cell growth and motility, was lower in the MDA-231 and PMTLuc knockdown cells compared with control cells. Transfection of an expression vector encoding constitutively active IKK2 into the 231-kd cells restored the ability of TβRIII-deficient cells to invade Matrigel and decreased their basal level of apoptosis. These data indicate that TβRIII differentially regulates cell growth, motility, and invasion in tumorigenic MDA-231 and PMTLuc cells and that these growth changes occur through the modulation of NF-κB activity. [Cancer Res 2008;68(18):7304–12]
Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study
Authors: K. Koskenvuo, U. Broms, T. Korhonen, L.A. Laitinen, A. Huunan-Seppälä, T. Keistinen, I. Autti-Rämö, J. Kaprio, M. Koskenvuo
Journal: European Respiratory Journal (2010)

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0–48.5) and for smokers with ≥12 pack-yrs was 27.3 (95% CI 12.6–59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (&lt;18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08–2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.
Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes.
Authors: H Kishimoto, Z Cai, A Brunmark, M R Jackson, P A Peterson, J Sprent
Journal: The Journal of Experimental Medicine (1996)

To ensure self tolerance, immature thymocytes with high binding affinity for self peptides linked to major histocompatibility complex (MHC) molecules are eliminated in situ via apoptosis (negative selection). The roles of two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in negative selection was examined by studying apoptosis of T cell receptor transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC class I-transfected Drosophila cells. When coexpressed on these cells, B7-1 and ICAM-1 act synergistically and cause strong class 1-restricted negative selection of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display opposite functions: negative selection is augmented by B7-1, but is inhibited by ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla, whereas ICAM-1 is expressed throughout the thymus. Because of this distribution, the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on the cortical epithelium may preclude or reduce negative selection and thereby promote positive selection. Conversely, the combined expression of B7-1 and ICAM-1 may define the medulla as the principal site of negative selection.
Acid suppression and paediatric asthma
Authors: S Birring
Journal: Thorax (2005)

▴ Stordal K, Johannesdottir GB, Bentsen BS, et al . Acid suppression does not change respiratory symptoms in children with asthma and gastro-oesophageal reflux. Arch Dis Child2005;90:956–60 [OpenUrl][1][Abstract/FREE Full Text][2] Gastro-oesophageal reflux is common in children with asthma but its relevance is unclear. The effects of proton pump inhibitors on asthma control in children are not known. Thirty six children … [1]: {openurl}?query=rft.jtitle%253DArchives%2Bof%2BDisease%2Bin%2BChildhood%26rft.stitle%253DArch.%2BDis.%2BChild.%26rft.issn%253D0003-9888%26rft.aulast%253DStordal%26rft.auinit1%253DK%26rft.volume%253D90%26rft.issue%253D9%26rft.spage%253D956%26rft.epage%253D960%26rft.atitle%253DAcid%2Bsuppression%2Bdoes%2Bnot%2Bchange%2Brespiratory%2Bsymptoms%2Bin%2Bchildren%2Bwith%2Basthma%2Band%2Bgastro-oesophageal%2Breflux%2Bdisease%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fadc.2004.068890%26rft_id%253Dinfo%253Apmid%252F16113133%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=archdischild&resid=90/9/956&atom=%2Fthoraxjnl%2F60%2F11%2F973.atom
Receptor Editing and Marginal Zone B Cell Development Are Regulated by the Helix-Loop-Helix Protein, E2A
Authors: Melanie W. Quong, Annica Martensson, Anton W. Langerak, Richard R. Rivera, David Nemazee, Cornelis Murre
Journal: The Journal of Experimental Medicine (2004)

Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate that E2A+/− B cells that express an autoreactive B cell receptor fail to mature due in part to an inability to activate secondary immunoglobulin (Ig) light chain gene rearrangement. Both RAG1/2 gene expression and RS deletion are severely defective in E2A+/− mice. Additionally, we demonstrate that E2A+/− mice show an increase in the proportion of marginal zone B cells with a concomitant decrease in the proportion of follicular B cells. In contrast, Id3-deficient splenocytes show a decline in the proportion of marginal zone B cells. Based on these observations, we propose that E-protein activity regulates secondary Ig gene rearrangement at the immature B cell stage and contributes to cell fate determination of marginal zone B cells. Additionally, we propose a model in which E-proteins enforce the developmental checkpoint at the immature B cell stage.
The draft genome, transcriptome, and microbiome of Dermatophagoides farinae reveal a broad spectrum of dust mite allergens
Authors: Ting-Fung Chan, Kun-Mei Ji, Aldrin Kay-Yuen Yim, Xiao-Yu Liu, Jun-Wei Zhou, Rui-Qi Li, Kevin Yi Yang, Jing Li, Meng Li, Patrick Tik-Wan Law, Yu-Lan Wu, Ze-Lang Cai, Hao Qin, Ying Bao, Ross Ka-Kit Leung, Patrick Kwok-Shing Ng, Ju Zou, Xiao-Jun Zhong, Pi-Xin Ran, Nan-Shan Zhong, Zhi-Gang Liu, Stephen Kwok-Wing Tsui
Journal: Journal of Allergy and Clinical Immunology (2014)

A sequenced house dust mite (HDM) genome would advance our understanding of HDM allergens, a common cause of human allergies.We sought to produce an annotated Dermatophagoides farinae draft genome and develop a combined genomic-transcriptomic-proteomic approach for elucidation of HDM allergens.A D farinae draft genome and transcriptome were assembled with high-throughput sequencing, accommodating microbiome sequences. The allergen gene structures were validated by means of Sanger sequencing. The mite's microbiome composition was determined, and the predominant genus was validated immunohistochemically. The allergenicity of a ubiquinol-cytochrome c reductase binding protein homologue was evaluated with immunoblotting, immunosorbent assays, and skin prick tests.The full gene structures of 20 canonical allergens and 7 noncanonical allergen homologues were produced. A novel major allergen, ubiquinol-cytochrome c reductase binding protein-like protein, was found and designated Der f 24. All 40 sera samples from patients with mite allergy had IgE antibodies against rDer f 24. Of 10 patients tested, 5 had positive skin reactions. The predominant bacterial genus among 100 identified species was Enterobacter (63.4%). An intron was found in the 13.8-kDa D farinae bacteriolytic enzyme gene, indicating that it is of HDM origin. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed a phototransduction pathway in D farinae, as well as thiamine and amino acid synthesis pathways, which is suggestive of an endosymbiotic relationship between D farinae and its microbiome.An HDM genome draft produced from genomic, transcriptomic, and proteomic experiments revealed allergen genes and a diverse endosymbiotic microbiome, providing a tool for further identification and characterization of HDM allergens and development of diagnostics and immunotherapeutic vaccines.
The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss
Authors: David J Miller, Georg Hemmrich, Eldon E Ball, David C Hayward, Konstantin Khalturin, Noriko Funayama, Kiyokazu Agata, Thomas CG Bosch
Journal: Genome biology (2007)

Abstract Background Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest - it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis , and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora . Results To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-κB could be identified in the anthozoan Hydra . Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra , however, and at least one MAC/PF gene appears to have been lost from Nematostella . Conclusion Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system.
OCT4
Authors: Timothy D. Jones, Thomas M. Ulbright, John N. Eble, Liang Cheng
Journal: Clinical Cancer Research (2004)

OCT4 (POU5F1, OCT3) immunostaining highlights pluripotent cells (embryonal carcinoma and seminoma) in primary testicular germ cell tumors, but its relative usefulness in diagnosing intratubular germ cell neoplasia, unclassified (IGCNU) is not well established. The present study aimed to establish OCT4 as a sensitive and specific maker for IGCNU, a putative precursor for adult germ cell tumors.We evaluated OCT4 immunostaining in 44 cases of IGCNU from patients who had testicular germ cell tumors. In addition, 27 of the 44 IGCNU sections were also examined with antibodies to placenta-like alkaline phosphatase, the most frequently used immunohistochemical marker for intratubular germ cell neoplasia. Sections from the testes of 10 patients who had undergone orchiectomy for hormonal treatment of prostate cancer and from autopsies of 10 patients without histories of germ cell tumors were also examined for OCT4 immunostaining. The immunoreactivity of the autopsy tissues was determined with vimentin staining, and all were reactive.In all 44 of the cases, antibody to OCT4 marked the nuclei of nearly all of the dysplastic cells of intratubular germ cell neoplasia but not non-neoplastic testicular cells. The staining intensity was strong in every case, and there was little or no background staining. All 20 of the control specimens (10 orchiectomy specimens from prostate cancer patients and 10 testes from autopsies) were completely negative for OCT4. The 27 cases that were stained with antiplacenta-like alkaline phosphatase antibodies showed staining of variable intensity in the areas of intratubular germ cell neoplasia, and there was a high level of background staining artifact.OCT4 is a sensitive and specific maker for intratubular germ cell neoplasia.
14C-UREA BREATH ANALYSIS, A NON-INVASIVE TEST FOR CAMPYLOBACTER PYLORI IN THE STOMACH
Authors: G.D Bell, J Weil, G Harrison, A Morden, P.H Jones, P.W Gant, J.E Trowell, A.K Yoong, T.K Daneshmend, R.F.A Logan
Journal: The Lancet (1987)
Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.
Authors: J Carstens, J Greisen, K T Jensen, H Vilstrup, E B Pedersen
Journal: Journal of the American Society of Nephrology (1998)

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.
Anonychia with bizarre flexural pigmentation—an autosomal dominant dermatosis
Authors: Julian Verbov
Journal: British Journal of Dermatology (1975)

A nulliparous female aged 26 years, who presented with long-standing sore and cracked soles, showed congenital anonychia, long-standing hyper-and-hypo-pigmentation in axillae and groins, dry palmar and plantar skin as well as other skin and hair abnormalities. She gave a family history of nail, hair and pigmentary abnormalities and examination of living affected relatives confirmed this. This appears to be a hitherto undescribed autosomal dominant syndrome.
CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
Authors: F S Wong, I Visintin, L Wen, R A Flavell, C A Janeway
Journal: The Journal of Experimental Medicine (1996)

T cells play an important role in the pathogenesis of diabetes in the nonobese diabetic (NOD) mouse. CD8 cytotoxic T cell lines and clones were generated from the lymphocytic infiltrate in the islets of Langerhans of young (7-wk-old). NOD mice by growing them on (NOD x B6-RIP-B7-1)F1 islets. These cells proliferate specifically to NOD islets and kill NOD islets in vitro. The cells are restricted by H-2Kd, and all bear T cell antigen receptor encoded by V beta 6. When these CD8 T cell lines and clones are adoptively transferred to irradiated female NOD, young NOD-SCID, and CB17-SCID mice, diabetes occurs very rapidly, within 10 d of transfer and without CD4 T cells.
Regression of High-Grade Malignancy in Mice by Bleomycin and Interleukin-12 Electrochemogenetherapy
Authors: Marina N. Torrero, William G. Henk, Shulin Li
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Bleomycin electrochemotherapy has been successfully used in preclinical studies and clinical trials for treating squamous cell carcinoma (SCC) and adenocarcinoma; however, it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment. In this study, we explore the coadministration of bleomycin and interleukin-12 (IL-12) followed by electroporation for treating primary and metastatic tumors. Experimental Design: Bleomycin, IL-12 plasmid DNA, or a combination of both were injected into high-grade malignant mammary tumors and SCCVII followed by electroporation. The tumor growth, survival, metastasis in lungs, CTL activity, and vascular density were analyzed. The results were analyzed by the two-sided Student's t test and Gehan's Wilcoxon test. Results: Coadministration of bleomycin and IL-12 via electroporation eradicates preestablished 4T1 mammary tumors in up to 60% of mice, inhibits metastatic tumor development, and extends the long-term survival. Likewise, coadministration of bleomycin and IL-12 via electroporation eradicates squamous cell carcinoma (SCCVII) in 100% of mice and prevents tumor redevelopment in 80% of mice. Neither bleomycin nor IL-12 alone is able to achieve the same therapeutic potency. The primary role of bleomycin is to inhibit the tumor vessel development; the primary role of IL-12 is to increase the immune response that extends the survival of treated mice and inhibits the tumor redevelopment. Conclusions: This combination modality has great potential to be translated in a clinical setting for treating high-grade malignancies and for preventing tumor redevelopment.
Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in Japanese chronic lymphocytic leukemia cases
Authors: Masayuki Imajoh, Yumiko Hashida, Ayuko Taniguchi, Mikio Kamioka, Masanori Daibata
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV) and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases. Findings We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T ( LT ) gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T ( ST ) gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. Conclusions This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.
Anatomic substrate of impaired antegrade conduction over an accessory atrioventricular pathway in the Wolff-Parkinson-White syndrome.
Authors: G J Klein, D B Hackel, J J Gallagher
Journal: Circulation (1980)

We present a patient with Wolff-Parkinson-White syndrome who died of a myocardial infarction 19 months after clinical electrophysiologic studies. These studies suggested the presence of a left atrioventricular accessory pathway that sustained conduction well in the retrograde direction but only intermittently in the antegrade direction. Postmortem examination of the heart revealed three accessory atrioventricular pathways in proximity to each other in the posterolateral atrioventricular region. One pathway showed complete fibrosis and two showed patchy fibrosis. The fibrosis suggests an anatomic basis for the impaired antegrade conduction observed in life.
Rapid excretion of gallium‐67 isotope in an iron‐overloaded patient receiving high‐dose intravenous deferoxamine
Authors: David L. Baker, Catherine S. Manno
Journal: American Journal of Hematology (1988)

Abstract A 23 year‐old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga‐67), which was initially nondiagnostic because of Ga‐67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney. To our knowledge the unusual interaction in vivo of DFO with Ga‐67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga‐67 scanning in this clinical situation, or an alternative isotopic scan, such as indium‐labelled white cells, should be considered.
Frequency of S492R Mutations in the Epidermal Growth Factor Receptor: Analysis of Plasma Dna from Metastatic Colorectal Cancer Patients Treated with Panitumumab or Cetuximab Monotherapy
Authors: K. Newhall, T. Price, M. Peeters, T.W. Kim, J. Li, S. Cascinu, P. Ruff, A.S. Suresh, A. Thomas, S. Tjulandin, S. Ogbagabriel, M. Boedigheimer, S. Sexson, K. Zhang, S. Murugappan, R. Sidhu
Journal: Annals of Oncology (2014)