tbuckley/cabot-search huggingface dataset:
Pigment Gallstones of the Common Bile Duct in Infancy
Authors: Bruno Descos, Olivier Bernard, Francis Brunelle, Jacques Valayer, Delphine Feldmann, Michelle Hadchouel, Daniel Alagille
Journal: Hepatology (1984)

Ten infants of less than 6 months of age presented with cholestatic jaundice and gallstones. Jaundice occurred after a lag period, and sepsis was present in three children. Ultrasound examination showed dilatation of intrahepatic and extrahepatic bile ducts in eight patients and detected cholelithiasis in three. Percutaneous transhepatic cholangiography and/or surgery allowed separation of the patients into two groups: (i) six children with lithiasis in the distal common bile duct, and (ii) four children with lithiasis associated with bile duct perforation at the junction between the cystic and common bile ducts with gallstones probably secondary to bile stasis and infection. Surgical treatment was confined to removal of calculi and drainage in eight children; biliary reconstructive surgery was necessary in the other two who had serious biliary duct lesions. No recurrence was observed after 1 to 7 years. The pigmentary nature of cholelithiasis was established by stone morphology in all cases, and by bile and stone analysis in several cases.
Abstract 2721: Novel biisoquinoimidazolium-derivatives for breast cancer therapy
Authors: Satya Narayan, Aruna S. Jaiswal, Sukwon Hong
Journal: Cancer Research (2014)

Abstract Breast cancer is the most frequently diagnosed cancer in women. This cancer is classified according to its expression of hormone/growth factor receptors. It is divided into three groups: (i) Estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) Human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). Most chemotherapeutic anti-cancer drugs used in the clinical practice include an anti-estrogenic agent that interferes with ER and prevents tumor progression; however, it is still a big challenge to manage the triple-negative breast tumors. Mitosis and other distinct pathways of apoptosis are considered as a potential target for the development of novel anti-mitotic drugs. In the present investigation, we designed the biisoquinoimidazoliums class of drugs which is structurally similar to anti-mitotic drugs. We synthesized various derivatives of biisoquinoimidazoliums, tested their potency, and suitability as therapeutic agents in preclinical biological system using clonogenic assay. Results showed a strong growth inhibitory effect of these compounds on both triple-positive and triple-negative breast cancer cell lines in the following order: DHO2-93-1 ≥ DHO2-85-3 ≥ DHO2-75-3 ≥ DHO2-85-1. DH02-75-1 also showed some activity, while DHO2-75-2 and DHO2-107-1 did not show any growth inhibitory effect on these cells. From these results, we concluded that DHO2-93-1 may have therapeutic implication as a novel anti-tumor drug for the intervention of both triple-positive and triple-negative breast cancers. Citation Format: Satya Narayan, Aruna S. Jaiswal, Sukwon Hong. Novel biisoquinoimidazolium-derivatives for breast cancer therapy. [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 2721. doi:10.1158/1538-7445.AM2014-2721
The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols
Authors: D. Andreou, S.S. Bielack, D. Carrle, M. Kevric, R. Kotz, W. Winkelmann, G. Jundt, M. Werner, S. Fehlberg, L. Kager, T. Kühne, S. Lang, M. Dominkus, G.U. Exner, J. Hardes, A. Hillmann, V. Ewerbeck, U. Heise, P. Reichardt, P. -U. Tunn
Journal: Annals of Oncology (2010)
Unusual presentation of a large tension bronchogenic cyst in an adult.
Authors: S P Tarpy, H Kornfeld, K Moroz, H L Lazar
Journal: Thorax (1993)

A routine chest radiograph in a 20 year old man revealed a giant air filled cavity of the left hemithorax under tension. At thoracotomy a large left lower lobe intraparenchymal cyst required lobectomy and the pathological findings were consistent with a bronchogenic cyst. Although tension bronchogenic cysts are common in infants, this case demonstrates their unusual presentation in an adult.
The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice
Authors: Mirco Castoldi, Maja Vujic Spasic, Sandro Altamura, Joacim Elmén, Morten Lindow, Judit Kiss, Jens Stolte, Richard Sparla, Lorenza A. D’Alessandro, Ursula Klingmüller, Robert E. Fleming, Thomas Longerich, Hermann J. Gröne, Vladimir Benes, Sakari Kauppinen, Matthias W. Hentze, Martina U. Muckenthaler
Journal: Journal of Clinical Investigation (2011)

Systemic iron homeostasis is mainly controlled by the liver through synthesis of the peptide hormone hepcidin (encoded by Hamp), the key regulator of duodenal iron absorption and macrophage iron release. Here we show that the liver-specific microRNA miR-122 is important for regulating Hamp mRNA expression and tissue iron levels. Efficient and specific depletion of miR-122 by injection of a locked-nucleic-acid-modified (LNA-modified) anti-miR into WT mice caused systemic iron deficiency, characterized by reduced plasma and liver iron levels, mildly impaired hematopoiesis, and increased extramedullary erythropoiesis in the spleen. Moreover, miR-122 inhibition increased the amount of mRNA transcribed by genes that control systemic iron levels, such as hemochromatosis (Hfe), hemojuvelin (Hjv), bone morphogenetic protein receptor type 1A (Bmpr1a), and Hamp. Importantly, miR-122 directly targeted the 3′ untranslated region of 2 mRNAs that encode activators of hepcidin expression, Hfe and Hjv. These data help to explain the increased Hamp mRNA levels and subsequent iron deficiency in mice with reduced miR-122 levels and establish a direct mechanistic link between miR-122 and the regulation of systemic iron metabolism.
Gα <sub>12/13</sub> Mediates α <sub>1</sub> -Adrenergic Receptor–Induced Cardiac Hypertrophy
Authors: Yoshiko Maruyama, Motohiro Nishida, Yoshiyuki Sugimoto, Shihori Tanabe, Justin H. Turner, Tohru Kozasa, Teiji Wada, Taku Nagao, Hitoshi Kurose
Journal: Circulation Research (2002)

In neonatal cardiomyocytes, activation of the G(q)-coupled alpha(1)-adrenergic receptor (alpha(1)AR) induces hypertrophy by activating mitogen-activated protein kinases, including c-Jun NH(2)-terminal kinase (JNK). Here, we show that JNK activation is essential for alpha(1)AR-induced hypertrophy, in that alpha(1)AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK. We also identified the classes and subunits of G proteins that mediate alpha(1)AR-induced JNK activation and hypertrophic responses by generating several recombinant adenoviruses that express polypeptides capable of inhibiting the function of specific G-protein subunits. alpha(1)AR-induced JNK activation was inhibited by the expression of carboxyl terminal regions of Galpha(q), Galpha(12), and Galpha(13). JNK activation was also inhibited by the Galpha(q/11)- or Galpha(12/13)-specific regulator of G-protein signaling (RGS) domains and by C3 toxin but was not affected by treatment with pertussis toxin or by expression of the carboxyl terminal region of G protein-coupled receptor kinase 2, a polypeptide that sequesters Gbetagamma. alpha(1)AR-induced hypertrophic responses were inhibited by Galpha(q/11)- and Galpha(12/13)-specific RGS domains, C3 toxin, and the carboxyl terminal region of G protein-coupled receptor kinase 2 but not by pertussis toxin. Activation of Rho was inhibited by carboxyl terminal regions of Galpha(12) and Galpha(13) but not by Galpha(q). Our findings suggest that alpha(1)AR-induced hypertrophic responses are mediated in part by a Galpha(12/13)-Rho-JNK pathway, in part by a G(q/11)-JNK pathway that is Rho independent, and in part by a Gbetagamma pathway that is JNK independent.
Chronic Administration of Valproic Acid Inhibits Prostate Cancer Cell Growth <i>In vitro</i> and <i>In vivo</i>
Authors: Qinghua Xia, Jennifer Sung, Wasim Chowdhury, Chien-lun Chen, Naseruddin Höti, Shabana Shabbeer, Michael Carducci, Ronald Rodriguez
Journal: Cancer Research (2006)

Abstract Valproic acid (VPA) is an established drug in the long-term therapy of seizure disorders. Recently, VPA has been associated with anticancer activity, an effect thought to be mediated through the inhibition of cellular histone deacetylase 1. We investigated the effect of various doses of VPA (0, 1.2, and 5.0 mmol/L) administered either acutely or chronically on histone acetylation, p21 gene expression, androgen receptor expression, prostate-specific antigen (PSA) expression, and cell survival and proliferation in prostate cancer cell lines. We also studied the effect of chronic VPA on tumor xenograft growth in vivo. Our results show that acute treatment (3 days) VPA can increase net histone H3 acetylation and up-regulate p21, AR, and cytosolic PSA expression. Interestingly, the effects on AR and PSA are reversed with chronic teatment. In addition, acute VPA reduces cell survival but has no effect on the subsequent proliferation of surviving cells following drug withdrawal. However, when VPA is chronically administered (10-14 days) to prostate cancer cells, even lower doses of VPA result in marked decreases in the net proliferation rate, correlating with increased caspase-2 and caspase-3 activation. These effects are evident in both androgen receptor-positive (LNCaP and C4-2) and androgen receptor-negative (DU145 and PC3) prostate cancer cells. Moreover, chronic VPA treatment results in statistically significant reduction of tumor xenograft growth in vivo. We conclude that acute treatment has nominal effects on prostate cancer cell survival and proliferation, but chronic VPA results in profound decreases in proliferation, independently of androgen regulation. (Cancer Res 2006; 66(14): 7237-44)
Optical coherence tomography measurement of macular and nerve fiber layer thickness in normal and glaucomatous human eyes
Authors: Viviane Guedes, Joel S Schuman, Ellen Hertzmark, Gadi Wollstein, Anthony Correnti, Ronald Mancini, David Lederer, Serineh Voskanian, Leonardo Velazquez, Helena M Pakter, Tamar Pedut-Kloizman, James G Fujimoto, Cynthia Mattox
Journal: Ophthalmology (2002)
Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation
Authors: David A. Tulis, William Durante, XiaoMing Liu, Alida J. Evans, Kelly J. Peyton, Andrew I. Schafer
Journal: Circulation (2001)

Background Recent studies have demonstrated that systemic pharmacological induction of heme oxygenase-1 (HO-1), the inducible isoform of the initial and rate-limiting enzyme for heme catabolism, attenuates neointima formation after experimental vascular injury. We have now investigated the ability of localized adenovirus-mediated HO-1 (Ad-HO-1) gene delivery to modify arterial remodeling after balloon angioplasty. Methods and Results Two weeks after balloon angioplasty in the rat carotid artery, elevated HO-1 protein was observed in the Ad-HO-1 arteries compared with those exposed to empty adenovirus (Ad-E) or to PBS. The arteries exposed to Ad-HO-1 exhibited significantly reduced neointimal area, medial wall area, neointimal area/medial wall area ratio, and neointimal thickness compared with arteries exposed to Ad-E. The Ad-E vessels showed subtle reductions in each morphometric parameter compared with PBS vessels. In a separate group of animals, concomitant treatment of Ad-HO-1 with the HO-1 inhibitor tin protoporphyrin completely restored each morphometric parameter to control levels. Arteries exposed to Ad-HO-1 demonstrated significantly increased TUNEL labeling of apoptotic nuclei and significantly decreased PCNA labeling of DNA synthesis in the medial wall 48 hours after injury. Conclusions These results indicate that HO-1 represents an important in vivo vasoprotective mediator that is capable of attenuating the pathophysiological remodeling response to endovascular injury and suggest that HO-1 may be a novel target for the treatment of vascular disease.
Multisite Phosphorylation Mechanism for Protein Kinase A Activation of the Smooth Muscle ATP-Sensitive K <sup>+</sup> Channel
Authors: Kathryn V. Quinn, Jonathan P. Giblin, Andrew Tinker
Journal: Circulation Research (2004)

The activation of ATP-sensitive K+ channels by protein kinase A in vascular smooth muscle is an important component of the action of vasodilators. In this study, we examine the molecular mechanisms of regulation of the cloned equivalent of this channel comprising the sulfonylurea receptor 2B and the inward rectifier 6.1 subunit (SUR2B/Kir6.1). Specifically, we focus on whether the channel is directly phosphorylated and the sites at which this occurs in the protein complex. We identify one site in Kir6.1 (S385) and two sites in SUR2B (T633 and S1465) using a combination of biochemical and functional assays. Our work supports a model in which multiple sites in the channel complex have to be phosphorylated before activation occurs.
Self-Tolerance Does Not Restrict the CD4+ T-Helper Response against the p53 Tumor Antigen
Authors: Marjolein M. Lauwen, Sander Zwaveling, Linda de Quartel, S. Carmela Ferreira Mota, Janine A.C. Grashorn, Cornelis J.M. Melief, Sjoerd H. van der Burg, Rienk Offringa
Journal: Cancer Research (2008)

Abstract Tumorigenesis is frequently associated with mutation and overexpression of p53, which makes it an attractive target antigen for T cell–mediated immunotherapy of cancer. However, the magnitude and breadth of the p53-specific T-cell repertoire may be restricted due to the ubiquitous expression of wild-type p53 in normal somatic tissues. In view of the importance of the CD4+ T-helper cell responses in effective antitumor immunity, we have analyzed and compared the p53-specific reactivity of this T cell subset in p53+/+ and p53−/− C57Bl/6 mice. This response was found to be directed against the same three immunodominant epitopes in both mouse types. Fine-specificity, magnitude, and avidity were not affected by self-tolerance. Immunization of p53−/− and p53+/+ mice with synthetic peptide vaccines comprising the identified epitopes induced equal levels of Th1 immunity. Our findings imply that the p53-specific CD4+ T-cell repertoire is not restricted by self-tolerance and is fully available for the targeting of cancer. [Cancer Res 2008;68(3):893–900]
Evidence for a lipid transfer protein as the major allergen of apricot
Authors: Elide A. Pastorello, Francesco Purello D’Ambrosio, Valerio Pravettoni, Laura Farioli, Gabriella Giuffrida, Mara Monza, Raffaella Ansaloni, Donatella Fortunato, Elisabetta Scibola, Federica Rivolta, Cristoforo Incorvaia, Anders Bengtsson, Amedeo Conti, Claudio Ortolani
Journal: Journal of Allergy and Clinical Immunology (2000)
Hypertensive Retinopathy
Authors: P. S. RAMALHO, C. T. DOLLERY
Journal: Circulation (1968)

Caliber changes in retinal vessels of groups of hypertensive patients were measured after the blood pressure had been lowered by successful renal surgery, posture with adrenergic blocking drugs, and parenteral hydralazine. The small arterioles dilated when the pressure was reduced, whatever means were used. Larger arterioles dilated in three younger hypertensive patients but in the remainder they were unchanged or narrowed by pressure reduction. Inhalation of oxygen constricts normal retinal arterioles but the response in hypertensive patients was much less. A response to oxygen was restored in some small arterioles that dilated when the blood pressure was lowered. As retinal arterioles have no adrenergic vasomotor supply, changes in their caliber probably occur because of autoregulation. Narrowing caused by autoregulation during a rise in systemic arterial pressure may become irreversible in long-standing hypertension because of structural changes in the vessel wall.
Does relationship exist between severity of vitamin D deficiency and development of active TB
Authors: Adeel Tariq Sahal, Joyutpal Das, Sushil Agarwal, Karanvir Singh, Martin Dedicoat, Alice Turner, Heinke Kunst
Journal: European Respiratory Journal (2012)

Introduction   Deficient serum vitamin D levels have been associated with impaired mycobacterial immunity and incidence of active tuberculosis (TB). However, the significance of level of vitamin D in LTBI and the risk of progression to active disease is less clear.   Methods    A retrospective review of vitamin D levels of all patients with active TB and LTBI was undertaken between January 2010 and December 2010 at Heart of England NHS foundation trust, Birmingham. We compared vitamin D levels in cases with active and latent TB to explore a relationship between severity of vitamin D deficiency and incidence of active/ latent TB.   Results   148 cases with LTBI and 113 with active TB were included in the study. 117 out of 148 patients with LTBI and 108 out of 113 active TB cases had a Vitamin D level performed. Median Vitamin D level in patients with TB was 5.7ng/ml (Range 2-46.4). Median Vitamin D level for LTBI was 7.8ng/ml (2-95.30). The difference in Vitamin D levels between latent and active TB cases was statistically significant with P =0.003 (calculated Using Mann Whitney U Test). Subgroup analysis, Median Vitamin D levels of non-white TB and LTBI population were 5.2 (Range 2.00 - 36.20) and 6.5ng/ml (Range 2.00 - 43.40) respectively, P value 0.001. Median Vitamin D levels of white TB and LTBI cases were 17.0 (Range 2.50 - 46.40) and 22.6ng/ml (Range 7.30 - 95.30) respectively, P value 0.25(cohort of white population much smaller than non-white).   Conclusions   Vitamin D levels were significantly lower in active compared to latent tuberculosis cases suggesting that degree of vitamin D deficiency may influences development of active TB. We feel prospective study is needed to evaluate it further.
Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes
Authors: Galit Alter, Maureen P. Martin, Nickolas Teigen, William H. Carr, Todd J. Suscovich, Arne Schneidewind, Hendrik Streeck, Michael Waring, Angela Meier, Christian Brander, Jeffrey D. Lifson, Todd M. Allen, Mary Carrington, Marcus Altfeld
Journal: The Journal of Experimental Medicine (2007)

Decline of peak viremia during acute HIV-1 infection occurs before the development of vigorous adaptive immunity, and the level of decline correlates inversely with the rate of AIDS progression, implicating a potential role for the innate immune response in determining disease outcome. The combined expression of an activating natural killer (NK) cell receptor, the killer immunoglobulin-like receptor (KIR) 3DS1, and its presumed ligand, human leukocyte antigen (HLA)–B Bw4-80I, has been associated in epidemiological studies with a slow progression to AIDS. We examined the functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types. NK cells expressing KIR3DS1 showed strong, significant dose- and cell contact–dependent inhibition of HIV-1 replication in target cells expressing HLA-B Bw4-80I compared with NK cells that did not express KIR3DS1. Furthermore, KIR3DS1+ NK cells and NKLs were preferentially activated, and lysed HIV-1 infected target cells in an HLA-B Bw4-80I–dependent manner. These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.
Spatial Relationship of the C-Terminal Domains of Dystrophin and β-Dystroglycan in Cardiac Muscle Support a Direct Molecular Interaction at the Plasma Membrane Interface
Authors: Shirley Stevenson, Stephen Rothery, Michael J. Cullen, Nicholas J. Severs
Journal: Circulation Research (1998)

Dystrophin and beta-dystroglycan are components of a complex of at least nine proteins (the dystrophin-glycoprotein complex) that physically link the membrane cytoskeleton in skeletal and cardiac muscle, through the plasma membrane, to the extracellular matrix. Mutations in the dystrophin gene, which result in an absence or a quantitative or qualitative alteration of dystrophin, cause a subset of familial dilated cardiomyopathies as well as Duchenne and Becker muscular dystrophy. Biochemical studies on isolated skeletal muscle molecules indicate that dystrophin is bound to the glycoprotein complex via beta-dystroglycan, with the C-terminus of beta-dystroglycan binding to the cysteine-rich domain and first half of the C-terminal domain of dystrophin. Ultrastructural labeling has demonstrated a close spatial relationship between dystrophin and beta-dystroglycan in intact skeletal muscle, but no previous ultrastructural labeling studies have examined the dystrophin/beta-dystroglycan interaction in cardiac muscle. In the present study, we have applied complementary immunoconfocal microscopy and double immunogold fracture-label, a freeze-fracture cytochemical technique that allows high-resolution visualization of labeled membrane components in thin section and in platinum-carbon replicas, to investigate the spatial relationship between dystrophin and beta-dystroglycan in rat cardiac muscle. When immunogold probes of two different sizes for the two proteins were used, "doublets" representing side-by-side antibody labeling were demonstrated in en face views at the level of the plasma membrane. The results support the conclusions that dystrophin and beta-dystroglycan directly interact at the cytoplasmic face of the rat cardiac muscle plasma membrane.
Substantial Shared Genetic Influences on Schizophrenia and Event-Related Potentials
Authors: Mei-Hua Hall, Frühling Rijsdijk, Marco Picchioni, Katja Schulze, Ulrich Ettinger, Timothea Toulopoulou, Elvira Bramon, Robin M. Murray, Pak Sham
Journal: American Journal of Psychiatry (2007)

Objective: Several components of event-related potentials—P50 suppression, P300 amplitude and latency, and mismatch negativity—have been proposed as potential endophenotypes for schizophrenia on the basis of family studies. The present study used a twin design to estimate the extent of genetic overlap between these indices and the liability to schizophrenia. Method: The authors measured mismatch negativity, P300, and P50 suppression in 16 monozygotic twin pairs concordant for schizophrenia, nine monozygotic twin pairs discordant for schizophrenia, and 78 healthy comparison twin pairs. The study design was based on a power calculation. Structural equation modeling was used to quantify the genetic and environmental contributions to the phenotypic covariance between schizophrenia and each of the event-related potential indices. Results: Significant phenotypic correlation with schizophrenia was found for each of the event-related potential components. Genetic factors were the main source of the phenotypic correlations. P50 suppression had the greatest genetic correlation with schizophrenia, followed by P300 amplitude, P300 latency, and mismatch negativity. Conclusions: All four event-related potential indices are potentially valid endophenotypes for schizophrenia, but P50 suppression and P300 amplitude show the closest genetic relationship to schizophrenia.