tbuckley/cabot-search huggingface dataset:
Concurrent cutaneous polyarteritis nodosa and arteritis temporalis in a 68-year-old woman
Authors: L.K. Andersen, T. Steiniche, I.T. Hansen, M.S. Deleuran
Journal: British Journal of Dermatology (2014)

Funding sources: None. Conflicts of interest: None declared. Dear Editor, Cutaneous polyarteritis nodosa (CPN) is a rare vasculitis affecting the small and medium arteries in the reticular dermis and subcutaneous tissue. CPN should be distinguished from systemic polyarteritis nodosa (PAN), which is an aggressive systemic vasculitis with internal organ involvement. Extracutaneous findings of CPN include fever, myalgia, arthralgia and neuropathy.1 In contrast, temporal arteritis (TA) or giant‐cell arteritis (GCA) is a vasculitis that involves the medium and large arteries, and may develop together with polymyalgia rheumatica.2 An overlapping vasculitic syndrome of PAN and TA has been reported in the literature.3 4 5 6 7 8 To our knowledge, CPN with TA has only been described in one previous case report.9 We report a 68‐year‐old woman who presented with livedo reticularis with necrotic centres in a starburst pattern on the back, chest and upper arms of 3‐week duration (Fig. 1). Extracutaneous findings included fever, myalgia and weakness in the thighs. She had no other neurological symptoms or symptoms from the gastrointestinal or genitourinary tract. She also denied having any cardiopulmonary symptoms. Her medical history included long‐term treatment for depression. A punch biopsy was performed on the upper arm and she was started on prednisolone 50 mg daily. Laboratory tests revealed normal haemoglobin, slightly elevated C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leucocytosis. Urine analysis, s‐creatinine, glomerular filtration rate and creatine kinase were normal. Hepatitis A, B and C serology were negative. Immunoglobulin levels, cryoglobulins, antinuclear antibody, antineutrophil cytoplasmic antibody and rheumatoid factor were normal. Echocardiography and bone marrow aspirate were normal. A computed tomography (CT) scan of the chest, abdomen and pelvis showed no sign of malignancy. A 18F‐fluorodeoxyglucose–positron emission tomography scan revealed a rectal adenoma, which was surgically removed. Histology of the punch biopsy showed vasculitis in the small and medium arteries in subcutaneous tissue (Fig. 2a, b), which are typical findings of PAN. An abdominal angiography showed no involvement of the abdominal vessels. A revised final diagnosis of CPN was made. The patient improved on prednisolone treatment, which was tapered off over the next few months. The cutaneous ulcers healed and the other symptoms disappeared. She had no further relapse.
TWIST-1 Is Overexpressed in Neoplastic Choroid Plexus Epithelial Cells and Promotes Proliferation and Invasion
Authors: Martin Hasselblatt, Sonja Mertsch, Björn Koos, Barbara Riesmeier, Heike Stegemann, Astrid Jeibmann, Manuel Tomm, Nicole Schmitz, Brigitte Wrede, Johannes E. Wolff, Wei Zheng, Werner Paulus
Journal: Cancer Research (2009)

Abstract The pathogenesis of choroid plexus papillomas, intraventricular papillary neoplasms most often occurring sporadically in children and young adults, remains poorly understood. To identify pathways operative in the development of choroid plexus papillomas, gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells (n = 7) were compared with that of normal choroid plexus epithelial cells laser microdissected from autopsy tissue (n = 8). On DNA microarray data analysis, 53 probe sets were differentially expressed in choroid plexus papilloma tumor cells (&amp;gt;7-fold). Up-regulation of TWIST1, WIF1, TRPM3, BCLAF1, and AJAP1, as well as down-regulation of IL6ST was confirmed using quantitative reverse transcription-PCR. Knockdown of Twist1 gene expression in the rat choroid plexus epithelial cell line Z310 significantly reduced proliferation as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell invasion in a Matrigel assay, whereas cell migration was not affected. Screening for expressional changes of cancer-related genes upon Twist1 knockdown revealed up-regulation of Cdkn1a, Cflar, and Serpinb2 and down-regulation of Figf. To conclude, using gene expression profiling, several genes differentially expressed in human choroid plexus papillomas could be identified. Among those, TWIST1 is highly expressed in choroid plexus papillomas and promotes proliferation and invasion. [Cancer Res 2009;69(6):2219–23]
Comparative efficacy and safety of a once-daily loratadine-pseudoephedrine combination versus its components alone and placebo in the management of seasonal allergic rhinitis
Authors: E BRONSKY, P BOGGS, S FINDLAY, S GAWCHIK, J GEORGITIS, H MANSMANN, L SHOLLER, J WOLFE, E MELTZER, R MORRIS
Journal: Journal of Allergy and Clinical Immunology (1995)
Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial
Authors: S Vincent Rajkumar, Susanna Jacobus, Natalie S Callander, Rafael Fonseca, David H Vesole, Michael E Williams, Rafat Abonour, David S Siegel, Michael Katz, Philip R Greipp
Journal: The Lancet Oncology (2009)
Oxidative Stress-Regulated Lentiviral TK/GCV Gene Therapy for Lung Cancer Treatment
Authors: Hanna M. Leinonen, Anna-Kaisa Ruotsalainen, Ann-Marie Määttä, Heidi M. Laitinen, Suvi M. Kuosmanen, Emilia Kansanen, Jere T. Pikkarainen, Jari P. Lappalainen, Haritha Samaranayake, Hanna P. Lesch, Minna U. Kaikkonen, Seppo Ylä-Herttuala, Anna-Liisa Levonen
Journal: Cancer Research (2012)

Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor that regulates protection against a wide variety of toxic insults to cells, including cytotoxic cancer chemotherapeutic drugs. Many lung cancer cells harbor a mutation in either Nrf2 or its inhibitor Keap1 resulting in permanent activation of Nrf2 and chemoresistance. In this study, we sought to examine whether this attribute could be exploited in cancer suicide gene therapy by using a lentiviral (LV) vector expressing herpes simplex virus thymidine kinase (HSV-TK/GCV) under the regulation of antioxidant response element (ARE), a cis-acting enhancer sequence that binds Nrf2. In human lung adenocarcinoma cells in which Nrf2 is constitutively overexpressed, ARE activity was found to be high under basal conditions. In this setting, ARE-HSV-TK was more effective than a vector in which HSV-TK expression was driven by a constitutively active promoter. In a mouse xenograft model of lung cancer, suicide gene therapy with LV-ARE-TK/GCV was effective compared with LV-PGK-TK/GCV in reducing tumor size. We conclude that ARE-regulated HSV-TK/GCV therapy offers a promising approach for suicide cancer gene therapy in cells with high constitutive ARE activity, permitting a greater degree of therapeutic targeting to those cells.
Influence of metabolic network structure and function on enzyme evolution.
Authors: Dennis Vitkup, Peter Kharchenko, Andreas Wagner
Journal: Genome biology (2006)

Most studies of molecular evolution are focused on individual genes and proteins. However, understanding the design principles and evolutionary properties of molecular networks requires a system-wide perspective. In the present work we connect molecular evolution on the gene level with system properties of a cellular metabolic network. In contrast to protein interaction networks, where several previous studies investigated the molecular evolution of proteins, metabolic networks have a relatively well-defined global function. The ability to consider fluxes in a metabolic network allows us to relate the functional role of each enzyme in a network to its rate of evolution.Our results, based on the yeast metabolic network, demonstrate that important evolutionary processes, such as the fixation of single nucleotide mutations, gene duplications, and gene deletions, are influenced by the structure and function of the network. Specifically, central and highly connected enzymes evolve more slowly than less connected enzymes. Also, enzymes carrying high metabolic fluxes under natural biological conditions experience higher evolutionary constraints. Genes encoding enzymes with high connectivity and high metabolic flux have higher chances to retain duplicates in evolution. In contrast to protein interaction networks, highly connected enzymes are no more likely to be essential compared to less connected enzymes.The presented analysis of evolutionary constraints, gene duplication, and essentiality demonstrates that the structure and function of a metabolic network shapes the evolution of its enzymes. Our results underscore the need for systems-based approaches in studies of molecular evolution.
A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13
Authors: Minyun Zhou, Xianchi Dong, Carsten Baldauf, Hua Chen, Yanfeng Zhou, Timothy A. Springer, Xinping Luo, Chen Zhong, Frauke Gräter, Jianping Ding
Journal: Blood (2011)
Long-Term Effects on Medical Costs of Improving Depression Outcomes in Patients With Depression and Diabetes
Authors: Wayne J. Katon, Joan E. Russo, Michael Von Korff, Elizabeth H.B. Lin, Evette Ludman, Paul S. Ciechanowski
Journal: Diabetes Care (2008)

The purpose of this study was to examine the 5-year effects on total health care costs of the Pathways depression intervention program for patients with diabetes and comorbid depression compared with usual primary care.The Pathways Study was conducted in nine primary care practices of a large HMO and enrolled 329 patients with diabetes and comorbid major depression. The current study analyzed the differences in long-term medical costs between intervention and usual care patients. Participants were randomly assigned to a nurse depression intervention (n = 164) or to usual primary care (n = 165). The intervention included education about depression, behavioral activation, and a choice of either starting with support of antidepressant medication treatment by the primary care doctor or problem-solving therapy in primary care. Interventions were provided for up to 12 months, and the main outcome measures are health costs over a 5-year period.Patients in the intervention arm of the study had improved depression outcomes and trends for reduced 5-year mean total medical costs of -$3,907 (95% CI -$15,454 less to $7,640 more) compared with usual care patients. A sensitivity analysis found that these cost differences were largely explained by the patients with depression and the most severe medical comorbidity.The Pathways depression collaborative care program improved depression outcomes compared with usual care with no evidence of greater long-term costs and with trends for reduced costs among the more severely medically ill patients with diabetes.
Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II
Authors: Klaus Schwarz, Achille Iolascon, Fatima Verissimo, Nikolaus S Trede, Wyatt Horsley, Wen Chen, Barry H Paw, Karl-Peter Hopfner, Karlheinz Holzmann, Roberta Russo, Maria Rosaria Esposito, Daniela Spano, Luigia De Falco, Katja Heinrich, Brigitte Joggerst, Markus T Rojewski, Silverio Perrotta, Jonas Denecke, Ulrich Pannicke, Jean Delaunay, Rainer Pepperkok, Hermann Heimpel
Journal: Nature Genetics (2009)
Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression
Authors: Jean-Eric Ghia, Patricia Blennerhassett, Stephen M. Collins
Journal: Journal of Clinical Investigation (2008)

Clinical and experimental evidence indicates that intestinal inflammatory conditions can be exacerbated by behavioral conditions such as depression. The recent demonstration of a tonic counterinflammatory influence mediated by the vagus nerve in experimental colitis provides a potential link between behavior and gut inflammation. Here we show that experimental conditions that induced depressive-like behaviors in mice increased susceptibility to intestinal inflammation by interfering with the tonic vagal inhibition of proinflammatory macrophages and that tricyclic antidepressants restored vagal function and reduced intestinal inflammation. These results show that reserpine-induced monoamine depletion and maternal separation, 2 models for depression, produced a vulnerability to colitis by a mechanism involving parasympathetic transmission and the presence of gut macrophages. The tricyclic antidepressant desmethylimipramine protected against this vulnerability by a vagal-dependent mechanism. Together these results illustrate the critical role of the vagus in both the vulnerability to inflammation induced by depressive-like conditions and the protection afforded by tricyclic antidepressants and rationalize a clinical evaluation of both parasympathomimetics and tricyclic antidepressants in treatment of inflammatory bowel disease.
Fatal asthma attributed to patent foramen ovale
Authors: ES Boon, BL Maesen, Y Valcke, J Koudstaal
Journal: European Respiratory Journal (1993)

A 37 year old woman was admitted to the hospital with acute severe asthma, shortly followed by respiratory failure and circulatory arrest. Despite intensive cardio-pulmonary resuscitation, during which extreme arterial hypoxaemia persisted, the patient died. Postmortem examination revealed a patent foramen ovale, with a diameter of 1 cm. A severe right-to-left shunt, initiated by acute pulmonary hypertension, was considered to be the cause of death. Because of the relatively high prevalence of patent foramen ovale in the normal population, we suggest this patency may enhance the risk of fatal outcome of acute severe asthma.
Multicenter Phase II Study of Everolimus in Patients With Previously Treated Metastatic Gastric Cancer
Authors: Toshihiko Doi, Kei Muro, Narikazu Boku, Yasuhide Yamada, Tomohiro Nishina, Hiroya Takiuchi, Yoshito Komatsu, Yasuo Hamamoto, Nobutsugu Ohno, Yoshie Fujita, Matthew Robson, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2010)

PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, has shown antitumor activity in gastric cancer in preclinical and phase I studies. This phase II study evaluated the efficacy and safety of everolimus in pretreated patients with advanced gastric cancer. PATIENTS AND METHODS Patients with advanced gastric cancer who experienced progression despite prior chemotherapy received everolimus 10 mg orally daily until disease progression or study discontinuation. The primary end point was disease control rate (DCR; ie, complete response, partial response, or stable disease). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS Fifty-three patients were assessable (median age, 63 years; 51% and 49% received one or two prior chemotherapy regimens, respectively). Although no complete or partial response was obtained, a decrease in tumor size from baseline was observed in 45% of patients by central review. The DCR was 56.0% (95% CI, 41.3% to 70.0%); median PFS was 2.7 months (95% CI, 1.6 to 3.0 months). At a median follow-up time of 9.6 months, median OS was 10.1 months (95% CI, 6.5 to 12.1 months). Common grade 3 or 4 adverse events included anemia, hyponatremia, increased gamma-glutamyltransferase, and lymphopenia. Grade 1 or 2 pneumonitis was reported in eight patients (15.1%). CONCLUSION Everolimus monotherapy resulted in a promising DCR in patients with previously treated advanced gastric cancer. Adverse events are consistent with the reported safety profile of everolimus. These results warrant further evaluation in patients with advanced gastric cancer.
Nor-ursodeoxycholic acid reverses hepatocyte-specific nemo-dependent steatohepatitis
Authors: N. Beraza, L. Ofner-Ziegenfuss, H. Ehedego, M. Boekschoten, S. C. Bischoff, M. Mueller, M. Trauner, C. Trautwein
Journal: Gut (2010)

Hepatocyte-specific NEMO/NF-κB deleted mice (NEMO(Δhepa)) develop spontaneous non-alcoholic steatohepatitis (NASH). Free fatty acids and bile acids promote DR5 expression. TRAIL/NK cell-mediated activation of TRAIL-R2/DR5 plays an important role during acute injury in NEMO(Δhepa) mice.To inhibit the progression of NASH in the absence of hepatocyte-NEMO/NF-kB signaling.NEMOf/f and NEMO(Δhepa) mice were fed with a low-fat diet, and with two anticholestatic diets; UDCA and NorUDCA. The impact of these treatments on the progression of NASH was evaluated.We show that high expression of DR5 in livers from NEMO(Δhepa) mice is accompanied by an abundant presence of bile acids (BAs), misregulation of BA transporters and significant alteration of lipid metabolism-related genes. Additionally, mice lacking NEMO in hepatocytes spontaneously showed ductular response at young age. Unexpectedly, feeding of NEMO(Δhepa) mice with low-fat diet failed to improve chronic liver injury. Conversely, anti-cholestatic treatment with nor-ursodeoxycholic acid (NorUDCA), but not with ursodeoxycholic acid (UDCA), led to a significant attenuation of liver damage in NEMO(Δhepa) mice. The strong therapeutic effect of NorUDCA relied on a significant downregulation of LXR-dependent lipogenesis and the normalisation of BA metabolism through mechanisms involving cross-talk between Cyp7a1 and SHP. This was associated with the significant improvement of liver histology, NEMO(Δhepa)/NorUDCA-treated mice showed lower apoptosis and reduced CyclinD1 expression, indicating attenuation of the compensatory proliferative response to hepatocellular damage. Finally, fibrosis and ductular reaction markers were significantly reduced in NorUDCA-treated NEMO(Δhepa) mice.Overall, our work demonstrates the contribution of bile acids metabolism to the progression of NASH in the absence of hepatocyte-NF-kB through mechanisms involving DR5-apoptosis, inflammation and fibrosis. Our work suggests a potential therapeutic effect of NorUDCA in attenuating the progression of NASH.
Progression From Newly Acquired Impaired Fasting Glucose to Type 2 Diabetes
Authors: Sean F. Dinneen, Robert A. Rizza
Journal: Diabetes Care (2007)

We read with interest the report by Nichols et al. (1) on progression from impaired fasting glucose (IFG) to type 2 diabetes among 5,452 members of the Kaiser Permanente Northwest HMO. Their analysis includes a very thorough assessment of the impact of the new American Diabetes Association (ADA) criteria for IFG on future risk of diabetes. They conclude that the older criteria for IFG (110–125 mg/dl) are more predictive of future diabetes. The authors suggest that their study is the first to report diabetes incidence in routine clinical practice using the …
Properties of isolated red pulp macrophages from mouse spleen.
Authors: A R Nusrat, S D Wright, A A Aderem, R M Steinman, Z A Cohn
Journal: The Journal of Experimental Medicine (1988)

Dense monolayers of large, adherent macrophages were prepared from the red pulp of mouse spleen. These sinus-lining phagocytes resembled liver Kupffer cells in morphology, as well as expression of F4/80 and class II MHC antigens and receptors for IgG. C3-coated red cells attached at low levels to spleen macrophages, but attachment and endocytosis were enhanced on fibronectin-coated surfaces. The ionophore A23187 induced spleen macrophages to synthesize prostaglandin E2, but like Kupffer cells, spleen macrophages did not synthesize leukotrienes and made relatively small amounts of HETE and 12-hydroxyheptadecanoic acid. Resident spleen macrophages did not produce H2O2, but splenic inflammatory cells, induced by infection of animals with Listeria monocytogenes, actively released H2O2. We conclude that the functional properties of resident, sinusoidal-lining macrophages in liver and spleen are similar to one another but distinct from other pools of phagocytes.
Diacylated Sulfoglycolipids Are Novel Mycobacterial Antigens Stimulating CD1-restricted T Cells during Infection with <i>Mycobacterium tuberculosis </i>
Authors: Martine Gilleron, Steffen Stenger, Zaima Mazorra, Frederick Wittke, Sabrina Mariotti, Gabriele Böhmer, Jacques Prandi, Lucia Mori, Germain Puzo, Gennaro De Libero
Journal: The Journal of Experimental Medicine (2004)

Mycobacterial lipids comprise a heterogeneous group of molecules capable of inducing T cell responses in humans. To identify novel antigenic lipids and increase our understanding of lipid-mediated immune responses, we established a panel of T cell clones with different lipid specificities. Using this approach we characterized a novel lipid antigen belonging to the group of diacylated sulfoglycolipids purified from Mycobacterium tuberculosis. The structure of this sulfoglycolipid was identified as 2-palmitoyl or 2-stearoyl-3-hydroxyphthioceranoyl-2′-sulfate-α-α′-d-trehalose (Ac2SGL). Its immunogenicity is dependent on the presence of the sulfate group and of the two fatty acids. Ac2SGL is mainly presented by CD1b molecules after internalization in a cellular compartment with low pH. Ac2SGL-specific T cells release interferon γ, efficiently recognize M. tuberculosis–infected cells, and kill intracellular bacteria. The presence of Ac2SGL-responsive T cells in vivo is strictly dependent on previous contact with M. tuberculosis, but independent from the development of clinically overt disease. These properties identify Ac2SGL as a promising candidate to be tested in novel vaccines against tuberculosis.
Endogenous Ligands for High-Affinity Recognition sites of Psychotropic Drugs
Authors: M L Barbaccia, E Costa, A Guidotti
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
The Linkage Method: A Novel Approach for SNP Detection and Haplotype Reconstruction from a Single Diploid Individual Using Next-Generation Sequence Data
Authors: E. Sasaki, R. P. Sugino, H. Innan
Journal: Molecular Biology and Evolution (2013)

When we sequence a diploid individual, the output actually comprises two genomes: one from the paternal parent and the other from the maternal parent. In this study, we introduce a novel heuristic algorithm for distinguishing single-nucleotide polymorphisms (SNPs) from the two parents and phasing them into haplotypes. The algorithm is unique because it simultaneously performs SNP calling and haplotype phasing. This approach can exploit the linkage information of nearby SNPs, which facilitates the efficient removal of haplotypes that originate from incorrectly mapped short reads. Using simulated data we demonstrated that our approach increased the accuracy of SNP calls. The haplotype reconstruction performance depended largely on the density of SNPs. Using current next-generation sequence technology with a relatively short read length, reasonable performance is expected when this approach is applied to species with an average of five heterozygous sites per 1 kb. The algorithm was implemented as the program “linkSNPs.”