tbuckley/cabot-search huggingface dataset:
Common warts from immunocompetent patients show the same distribution of human papillomavirus types as common warts from immunocompromised patients
Authors: A. RUBBEN, R. KRONES, B. SCHWETSCHENAU, E.-I. GKUSSENDORF-CONKN
Journal: British Journal of Dermatology (1993)

Journal Article Common warts from immunocompetent patients show the same distribution of human papillomavirus types as common warts from immunocompromised patients Get access A. RÜBBEN, A. RÜBBEN Hautklinik (Department of Dermatology) der RWTH Aachen, Pauwelsstrasse 30, 5100 Aachen, Germany Dr A.Rübben. Search for other works by this author on: Oxford Academic Google Scholar R. KRONES, R. KRONES Hautklinik (Department of Dermatology) der RWTH Aachen, Pauwelsstrasse 30, 5100 Aachen, Germany Search for other works by this author on: Oxford Academic Google Scholar B. SCHWETSCHENAU, B. SCHWETSCHENAU Hautklinik (Department of Dermatology) der RWTH Aachen, Pauwelsstrasse 30, 5100 Aachen, Germany Search for other works by this author on: Oxford Academic Google Scholar E.‐I. GKUSSENDORF‐CONKN E.‐I. GKUSSENDORF‐CONKN Hautklinik (Department of Dermatology) der RWTH Aachen, Pauwelsstrasse 30, 5100 Aachen, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 3, 1 March 1993, Pages 264–270, https://doi.org/10.1111/j.1365-2133.1993.tb00169.x Published: 01 March 1993 Article history Accepted: 06 October 1992 Published: 01 March 1993
Early Detection of the First Episode of Schizophrenia and Suicidal Behavior
Authors: Ingrid Melle, Jan Olav Johannesen, Svein Friis, Ulrik Haahr, Inge Joa, Tor K. Larsen, Stein Opjordsmoen, Bjørn R. Rund, Erik Simonsen, Per Vaglum, Thomas McGlashan
Journal: American Journal of Psychiatry (2006)

Objective: The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts. Method: The authors examined consecutive patients with nonorganic, nonaffective psychosis who sought initial treatment at psychiatric treatment units in four catchment areas: two that had an early detection program and two that did not. Results: The rate of severe suicidality (plans or attempts) was significantly higher in subjects from communities without the early detection program relative to those from early detection communities, even after adjustments for known predictors of suicidality. Conclusion: Early detection programs that bring patients into treatment at lower symptom levels may reduce suicidality risk at first treatment contact.
Rapid-onset febrile dermatosis
Authors: M Decisier, V Duhalde, P Faure, A Ammoury, M Gony, J Moreau, J L Montastruc, H Bagheri
Journal: Gut (2008)

HC Emsley, SP Wardle, DG Sims, ML Chiswick, SW D9Souza. Increased survival and deteriorating developmental outcome in 23 to 25 week old gestation infants, 1990–4 compared with 1984–9. Arch Dis Child Fetal Neonatal Ed. 1998 Mar;78:F99–104.
Nociceptors: the sensors of the pain pathway
Authors: Adrienne E. Dubin, Ardem Patapoutian
Journal: Journal of Clinical Investigation (2010)

Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics.
Identification of miRNomes in Human Liver and Hepatocellular Carcinoma Reveals miR-199a/b-3p as Therapeutic Target for Hepatocellular Carcinoma
Authors: Jin Hou, Li Lin, Weiping Zhou, Zhengxin Wang, Guoshan Ding, Qiongzhu Dong, Lunxiu Qin, Xiaobing Wu, Yuanyuan Zheng, Yun Yang, Wei Tian, Qian Zhang, Chunmei Wang, Qinghua Zhang, Shi-Mei Zhuang, Limin Zheng, Anmin Liang, Wenzhao Tao, Xuetao Cao
Journal: Cancer Cell (2011)
The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study
Authors: Jenny J Ko, Wanling Xie, Nils Kroeger, Jae-lyun Lee, Brian I Rini, Jennifer J Knox, Georg A Bjarnason, Sandy Srinivas, Sumanta K Pal, Takeshi Yuasa, Martin Smoragiewicz, Frede Donskov, Ravindran Kanesvaran, Lori Wood, D Scott Ernst, Neeraj Agarwal, Ulka N Vaishampayan, Sun-young Rha, Toni K Choueiri, Daniel Y C Heng
Journal: The Lancet Oncology (2015)
Spleen Tyrosine Kinase Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia
Authors: Maike Buchner, Simon Fuchs, Gabriele Prinz, Dietmar Pfeifer, Kilian Bartholomé, Meike Burger, Nina Chevalier, Laurent Vallat, Jens Timmer, John G. Gribben, Hassan Jumaa, Hendrik Veelken, Christine Dierks, Katja Zirlik
Journal: Cancer Research (2009)

Abstract B-cell receptor signaling contributes to apoptosis resistance in chronic lymphocytic leukemia (CLL), limiting the efficacy of current therapeutic approaches. In this study, we investigated the expression of spleen tyrosine kinase (SYK), a key component of the B-cell receptor signaling pathway, in CLL and its role in apoptosis. Gene expression profiling identified enhanced expression of SYK and downstream pathways in CLL compared with healthy B cells. Immunoblotting showed increased expression and phosphorylation of SYK, PLCγ2, signal transducers and activators of transcription 3, and extracellular signal regulated kinase 1/2 in CLL compared with healthy B cells, suggesting enhanced activation of these mediators in CLL. SYK inhibitors reduced phosphorylation of SYK downstream targets and induced apoptosis in primary CLL cells. With respect to prognostic factors, SYK inhibitors exerted stronger cytotoxic effects in unmutated and ZAP70+ cases. Cytotoxic effects of SYK inhibitors also associated with SYK protein expression, potentially predicting response to therapy. Combination of fludarabine with SYK Inhibitor II or R406 increased cytotoxicity compared with fludarabine therapy alone. We observed no stroma-contact–mediated drug resistance for SYK inhibitors as described for fludarabine treatment. CD40 ligation further enhanced efficacy of SYK inhibition. Our data provide mechanistic insight into the recently observed therapeutic effects of the SYK inhibitor R406 in CLL. Combination of SYK inhibitors with fludarabine might be a novel treatment option particularly for CLL patients with poor prognosis and should be further evaluated in clinical trials. [Cancer Res 2009;69(13):5424–32]
A Computerized Handheld Decision-Support System to Improve Pulmonary Embolism Diagnosis
Authors: Pierre-Marie Roy
Journal: Annals of Internal Medicine (2009)

Background: Testing for pulmonary embolism often differs from that recommended by evidence-based guidelines. Objective: To assess the effectiveness of a handheld clinical decision-support system to improve the diagnostic work-up of suspected pulmonary embolism among patients in the emergency department. Design: Cluster randomized trial. Assignment was by random-number table, providers were not blinded, and outcome assessment was automated. (ClinicalTrials.gov registration number: NCT00188032) Setting: 20 emergency departments in France. Patients: 1103 and 1768 consecutive outpatients with suspected pulmonary embolism. Intervention: After a preintervention period involving 20 centers and 1103 patients, in which providers grew accustomed to inputting clinical data into handheld devices and investigators assessed baseline testing, emergency departments were randomly assigned to activation of a decision-support system on the devices (10 centers, 753 patients) or posters and pocket cards that showed validated diagnostic strategies (10 centers, 1015 patients). Measurements: Appropriateness of diagnostic work-up, defined as any sequence of tests that yielded a posttest probability less than 5% or greater than 85% (primary outcome) or as strict adherence to guideline recommendations (secondary outcome); number of tests per patient (secondary outcome). Results: The proportion of patients who received appropriate diagnostic work-ups was greater during the trial than in the preintervention period in both groups, but the increase was greater in the computer-based guidelines group (adjusted mean difference in increase, 19.3 percentage points favoring computer-based guidelines [95% CI, 2.9 to 35.6 percentage points]; P = 0.023). Among patients with appropriate work-ups, those in the computer-based guidelines group received slightly fewer tests than did patients in the paper guidelines group (mean tests per patient, 1.76 [SD, 0.98] vs. 2.25 [SD, 1.04]; P < 0.001). Limitation: The study was not designed to show a difference in the clinical outcomes of patients during follow-up. Conclusion: A handheld decision-support system improved diagnostic decision making for patients with suspected pulmonary embolism in the emergency department. Primary Funding Source: French National Hospital Clinical Research Project.
NUP98-HOXA9 Induces Long-term Proliferation and Blocks Differentiation of Primary Human CD34+ Hematopoietic Cells
Authors: Akiko Takeda, Charles Goolsby, Nabeel R. Yaseen
Journal: Cancer Research (2006)

Abstract NUP98-HOXA9, the chimeric protein resulting from the t(7;11)(p15;p15) chromosomal translocation, is a prototype of several NUP98 fusions that occur in myelodysplastic syndromes and acute myeloid leukemia. We examined its effect on differentiation, proliferation, and gene expression in primary human CD34+ hematopoietic cells. Colony-forming cell (CFC) assays in semisolid medium combined with morphologic examination and flow cytometric immunophenotyping revealed that NUP98-HOXA9 increased the numbers of erythroid precursors and impaired both myeloid and erythroid differentiation. In continuous liquid culture, cells transduced with NUP98-HOXA9 exhibited a biphasic growth curve with initial growth inhibition followed by enhanced long-term proliferation, suggesting an increase in the numbers of primitive self-renewing cells. This was confirmed by a dramatic increase in the numbers of long-term culture-initiating cells, the most primitive hematopoietic cells detectable in vitro. To understand the molecular mechanisms underlying the effects of NUP98-HOXA9 on hematopoietic cell proliferation and differentiation, oligonucleotide microarray analysis was done at several time points over 16 days, starting at 6 hours posttransduction. The early growth suppression was preceded by up-regulation of IFNβ1 and accompanied by marked up-regulation of IFN-induced genes, peaking at 3 days posttransduction. In contrast, oncogenes such as homeobox transcription factors, FLT3, KIT, and WT1 peaked at 8 days or beyond, coinciding with increased proliferation. In addition, several putative tumor suppressors and genes associated with hematopoietic differentiation were repressed at later time points. These findings provide a comprehensive picture of the changes in proliferation, differentiation, and global gene expression that underlie the leukemic transformation of human hematopoietic cells by NUP98-HOXA9. (Cancer Res 2006; 66(13): 6628-37)
Resting Respiratory Tract Dendritic Cells Preferentially Stimulate T Helper Cell Type 2 (Th2) Responses and Require Obligatory Cytokine Signals for Induction of Th1 Immunity
Authors: Philip A. Stumbles, Jennifer A. Thomas, Carolyn L. Pimm, Peter T. Lee, Thierry J. Venaille, Stephen Proksch, Patrick G. Holt
Journal: The Journal of Experimental Medicine (1998)

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the “default” T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2–3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-γ by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing– associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor α or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.
Ribosomal S6 Kinase 2 Is a Key Regulator in Tumor Promoter–Induced Cell Transformation
Authors: Yong-Yeon Cho, Ke Yao, Hong-Gyum Kim, Bong Seok Kang, Duo Zheng, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2007)

Abstract The ribosomal S6 kinase 2 (RSK2), a member of the p90RSK (RSK) family of proteins, is a widely expressed serine/threonine kinase that is activated by extracellular signal-regulated kinase 1/2 and phosphoinositide-dependent kinase 1 in response to many growth factors and peptide hormones. Its activation signaling enhances cell survival. However, the roles of RSK2 in cell transformation have not yet been elucidated. Here, we found that RSK2 is a critical serine/threonine kinase for the regulation of cell transformation. When cells were stimulated with tumor promoters, such as epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylation of RSK was increased within 5 min. Cell proliferation was suppressed in RSK2−/− mouse embryonic fibroblasts (MEFs) compared with RSK2+/+ MEFs. Moreover, RSK2−/− MEFs accumulated at the G1 phase of the cell cycle under normal cell culture conditions as well as after stimulation with EGF or TPA. In the anchorage-independent cell transformation assay (soft agar), stable expression of RSK2 in JB6 cells significantly enhanced colony formation in either the presence or absence of tumor promoters. Furthermore, knockdown of RSK2 with small interfering RNA-RSK2 suppressed constitutively active Ras (RasG12V)-induced foci formation in NIH3T3 cells. In addition, kaempferol, an inhibitor of RSK2, suppressed EGF-induced colony formation of JB6 Cl41 cells in soft agar, which was associated with inhibition of histone H3 phosphorylation (Ser10). These results showed that RSK2 is a key regulator for cell transformation induced by tumor promoters such as EGF and TPA. [Cancer Res 2007;67(17):8104–12]
Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.)
Authors: R. Kushwaha
Journal: Human Reproduction Update (1998)

Diet-induced hyperlipidaemia in baboons is similar to that in humans. As in humans, the ratio between low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol is a major determinant of atherosclerosis. Baboons, like humans and other non-human primates, vary in their lipaemic responses to dietary lipids. By selective breeding based on variability in plasma and lipoprotein cholesterol response to diet, lines of baboons with high and low responses of various lipoproteins have been developed. Genetic analyses suggest that lipoprotein patterns in responses to dietary cholesterol and fat are heritable. Metabolic and molecular studies of high and low LDL and HDL cholesterol responses to dietary lipids have suggested that different mechanisms regulate plasma LDL cholesterol on the chow and on the high cholesterol-high fat (HCHF) diet. On the chow diet, plasma LDL cholesterol levels are positively associated with cholesterol absorption and negatively associated with hepatic LDL receptor levels and, thus, cholesterol absorption and LDL receptors seem to regulate plasma LDL cholesterol levels. However, when the animals consume a human-like fat- and cholesterol-enriched diet, plasma LDL cholesterol levels are not associated with either cholesterol absorption or hepatic LDL receptor mRNA levels, but are negatively associated with plasma 27-hydroxycholesterol concentrations, hepatic sterol 27-hydroxylase activity, and mRNA levels. Hepatic sterol 27-hydroxylase activity and mRNA levels are induced by dietary cholesterol and fat in low responding baboons more than in high responding baboons. Thus, the ability to induce sterol 27-hydroxylase determines the LDL cholesterol response in baboons. High HDL response baboons often have high levels of HDL1 in their plasma. Our studies suggest that the N-terminal fragment of apo C-I with 38 amino acids and a molecular weight of 4 kDa acts as a cholesteryl ester transfer inhibitor peptide in high HDL1 baboons. The inhibitor peptide associates with apo A-1 in HDL to produce a modified apo A-1 protein with a molecular weight of 31 kDa. The inhibitor peptide is a gene product and the presence of this peptide produces an antiatherogenic high HDL1 phenotype.
Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroentero-pancreatic neuroendocrine protein, gamma trace.
Authors: D H Cohen, H Feiner, O Jensson, B Frangione
Journal: The Journal of Experimental Medicine (1983)

Amyloid fibrils were isolated from the leptomeningeal blood vessels obtained at autopsy from three Icelandic patients dying of Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA) and verified by Congo red staining and electron microscopy. Gel filtration on Sephadex and Ultrogel columns yielded predominantly one component (molecular weight 11,500 daltons) and also another minor component (molecular weight 15,800 daltons). Automated amino terminal sequencing showed these proteins to be similar (36 residues) to a recently described human protein, gamma trace, beginning at its eleventh amino terminal residue. The amyloid deposits in all three patients stained with rabbit anti-gamma trace antiserum. Although the function of gamma trace is not known, it appears to have structural homology with several hormones and has been localized to the brain, pancreas and pituitary. The amyloid fibril subunits seem to have polymerized after cleavage of the amino terminal decapeptide from gamma trace-related proteins. Therefore, HCHWA appears to be the first genetically determined disease related to the gastroenteropancreatic neuroendocrine system.
STRUCTURAL REQUIREMENTS FOR LATHYROGENIC AGENTS
Authors: C. I. Levene
Journal: The Journal of Experimental Medicine (1961)

Using the chick embryo assay system, a series of organic compounds was tested for lathyrogenic activity; lathyrogenic compounds were shown to fall into 4 groups-nitriles, ureides, and 2 new groups-hydrazides and hydrazines, forming a spectrum of diminishing potency in their ability to produce solubility of collagen and skeletal deformities. Pyridoxal was seen to reverse to a great degree the effects on collagen solubility and skeletal deformity produced by the ureides and hydrazides, though not by the nitriles; its effect was considered to be due to the formation of a Schiff's complex between the aldehyde and the terminal amine of the lathyrogen. Evidence is presented to show that lathyrogens do not act as inhibitors of monoamine oxidases or as chelate-forming agents, nor, in the case of isoniazid, as an anti-nicotinamide agent.
Antiproliferative Action of Vitamin D-Related Compounds and Insulin-Like Growth Factor-Binding Protein 5 Accumulation
Authors: F. Rozen, X.-F. Yang, H. Huynh, M. Pollak
Journal: JNCI Journal of the National Cancer Institute (1997)

Vitamin D-related compounds can inhibit cancer cell growth, but the biologic mechanism of this inhibition remains to be determined. We investigated the possibility that these compounds interfere with the activity of insulin-like growth factors. Such activity can be suppressed or otherwise modulated by specific insulin-like growth factor-binding proteins.The human breast cancer cell line MCF-7 was used in this study. The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and two related compounds, EB1089 and KH1060, on cell proliferation were assessed by monitoring cell numbers and by measuring cellular incorporation of [3H]thymidine. Changes in the accumulation of insulin-like growth factor-binding proteins in cell-conditioned media (i.e., culture fluids) were assessed by means of standard protein blotting techniques; ligand blots were probed with [125I]insulin-like growth factor I, and immunoblots were probed with antibodies raised against specific binding proteins. Binding protein messenger RNA levels were determined by use of RNA blotting methods and complementary DNA probes.At concentrations of 10(-8) M and 10(-9) M, EB1089 and KH1060 exhibited stronger antiproliferative activity than 1,25(OH)2D3. When each of the vitamin D-related compounds was used separately at a concentration of 10(-9) M, a 20- to 25-fold increase in the concentration of insulin-like growth factor-binding proteins in MCF-7 cell-conditioned media was observed; this binding capacity was increased nine-fold, ninefold, and threefold, respectively, in the presence of 10(-10) M EB1089, KH1060, and 1,25(OH)2D3. Immunoblotting experiments demonstrated that all three vitamin D-related compounds induced the accumulation of insulin-like growth factor-binding protein 5 in cell-conditioned media. The accumulation of this binding protein was associated with an increase in cellular expression of its messenger RNA. EB1089 and 1,25(OH)2D3 attenuated the growth-promoting activity of insulin-like growth factor I on MCF-7 cells; however, these compounds did not inhibit the growth-promoting activity of long R3 IGF-I, an insulin-like growth factor I analogue with greatly reduced affinity for insulin-like growth factor-binding proteins.Our results indicate that vitamin D-related compounds stimulate production of insulin-like growth factor-binding protein 5, thereby indirectly suppressing cell proliferation.