tbuckley/cabot-search huggingface dataset:
Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial
Authors: William E Boden, Wiek H van Gilst, Rudy G Scheldewaert, Ian R Starkey, Marc F Carlier, Desmond G Julian, Anne Whitehead, Michel E Bertrand, Jacques J Col, Ole Lederballe Pedersen, Kong I Lie, Jean-P Santoni, Kim M Fox
Journal: The Lancet (2000)
FOXM1c Promotes Pancreatic Cancer Epithelial-to-Mesenchymal Transition and Metastasis via Upregulation of Expression of the Urokinase Plasminogen Activator System
Authors: Chen Huang, Dacheng Xie, Jiujie Cui, Qi Li, Yong Gao, Keping Xie
Journal: Clinical Cancer Research (2014)

The transcription factor Forkhead box M1 (FOXM1) plays important roles in the formation of several human tumors, including pancreatic cancer. However, the molecular mechanisms by which FOXM1 promotes pancreatic tumor epithelial-to-mesenchymal transition (EMT) and metastasis are unknown.The effect of altered expression of FOXM1 and urokinase-type plasminogen activator receptor (uPAR) on EMT and metastasis was examined using animal models of pancreatic cancer. Also, the underlying mechanisms of altered pancreatic cancer invasion and metastasis were analyzed using in vitro molecular biology assays. Finally, the clinical relevance of dysregulated FOXM1/uPAR signaling was investigated using pancreatic tumor and normal pancreatic tissue specimens.Pancreatic tumor specimens and cell lines predominantly overexpressed the FOXM1 isoform FOXM1c. FOXM1c overexpression promoted EMT in and migration, invasion, and metastasis of pancreatic cancer cells, whereas downregulation of FOXM1 expression inhibited these processes. The level of FOXM1 expression correlated directly with that of uPAR expression in pancreatic cancer cell lines and tumor specimens. Moreover, FOXM1c overexpression upregulated uPAR expression in pancreatic cancer cells, whereas inhibition of FOXM1 expression suppressed uPAR expression. Furthermore, transfection of FOXM1c into pancreatic cancer cells directly activated the uPAR promoter, whereas inhibition of FOXM1 expression by FOXM1 siRNA suppressed its activation in these cells. Finally, we identified an FOXM1-binding site in the uPAR promoter and demonstrated that FOXM1 protein bound directly to it. Deletion mutation of this site significantly attenuated uPAR promoter activity.Our findings demonstrated that FOXM1c contributes to pancreatic cancer development and progression by enhancing uPAR gene transcription, and thus, tumor EMT and metastasis.
Leptin in hepatic fibrosis: Evidence for increased collagen production in stellate cells and lean littermates of<i>ob/ob</i>mice
Authors: Neeraj K. Saxena, Kazuo Ikeda, Don C. Rockey, Scott L. Friedman, Frank A. Anania
Journal: Hepatology (2002)

Leptin is a 16-kd hormone that mediates a range of metabolic effects by using a transduction pathway from the long form of the leptin receptor, OB-R L, through Janus kinase-signal transducer and activator of transcription (Jak-Stat) signaling components. Leptin is produced by hepatic stellate cells (HSCs) but only following their “activation.” Because activation of stellate cells is a central event in the fibrotic response to liver injury, we hypothesized that leptin may directly stimulate fibrogenesis in activated stellate cells via OB-R L . We analyzed leptin receptors and their signaling partners in a stellate cell line (HSC-T6) as well as in primary stellate cell isolates. We also examined the effect of leptin on stellate cell expression of α 2 (I) collagen messenger RNA (mRNA) levels by ribonuclease protection analysis (RPA). Finally, we examined the role of leptin in in vivo fibrogenesis by inducing a wounding response in ob/ob mice, which lack functional leptin. HSC-T6 and culture-activated stellate cells expressed OB-R L . Scatchard analysis verified specific binding of leptin to HSCs, with an association constant (K d ) equal to 660 ± 5.8 pmol/L. Exposure of HSCs to leptin resulted in significant increases in α 2 (I) collagen mRNA expression. Transient transfection with a promoter reporter construct showed a 3-fold increase in α 2 (I) collagen transgene activity. Leptin stimulated activation of Stat3 in activated HSCs. Finally, lean animals, but not ob/ob littermates, had significant fibrosis as assessed by picrosirius red staining and abundant α-smooth muscle actin staining. In conclusion, these results indicate that leptin is profibrogenic in activated HSCs and can signal via the Jak-Stat pathway. Up-regulation of leptin signaling in liver injury could contribute to enhanced fibrogenesis, particularly in states in which leptin levels are high.
IgE+ B cells are scarce, but allergen-specific B cells with a memory phenotype circulate in patients with allergic rhinitis
Authors: K. J. Wong, V. Timbrell, Y. Xi, J. W. Upham, A. M. Collins, J. M. Davies
Journal: Allergy (2015)

Despite the critical role of immunoglobulin E (IgE) in allergy, circulating IgE+ B cells are scarce. Here, we describe in patients with allergic rhinitis B cells with a memory phenotype responding to a prototypic aeroallergen.Fifteen allergic rhinitis patients with grass pollen allergy and 13 control subjects were examined. Blood mononuclear cells stained with carboxyfluorescein diacetate succinimidyl ester (CFSE) were cultured with Bahia grass pollen. Proliferation and phenotype were assessed by multicolour flow cytometry.In blood of allergic rhinitis patients with high serum IgE to grass pollen, most IgE(hi) cells were CD123+ HLA-DR(-) basophils, with IgE for the major pollen allergen (Pas n 1). Both B and T cells from pollen-allergic donors showed higher proliferation to grass pollen than nonallergic donors (P = 0.002, and 0.010, respectively), whereas responses to vaccine antigens and mitogen did not differ between groups. Allergen-driven B cells that divided rapidly (CD19(mid) CD3(-) CFSE(lo) ) showed higher CD27 (P = 0.008) and lower CD19 (P = 0.004) and CD20 (P = 0.004) expression than B cells that were slow to respond to allergen (CD19(hi) CD3(-) CFSE(mid) ). Moreover, rapidly dividing allergen-driven B cells (CD19(mid) CFSE(lo) CD27(hi) ) showed higher expression of the plasmablast marker CD38 compared with B cells (CD19(hi) CFSE(mid) CD27(lo) ) that were slow to divide.Patients with pollen allergy but not control donors have a population of circulating allergen-specific B cells with the phenotype and functional properties of adaptive memory B-cell responses. These cells could provide precursors for allergen-specific IgE production upon allergen re-exposure.
HLA-DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population
Authors: Shiou-Hwa Jee, Tsen-Fang Tsai, Wei-Ling Tsai, Shwu-Huey Liaw, Chun-Hsiang Chang, Chung-YI HU
Journal: British Journal of Dermatology (1998)

Journal Article HLA‐DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population Get access Shiou‐Hwa Jee, Shiou‐Hwa Jee Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar Tsen‐Fang Tsai, Tsen‐Fang Tsai Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar Wei‐Ling Tsai, Wei‐Ling Tsai Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar Shwu‐Huey Liaw, Shwu‐Huey Liaw Institute of Molecular Medicine, Search for other works by this author on: Oxford Academic Google Scholar Chun‐Hsiang Chang, Chun‐Hsiang Chang Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar Chung‐YI HU Chung‐YI HU School of Medical Technology, National Taiwan University College of Medicine, No. 7, Chung‐Shan South Road, Taipei, Taiwan Chung‐YiHu School of Medical Technology, National Taiwan University College of Medicine, No. 7, Chung‐Shan South Road, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 6, 1 December 1998, Pages 978–983, https://doi.org/10.1046/j.1365-2133.1998.02552.x Published: 01 December 1998
Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies.
Authors: D Sahali, N Mulliez, F Chatelet, R Dupuis, P Ronco, P Verroust
Journal: The Journal of Experimental Medicine (1988)

Intermicrovillar areas and apical vesicles characterized by an extensive clathrin coat can be identified in some epithelial cell types. We describe a 280-kD protein, characteristic of these areas in the proximal tubule brush border and epithelial cells of the visceral yolk sac. When injected to 9-d pregnant rats, mAbs to the 280-kD protein regularly induced fetal resorption and/or malformations. Antibodies to a 330-kD protein that is also coated-pit-restricted had no effect. Our observations point to a key function for p280 and suggest that immunity to specific constituents of the receptor-mediated endocytotic system may be involved in the induction of fetal abnormalities.
Adolescent and Young Adult Oncology Training for Health Professionals: A Position Statement
Authors: Brandon Hayes-Lattin, Beth Mathews-Bradshaw, Stuart Siegel
Journal: Journal of Clinical Oncology (2010)

We outline here the essential elements of training for health care professionals who work with adolescent and young adult (AYA) patients with cancer. Research is emerging that a number of cancers manifest themselves differently in the AYA population, both in terms of biology and treatment response. In addition, there are a number of issues uniquely experienced by the AYA population that are critical for health care professionals working within AYA oncology (AYAO) to understand. The LIVESTRONG Young Adult Alliance, a Lance Armstrong Foundation program and a result of the Adolescent and Young Adult Oncology Progress Review Group cosponsored by the Lance Armstrong Foundation and the National Cancer Institute, assembled a group of experts representing relevant medical, psychosocial, and advocacy disciplines to create a blueprint for the training and development of health care professionals caring for AYA patients with cancer. The Alliance recommends that all health care professionals working in AYAO receive training that provides expertise in the following three critical areas: AYA-specific medical knowledge; care delivery specific to AYAs relative to pediatric and older adult populations; and competency in application and delivery of AYA-specific practical knowledge. These three areas should form the foundation for curricula and programs designed to train health care professionals caring for AYAO patients.
Where Manchester leads on control of health and social care budget London should follow
Authors: A. Darzi
Journal: BMJ (2015)

The plan to pass control of the entire health and social care budget of £6bn (€8.3bn; $8.7bn) a year to Greater Manchester local authority is bold, innovative, and exciting.1 It is a landmark on the NHS’s route towards a holistic integrated service that unites health and social care.

But what is good for Manchester is also …
Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia.
Authors: D Pajkrt, J E Doran, F Koster, P G Lerch, B Arnet, T van der Poll, J W ten Cate, S J van Deventer
Journal: The Journal of Experimental Medicine (1996)

High-density lipoprotein (HDL) has been found to neutralize LPS activity in vitro and in animals in vivo. We sought to determine the effects of reconstituted HDL (rHDL) on LPS responsiveness in humans in a double-blind, randomized, placebo-controlled, cross-over study. rHDL, given as a 4-h infusion at 40 mg/kg starting 3.5 h before endotoxin challenge (4 ng/kg), reduced flu-like symptoms during endotoxemia, but did not influence the febrile response. rHDL potently reduced the endotoxin-induced release of TNF, IL-6, and IL-8, while only modestly attenuating the secretion of proinflammatory cytokine inhibitors IL-1ra, soluble TNF receptors and IL-10. In addition, rHDL attenuated LPS-induced changes in leukocyte counts and the enhanced expression of CD11b/CD18 on granulocytes. Importantly, rHDL infusion per se, before LPS administration, was associated with a downregulation of CD14, the main LPS receptor, on monocytes. This effect was biologically relevant, since monocytes isolated from rHDL-treated whole blood showed reduced expression of CD14 and diminished TNF production upon stimulation with LPS. These results suggest that rHDL may inhibit LPS effects in humans in vivo not only by binding and neutralizing LPS but also by reducing CD14 expression on monocytes.
Major Effect of the Syndrome of Rapid-Onset End-Stage Renal Disease on the Use of Arteriovenous Fistulas
Authors: Macaulay Amechi Chukwukadibia Onuigbo
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Identification of Cystatin B as a Potential Serum Marker in Hepatocellular Carcinoma
Authors: Mi-Jin Lee, Gyung-Ran Yu, Seon-Hwa Park, Baik-Hwan Cho, Jong-Seong Ahn, Hae-Joon Park, Eun-Young Song, Dae-Ghon Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The poor survival rate of hepatocellular carcinoma (HCC) is in part due to the inability to diagnose patients at an early stage. Therefore, the aim of this study was to search for candidate serum marker for HCC and to test their ability to distinguish a HCC from benign liver disease. Experimental Design: Genome-wide analysis by a microarray in 40 HCC patients was done between HCC and paired nontumor liver tissues. Expression of cystatin B (CSTB) was examined by mRNA expression analysis and immunohistochemistry. The serum CSTB levels were measured using a sandwich ELISA method in four groups, including normal healthy subjects (group 1, n = 52) and patients with noncirrhotic chronic hepatitis (group 2, n = 53), cirrhosis (group 3, n = 43), and HCC (group 4, n = 62). Results: Microarray and statistical analyses identified 248 genes that were expressed differently between HCC and nontumor liver tissues. One of them, CSTB, was expressed preferentially in the HCCs compared with the nontumor tissues, 36 of 45 specimens (80%) by Northern blot and semiquantitative reverse transcription-PCR analyses. The serum CSTB level was much higher in HCC patients than in those with nonmalignant chronic liver disease (groups 2 and 3; P &amp;lt; 0.0001). The receiver operating characteristic curve indicated 5.34 ng/mL to be the optimal value for CSTB, and the sensitivity and specificity for this CSTB value were 85.5% (95% confidence interval, 74.2-93.1%) and 53.1% (95% confidence interval, 42.7-63.4%), respectively, in distinguishing between patients with HCC and those with nonmalignant chronic liver disease. Conclusion: CSTB is specifically overexpressed in most HCCs and is also elevated in the serum of a large proportion of HCC patients. CSTB or the combination of CSTB and α-fetoprotein may be a useful marker for diagnosing patients with HCC with a high sensitivity.
One stage repair for an oesophageal fistula after pneumonectomy using an omental pedicle flap.
Authors: M Asaoka, M Imaizumi, M Kajita, T Uchida, T Niimi, T Abe
Journal: Thorax (1988)

A 67 year old man developed an oesophageal fistula after a pneumonectomy that was complicated by an empyema. An omental pedicle flap was brought through the diaphragm to repair the fistula and to fill the empyema space. The outcome was successful.
Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo
Authors: Milica Vukmanovic-Stejic, Yan Zhang, Joanne E. Cook, Jean M. Fletcher, Arthur McQuaid, Joanne E. Masters, Malcolm H.A. Rustin, Leonie S. Taams, Peter C.L. Beverley, Derek C. Macallan, Arne N. Akbar
Journal: Journal of Clinical Investigation (2006)

While memory T cells are maintained by continuous turnover, it is not clear how human regulatory CD4+CD45RO+CD25hi Foxp3+ T lymphocyte populations persist throughout life. We therefore used deuterium labeling of cycling cells in vivo to determine whether these cells could be replenished by proliferation. We found that CD4+CD45RO+Foxp3+CD25hi T lymphocytes were highly proliferative, with a doubling time of 8 days, compared with memory CD4+CD45RO+Foxp3–CD25– (24 days) or naive CD4+CD45RA+Foxp3–CD25– populations (199 days). However, the regulatory population was susceptible to apoptosis and had critically short telomeres and low telomerase activity. It was therefore unlikely to be self regenerating. These data are consistent with continuous production from another population source. We found extremely close TCR clonal homology between regulatory and memory CD4+ T cells. Furthermore, antigen-related expansions within certain TCR Vβ families were associated with parallel numerical increases of CD4+CD45RO+CD25hiFoxp3+ Tregs with the same Vβ usage. It is therefore unlikely that all human CD4+CD25+Foxp3+ Tregs are generated as a separate functional lineage in the thymus. Instead, our data suggest that a proportion of this regulatory population is generated from rapidly dividing, highly differentiated memory CD4+ T cells; this has considerable implications for the therapeutic manipulation of these cells in vivo.
In Utero and in Vitro Exposure to β-Lactams Impair Kidney Development in the Rat
Authors: SYLVIE NATHANSON, EVELYNE MOREAU, CLAUDIE MERLET-BENICHOU, THIERRY GILBERT
Journal: Journal of the American Society of Nephrology (2000)

Abstract. β-Lactam antibiotics are widely used because of their lack of toxicity in humans. However, during pregnancy, exposure of the fetus is likely to occur because β-lactam antibiotics cross the placenta. The potential adverse effects of two penicillins (ampicillin, amoxicillin) and of one cephalosporin (ceftriaxone) were examined in rat kidney development. Two experimental approaches were used: metanephros organ cultures to analyze the direct effect of the drug and maternal treatment to assess the consequences of in utero exposure. For in vitro experiments, metanephroi were removed from 14-d-old fetuses and grown with or without the antibiotic at a concentration ranging from 10 to 1000 μg/ml for 6 d. For in vivo experiments, pregnant rats were treated with penicillin at 100 mg/kg per d for 5 d, a period overlapping early renal organogenesis. Both penicillins alter renal development in vitro in a dose-dependent manner, from a dose of 10 μg/ml for ampicillin and 100 μg/ml for amoxicillin. In young animals exposed to penicillins in utero , a mild oligonephronia was present and cystic tubule dilation was observed in newborn and in young animals as well. Ceftriaxone weakly impairs in vitro nephrogenesis except at the dose of 1000 μg/ml that blocks kidney development completely. No effect on nephron ontogeny was observed following in utero exposure, but an interstitial inflammation was present in the medulla of 2-wk-old rats. In conclusion, these data show that β-lactams, at therapeutic doses, are harmful to fetal rat kidneys.
Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells.
Authors: J Zhang, E H Berenstein, R L Evans, R P Siraganian
Journal: The Journal of Experimental Medicine (1996)

Aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine phosphorylation and activation of Syk, a cytoplasmic protein tyrosine kinase. To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions. In these Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. Fc epsilon RI aggregation induced tyrosine phosphorylation of the beta and gamma subunits of the receptor, but no increase in the tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2 and no detectable increase in intracellular free Ca2+ concentration. By transfection, cloned lines were established with stable expression of Syk. In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2, an increase in intracellular free Ca2+ and histamine release. These results demonstrate that Syk plays a critical role in the early Fc epsilon RI-mediated signaling events. It further demonstrates that Syk activation occurs downstream of receptor phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations.
Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase
Authors: Koichi Yoshimura, Hiroki Aoki, Yasuhiro Ikeda, Kozo Fujii, Norio Akiyama, Akira Furutani, Yoshinobu Hoshii, Nobuyuki Tanaka, Romeo Ricci, Tokuhiro Ishihara, Kensuke Esato, Kimikazu Hamano, Masunori Matsuzaki
Journal: Nature Medicine (2005)
Assessment of Diabetic Retinopathy Using Nonmydriatic Ultra-Widefield Scanning Laser Ophthalmoscopy (Optomap) Compared With ETDRS 7-Field Stereo Photography
Authors: Marcus Kernt, Indrawati Hadi, Florian Pinter, Florian Seidensticker, Christoph Hirneiss, Christos Haritoglou, Anselm Kampik, Michael W. Ulbig, Aljoscha S. Neubauer
Journal: Diabetes Care (2012)

To compare the diagnostic properties of a nonmydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) versus mydriatic Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field photography for diabetic retinopathy (DR) screening.A consecutive series of 212 eyes of 141 patients with different levels of DR were examined. Grading of DR and clinically significant macular edema (CSME) from mydriatic ETDRS 7-field stereo photography was compared with grading obtained by Optomap Panoramic 200 SLO images. All SLO scans were performed through an undilated pupil, and no additional clinical information was used for evaluation of all images by the two independent, masked, expert graders.Twenty-two eyes from ETDRS 7-field photography and 12 eyes from Optomap were not gradable by at least one grader because of poor image quality. A total of 144 eyes were analyzed regarding DR level and 155 eyes regarding CSME. For ETDRS 7-field photography, 22 eyes (18 for grader 2) had no or mild DR (ETDRS levels ≤ 20) and 117 eyes (111 for grader 2) had no CSME. A highly substantial agreement between both Optomap DR and CSME grading and ETDRS 7-field photography existed with κ = 0.79 for DR and 0.73 for CSME for grader 1, and κ = 0.77 (DR) and 0.77 (CSME) for grader 2.Determination of CSME and grading of DR level from Optomap Panoramic 200 nonmydriatic images show a positive correlation with mydriatic ETDRS 7-field stereo photography. Both techniques are of sufficient quality to assess DR and CSME. Optomap Panoramic 200 images cover a larger retinal area and therefore may offer additional diagnostic properties.