tbuckley/cabot-search huggingface dataset:
Human Autoimmune Sera as Molecular Probes for the Identification of an Autoantigen Kinase Signaling Pathway
Authors: Makoto Kamachi, Truc M. Le, Susan J. Kim, Meghan E. Geiger, Paul Anderson, Paul J. Utz
Journal: The Journal of Experimental Medicine (2002)

Using human autoimmune sera as molecular probes, we previously described the association of phosphorylated serine/arginine splicing factors (SR splicing factors) with the U1-small nuclear ribonucleoprotein (U1-snRNP) and U3-small nucleolar RNP (snoRNP) in apoptotic cells. SR proteins are highly conserved autoantigens whose activity is tightly regulated by reversible phosphorylation of serine residues by at least eight different SR protein kinase kinases (SRPKs), including SRPK1, SRPK2, and the scleroderma autoantigen topoisomerase I. In this report, we demonstrate that only one of the known SRPKs, SRPK1, is associated with the U1-snRNP autoantigen complex in healthy and apoptotic cells. SRPK1 is activated early during apoptosis, followed by caspase-mediated proteolytic inactivation at later time points. SRPKs are cleaved in vivo after multiple apoptotic stimuli, and cleavage can be inhibited by overexpression of bcl-2 and bcl-xL, and by exposure to soluble peptide caspase inhibitors. Incubation of recombinant caspases with in vitro–translated SRPKs demonstrates that SRPK1 and SRPK2 are in vitro substrates for caspases-8 and -9, respectively. In contrast, topoisomerase I is cleaved by downstream caspases (-3 and -6). Since each of these SRPKs sits at a distinct checkpoint in the caspase cascade, SRPKs may serve an important role in signaling pathways governing apoptosis, alternative mRNA splicing, SR protein trafficking, RNA stability, and possibly the generation of autoantibodies directed against splicing factors.
Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis
Authors: Bart Smeets, Christoph Kuppe, Eva-Maria Sicking, Astrid Fuss, Peggy Jirak, Toin H. van Kuppevelt, Karlhans Endlich, Jack F.M. Wetzels, Hermann-Josef Gröne, Jürgen Floege, Marcus J. Moeller
Journal: Journal of the American Society of Nephrology (2011)

The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis.
Eruptions from Bromides and Iodides: A Portion of a Lecture on "Drug Eruptions."
Authors: H. R. Crocker
Journal: BMJ (1893)

IT is aln unfortunate circumstance sonmetimes attending our * tlerapeutic efforts to alleviate or cure disease that by the actioni of the drugs we employ we may unwittingly produce disorders of various organs whichl may lead to consequences *a serious as the original disease itself, and, if the drug be persisted in, may even have a fatal result.The skin lesions
Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 Trial
Authors: Evelien Kneppers, Bronno van der Holt, Marie-Jose Kersten, Sonja Zweegman, Ellen Meijer, Gerwin Huls, Jan J. Cornelissen, Jeroen J. Janssen, Cynthia Huisman, Petra B. Cornelisse, Cheryl P. Bruijnen, Maarten Emmelot, Pieter Sonneveld, Henk M. Lokhorst, Tuna Mutis, Monique C. Minnema
Journal: Blood (2011)
Unions clash with government on NHS job cut figures
Authors: Adrian O’Dowd
Journal: BMJ (2011)

Unions have clashed with the English government over claims that more than 50 000 posts from the NHS will be cut over the next five years—more than double previous estimates.

A campaign website opposed to the NHS changes, False Economy, which is supported by the Trades Union Congress, published the figures based on its investigation into planned and potential cuts across the NHS. But the Department of Health has dismissed the figures as inaccurate and “scaremongering.”

The False Economy website said it had gathered data from NHS trusts under the Freedom of Information Act, together with figures sourced by the Royal College of Nursing, press reports and foundation trusts’ annual plans published by the national regulator Monitor.

The total of confirmed, planned and potential NHS staff cuts across the UK over the next five years currently stood at 53 150 posts, said the website, and that figure was likely …
Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers
Authors: Xiaoming Wang, Bryan Cho, Kazuhiro Suzuki, Ying Xu, Jesse A. Green, Jinping An, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2011)

Follicular dendritic cells (FDCs) retain and display opsonized antigens in primary follicles and germinal centers (GCs). However, their roles beyond antigen presentation have been incompletely defined. In this study, we tested the impact of selective FDC ablation on short-term follicle and GC function. Within 2 d of FDC ablation, primary follicles lost their homogeneity and became disorganized bands of cells around T zones. These B cell areas retained CXCL13-expressing stromal cells but often exhibited inappropriate ER-TR7 and CCL21 expression. Ablation of GC FDCs led to the disappearance of GCs. When B cell death was prevented using a Bcl2 transgene, FDC ablation led to splenic GC B cell dispersal. Mesenteric lymph node GCs were more resistant but became dispersed when sphingosine-1-phosphate receptor-2 was also removed. These experiments indicate that FDCs help maintain primary follicles as a B cell exclusive niche and define a critical role for FDCs in cell retention within GCs.
Are dilating bile ducts a cause for concern?
Authors: M L WILKINSON
Journal: Gut (1999)

See article on page 741 

Whether the bile duct dilates after cholecystectomy is a hoary old chestnut dating back to Oddi and hotly debated in the era of intravenous cholangiography but is still of practical importance now. In this issue Majeed et al (see page 741) report a careful, but uncontrolled study from Sheffield examining this question. Fifty nine patients undergoing cholecystectomy had their common hepatic duct diameters measured ultrasonographically before and three, six, 12, and 60 months after surgery. Those with ducts of >5 mm preoperatively were excluded. A slight mean increase was found and more importantly, perhaps, about 5% of subjects at six months and one year had ducts greater than the arbitrary cut off limit of 6 mm. At five years only one of the 48 at risk seemed to maintain the increase in size. One wonders whether the radiologist’s technique and interpretation at five years were identical to those at the outset. Furthermore, by the end of the study the ultrasound machine was at least nine years …
Atheroprotective role of high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P)
Authors: F. Poti, M. Simoni, J.-R. Nofer
Journal: Cardiovascular Research (2014)

Numerous epidemiological studies documented an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and the extent of atherosclerotic disease. However, clinical interventions targeting HDL cholesterol failed to show clinical benefits with respect to cardiovascular risk reduction, suggesting that HDL components distinct from cholesterol may account for anti-atherogenic effects attributed to this lipoprotein. Sphingosine-1-phosphate (S1P)—a lysosphingolipid exerting its biological activity via binding to specific G protein-coupled receptors and regulating a wide array of biological responses in a variety of different organs and tissues including the cardiovascular system—has been identified as an integral constituent of HDL particles. In the present review, we discuss current evidence from epidemiological studies, experimental approaches in vitro, and animal models of atherosclerosis, suggesting that S1P contributes to atheroprotective effects exerted by HDL particles.
Responses to gastric distension in functional dyspepsia
Authors: G A M Salet, M Samsom, J M M Roelofs, G P van Berge Henegouwen, A J P M Smout, L M A Akkermans
Journal: Gut (1998)

Background —Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the compliance and adaptive relaxation of the proximal stomach contribute to the symptoms. Aims —To investigate whether abnormal relaxation or adaptation of the proximal stomach during the interdigestive state and the postprandial phase could explain the symptoms of functional dyspepsia. Subjects —Twelve volunteers and 12 patients with dysmotility-like functional dyspepsia were included in the study. Methods —An electronic barostat was used to investigate adaptation to distension of the proximal stomach and accommodation in response to a liquid meal. Dyspeptic symptoms during distension and accommodation were assessed. Results —When the subjects were in the fasting state, the pressure-volume curve showed slightly higher compliance in the dyspeptic patients (p&lt;0.05). Patients not only had a higher score for nausea, bloating, and pain but also the increase in nausea and pain scores with intragastric pressure was higher than in volunteers (p&lt;0.05). The increase in intragastric bag volume in response to a meal was significantly lower in patients (p&lt;0.05). Both bloating and pain significantly increased in the patients (p&lt;0.05), but not in the healthy volunteers. Conclusions —Patients with functional dyspepsia show slightly higher compliance to mechanical distension. Their visceral perception of mechanical stress is enhanced. In contrast with the balloon distension, relaxation after a meal was less. Therefore the postprandial symptoms cannot be explained fully by greater global tension in the stomach wall, as assessed by the barostat technique. Visceral hypersensitivity plays a major role in the pathogenesis of the symptoms.
Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis
Authors: Annie Pardo, Kevin Gibson, José Cisneros, Thomas J Richards, Yinke Yang, Carina Becerril, Samueal Yousem, Iliana Herrera, Victor Ruiz, Moisés Selman, Naftali Kaminski
Journal: PLoS Medicine (2005)

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung. Methods and Findings Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients. To study the fibrosis-relevant effects of osteopontin we stimulated primary human lung fibroblasts and alveolar epithelial cells (A549) with recombinant osteopontin. Osteopontin induced a significant increase of migration and proliferation in both fibroblasts and epithelial cells. Epithelial growth was inhibited by the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) and antibody to CD44, while fibroproliferation was inhibited by GRGDS and antibody to αvβ3 integrin. Fibroblast and epithelial cell migration were inhibited by GRGDS, anti-CD44, and anti-αvβ3. In fibroblasts, osteopontin up-regulated tissue inhibitor of metalloprotease-1 and type I collagen, and down-regulated matrix metalloprotease-1 (MMP-1) expression, while in A549 cells it caused up-regulation of MMP-7. In human IPF lungs, osteopontin colocalized with MMP-7 in alveolar epithelial cells, and application of weakest link statistical models to microarray data suggested a significant interaction between osteopontin and MMP-7. Conclusions Our results provide a potential mechanism by which osteopontin secreted from the alveolar epithelium may exert a profibrotic effect in IPF lungs and highlight osteopontin as a potential target for therapeutic intervention in this incurable disease.
Association of Mild to Moderate Kidney Dysfunction and Coronary Calcification
Authors: Joachim H. Ix, Ronit Katz, Bryan Kestenbaum, Linda F. Fried, Holly Kramer, Catherine Stehman-Breen, Michael G. Shlipak
Journal: Journal of the American Society of Nephrology (2008)

Coronary artery calcification (CAC) is prevalent and predicts mortality among patients with ESRD, but whether less severe kidney dysfunction is associated with CAC is uncertain. To address this question, 6749 participants of the Multi-Ethnic Study of Atherosclerosis, who were middle-aged and without known cardiovascular disease, were evaluated. Renal function was categorized by cystatin C quartiles and estimated GFR (eGFR; < to >60 ml/min per 1.73 m(2)), and CAC was evaluated by computed tomography (CT). Fifty percent of participants had CAC, mean cystatin C was 0.90 mg/L, and 10% had eGFR <60 ml/min per 1.73 m(2). In unadjusted analysis, kidney dysfunction by either measure was strongly associated with CAC; however, the associations were lost after adjustment for age, gender, race, hypertension, and IL-6 (relative risk 1.04 [95% confidence interval 0.97 to 1.11] for the highest cystatin C quartile compared with the lowest, and relative risk 1.03 [95% confidence interval 0.98 to 1.08] for eGFR below compared with above 60 m/min per 1.73 m(2)). Similarly, neither higher cystatin C nor eGFR <60 was associated with severity of CAC. These results suggest that a higher burden of CAC is unlikely to explain the association between mild to moderate kidney dysfunction and cardiovascular mortality.
Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin.
Authors: S D Huan, J C Yau, F R Dunphy, R O Wallerstein, K Dicke, V Spencer, C F LeMaistre, A B Deisseroth, G N Hortobagyi, F A Holmes
Journal: Journal of Clinical Oncology (1991)

Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients.
Molecular evolution of neuropeptides in the genus Drosophila
Authors: Christian Wegener, Anton Gorbashov
Journal: Genome biology (2008)

Neuropeptides comprise the most diverse group of neuronal signaling molecules. They often occur as multiple sequence-related copies within single precursors (the prepropeptides). These multiple sequence-related copies have not arisen by gene duplication, and it is debated whether they are mutually redundant or serve specific functions. The fully sequenced genomes of 12 Drosophila species provide a unique opportunity to study the molecular evolution of neuropeptides.We data-mined the 12 Drosophila genomes for homologs of neuropeptide genes identified in Drosophila melanogaster. We then predicted peptide precursors and the neuropeptidome, and biochemically identified about half of the predicted peptides by direct mass spectrometric profiling of neuroendocrine tissue in four species covering main phylogenetic lines of Drosophila. We found that all species have an identical neuropeptidome and peptide hormone complement. Calculation of amino acid distances showed that ortholog peptide copies are highly sequence-conserved between species, whereas the observed sequence variability between peptide copies within single precursors must have occurred prior to the divergence of the Drosophila species.We provide a first genomic and chemical characterization of fruit fly neuropeptides outside D. melanogaster. Our results suggest that neuropeptides including multiple peptide copies are under stabilizing selection, which suggests that multiple peptide copies are functionally important and not dispensable. The last common ancestor of Drosophila obviously had a set of neuropeptides and peptide hormones identical to that of modern fruit flies. This is remarkable, since drosophilid flies have adapted to very different environments.
Pulmonary Vascular Congestion Selectively Potentiates Airway Responsiveness in Piglets
Authors: TORSTEN UHLIG, JOHANNES H. WILDHABER, NEIL CARROLL, DEBRA J. TURNER, PETER R. GRAY, NIGEL DORE, ALAN L. JAMES, PETER D. SLY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals. Congestion alone resulted in small increased in baseline airway (Raw) (14.6 ± 3.7%) and tissue (Rti) resistance (8.1 ± 6.5%). Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 ± 10.3% and 42.2 ± 29.5%, respectively. The increase in Raw with MCh in the presence of vascular engorgement was significantly greater (67.8 ± 18.9%) but the increase in Rti (38.1 ± 13.2%) was similar to that seen in the control group. Morphometric measurements were performed on transverse sections of large and small airways from nine additional piglets (three congested only, three MCh only, and three congestion plus MCh). The thickness of the inner airway wall was similar in all groups. Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets. Compared with MCh only and engorgement only, the amount of airway smooth muscle shortening was greater (p < 0.05) in all airway size groups in piglets that underwent engorgement plus MCh challenge. The results of this study demonstrate that pulmonary vascular engorgement, induced by increased left atrial pressure, selectively enhances the airway, but not the parenchymal, response to inhaled MCh. These changes are associated with increased thickness of the outer airway wall in response to vascular congestion, suggesting that uncoupling of the mechanical interdependence between the airway smooth muscle and the lung parenchyma may have occurred. Mechanical uncoupling may reduce the load opposing smooth muscle shortening resulting in increased airway narrowing in response to low doses of inhaled methacholine.
The Membranous Epithelial (M) Cell and the Mucosal Immune System
Authors: J L Wolf, W A Bye
Journal: Annual Review of Medicine (1984)

Membranous epithelial (M) cells are specialized epithelial cells overlying the subepithelial lymphoid follicles in the gastrointestinal and respiratory tracts. Antigens, including some viruses and bacteria, penetrate the mucosal barrier via the M cell, which endocytoses and transports antigens and microorganisms into the Peyer's patch or bronchial-associated lymphoid tissue. Here antigens may initiate an immune response and/or disseminate and induce disease. This review discusses the structure and function of the M cell, its role in macromolecular uptake, and its interaction with the immune system.
Reporter Gene Imaging in Therapy and Diagnosis
Authors: Pritha Ray, Abhijit De
Journal: Theranostics (2012)

Noninvasive molecular imaging using reporter genes is a relatively recent field in biomedical imaging that holds great promises for disease diagnosis and therapy. As modern medicine is moving towards personalized medicine, targeted biomolecule based therapies is gaining popularity that requires careful and systematic validation. Reporter genes have emerged as important generalizable tools to overcome the shortcomings of direct evaluation of individual biomolecules and are being applied in various fields such as cell therapy, stem cell therapy, immune therapy, viral gene delivery through optical, radionuclide, magnetic resonance imaging techniques. New approaches to image protein-protein interaction, protein phosphorylation, protein folding that are crucial parameters for theranostic study using reporter genes are being developed. All these new technologies and relevant preclinical and clinical researches will determine the success of early detection and personalized therapy in the future.
IS EOSINOPHILIA OF DIAGNOSTIC IMPORTANCE IN DERMATITIS HERPETIFORMIS?
Authors: J. O'D. ALEXANDER
Journal: British Journal of Dermatology (1961)

Journal Article IS EOSINOPHILIA OF DIAGNOSTIC IMPORTANCE IN DERMATITIS HERPETIFORMIS? Get access J. O'D. ALEXANDER, M.B., Ch.B., F.R.F.P.S.(G.). J. O'D. ALEXANDER, M.B., Ch.B., F.R.F.P.S.(G.). Department of Dermatology, Glasgow Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 7, 1 July 1961, Pages 267–272, https://doi.org/10.1111/j.1365-2133.1961.tb14443.x Published: 01 July 1961