tbuckley/cabot-search huggingface dataset:
Nephrotic Plasma Alters Slit Diaphragm–Dependent Signaling and Translocates Nephrin, Podocin, and CD2 Associated Protein in Cultured Human Podocytes
Authors: Richard J.M. Coward, Rebecca R. Foster, David Patton, Lan Ni, Rachel Lennon, David O. Bates, Steven J. Harper, Peter W. Mathieson, Moin A. Saleem
Journal: Journal of the American Society of Nephrology (2005)

Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the slit diaphragm (SD) proteins nephrin, podocin, and CD2-associated protein (CD2AP) to function optimally. The effects of normal human plasma and nephrotic plasma on podocytes were tested, focusing particularly on the SD complex. With the use of a conditionally immortalized human podocyte cell line, it first was shown that exposure to normal and non-nephrotic human plasma leads to a concentration of nephrin, podocin, CD2AP, and actin at the cell surface. Next, the effects of plasma from patients with nephrotic conditions to non-nephrotic conditions were compared. When exposed to all nephrotic plasma samples (and a non-human serum control), nephrin podocin and CD2AP assumed a cytoplasmic distribution; nephrin and synaptopodin were selectively downregulated, and the relocation of nephrin induced by nephrotic plasma could be rescued back to the plasma membrane by co-incubation with non-nephrotic plasma. Furthermore, intracellular calcium signaling was altered by nephrotic plasma, which was mediated by tyrosine kinase phosphorylation. With the use of nephrin mutant human cell lines, it was shown that this signaling and translocation response to normal plasma is nephrin dependent. This work demonstrates that nephrotic plasma seems to be deficient in factors that act via the podocyte SD complex, which are essential in maintaining its physiologic function.
Gene Expression Profiling Reveals Cross-talk between Melanoma and Fibroblasts: Implications for Host-Tumor Interactions in Metastasis
Authors: Paul G. Gallagher, Yongde Bao, Alyson Prorock, Paola Zigrino, Roswitha Nischt, Vincenzo Politi, Cornelia Mauch, Bojan Dragulev, Jay William Fox
Journal: Cancer Research (2005)

Abstract Host-tumor interaction is considered critical in carcinogenesis, tumor invasion, and metastasis. To explore the reciprocal effects of host-tumor interaction, we developed a system to assess the gene expression patterns of A2058 human melanoma cells cocultured in fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered. Interleukin-11 and inhibitor of DNA-binding domain-1 gene expression in the cocultured A2058 cells was down-regulated, indicative of a proinflammatory response and resistance to apoptosis, respectively. The overall pattern of up-regulated genes indicated triggering of the proinflammatory process. In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts. These results were corroborated by additional coculture experiments with the melanoma cell lines WM-164, BLM, and SK-Mel-28 and immunohistochemistry on invasive human melanoma sections. Taken together, these results indicate that tumor cells cause a proinflammatory and melanoma growth-promoting response in stromal fibroblasts. The role of inflammation in carcinogenesis, tumor promotion, invasion, and metastasis is viewed as being increasingly important and the results of these studies underscore this as well as identify certain key proteins that are expressed as a result of the complex interactive processes in the host-tumor microenvironment.
A Purine Scaffold HSP90 Inhibitor BIIB021 Has Selective Activity against KSHV-Associated Primary Effusion Lymphoma and Blocks vFLIP K13-Induced NF-κB
Authors: Ramakrishnan Gopalakrishnan, Hittu Matta, Preet M. Chaudhary
Journal: Clinical Cancer Research (2013)

Kaposi sarcoma-associated herpes virus (KSHV)-associated primary effusion lymphomas (PEL) have extremely poor prognosis when treated with conventional chemotherapy. KSHV-encoded viral FLICE-inhibitory protein (vFLIP) K13 binds to the IkappaB kinase (IKK) complex to constitutively activate the NF-κB pathway, which has been shown to be essential for the survival and proliferation of PEL cells. The molecular chaperone HSP90 is a component of the IKK complex and is required for its activity.We have analyzed the effect of HSP90 inhibitors on the survival and proliferation of PEL cells and on the activity of the NF-κB pathway.We show that BIIB021, a purine scaffold-based orally administrable HSP90 inhibitor, shows preferential cytotoxicity toward PEL cells as compared with non-PEL cells. The cytotoxic effect of BIIB021 against PEL was associated with induction of cell-cycle arrest and apoptosis. BIIB021 blocked the expression of a number of cellular proteins involved in the regulation of cell cycle and apoptosis. BIIB021 also blocked constitutive NF-κB activity present in PEL cells, in part, by blocking the interaction of vFLIP K13 with the IKK complex subunits. In a xenograft model of PEL, BIIB021 significantly reduced tumor growth.BIIB021 blocks constitutive NF-κB activity in PEL and shows preferential antitumor activity against PEL in vitro and in vivo. BIIB021 may be a promising agent for treatment of PEL.
GP pilots are "last chance saloon" for care.data scheme
Authors: A. O'Dowd
Journal: BMJ (2015)

GPs piloting the controversial data sharing care.data scheme in England are the “last chance saloon” for the project, MPs have been told.

IT leaders at NHS England have promised that the scheme will not be rolled out nationally until it is deemed to be working well and protecting patients’ confidentiality. Under the scheme, GPs’ health records will be shared with the national Health and Social Care Information Centre and linked to existing information on hospital records to help ensure quality and safety of services and provide information for research.

The scheme was due to be rolled out in spring last year but was delayed after claims that the NHS failed to properly consult on it and …
p38 MAPK mediates fibrogenic signal through smad3 phosphorylation in rat myofibroblasts
Authors: Fukiko Furukawa, Koichi Matsuzaki, Shigeo Mori, Yoshiya Tahashi, Katsunori Yoshida, Yasushi Sugano, Hideo Yamagata, Masanori Matsushita, Toshihito Seki, Yutaka Inagaki, Mikio Nishizawa, Junichi Fujisawa, Kyoichi Inoue
Journal: Hepatology (2003)

Hepatic stellate cells (HSCs) spontaneously transdifferentiate into myofibroblast (MFB)–phenotype on plastic dishes. This response recapitulates the features of activation in vivo. Transforming growth factor β (TGF–β) plays a prominent role in stimulating liver fibrogenesis by MFBs. In quiescent HSCs, TGF–β signaling involves TGF–β type I receptor (TβRI)–mediated phosphorylation of serine residues within the conserved SSXS motif at the C–terminus of Smad2 and Smad3. The middle linker regions of Smad2 and Smad3 also are phosphorylated by mitogenactivated protein kinase (MAPK). This study elucidates the change of Smad3–mediated signals during the transdifferentiation process. By using antibodies highly specific to the phosphorylated C–terminal region and the phosphorylated linker region of Smad3, we found that TGF–β–dependent Smad3 phosphorylation at the C–terminal region decreased, but that the phosphorylation at the linker region increased in the process of transdifferentiation. TGF–β activated the p38 MAPK pathway, further leading to Smad3 phosphorylation at the linker region in the cultured MFBs, irrespective of Smad2. The phosphorylation promoted hetero–complex formation and nuclear translocation of Smad3 and Smad4. Once combined with TβRI–phosphorylated Smad2, the Smad3 and Smad4 complex bound to plasminogen activator inhibitor–type I promoter could enhance the transcription. In addition, Smad3 phosphorylation mediated by the activated TβRI was impaired severely in MFBs during chronic liver injury, whereas Smad3 phosphorylation at the linker region was remarkably induced by p38 MAPK pathway. In conclusion, p38 MAPK—dependent Smad3 phosphorylation promoted extracellular matrix production in MFBs both in vitro and in vivo. (Hepatology 2003;38:879-889).
Targeting phospholipase D1 attenuates intestinal tumorigenesis by controlling β-catenin signaling in cancer-initiating cells
Authors: Dong Woo Kang, Chi Yeol Choi, Yong-Hee Cho, Huasong Tian, Gilbert Di Paolo, Kang-Yell Choi, Do Sik Min
Journal: The Journal of Experimental Medicine (2015)

Expression of the Wnt target gene phospholipase D1 (PLD1) is up-regulated in various carcinomas, including colorectal cancer (CRC). However, the mechanistic significance of its elevated expression in intestinal tumorigenesis remains unknown. In this study, we show that genetic and pharmacological targeting of PLD1 disrupts spontaneous and colitis-associated intestinal tumorigenesis in Apc(Min/+) and azoxymethane/dextran sodium sulfate mice models. Intestinal epithelial cell-specific PLD1 overexpression in Apc(Min/+) mice accelerated tumorigenesis with increased proliferation and nuclear β-catenin levels compared with Apc(Min/+) mice. Moreover, PLD1 inactivation suppressed the self-renewal capacity of colon cancer-initiating cells (CC-ICs) by decreasing expression of β-catenin via E2F1-induced microRNA (miR)-4496 up-regulation. Ultimately, low expression of PLD1 coupled with a low level of CC-IC markers was predictive of a good prognosis in CRC patients, suggesting in vivo relevance. Collectively, our data reveal that PLD1 has a crucial role in intestinal tumorigenesis via its modulation of the E2F1-miR-4496-β-catenin signaling pathway. Modulation of PLD1 expression and activity represents a promising therapeutic strategy for the treatment of intestinal tumorigenesis.
Regional blood flow and vascular resistance in the spontaneously hypertensive rat
Authors: A. J. TOBIA, J. Y. LEE, G. M. WALSH
Journal: Cardiovascular Research (1974)

Journal Article Regional blood flow and vascular resistance in the spontaneously hypertensive rat Get access ALFONSO J. TOBIA, ALFONSO J. TOBIA From the Department of Pharmacology, University of Georgia School of Pharmacy, Athens, Georgia 30602, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar JANG Y. LEE, JANG Y. LEE From the Department of Pharmacology, University of Georgia School of Pharmacy, Athens, Georgia 30602, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar GERALD M. WALSH GERALD M. WALSH From the Department of Pharmacology, University of Georgia School of Pharmacy, Athens, Georgia 30602, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 6, November 1974, Pages 758–762, https://doi.org/10.1093/cvr/8.6.758 Published: 01 November 1974
The STARD Statement for Reporting Studies of Diagnostic Accuracy: Explanation and Elaboration
Authors: Patrick M. Bossuyt, Johannes B. Reitsma, David E. Bruns, Constantine A. Gatsonis, Paul P. Glasziou, Les M. Irwig, David Moher, Drummond Rennie, Henrica C.W. de Vet, Jeroen G. Lijmer
Journal: Annals of Internal Medicine (2003)

The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in the study and to evaluate the generalizability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the reporting the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding, and dissemination of the checklist. The document contains a clarification of the meaning, rationale, and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart, and this explanation and elaboration document should be useful resources to improve reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in health care.
Adolescents with acute lymphoblastic leukemia treated at pediatric versus adult hospitals
Authors: J.D. Pole, S.M.H. Alibhai, M.C. Ethier, O. Teuffel, C. Portwine, S. Zelcer, D.L. Johnston, M. Silva, S. Alexander, J.M. Brandwein, L. Sung
Journal: Annals of Oncology (2012)
Immune human lymphocytes produce an acid-labile α-interferon
Authors: FR Balkwill, DB Griffin, HA Band, PCL Beverley
Journal: The Journal of Experimental Medicine (1983)

We have described in this paper a novel human interferon (IFN) with antigenic and cross-species reactivity of alpha-IFN and physicochemical properties of gamma-IFN. This IFN is produced by normal peripheral blood mononuclear cells during an immune response but has also been associated with autoimmune disease (10). The system described here will be useful in elucidating the biological significance and cell of origin of this IFN.
ISOLATION AND PROPERTIES OF A SURFACE ANTIGEN OF STAPHYLOCOCCUS AUREUS
Authors: Stephen I. Morse
Journal: The Journal of Experimental Medicine (1962)

A technique is described for the isolation and purification of an antigen released into the culture medium by Staphylococcus aureus strain Smith. The antigen was found to be homogeneous when examined by free electrophoresis and analytic ultracentrifugation. Immunologic homogeneity was established by immunoelectrophoresis and quantitative precipitin tests using high titer antiserum prepared against the homologous organism. Chemical analysis showed that the antigen contained 70 per cent carbohydrate, of which approximately 30 to 35 per cent was believed to be glucosamine. The analytic data suggested that another amino sugar, probably carboxylated, was also present, but extreme lability of this compound to mild hydrolytic procedures has thus far precluded further identification. The remainder of the antigen was composed of alanine, glutamic acid, aspartic acid, lysine, glycine, serine, and threonine. No muramic acid was found. The chemical and physical data indicate that the antigen described herein is a previously unrecognized component of Staphylococcus aureus. The purified compound was capable of absorbing agglutinating antibody from antiserum prepared against S. aureus Smith, indicating that it was a surface component of this encapsulated staphylococcus. It is proposed that the antigen be known as the Smith surface antigen (SSA). The injection of SSA into rabbits did not produce precipitating antibodies. However, SSA did precipitate at low concentrations (0.5 microg/ml) with antiserum prepared against S. aureus Smith and one other strain of S. aureus tested. Antiserum against two other aureus strains reacted only with high concentrations of SSA. SSA did not react with S. albus antiserum or with normal sera from several animal species. Experiments are in progress to define further the distribution of SSA. Intradermal injection of small quantities of SSA into rabbits immunized with S. aureus Smith evoked a reaction of cutaneous hypersensitivity, which was maximal in 8 to 12 hours. SSA appeared to be the substance responsible for the ability of S. aureus Smith to resist engulfment by phagocytes, since absorption of Smith antiserum with SSA effectively removed opsonizing antibodies. SSA induced protection in mice against experimental staphylococcal disease. The subcutaneous injection of 0.1 microg resulted in protection against a subsequent intraperitoneal challenge with 50 to 100 LD(50)'s of S. aureus Smith suspended in mucin. Increasing as well as decreasing the immunizing dose resulted in significantly less protection.
Initiation of Adjuvant Hormone Therapy by Medicaid Insured Women With Nonmetastatic Breast Cancer
Authors: R. L. Yung, M. J. Hassett, K. Chen, F. C. Gesten, P. J. Roohan, F. P. Boscoe, A. H. Sinclair, M. J. Schymura, D. Schrag
Journal: JNCI Journal of the National Cancer Institute (2012)

Hormone therapy is the mainstay of adjuvant treatment for hormone receptor positive (HR-positive) nonmetastatic breast cancer. We evaluated adjuvant hormone therapy (AHT) initiation among Medicaid-insured women aged 21–64 years with stage I–III HR-positive breast cancer. We used multivariable logistic regression to identify independent predictors of AHT initiation. Within 1 year of diagnosis, 68% (1049/1538) initiated AHT; by 18 months, 80% (1168/1461) initiated AHT. In multivariable analysis, women less likely to initiate AHT had more comorbidity (≥2 vs none: adjusted odds ratio (AOR) = 0.55; 95% CI = 0.32 to 0.97), more advanced disease (stage III vs I: AOR = 0.27; 95% CI = 0.18 to 0.39), and no radiation after breast conserving surgery (AOR = 0.15; 95% CI = 0.10 to 0.22). Race, age, and history of mental health disorders were not independently associated with initiation of AHT. Among initiators of AHT, 58% (604/1049) were adherent to treatment for the year after initiation. Despite comprehensive prescription coverage, only 39% (604/1538) received optimal AHT including prompt initiation and adherence for the year after treatment. Partnerships between Medicaid programs and cancer registries may help identify at-risk women and facilitate the implementation of quality improvement strategies.
Shoulder joint loading in the high performance flat and kick tennis serves
Authors: Machar Reid, Bruce Elliott, Jacque Alderson
Journal: British Journal of Sports Medicine (2007)

To quantify and compare the full body kinematics and shoulder joint kinetics during the high-performance tennis flat (FS) and kick serves (KS).A 12-camera 250 Hz, Vicon motion analysis system recorded the three-dimensional FS and KS of 12 high-performance male players. A total of 22 paired Student's t tests, with an accompanying partial Bonferroni correction (p<0.01), determined statistically significant differences between the variables of interest in both serves.Higher peak horizontal, vertical and absolute racquet velocities were developed during the FS, while higher lateral velocities characterised the KS. Similar shoulder joint kinematics and kinetics punctuated both serves, but with some variation in trunk and lower limb mechanics.Similar shoulder joint kinetics assisted the development of varying three-dimensional racquet velocities in the FS and KS. The comparable shoulder joint loading conditions point to the repetitive, long-term performance of either serve as relevant in shoulder joint injury pathologies.
Arsonate-specific murine T cell clones. I. Genetic control and antigen specificity
Authors: B Hertel-Wulf, JW Goodman, CG Fathman, GK Lewis
Journal: The Journal of Experimental Medicine (1983)

The antigen-induced proliferative response of lymph node cells (LNC) from mice sensitized to the monofunctional antigen L-tyrosine-p-azobenzenearsonate (ABA-Tyr) was used to monitor genetic control. All strains tested mounted significant responses, but those that were H-2(b) at both the I-A and I-E loci [B10., B6., B10.A(18R), A.BY, and C3H.SW] gave consistently weaker responses than other haplotypes. The F(1) progeny of matings between high and low responder phenotype parents (DBA/2 and B6, respectively) were high responders, establishing the dominance of the responder trait. Proliferative responses of LNC to ABA-Tyr were blocked by the appropriate anti-Ia monoclonal reagents. For example, B10.A(4R) LNCI (I-A(k), I-E(b)) were blocked by anti-I-A(k), whereas B10.A(3R) LNC (I-A(b), I-E(k)) were blocked by anti-I-E(k). Long-term cultures of T cell lines specifically reactive to ABA-Tyr were established from LNC of A/J mice immunized with ABA-Tyr and were cloned by limiting dilution. The proliferative responses to ABA-Tyr of 14 out of 15 clones tested were I-A restricted on the basis of activation by antigen-presenting cells from appropriate recombinant strains and the blocking activity of the monoclonal anti-Ia antibodies. The response of the other clone was I-E restricted. The fine antigen specificity of the clones was studied using structural analogs of the homologous antigen to induce proliferation. The clones could be divided into three types with respect to responsiveness to ABA-histidine (ABA-His). One group responded about equally well to ABA-His and ABA-Tyr. A second set responded less strongly to ABA-His than to ABA-Tyr, while the third showed no response above background to ABA- His. In all instances, the ABA-His-responding clones discriminated exquisitely between the 2-azo and 4-azo histidine isomers, responding only to the 4-azo compound. These T cell clones provide extremely useful tools for studies of T cell specificity, antigen recognition and lymphoid cell interaction systems.
Solution‐Gated Graphene Transistors for Chemical and Biological Sensors
Authors: Feng Yan, Meng Zhang, Jinhua Li
Journal: Advanced Healthcare Materials (2013)

Graphene has attracted much attention in biomedical applications for its fascinating properties. Because of the well‐known 2D structure, every atom of graphene is exposed to the environment, so the electronic properties of graphene are very sensitive to charged analytes (ions, DNA, cells, etc.) or an electric field around it, which renders graphene an ideal material for high‐performance sensors. Solution‐gated graphene transistors (SGGTs) can operate in electrolytes and are thus excellent candidates for chemical and biological sensors, which have been extensively studied in the recent 5 years. Here, the device physics, the sensing mechanisms, and the performance of the recently developed SGGT‐based chemical and biological sensors, including pH, ion, cell, bacterial, DNA, protein, glucose sensors, etc., are introduced. Their advantages and shortcomings, in comparison with some conventional techniques, are discussed. Conclusions and challenges for the future development of the field are addressed in the end.
Last of the Human Protists: The Phylogeny and Genetic Diversity of Iodamoeba
Authors: C. R. Stensvold, M. Lebbad, C. G. Clark
Journal: Molecular Biology and Evolution (2011)

Iodamoeba is the last genus of obligately parasitic human protist whose phylogenetic position is unknown. Iodamoeba small subunit ribosomal DNA sequences were obtained using samples from three host species, and phylogenetic analyses convincingly placed Iodamoeba as a sister taxon to Endolimax. This clade in turn branches among free-living amoeboflagellates of the genus Mastigamoeba. Two Iodamoeba ribosomal lineages (RL1 and RL2) were detected whose sequences differ by 31%, each of which is found in both human and nonhuman hosts.
Cardioversion 125 times without necrosis.
Authors: P A Cann, C F Corke
Journal: BMJ (1981)

Crohn’s disease (CD) is a chronic inflammatory condition, which typically involves the small and large bowel but can affect any part of the gastrointestinal tract. Common symptoms include abdominal pain, diarrhoea, fatigue, weight loss and malnutrition. Complications of CD include gallstone formation and cholecystitis. Impaired reabsorption of bile salts in the small bowel and CD-related surgeries are key factors in the development of CD-related gallstones, although other factors are also important. Direct CD-related inflammation of the gallbladder is very unusual and the typical histological features of CD are rarely encountered in cholecystectomy specimens of individuals with CD. We present a case of a man in his early 60s with CD, previous right hemicolectomy and a history of gallstones, who presented with chronic cholecystitis. Following cholecystectomy, pathological examination of the gallbladder unexpectedly demonstrated typical features of CD, including lymphoid aggregates and non-caseating mucosal granulomata.