tbuckley/cabot-search huggingface dataset:
Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1β and tumour necrosis factor α
Authors: S-M Dai, K Nishioka, K Yudoh
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine whether IL18 has any indirect effects on osteoclastogenesis mediated by T cells in RA synovium, and compare its effects with those of IL1β and TNFα. <b>Methods:</b> Resting T cells were isolated from peripheral blood of healthy donors, and stimulated with 2 μg/ml phytohaemagglutinin (PHA) and 0.5 ng/ml IL2 for 24 hours. Synovial T cells were isolated from RA synovial tissue. The levels of soluble receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), IFNγ, M-CSF, and GM-CSF were determined by ELISA. Membrane bound RANKL expression was analysed by flow cytometry. Commercially available human osteoclast precursors were cocultured with T cells to induce osteoclast formation, which was determined with tartrate resistant acid phosphatase staining and pit formation assay. <b>Results:</b> In PHA prestimulated T cells or RA synovial T cells, IL18, IL1β, or TNFα increased soluble RANKL production and membrane bound RANKL expression in a dose dependent manner. IL18, IL1β, and TNFα did not induce M-CSF, GM-CSF, IFNγ, or OPG production in PHA prestimulated T cells or RA synovial T cells. IL18 increased the number of osteoclasts and bone resorption area on dentine slices in the coculture of human osteoclast precursors with PHA prestimulated T cells or RA synovial T cells; its ability was equivalent to that of IL1β, but less potent than that of TNFα. In the coculture system, OPG completely blocked osteoclast induction by IL18 or IL1β, and greatly inhibited induction by TNFα. <b>Conclusion:</b> IL18, IL1β, or TNFα can indirectly stimulate osteoclast formation through up regulation of RANKL production from T cells in RA synovitis; IL18 is as effective as IL1β, but less potent than TNFα.
Uptake and subcellular localisation of bismuth in the gastrointestinal mucosa of rats after short term administration of colloidal bismuth subcitrate.
Authors: D Stiel, D J Murray, T J Peters
Journal: Gut (1985)

Despite the topical action of colloidal bismuth subcitrate in promoting the healing of peptic ulcers, slight absorption of bismuth from the gastrointestinal tract has been reported in colloidal bismuth subcitrate-treated animals and man. The uptake and subcellular distribution of bismuth by the gastrointestinal tract of rats after 24 hours of colloidal bismuth subcitrate administration was studied. Mucosal uptake of bismuth (mean +/- SEM nmol/g protein) by gastric fundus (8.85 +/- 1.0) and antrum (7.23 +/- 1.50) was similar, but was significantly less than duodenum (19.2 +/- 3.7, p less than 0.05), jejunum (26.9 +/- 2.4, p less than 0.001) or ileum (22.4 +/- 2.2, p less than 0.001). Bismuth concentrations in antral and duodenal mucosae fell progressively over 72 hours to approximately 10% of initial concentrations (p less than 0.02). Subcellular fractionation studies of colloidal bismuth subcitrate treated duodenal enterocytes showed a brush border membrane and cytosolic localisation. These data suggest that some gastrointestinal mucosal uptake of bismuth occurs in colloidal bismuth subcitrate treated rats.
Intrinsic mineralocorticoid agonist activity of some nonsteroidal anti-inflammatory drugs. A postulated mechanism for sodium retention.
Authors: D Feldman, C Couropmitree
Journal: Journal of Clinical Investigation (1976)

Because some nonsteroidal anti-inflammatory drugs (NSAID) induce salt and water retention and exhibit other steroid-like actions, studies were performed to ascertain whether these drugs possess intrinsic mineralocorticoid agonist activity. In vitro competitive binding assays utilizing tissue from adrenalectomized rats demonstrated that some NSAID can displace [3H]-aldosterone from renal cytoplasmic mineralocorticoid receptors. Displacement potency for these sites was in the sequence: aldosterone greater than spironolactone greater than phenylbutazone (PBZ) greater than aspirin (ASA) greater than indomethacin (IDM). Concentration ratios required to obtain significant displacement of [3H]aldosterone were high but clearly within the therapeutic range for PBZ and ASA but not IDM. The analogues oxyphenbutazone (OBZ) and sodium salicylate (SS) were similar in binding activity to PBZ and ASA, respectively. Lineweaver-Burk analysis revealed that the inhibition of [3H]aldosterone binding was competitive in nature. In addition, PBZ was shown to prevent the nuclear binding of [3H]aldosterone. In vivo injection of PBZ and ASA resulted in competition for [3H]aldosterone renal binding comparable to the in vitro studies. Administration of PBZ and OBZ to adrenalectomized rats resulted in significant salt retention whereas ASA and SS did not differ significantly from controls. Salt retention elicited by PBZ and OBZ was inhibited by spironolactone, a competitive mineralocorticoid antagonist. These data suggest that, despite nonsteroidal structures, PBZ and OBZ induce salt retention via a receptor-mediated mineralocorticoid pathway analogous to aldosterone action.
The Role of Cell Density and Intratumoral Heterogeneity in Multidrug Resistance
Authors: Orit Lavi, James M. Greene, Doron Levy, Michael M. Gottesman
Journal: Cancer Research (2013)

Abstract Recent data have demonstrated that cancer drug resistance reflects complex biologic factors, including tumor heterogeneity, varying growth, differentiation, apoptosis pathways, and cell density. As a result, there is a need to find new ways to incorporate these complexities in the mathematical modeling of multidrug resistance. Here, we derive a novel structured population model that describes the behavior of cancer cells under selection with cytotoxic drugs. Our model is designed to estimate intratumoral heterogeneity as a function of the resistance level and time. This updated model of the multidrug resistance problem integrates both genetic and epigenetic changes, density dependence, and intratumoral heterogeneity. Our results suggest that treatment acts as a selection process, whereas genetic/epigenetic alteration rates act as a diffusion process. Application of our model to cancer treatment suggests that reducing alteration rates as a first step in treatment causes a reduction in tumor heterogeneity and may improve targeted therapy. The new insight provided by this model could help to dramatically change the ability of clinical oncologists to design new treatment protocols and analyze the response of patients to therapy. Cancer Res; 73(24); 7168–75. ©2013 AACR.
Effects of Blocking Platelet-Derived Growth Factor-Receptor Signaling in a Mouse Model of Experimental Prostate Cancer Bone Metastases
Authors: H. Uehara, S. J. Kim, T. Karashima, D. L. Shepherd, D. Fan, R. Tsan, J. J. Killion, C. Logothetis, P. Mathew, I. J. Fidler
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Expression of platelet-derived growth factor (PDGF) and activation (by autophosphorylation) of its receptor (PDGF-R), a tyrosine kinase, are associated with the growth of metastatic prostate tumor cells in the bone parenchyma. The tyrosine kinase inhibitor STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. We examined the effects of STI571, given alone or with paclitaxel (Taxol), on tumor growth in a mouse model of prostate cancer metastasis. Methods: Human prostate cancer PC-3MM2 cells were injected into the tibias of male nude mice. Three days later the mice (20 per group) were randomly assigned to 5 weeks of treatment with oral and injected water (control), daily oral STI571, weekly injected paclitaxel, or STI571 plus paclitaxel. Lesions in bone and the surrounding muscles were then harvested and analyzed by histology, western blotting (for PDGF-R phosphorylation), immunohistochemistry (for expression of proangiogenic molecules), and double immunofluorescence (to identify endothelial cells and apoptotic tumor cells). Growth of bone lesions was monitored by digital radiography. Bone lesions from control mice were used to establish short-term cell cultures for analysis of PDGF-R phosphorylation. All statistical tests were two-sided. Results: PC-3MM2 cells cultured from bone lesions and treated in vitro with STI571 had less phosphorylated PDGF-R than untreated cells. In control mice, bone lesions expressed high levels of PDGF and activated (i.e., phosphorylated) PDGF-R, whereas lesions in the adjacent musculature did not. Activated PDGF-R was present on the surface of endothelial cells within the bone lesions but not in endothelial cells of uninjected bone. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than mice treated with water or paclitaxel alone (P<.001 for all). Mice treated with STI571 or STI571 plus paclitaxel had less phosphorylated PDGF-R on tumor cells and tumor-associated endothelial cells, less tumor cell proliferation, statistically significantly more apoptotic tumor cells (all P<.001), and fewer tumor-associated endothelial cells (P<.001) than control mice. Conclusions: Endothelial cells appear to express phosphorylated PDGF-R when they are exposed to tumor cells that express PDGF. Using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis.
Goals and Habits in the Brain
Authors: Ray J. Dolan, Peter Dayan
Journal: Neuron (2013)

An enduring and richly elaborated dichotomy in cognitive neuroscience is that of reflective versus reflexive decision making and choice. Other literatures refer to the two ends of what is likely to be a spectrum with terms such as goal-directed versus habitual, model-based versus model-free or prospective versus retrospective. One of the most rigorous traditions of experimental work in the field started with studies in rodents and graduated via human versions and enrichments of those experiments to a current state in which new paradigms are probing and challenging the very heart of the distinction. We review four generations of work in this tradition and provide pointers to the forefront of the field's fifth generation.
343 MMP-9 overexpression in murine liver: Embryonic lethality and influence on liver homeostasis in juvenile mice
Authors: F.R. Thieringer, E. Czochra, E. Meyer, U. Schmitt, B. Anthon, J.E. Garcia-Lazaro, A.W. Lohse, E.R. Galle, S. Kanzler
Journal: Journal of Hepatology (2006)
Biochemistry and Pathology of Connective Tissue
Authors: D. L. Gardner
Journal: Annals of the Rheumatic Diseases (1975)

the importance of their associated rheumatic manifestations.The chapter about haemophilia demonstrates how much can be done for this daunting problem by an integrated team of haematologists and orthopaedic surgeons.These are but a few examples of the rich clinical seams which the contributors have mined.The series will continue with publication of three issues each year, the next three being devoted to current management of rheumatoid arthritis, systemic lupus erythematosus, and diagnosis and assessment.
Proportion of patients experiencing four preventable harms during NHS treatment falls from 8.9% to 6.1% over two years
Authors: N. Hawkes
Journal: BMJ (2014)

The proportion of NHS patients in England who encountered harms during care in all settings decreased in the year to October 2014, data from the Health and Social Care Information Centre have shown.1

In the 13 month period from October 2013 …
IFN-α and Bortezomib Overcome Bcl-2 and Mcl-1 Overexpression in Melanoma Cells by Stimulating the Extrinsic Pathway of Apoptosis
Authors: Gregory B. Lesinski, Ene T. Raig, Kristan Guenterberg, Lloyd Brown, Michael R. Go, Nisha N. Shah, Adrian Lewis, Megan Quimper, Erinn Hade, Gregory Young, Abhik Ray Chaudhury, Katherine J. Ladner, Denis C. Guttridge, Page Bouchard, William E. Carson
Journal: Cancer Research (2008)

Abstract We hypothesized that IFN-α would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-α induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase. Bortezomib plus IFN-α was effective at inducing apoptosis in melanoma cells that overexpressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The proapoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD before the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or small interfering RNA targeting Fas. These data suggest that bortezomib and IFN-α act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-α displayed statistically significant antitumor activity compared with either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-α for malignant melanoma. [Cancer Res 2008;68(20):8351–60]
Localized lichen myxoedematosus (papular mucinosis) associated with morbid obesity: report of two cases
Authors: M. Saez-Rodriguez, M. Garcia-Bustinduy, A. Lopez-Alba, A. Noda-Cabrera, F. Guimera-Martin-Neda, S. Dorta-Alom, M. Escoda-Garcia, E. Fagundo-Gonzalez, R. Sanchez-Gonzalez, A. Martin-Herrera, R. Garcia-Montelongo
Journal: British Journal of Dermatology (2003)

Cutaneous diseases are often found in obese patients but, to our knowledge, mucinous disorders have not been previously reported in association with obesity. Two cases of localized lichen myxoedematosus (papular mucinosis) in two women with morbid obesity are described. Both patients underwent a low‐calorie diet for a 1‐year period in one case, and for 4 months in the other one, as the only treatment. There was complete resolution of cutaneous lesions at the same time that an important weight loss was observed. Nevertheless, although spontaneous regression is not frequent, it could not be disregarded in either of these two cases.
The Safety of Diethyltoluamide Insect Repellents
Authors: R. P. Moody
Journal: JAMA (1989)

To the Editor. —  I am writing in reference to the letter to the editor by Davies et al and the reply by Tenenbein 1 in the April 15, 1988, issue of JAMA concerning the safety of N,N -diethyl- m -toluamide (DEET)—based insect repellents. The criticism expressed by Davies et al that a previous article by Tenenbein 2 was incorrect in extrapolating DEET toxicity data from ingestion studies to topical applications was questioned. Tenenbein 1 pointed out inconsistencies between the data of Davies et al and those of a study by Wu et al. 3 We recently reported 4 that DE ET is absorbed rapidly after topical applications in rats, monkeys, and man and that anatomic site—related differences were observed in the monkey, with 68% ± 9% being absorbed from the ventral forepaw. This observation should cause concern since the monkey ventral forepaw corresponds with the human palmar surface, 4
Studies on an epidemic of respiratory disease caused by Mycoplasma pneumoniae.
Authors: T. Feizi, H. Maclean, R. G. Sommerville, J. G. Selwyn
Journal: BMJ (1967)

Pneumonia in Glasgow-Gist et al.MEDIBCA JouR. 457 months of 1963 the notifications for children were falling after the peak of the respiratory syncytial outbreak, while those for adults were rising as the influenza outbreak developed.We are grateful to Dr. W. A. Home, Medical Officer of Health for Glasgow, for access to pneumonia statistics kindly provided by Miss Mary Knox.We also thank our clinical colleagues in hospital and general practice for their co-operation in these studies, and our technical staff for their assistance.
A Lot to Ask
Authors: Susan A. Glod
Journal: Annals of Internal Medicine (2011)

On Being a Doctor6 September 2011A Lot to AskSusan A. Glod, MDSusan A. Glod, MDFrom Penn State Milton S. Hershey Medical Center, Hershey, PA 17033-0850.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-5-201109060-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Jane was 39 years old but didn't look it. Her face was round from steroids, and wispy patches of fine hair clung to her mostly bald scalp. She topped this off with a pair of severe-looking reading glasses that gave visitors the impression of a professorial infant. Her tracheostomy prevented her from speaking, and her bed was surrounded by notebooks, pens, and the odd scraps of paper that she used when communicating with the rest of the world. Any visitor who used any of the above information to assume that Jane was not intelligent, educated, and well-spoken was in for ... Author, Article, and Disclosure InformationAffiliations: From Penn State Milton S. Hershey Medical Center, Hershey, PA 17033-0850.Corresponding Author: Susan A. Glod, MD, Division of General Internal Medicine, Penn State Milton S. Hershey Medical Center, Mail Code H106, 500 University Drive, PO Box 850, Hershey, PA 17033-0850; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 September 2011Volume 155, Issue 5Page: 333KeywordsAmbulancesComputersHospital medicineLungsLymphomaRespiratory failureSteroidsTechniciansTracheostomyVentilators ePublished: 6 September 2011 Issue Published: 6 September 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Autoantibody formation against a 190-kDa antigen of the desmosomal plaque in pemphigus foliaceus
Authors: R. GHOHESTANI, P. JOLY, D. GILBERT, J.F. NICOLAS, E. THOMINE, E. COZZANI, PH. LAURET, A. CLAUDY, F. TRON
Journal: British Journal of Dermatology (1997)

We report changes in the antigen recognition pattern of sera from two pemphigus foliaceus patients with a long-term follow-up. The patients' sera were analysed by immunoblotting using different antigenic sources: cultured human keratinocytes, bovine tongue epithelium and a recombinant protein corresponding to the C-terminal end of the 230-kDa bullous pemphigoid antigen. While initial serum samples reacted exclusively with the 160-kDa desmoglein 1, the later sera reacted both with desmoglein 1 and a 190-kDa antigen immunolocalized to the desmosomal plaque, previously demonstrated to be recognized by sera of some patients with paraneoplastic pemphigus. IgG subclass analysis further showed that antidesmoglein 1 antibodies were of IgG1 and/or IgG4 subclasses, while anti-190-kDa antibodies were IgG3. The patients were free of malignancy.
Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study.
Authors: R Taylor, L Lovelock, W M Tunbridge, K G Alberti, R G Brackenridge, P Stephenson, E Young
Journal: BMJ (1990)

OBJECTIVE--To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy. DESIGN--Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist. SETTING--Outpatient diabetic clinics of three teaching hospitals and three district general hospitals. PATIENTS--2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle. MAIN OUTCOME MEASURES--Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported. RESULTS--Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral. Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons. Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed. Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01). Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001). CONCLUSIONS--Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy.
Sensitization to Erythrocytes
Authors: Donald S. Waldorf
Journal: JAMA (1968)

In this case of sensitization to erythrocytes, painful purpuric nodules, evanescent neurological complaints, and abdominal pain developed in a patient three weeks after a traumatic ecchymosis. All hematologic and blood clotting studies were normal. Lesions could be reproduced locally by intradermal injections of either autologous whole red blood cells, autologus red blood cell stroma, or purified protein derivative (PPD) of tubercle bacilli, but they could not be reproduced by similar preparations of autologous red blood cell hemolysate, autologus plasma, histamine, calf-thymus deoxyribonucleic acid, salmon-sperm DNA, phosphatidyl-I-serine, or old tuberculin. The patient had an excellent response to cyproheptadine hydrochloride but later was free of lesions after spontaneously stopping treatment.
Toxic Shock Syndrome in Utah: A Case-Control and Surveillance Study
Authors: ROBERT H. LATHAM
Journal: Annals of Internal Medicine (1982)

In 1980, a case-control study done in Utah using 29 women hospitalized with toxic shock syndrome and 91 neighborhood controls showed a statistically significant association between the use of tampons, in particular, the use of a single brand of tampons, Rely (Procter & Gamble), and the illness. A decline in cases of toxic shock syndrome in Utah has been noted since September 1980, when Rely tampons were withdrawn from the market. Changes in surveillance activities and reporting do not appear to be important contributors to this decline. The annual attack rate based on cases occurring in the first 9 months of 1980 was 12.3 per 100 000 female subjects aged 12 to 49 years; during the subsequent 9 months, the illness rate declined to 4.8 cases per 100 000.
Polypharmacy in Psychiatry: Patterns of Differential Treatment
Authors: SIDNEY MERLIS, CHARLES SHEPPARD, LOIS COLLINS, DIANE FIORENTINO
Journal: American Journal of Psychiatry (1970)

The authors studied 500 psychiatric patients who had been treated polypharmaceutically. The group was divided into thirds—one-third remaining on their original two medications, one-third on two placebos but no active medication, and one-third on one placebo and one psychoactive drug. While there were significant changes in patient pathologies, the female trend was different from the male. Analyzing the data, the authors conclude that polypharmacy, especially in men, is often an inadequate form of treatment.