tbuckley/cabot-search huggingface dataset:
Adoptive cellular gene therapy of autoimmune arthritis using a combination of lentivirally transduced dendritic cells
Authors: U Purath, R J Creusot, C Garrison Fathman, U Muller-Ladner, E Neumann, I H Tarner
Journal: Annals of the Rheumatic Diseases (2010)

Purpose In order to minimise systemic side effects of immune-modulating therapy in rheumatoid arthritis (RA), local delivery of anti-infl ammatory molecules to the infl amed joints would be desirable.Immune cells are promising vehicle cells for site-specifi c gene transfer because of their ability to migrate into infl amed tissues such as arthritic joints.In previous studies we have shown that gene transfer of single anti-infl ammatory molecules by genetically modifi ed lymphocytes prevents the onset of arthritis in collagen-induced arthritis (CIA) but does not ameliorate established disease despite site-specifi c homing.We therefore hypothesised that the combined transfer of anti-infl ammatory molecules would be more effective.Dendritic cells (DC) were chosen because they are potent antigen-presenting cells that modulate infl ammatory responses when expressing anti-infl ammatory molecules.Methods DC were isolated from murine bone marrow by magnetic bead-separation of T cells, B cells and granulocytes cultured in the presence of interleukin 4 (IL4) and granulocyte-macrophage colony stimulating factor (GM-CSF) and transduced using three different lentiviral bicistronic constructs encoding GFP and IL12p40 (DCp40), anti-TNF scFv (DCTNF) or human galectin-1 (DCGal-1), respectively.Different dual (DCp40+DCGal-1, DCp40+DCTNF, DCGal-1+DCTNF) and triple (DCp40+DCGal-1+DCTNF) combinations of transduced cells were adoptively transferred into DBA/1 mice after the onset of clinical arthritis.Clinical disease severity, histological severity (pannus formation, cartilage degradation and bone erosion), local cytokine expression were analysed and DC migration was examined histologically.Results Transduced DC were found to migrate into the infl amed paws.However, the in vivo life span of these cells remains unclear.The combined transfer of DCp40+DCGal-1 resulted in a signifi cant reduction of pannus formation and bone erosion, whereas the other combinations did not.Clinically, there was a trend towards less disease severity in this treatment group which did not reach signifi cance.Local expression of IL10 in the paws was increased in the DCp40+DCGal-1 group whereas interferon gamma was reduced and tumour necrosis factor unaltered.Splenic expression of all three cytokines was reduced in this treatment group.Of note, triple gene therapy was not superior to the combination of DCp40 and DCGal-1.Conclusions Lentivirally-transduced DC are able to migrate into infl amed joints in CIA.The combined transfer of IL12p40 and galectin-1 has anti-destructive effects and shifts the local cytokine expression towards a Th2 pattern, while clinical effi cacy is limited.Routine application is impeded by on August 10,
Inhibition of photosensitivity in erythropoietic protoporphyria with terfenadine
Authors: P.M. FARR, B.L. DIFFEY, J.N.S. MATTHEWS
Journal: British Journal of Dermatology (1990)

Journal Article Inhibition of photosensitivity in erythropoietic protoporphyria with terfenadine Get access P.M. FARR, P.M. FARR Department of Dermarology, Royal Victoria Infirmary, Newcastle upon Tyne Dr P.M. Farr, Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE14LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar B.L. DIFFEY, B.L. DIFFEY Department of Medical Physic. Dryburn Hospital, Durham Search for other works by this author on: Oxford Academic Google Scholar J.N.S. MATTHEWS J.N.S. MATTHEWS Department of Medical Statistics, University of Newcastle upon Tyne, Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 6, 1 June 1990, Pages 809–815, https://doi.org/10.1111/j.1365-2133.1990.tb06270.x Published: 01 June 1990
TGF -associated MUC2 and MUC3 expression of the gastric epithelium in Menetrier's disease during remission of ulcerative colitis
Authors: K.-P. Zimmer, M. Heine, G. Weissen-Plenz, K. A. Scholand, H. Herbst, H. Y. Naim
Journal: Gut (2011)

The broad clinical heterogeneity of Menetrier's disease (MD) has been recently described by Rich et al .1 There are few reports on MD patients with a history of ulcerative colitis (UC). Overexpression of the transforming growth factor α (TGFα) leads to gastric epithelium abnormalities similar to those of MD.2 A significant increase in TGFα levels has been observed in inactive UC compared with healthy controls. TGFα could be the link between both inactive UC and the development of MD.

TGFα stimulates gastric cell proliferation as well as mucin biosynthesis. Normal gastric mucosa expresses MUC1 and MUC5Ac in foveolar epithelium and MUC6 in the glands, while MUC2 and MUC3 are predominantly expressed in goblet cells and enterocytes, respectively, of the small intestine.

We investigated mucin expression in a …
Tumor Suppressor Functions of <i>ARLTS1</i> in Lung Cancers
Authors: Sai Yendamuri, Francesco Trapasso, Manuela Ferracin, Rossano Cesari, Cinzia Sevignani, Masayoshi Shimizu, Shashi Rattan, Tamotsu Kuroki, Kristoffel R. Dumon, Florencia Bullrich, Chang-gong Liu, Massimo Negrini, Noel N. Williams, Larry R. Kaiser, Carlo M. Croce, George A. Calin
Journal: Cancer Research (2007)

Abstract ARLTS1 is a newly characterized tumor suppressor gene located at chromosome 13q14.3 and involved in the pathogenesis of various types of tumors: two single-nucleotide polymorphisms, one of them responsible for protein truncation, were found statistically associated with familial malignancies, whereas DNA hypermethylation and genomic deletions have been identified as a mechanism of ARLTS1 down-regulation in sporadic cancers. We found that in a large portion of lung carcinomas (37%) and in all analyzed lung cancer cell lines, ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After its restoration by adenoviral transduction, ARLTS1-negative A549 and H1299 cells underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the ability of A549 and H1299 to form tumors in nude mice. Finally, we identified ∼650 transcripts differentially expressed after restoration of ARLTS1 expression in A549 cells, suggesting that various pathways involved in cell survival, proliferation, signaling, and development mediate the effects of wild-type ARLTS1 in a lung cancer system. [Cancer Res 2007;67(16):7738–45]
Hypersecretion of Aldosterone in Dogs with a Chronic Aortic-caval Fistula and High Output Heart Failure
Authors: JAMES O. DAVIS, JOHN URQUHART, JAMES T. HIGGINS, ELLIS C. RUBIN, PHYLLIS M. HARTROFT
Journal: Circulation Research (1964)

Hypersecretion of aldosterone occurred at the onset of signs of congestive heart failure in a large series of dogs with a large infrarenal aortic-caval fistula. There was evidence of right heart failure in all animals and in four of the dogs râles or frank pulmonary edema was present. Marked sodium retention and ascites or edema were consistent findings and in the majority of the animals central venous pressure was elevated. Hypophysectomy was followed by a striking fall in both aldosterone and corticosterone secretion but in several animals hypersecretion of aldosterone was evident in the absence of the anterior pituitary. Subsequent acute bilateral nephrectomy of these hypophysectomized dogs resulted in a marked drop of aldosterone secretion to a very low level, and a precipitous fall in arterial pressure frequently occurred. An intravenous infusion of a saline extract of each animal's kidneys produced a striking elevation in aldosterone output; corticosterone secretion and arterial pressure increased consistently. The kidneys of these dogs with heart failure secondary to an A-V fistula frequently showed hypergranulation and hyperplasia of the juxtaglomerular cells. The present findings suggest that the increased rate of aldosterone secretion was mediated by the renin-angiotensin system. Measurements of arterial pressure and renal hemodynamic function demonstrated a fall of mean renal arterial pressure, glomerular filtration rate, and renal plasma flow, whereas arterial pulse pressure above the fistula and presumably in the kidneys was increased. The data suggest that decreased pulse pressure is unnecessary for activation of the renal mechanism leading to hyperaldosteronism.
Dermoscopy uncovers clinically undetectable pigmentation in basal cell carcinoma
Authors: A. Lallas, G. Argenziano, A. Kyrgidis, Z. Apalla, E. Moscarella, C. Longo, G. Ferrara, S. Piana, E. Benati, E. Zendri, E. Sotiriou, I. Zalaudek
Journal: British Journal of Dermatology (2013)

The presence of pigmentation might influence the management of basal cell carcinoma (BCC), with pigmented BCC responding poorly to certain treatments. Clinical studies report on a generally lower frequency of pigmentation compared with dermoscopic and histopathological studies, but the true frequency at which pigmentation occurs in clinically nonpigmented BCC has not been studied in detail.To compare the clinical and dermoscopic frequency of pigmentation in a series of histopathologically diagnosed BCCs and to correlate it with patient demographics, tumour location and histopathological subtype.Clinical and dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of pigmentation. Dichotomous outcome variables were clinically pigmented and dermoscopically pigmented BCC. All separate dermoscopic variables were included in the analysis. Differences in proportions were evaluated using Pearson's chi-square test.Five hundred and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female ratio of 1.35 : 1 were included in the study. Clinically, 295 tumours were judged as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29.8%). Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern (n = 184, 36.3%), followed by multiple blue-grey dots/globules (n = 147, 29%) and maple-leaf-like areas (n = 70, 13.8%). Superficial tumours exhibited mainly maple-leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC was most frequently typified by the presence of blue-grey ovoid nests.Dermoscopy allows detection of pigmentation in about 30% of clinically nonpigmented BCCs, providing additional information that may aid the clinical choice of adequate treatment modalities.
American Diabetes Association 60th Scientific Sessions, 2000
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2001)

This is the sixth in a continuing series of articles on the American Diabetes Association (ADA) 60th Scientific Sessions held in San Antonio, TX, in June 2000. It covers topics related to use of fasting versus 2-h glucose for diagnosis of diabetes, diabetes and cancer, glycemic control, monitoring, and hypoglycemia.

### Postload Glycemia in the Diagnosis of Diabetes

At a symposium on diagnostic criteria for diabetes James Gavin, Chevy Chase, MD, discussed the dilemma that fasting and post–glucose load glucose levels are differently regulated and that diagnosis based on the two criteria therefore define somewhat different populations. The use of fasting glucose has several advantages. It is more convenient to perform and limits a missed diagnosis of diabetes. Gavin noted that microvascular complications begin to occur above a fasting glucose of 126 mg/dl. A concern, however, is that more than half of patients with diabetes diagnosed by a glucose tolerance test have a fasting glucose below 126 mg/dl. Given new data showing that the fasting glucose level is less predictive of cardiovascular disease (CVD) risk than postchallenge glucose level, Gavin concluded that “fundamentally, we are back at ‘square one’ in asking ‘What is diabetes?’” Daniel Porte, San Diego, CA, noted that “cause and effect is not necessary when we see associations,” an important caveat in the new emphasis on glucose tolerance testing and postchallenge glycemia for diabetes diagnosis.

Jaakko Tuomilehto, Helsinki, Finland, reviewed data from the Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) Study of 18,048 men and 7,316 women aged 30 years or older followed for an average of 7 years after glucose tolerance testing, addressing the question of whether fasting glucose or 2-h postload glucose better predicts mortality (1) There were a total of 1,836 deaths. The World Health Organization (WHO) criteria for diabetes, based mainly on 2-h glucose >200 mg/dl, and the …
Improving clinical practice using clinical decision support systems: a systematic review of trials to identify features critical to success
Authors: Kensaku Kawamoto, Caitlin A Houlihan, E Andrew Balas, David F Lobach
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To identify features of clinical decision support systems critical for improving clinical practice. <b>Design</b> Systematic review of randomised controlled trials. <b>Data sources</b> Literature searches via Medline, CINAHL, and the Cochrane Controlled Trials Register up to 2003; and searches of reference lists of included studies and relevant reviews. <b>Study selection</b> Studies had to evaluate the ability of decision support systems to improve clinical practice. <b>Data extraction</b> Studies were assessed for statistically and clinically significant improvement in clinical practice and for the presence of 15 decision support system features whose importance had been repeatedly suggested in the literature. <b>Results</b> Seventy studies were included. Decision support systems significantly improved clinical practice in 68% of trials. Univariate analyses revealed that, for five of the system features, interventions possessing the feature were significantly more likely to improve clinical practice than interventions lacking the feature. Multiple logistic regression analysis identified four features as independent predictors of improved clinical practice: automatic provision of decision support as part of clinician workflow (P &lt; 0.00001), provision of recommendations rather than just assessments (P = 0.0187), provision of decision support at the time and location of decision making (P = 0.0263), and computer based decision support (P = 0.0294). Of 32 systems possessing all four features, 30 (94%) significantly improved clinical practice. Furthermore, direct experimental justification was found for providing periodic performance feedback, sharing recommendations with patients, and requesting documentation of reasons for not following recommendations. <b>Conclusions</b> Several features were closely correlated with decision support systems9 ability to improve patient care significantly. Clinicians and other stakeholders should implement clinical decision support systems that incorporate these features whenever feasible and appropriate.
From the Genetic Code to Neuromics
Authors: Roger N. Rosenberg
Journal: JAMA Neurology (2013)

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 Neurology 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 Neurology journal
Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy
Authors: Susan L. Greenspan, Joel B. Nelson, Donald L. Trump, Julie M. Wagner, Megan E. Miller, Subashan Perera, Neil M. Resnick
Journal: Journal of Clinical Oncology (2008)

Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT.A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers.Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% +/- 0.7) and hip (mean, 1.3% +/- 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, -1.9% +/- 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (+/- 1.2%) increase at the spine and a 3.2% (+/- 1.5%) at the hip (both P < .05). Bone turnover remained suppressed.Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.
C-Reactive Protein and Glycemic Control in Adults With Diabetes
Authors: David S.H. Bell, Robert W. Hardy, Renee Desmond
Journal: Diabetes Care (2004)

King et al. (1) recently suggested an association between glycemic control and systemic inflammation, i.e., between HbA1c levels and highly sensitive C-reactive protein (hsCRP) levels, based on data from 1,018 participants in the Third National Health and Nutrition Examination Survey. This report prompted us to search for a similar association in our clinical practice.

Since hsCRP levels can be lowered by statins, thiazolidinediones (TZDs), and anti-inflammatory drugs, we first looked at 64 C-peptide-negative type 1 diabetic patients whose only medication was insulin and found no …
Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer
Authors: M M Hyttinen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate the influence of inactivation of one allele ("heterozygous knockout" or "heterozygous inactivation") of the type II procollagen gene (Col2a1) on the biomechanical properties and structure of the articular cartilage and subchondral bone in 15 month old mice. <h3>METHODS</h3> Indentation stiffness of the humerus head articular cartilage was measured by a microindentation method. Cartilage and subchondral bone were prepared for digital densitometry of proteoglycans (PGs), polarised light microscopy (PLM) of collagen, and osteoarthrosis (OA) grading. <h3>RESULTS</h3> Heterozygous inactivation of the Col2a1 gene softened articular cartilage (p=0.002) as measured by indentation stiffness ((mean (SEM) 0.50 (0.07) MPa<i>v</i> 0.94 (0.13) MPa in controls). Fibrillar collagen network exhibited lower birefringence in the intermediate (p=0.04) and deep zones (p=0.01) of cartilage by PLM, indicating either decreased collagen content or a lower degree of fibril parallelism in the knockout mice. The total and zonal thicknesses of articular cartilage were unchanged. Zonal PG contents did not differ significantly. In knockout mice, the prevalence of superficial fibrillation—that is, a sign of OA, was higher than in controls (73%<i>v</i> 21%, p=0.002). The collagen induced birefringence of the superficial zone was not reduced. The subchondral bone volume fraction was lower in knockout mice than in controls, 31%<i>v</i> 43% (p=0.01), and optical retardation values in PLM of bone collagen were slightly but significantly lower (p=0.01). <h3>CONCLUSION</h3> Heterozygous inactivation of the Col2a1 gene made articular cartilage softer, altered the collagenous network, reduced subchondral bone volume, and altered its microstructure. Changes in the cartilage collagen network probably contributed to increased susceptibility to OA.
Long-Term Comparison of Drug-Eluting Stents and Coronary Artery Bypass Grafting for Multivessel Coronary Revascularization
Authors: Duk-Woo Park, Young-Hak Kim, Hae-Geun Song, Jung-Min Ahn, Junhyok Oh, Won-Jang Kim, Jong-Young Lee, Soo-Jin Kang, Seung-Whan Lee, Cheol-Whan Lee, Seong-Wook Park, Sung-Cheol Yun, Sung Ho Jung, Suk-Jung Choo, Cheol-Hyun Chung, Jae-Won Lee, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2011)
Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin
Authors: Allison L Mathes, Romy B Christmann, Giuseppina Stifano, Alsya J Affandi, Timothy R D J Radstake, G Alessandra Farina, Cristina Padilla, Sarah McLaughlin, Robert Lafyatis
Journal: Annals of the Rheumatic Diseases (2013)

To characterise global chemokine expression in systemic sclerosis (SSc) skin in order to better understand the relationship between chemokine expression and vascular inflammation in this disease.We investigated chemokine mRNA expression in the skin through quantitative PCR analysis comparing patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with healthy controls. We tested correlations between the most regulated chemokines and vascular inflammation and macrophage recruitment. CCL19 expression was examined in human primary immune cells treated with innate immune activators.The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin, and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with markers of vascular inflammation and macrophage recruitment. Immunofluorescence data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro studies on human primary cells demonstrated that CCL19 expression was induced after toll-like receptor activation of peripheral blood mononuclear cells and separated populations of CD14 monocytes.CCL18, CCL19 and CXCL13-chemoattractants for macrophage and T cell recruitment-were three of six chemokines with the highest expression in dcSSc skin. Increased CCL19 expression in the skin suggests a role for CCL19 in the recruitment of immune cells to the peripheral tissue. Induction of CCL19 in macrophages but not structural cells indicates a role for skin-resident or recruited immune cells in perivascular inflammation. This study demonstrates that CCL19 is a sensitive marker for the perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.