tbuckley/cabot-search huggingface dataset:
Bruton's Tyrosine Kinase Is Required For Lipopolysaccharide-induced Tumor Necrosis Factor α Production
Authors: Nicole J. Horwood, Tara Mahon, John P. McDaid, Jamie Campbell, Hiroyuki Mano, Fionula M. Brennan, David Webster, Brian M.J. Foxwell
Journal: The Journal of Experimental Medicine (2003)

Lipopolysaccharide (LPS), a product of Gram-negative bacteria, is potent mediator of tumor necrosis factor (TNF)α production by myeloid/macrophage cells. Inhibitors capable of blocking the signaling events that result in TNFα production could provide useful therapeutics for treating septic shock and other inflammatory diseases. Broad spectrum tyrosine inhibitors are known to inhibit TNFα production, however, no particular family of tyrosine kinases has been shown to be essential for this process. Here we show that the Bruton's tyrosine kinase (Btk)-deficient mononuclear cells from X-linked agammaglobulinemia patients have impaired LPS-induced TNFα production and that LPS rapidly induces Btk kinase activity in normal monocytes. In addition, adenoviral overexpression of Btk in normal human monocytes enhanced TNFα production. We examined the role of Btk in TNFα production using luciferase reporter adenoviral constructs and have established that overexpression of Btk results in the stabilization of TNFα mRNA via the 3′ untranslated region. Stimulation with LPS also induced the activation of related tyrosine kinase, Tec, suggesting that the Tec family kinases are important components for LPS-induced TNFα production. This study provides the first clear evidence that tyrosine kinases of the Tec family, in particular Btk, are key elements of LPS-induced TNFα production and consequently may provide valuable therapeutic targets for intervention in inflammatory conditions.
Smooth Muscle Cells in Transplant Atherosclerotic Lesions Are Originated From Recipients, but Not Bone Marrow Progenitor Cells
Authors: Yanhua Hu, Fergus Davison, Burkhard Ludewig, Martin Erdel, Manuel Mayr, Manfred Url, Hermann Dietrich, Qingbo Xu
Journal: Circulation (2002)

Smooth muscle cell (SMC) accumulation in the intima of vessels is a key event in the pathogenesis of transplant atherosclerosis. The traditional hypothesis that SMCs in the lesion are derived from the media of the donor vessel has been challenged by recent observations, but the cell origin is still not well established.Here, we use a simplified model of artery allografts in transgenic mice to clearly identify the source of SMCs in transplant atherosclerosis. Aortic segments donated by BALB/c mice allografted to ROSA26 (C57B/6) mice expressing beta-galactosidase (gal) in all tissues showed that neointimal cells derived exclusively from host cells. It was also demonstrated that SMCs of neointimal and atherosclerotic lesions in vessels allografted to mice expressing beta-gal only in SMCs (SM-LacZ) or to apoE-deficient/SM-LacZ mice originated from the recipient, and not donor vessels. Interestingly, bone marrow transplantation of SM-LacZ beta-gal-expressing cells into aortic allograft recipients revealed completely negative beta-gal staining of neointimal and atherosclerotic lesions. However, a population of beta-gal-positive cells in lesions of allografts was observed in chimeric mice with ROSA26 beta-gal-expressing marrow cells. When bone marrow cells from both ROSA26 and SM-LacZ mice were cultured and stimulated with platelet-derived growth factor-BB, alpha-actin and beta-gal double-positive cells were found, suggesting that bone marrow cells have an ability to differentiate into SMCs.Thus, we provide strong evidence that SMCs of neointimal and atherosclerotic lesions in allografts are derived from the recipients and that non-bone marrow-derived progenitor cells are a possible source of SMCs in atherosclerotic lesions.
Immunocytochemical localisation of parietal cells and G cells in the developing human stomach.
Authors: E J Kelly, M Lagopoulos, J N Primrose
Journal: Gut (1993)

Previous studies on the distribution of parietal cells and G cells in normal adult stomachs have shown that in about 20% of specimens parietal cells extended to the pylorus. This study aimed to examine the distribution of parietal cells and G cells in the body and antrum of the developing human stomach in relation to anatomical landmarks, using histological and immunocytochemical methods. In all 15 fetal stomachs examined, parietal cells extended to the pylorus and expressed intrinsic factor and hydrogen-potassium-ATPase activity from week 13 of gestation. By contrast, in only one of the five infant stomachs did parietal cells extend to the pylorus: this is identical to the distribution in the adult. G cells developed in the antrum from 18 weeks' gestation and their distribution did not differ between the fetal and infant stomachs. These findings indicate that parietal cells disappear from the antrum of the stomach in the third trimester of pregnancy, but this process fails to occur in approximately 20% of the population.
G.M.C. Retention Fee
Authors: O. Alabaster, R. J. Andrews, D. H. Austwick, J. Beardshaw, A. M. Birch, S. K. Biswas, M. D. Buckley-Sharp, J. A. Casson, J. Cowie, J. H. Cummings, J. M. Cushnie, J. L. Dyson, B. Elliott, S. Fahmy, B. A. Friedman, P. Friedman, P. M. Fullman, D. T. Goradia, J. Haas, K. S. Haworth, S. Holt, C. D. Hopkins, J. C. W. Ickringhill, M. Impallomeni, M. K. Jalalluddin, G. Karmi, M. B. Kelly, R. D. Levis, H. B. McMichael, M. W. McNicol, B. Mackie, A. Mehta, R. A. Meyer, G. L. Mills, J. R. Mikhail, N. Mistry, V. G. Mistry, F. R. Munshi, J. F. Newcombe, P. Noone, T. O. O. Ogunlesi, J. Parker-Williams, J. Phemister, R. Poston, T. D. Prempeh, F. Pygott, Z. Radwanski, S. Rao, M. Redfern, J. F. Riordan, H. Shawdon, V. L. Steinberg, M. E. M. Stephens, R. B. Stern, E. Taylor, W. T. Davies, S. E. Vanhein-Wallace, S. V. Kumar, S. L. Vohra, J. Williams, J. R. B. Young
Journal: BMJ (1970)
Treatment of Systemic Mycoses with Ketoconazole: Emphasis on Toxicity and Clinical Response in 52 Patients
Authors: WILLIAM E. DISMUKES
Journal: Annals of Internal Medicine (1983)

The pharmacology, in-vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21 %). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.
Changes Over Time in High Out-of-Pocket Health Care Burden in U.S. Adults With Diabetes, 2001–2011
Authors: Rui Li, Lawrence E. Barker, Sundar Shrestha, Ping Zhang, O. Kenrick Duru, Tony Pearson-Clarke, Edward W. Gregg
Journal: Diabetes Care (2014)

High out-of-pocket (OOP) costs can be an obstacle to health care access and treatment compliance. This study investigated trends in high OOP health care burden in people with diabetes.Using Medical Expenditure Panel Survey 2001-2011 data, we examined trends in the proportion of people aged 18-64 years with diabetes facing a high OOP burden. We also examined whether the trend differed by insurance status (private insurance, public insurance, or no insurance) or by income level (poor and near poor, low income, middle income, or high income).In 2011, 23% of people with diabetes faced high OOP burden. Between 2001-2002 and 2011, the proportion of people facing high OOP burden fell by 5 percentage points (P < 0.01). The proportion of those who were publicly insured decreased by 22 percentage points (P < 0.001) and of those who were uninsured by 12 percentage points (P = 0.01). Among people with diabetes who were poor and near poor and those with low income, the proportion facing high OOP burden decreased by 21 (P < 0.001) and 13 (P = 0.01) percentage points, respectively; no significant change occurred in the proportion with private insurance or middle and high incomes between 2001-2002 and 2011.The past decade has seen a narrowing of insurance coverage and income-related disparities in high OOP burden in people with diabetes; yet, almost one-fourth of all people with diabetes still face a high OOP burden.
Problem Solving and Diabetes Self-Management
Authors: Russell E. Glasgow, Lawrence Fisher, Marilyn Skaff, Joe Mullan, Deborah J. Toobert
Journal: Diabetes Care (2006)

Problem solving is a core aspect of effective diabetes and chronic illness self-management, yet there are relatively few objective evaluations of problem-solving skills, especially in large, multiracial samples.A multiracial sample of 506 adults who have type 2 diabetes were assessed on a variety of patient characteristics, self-management behaviors, and biological and psychosocial measures. They also completed the Diabetes Problem-Solving Interview (DPSI).DPSI scores revealed significant variability across patients in problem-solving skill and were related to a number of comorbid conditions and complications but not to several other demographic factors, including race/ethnicity. Problem solving was also related to self-management behaviors (eating and exercise patterns), biological variables (A1C and lipids), and psychosocial measures (Diabetes Distress Scale) in multivariable analyses controlling for a variety of potential confounding factors.Diabetes problem solving, as measured by the DPSI, is an important patient skill related to several key diabetes management variables that appears applicable across racial and ethnic groups. Future research is needed to identify the generality versus specificity of diabetes problem solving and practical interventions to enhance problem-solving skills.
Discovery of genes affecting resistance of barley to adapted and non-adapted powdery mildew fungi
Authors: Dimitar Douchkov, Stefanie Lück, Annika Johrde, Daniela Nowara, Axel Himmelbach, Jeyaraman Rajaraman, Nils Stein, Rajiv Sharma, Benjamin Kilian, Patrick Schweizer
Journal: Genome biology (2014)

Abstract Background Non-host resistance, NHR, to non-adapted pathogens and quantitative host resistance, QR, confer durable protection to plants and are important for securing yield in a longer perspective. However, a more targeted exploitation of the trait usually possessing a complex mode of inheritance by many quantitative trait loci, QTLs, will require a better understanding of the most important genes and alleles. Results Here we present results from a transient-induced gene silencing, TIGS, approach of candidate genes for NHR and QR in barley against the powdery mildew fungus Blumeria graminis . Genes were selected based on transcript regulation, multigene-family membership or genetic map position. Out of 1,144 tested RNAi-target genes, 96 significantly affected resistance to the non-adapted wheat- or the compatible barley powdery mildew fungus, with an overlap of four genes. TIGS results for QR were combined with transcript regulation data, allele-trait associations, QTL co-localization and copy number variation resulting in a meta-dataset of 51 strong candidate genes with convergent evidence for a role in QR. Conclusions This study represents an initial, functional inventory of approximately 3% of the barley transcriptome for a role in NHR or QR against the powdery mildew pathogen. The discovered candidate genes support the idea that QR in this Triticeae host is primarily based on pathogen-associated molecular pattern-triggered immunity, which is compromised by effector molecules produced by the compatible pathogen. The overlap of four genes with significant TIGS effects both in the NHR and QR screens also indicates shared components for both forms of durable pathogen resistance.
Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans
Authors: Madhusudhan Budatha, Shayzreen Roshanravan, Qian Zheng, Cecilia Weislander, Shelby L. Chapman, Elaine C. Davis, Barry Starcher, R. Ann Word, Hiromi Yanagisawa
Journal: Journal of Clinical Investigation (2011)

Pelvic organ prolapse (POP) is a common condition affecting almost half of women over the age of 50. The molecular and cellular mechanisms underlying this condition, however, remain poorly understood. Here we have reported that fibulin-5, an integrin-binding matricellular protein that is essential for elastic fiber assembly, regulated the activity of MMP-9 to maintain integrity of the vaginal wall and prevented development of POP. In murine vaginal stromal cells, fibulin-5 inhibited the β1 integrin–dependent, fibronectin-mediated upregulation of MMP-9. Mice in which the integrin-binding motif was mutated to an integrin-disrupting motif (Fbln5RGE/RGE) exhibited upregulation of MMP-9 in vaginal tissues. In contrast to fibulin-5 knockouts (Fbln5–/–), Fbln5RGE/RGE mice were able to form intact elastic fibers and did not exhibit POP. However, treatment of mice with β-aminopropionitrile (BAPN), an inhibitor of matrix cross-linking enzymes, induced subclinical POP. Conversely, deletion of Mmp9 in Fbln5–/– mice significantly attenuated POP by increasing elastic fiber density and improving collagen fibrils. Vaginal tissue samples from pre- and postmenopausal women with POP also displayed significantly increased levels of MMP-9. These results suggest that POP is an acquired disorder of extracellular matrix and that therapies targeting matrix proteases may be successful for preventing or ameliorating POP in women.
Skin-associated lymphocytes in the peripheral blood of patients with atopic dermatitis: Signs of subset expansion and stimulation
Authors: Michael N. Dworzak, Gertraud Fröschl, Dieter Printz, Christine Fleischer, Ulrike Pötschger, Gerhard Fritsch, Helmut Gadner, Waltraud Emminger
Journal: Journal of Allergy and Clinical Immunology (1999)
The landscape of DNA repeat elements in human heart failure
Authors: Syed Haider, Lina Cordeddu, Emma Robinson, Mehregan Movassagh, Lee Siggens, Ana Vujic, Mun-Kit Choy, Martin Goddard, Pietro Lio, Roger Foo
Journal: Genome biology (2012)

Abstract Background The epigenomes of healthy and diseased human hearts were recently examined by genome-wide DNA methylation profiling. Repetitive elements, heavily methylated in post-natal tissue, have variable methylation profiles in cancer but methylation of repetitive elements in the heart has never been examined. Results We analyzed repetitive elements from all repeat families in human myocardial samples, and found that satellite repeat elements were significantly hypomethylated in end-stage cardiomyopathic hearts relative to healthy normal controls. Satellite repeat elements are almost always centromeric or juxtacentromeric, and their overexpression correlates with disease aggressiveness in cancer. Similarly, we found that hypomethylation of satellite repeat elements correlated with up to 27-fold upregulation of the corresponding transcripts in end-stage cardiomyopathic hearts. No other repeat family exhibited differential methylation between healthy and cardiomyopathic hearts, with the exception of the Alu element SINE1/7SL, for which a modestly consistent trend of increased methylation was observed. Conclusions Satellite repeat element transcripts, a form of non-coding RNA, have putative functions in maintaining genomic stability and chromosomal integrity. Further studies will be needed to establish the functional significance of these non-coding RNAs in the context of heart failure.
Deux épidémies de trichinellose dans l'état de Rhénanie du Nord-Westphalie, Allemagne, 1998
Authors: S Rehmet, G Sinn, O Robstad, H David, D Lesser, K Nöckler, G Scherholz, D Erkrath, D Pechmann, L R Petersen, R Kundt, G Oltmans, R Lange, J Laumen, U Nogay, M Dixius, J Eichenberg, F Dinse, D Stegemann, W Lotz, D Franke, P Hag, A Ammon
Journal: Eurosurveillance (1999)

En Allemagne, la trichinellose et les deces par trichinellose sont a declaration obligatoire. Alors que de 1987 a 1997, le nombre de cas annuels rapportes n‘excedait pas 10, 52 cas de trichinellose ont ete identifies de novembre 1998 a janvier 1999 par les systemes surveillance en sante publique de 11 villes et districts de l'etat de Rhenanie du Nord-Westphalie. Cet article resume l'investigation de ces cas qui a montre que les deux epidemies, l'une causee par de la viande hachee contaminee, l'autre par de la saucisse crue fumee de fabrication industrielle (Mettwurst), etaient survenues simultanement. Un dossier sur la trichinellose, sa transmission et ses causes a recemment fait l'objet d'un numero special d'Eurosurveillance (1).
The Ability of Versican to Simultaneously Cause Apoptotic Resistance and Sensitivity
Authors: David P. LaPierre, Daniel Y. Lee, Sen-Zhu Li, Yi-Zhen Xie, Ling Zhong, Wang Sheng, Zhaoqun Deng, Burton B. Yang
Journal: Cancer Research (2007)

Abstract Expression of the extracellular matrix proteoglycan versican is associated with more than 10 types of cancers, often being secreted by stromal cells in response to tumor signals. Previous work in our lab has shown that overexpression of the V1 versican isoform in cultured fibroblasts (V1 cells) increases both proliferation and apoptotic resistance. We show here that V1 cells induced tumor formation in nude mice and that, in keeping with previously shown apoptotic resistance, V1 cells have down-regulated Fas mRNA and protein levels. Unexpectedly, however, V1 cells were found to be sensitized to a wide range of cytotoxic agents. This combination of selective apoptotic resistance and sensitivity is often seen in cancer cells. V1 cells were also shown to have high resting levels of p53 and murine double minute-2 proteins, correlating with apoptotic sensitivity. Treatment with UV radiation induced p21 expression in vector-transfected cells but not in V1 cells. As p21 induces cell cycle arrest and inhibits apoptosis, its loss in V1 cells, coupled with high resting levels of proapoptotic p53, may be at least partially involved in their premature death following cytotoxic treatment. This study further supports the importance of versican in cancer cell biology and the complexity of apoptosis regulation. [Cancer Res 2007;67(10):4742–50]
Cost-Effectiveness of Computed Tomographic Colonography Screening for Colorectal Cancer in the Medicare Population
Authors: Amy B. Knudsen, Iris Lansdorp-Vogelaar, Carolyn M. Rutter, James E. Savarino, Marjolein van Ballegooijen, Karen M. Kuntz, Ann G. Zauber
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundThe Centers for Medicare and Medicaid Services (CMS) considered whether to reimburse computed tomographic colonography (CTC) for colorectal cancer screening of Medicare enrollees. To help inform its decision, we evaluated the reimbursement rate at which CTC screening could be cost-effective compared with the colorectal cancer screening tests that are currently reimbursed by CMS and are included in most colorectal cancer screening guidelines, namely annual fecal occult blood test (FOBT), flexible sigmoidoscopy every 5 years, flexible sigmoidoscopy every 5 years in conjunction with annual FOBT, and colonoscopy every 10 years.
Large melanoma metastases to the gastrointestinal tract.
Authors: J M Silverman, J A Hamlin
Journal: Gut (1989)

It is well known that malignant melanoma can metastasize widely. Although these metastases in the gastrointestinal tract usually appear as small 9bull9s-eye9 or 9target9 lesions, there are a few reports of relatively large melanoma metastases. We report five cases of large melanoma lesions metastatic to the alimentary canal. We also emphasise the consideration of a thorough gastrointestinal tract evaluation in patients with malignant melanoma especially if they are symptomatic.
IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease
Authors: T Kobayashi, S Okamoto, T Hisamatsu, N Kamada, H Chinen, R Saito, M T Kitazume, A Nakazawa, A Sugita, K Koganei, K Isobe, T Hibi
Journal: Gut (2008)

A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 (IL17) has been reported to play important roles in various inflammatory diseases. IL23 is also focused upon for its potential to promote Th17. Here, the roles of the IL23/IL17 axis in inflammatory bowel diseases such as ulcerative colitis (UC) and Crohn's disease (CD) were investigated.Mucosal samples were obtained from surgically resected specimens (controls, n = 12; UC, n = 17; CD, n = 22). IL17 production by isolated peripheral blood (PB) and lamina propria (LP) CD4(+) cells was examined. Quantitative PCR amplification was performed to determine the mRNA expression levels of IL17, interferon gamma (IFNgamma), IL23 receptor (IL23R) and retinoic acid-related orphan receptor gamma (RORC) in LP CD4(+) cells, and IL12 family members, such as IL12p40, IL12p35 and IL23p19, in whole mucosal specimens. The effects of exogenous IL23 on IL17 production by LP CD4(+) cells were also examined.IL17 production was higher in LP CD4(+) cells than in PB. Significant IL17 mRNA upregulation in LP CD4(+) cells was found in UC, while IFNgamma was increased in CD. IL23R and RORC were upregulated in LP CD4(+) cells isolated from both UC and CD. IL17 production was significantly increased by IL23 in LP CD4(+) cells from UC but not CD. Upregulated IL23p19 mRNA expression was correlated with IL17 in UC and IFNgamma in CD.IL23 may play important roles in controlling the differential Th1/Th17 balance in both UC and CD, although Th17 cells may exist in both diseases.