tbuckley/cabot-search huggingface dataset:
Cytokine alterations in lichen sclerosus: an immunohistochemical study
Authors: A.M. Farrell, D. Dean, P.R. Millard, F.M. Charnock, F. Wojnarowska
Journal: British Journal of Dermatology (2006)

Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain.To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes.An immunohistochemical study of 12 specimens of genital lichen sclerosus and one specimen of extragenital lichen sclerosus was undertaken using monoclonal antibodies to interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal vulva obtained during gynaecological procedures, three specimens of normal skin, adjacent uninvolved thigh from three of the patients with lichen sclerosus, five specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and two specimens from chronic wounds.The lichen sclerosus specimens demonstrated slightly increased staining for IFN-gamma within the epidermis compared with the normal vulva and nonvulval skin. There was increased dermal staining for IFN-gamma both within the pale zone of the upper dermis and within the inflammatory zone below this. We confirmed our previous demonstration that in lichen sclerosus HLA-DR immunostaining is increased in association with vascular endothelium, the inflammatory cell infiltrate and around the keratinocytes. The areas of the epidermis with the strongest immunostaining for HLA-DR generally also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens the zone of inflammation also demonstrated increased immunostaining for TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased staining for ICAM-1.The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.
Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype
Authors: Andrea Pellagatti, Mario Cazzola, Aristoteles A N Giagounidis, Luca Malcovati, Matteo G Della Porta, Sally Killick, Lisa J Campbell, Li Wang, Cordelia F Langford, Carrie Fidler, David Oscier, Carlo Aul, James S Wainscoat, Jacqueline Boultwood
Journal: Blood (2006)
High-level β-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells
Authors: Suzan Imren, Mary E. Fabry, Karen A. Westerman, Robert Pawliuk, Patrick Tang, Patricia M. Rosten, Ronald L. Nagel, Philippe Leboulch, Connie J. Eaves, R. Keith Humphries
Journal: Journal of Clinical Investigation (2004)

Transplantation of genetically corrected autologous hematopoietic stem cells is an attractive approach for the cure of sickle-cell disease and β-thalassemia. Here, we infected human cord blood cells with a self-inactivating lentiviral vector encoding an anti-sickling βA-T87Q-globin transgene and analyzed the transduced progeny produced over a 6-month period after transplantation of the infected cells directly into sublethally irradiated NOD/LtSz-scid/scid mice. Approximately half of the human erythroid and myeloid progenitors regenerated in the mice containing the transgene, and erythroid cells derived in vitro from these in vivo–regenerated cells produced high levels of βA-T87Q-globin protein. Linker-mediated PCR analysis identified multiple transgene-positive clones in all mice analyzed with 2.1 ± 0.1 integrated proviral copies per cell. Genomic sequencing of vector-containing fragments showed that 86% of the proviral inserts had occurred within genes, including several genes implicated in human leukemia. These findings indicate effective transduction of very primitive human cord blood cells with a candidate therapeutic lentiviral vector resulting in the long-term and robust, erythroid-specific production of therapeutically relevant levels of β-globin protein. However, the frequency of proviral integration within genes that regulate hematopoiesis points to a need for additional safety modifications.
Scots think healthy food is "boring and tasteless"
Authors: B. Christie
Journal: BMJ (2001)

Healthy eating is making people miserable. Research carried out in Scotland for the Food Standards Agency found that people think of healthy eating as being regimented, boring, and tasteless.

The agency said that the findings are important and should be used to develop new methods of encouraging the public to eat better. In particular, it would like to see greater emphasis placed on highlighting the life enhancing benefits of a healthy …
Oral treatment with itraconazole of aspergilloma in cavitary lung cancer
Authors: N Impens, J De Greve, K De Beule, M Meysman, S De Beuckelaere, W Schandevyl
Journal: European Respiratory Journal (1990)

We report a case of aspergilloma in a necrotic small cell lung cancer, where poor pulmonary function and performance status of the patient precluded surgical treatment. High dose Itraconazole, a new oral anti-mycotic drug, was given for 13 months. During this treatment there was a decrease of the fungus ball size and no haemoptysis. Moreover control of the aspergilloma allowed chemotherapeutic treatment of the underlying bronchocarcinoma.
Glucocorticoid deficiency increases phospholipase A2 activity in rats.
Authors: B S Vishwanath, F J Frey, M J Bradbury, M F Dallman, B M Frey
Journal: Journal of Clinical Investigation (1993)

An important mechanism for the antiinflammatory effect of pharmacological doses of glucocorticoids is the inhibition of arachidonic acid release from phospholipids by phospholipase A2 (PLA2). As a corollary, one might predict that low endogenous concentrations of glucocorticoids favor inflammatory disease states. Indeed, clinical and experimental observations revealed an association between glucocorticoid deficiency and disease states caused by immunological and/or inflammatory mechanisms. The purpose of the present investigation was to study the regulation of PLA2 mRNA, protein, and enzyme activity in adrenalectomized (ADX) rats where glucocorticoid concentrations were below physiological levels. The mRNA of group I and II PLA2 were measured by PCR. Group II PLA2 mRNA was increased by 126 +/- 9% in lung tissue of ADX rats, whereas group I PLA2 was increased only by 27 +/- 1.5%. The increase in group II mRNA in ADX rats was reflected by a corresponding increase of group II PLA2 protein (70-100%) in lung, spleen, liver, and kidney. This increase was reversed by the administration of exogenous corticosterone. After ADX, the percentage increase in total PLA2 activity was higher than that of mRNA or PLA2 protein, suggesting that the activity of the enzyme was modulated by inhibitors or activators. The concentration of lipocortin-I, an inhibitor of PLA2 enzyme was strongly correlated with the activity of PLA2 in the tissues (lung, spleen, liver, and kidney). In all these tissues, the concentrations of lipocortin-I declined after ADX. Thus upregulation of PLA2 enzyme and downregulation of lipocortin-I might account for the enhanced inflammatory response in hypoglucocorticoid states.
Analysis of physical interactions between peptides and HLA molecules and application to the detection of human immunodeficiency virus 1 antigenic peptides.
Authors: J Choppin, F Martinon, E Gomard, E Bahraoui, F Connan, M Bouillot, J P Lévy
Journal: The Journal of Experimental Medicine (1990)

The physical association of 40 antigenic peptides and purified HLA class I and class II molecules was monitored using a direct peptide binding assay (PBA) in solid phase and an inhibition peptide binding assay (IPBA) in which the competing peptide was present in a soluble phase. We also examined the ability of different peptides to inhibit the lytic activity of human antiviral cytolytic T cells towards cells incubated with the corresponding target peptide. Our results showed that: (a) Binding of a given human T cell-recognized peptide to several HLA class I and class II molecules occurred frequently. Nevertheless, preferential binding of peptides to their respective restriction molecules was also observed. (b) Binding of HLA molecules to peptides recognized by murine T cells occurred less frequently. (c) 11 of 24 (46%) randomly selected HIV-1 peptides contained agretopic residues allowing their binding to HLA molecules. (d) The kinetics of HLA/peptide association depended on the peptide tested and were faster than or similar to those reported for Ia molecules. Dissociation of these complexes was very low. (e) Peptide/HLA molecule binding was dependent on length, number of positive charges, and presence of hydrophobic residue in the peptide. (f) A correlation was demonstrated between a peptide inhibitory effect in the IPBA and its blocking effect in the cytolytic test. Our data indicated that the restriction phenomenon observed in T cell responses was not strictly related to either an elective HLA/peptide association, or a high binding capacity of a peptide to HLA molecules. These data also showed that the PBA and IPBA are appropriate for the detection of agretopic residues within HIV-1 proteins.
Dietary Pectin and Glycemic Control in Diabetes
Authors: D F Gardner, L Schwartz, M Krista, T J Merimee
Journal: Diabetes Care (1984)

Seventeen diabetic subjects requiring insulin and who exhibited glycemic stability over a 9–12-mo control period received 5 g of pectin with each meal and at bedtime for 3 mo. Hemoglobin A1c (HbA1c) and glycosylated serum protein were measured in each patient on multiple occasions to assess glycemic control. No clear-cut change in these measurements occurred during the period of pectin ingestion. These data are not consistent with a beneficial effect of high-pectin diets in people with diabetes.
Cyclin D1b Is Aberrantly Regulated in Response to Therapeutic Challenge and Promotes Resistance to Estrogen Antagonists
Authors: Ying Wang, Jeffry L. Dean, Ewan K.A. Millar, Thai Hong Tran, Catriona M. McNeil, Craig J. Burd, Susan M. Henshall, Fransiscus E. Utama, Agnieszka Witkiewicz, Hallgeir Rui, Robert L. Sutherland, Karen E. Knudsen, Erik S. Knudsen
Journal: Cancer Research (2008)

Cyclin D1 is a key mediator of cell cycle progression that is aberrantly regulated in multiple cancers, especially in breast cancers. A number of studies have indicated that a polymorphism in a splice donor site in the cyclin D1 gene is associated with alternative splicing and the production of the alternative cyclin D1b transcript. Furthermore, this polymorphism is selectively associated with disease outcomes. However, relatively little is known regarding the protein product of the alternatively spliced message, cyclin D1b. Using antibodies specific for cyclin D1b, it was found that this protein is readily detectable in a number of cancer cell lines and primary breast cancers. Whereas cyclin D1b interacts with cyclin-dependent kinase 4 (CDK4), it is relatively inefficient at mediating RB phosphorylation and cell cycle progression in model systems due to the lack of exon 5 of cyclin D1-encoded sequences. However, cyclin D1b protein levels are not significantly attenuated by DNA damage or antiestrogen treatment, indicating that the protein may have significant effect on the response to such therapeutic modalities. Whereas enforced expression of cyclin D1b was not sufficient to abrogate DNA damage checkpoint responses, it did efficiently overcome cell cycle arrest mediated by antiestrogen therapeutics. This action of cyclin D1b was not associated with effects on estrogen receptor activity, but was rather dependent on functional association with CDK4. Combined, these studies indicate that the cyclin D1b protein is aberrantly regulated and could contribute to therapeutic failure in the context of ER-positive breast cancer.
Nickel allergy as risk factor for hand eczema: a population-based study
Authors: A. Josefson, G. Färm, A. Magnuson, B. Meding
Journal: British Journal of Dermatology (2009)

In population-based studies using self-reported nickel allergy, a hand eczema prevalence of 30-43% has been reported in individuals with nickel allergy. In a previous Swedish study, 958 schoolgirls were patch tested for nickel. In a questionnaire follow up 20 years later no association was found between nickel allergy and hand eczema.To investigate further the relation between nickel allergy and hand eczema.Three hundred and sixty-nine women, still living in the same geographical area, now aged 30-40 years, were patch tested and clinically investigated regarding hand eczema.Patch testing showed 30.1% nickel-positive individuals. The adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 years in relation to nickel patch test results was 1.03 (95% confidence interval, CI 0.71-1.50). A history of childhood eczema was reported by 35.9%, and the PPR for hand eczema in relation to childhood eczema was 3.68 (95% CI 2.45-5.54). When analysing the relation separately in women with and without a history of childhood eczema a statistical interaction was found. The hand eczema risk was doubled in nickel-positive women without a history of childhood eczema, with a PPR of 2.23 (95% CI 1.10-4.49) for hand eczema after age 15 years.A doubled risk for hand eczema was found in nickel-positive women without a history of childhood eczema. When analysing all participants, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. The risk for hand eczema in nickel-positive women may previously have been overestimated.
High Prevalence of Hypovitaminosis D in Female Type 2 Diabetic Population
Authors: Giancarlo Isaia, Ruben Giorgino, Silvano Adami
Journal: Diabetes Care (2001)

Animal studies have demonstrated lower levels of 1,25(OH)2D3 in a type 2 diabetes model compared with controls (1). Alterations in circulating vitamin D3 metabolites, such as decreased 1α-hydroxylase activity and enhanced renal 25-hydroxylase activity, have been found in both experimental and human diabetes. These alterations in vitamin D metabolism may be associated with the deranged mineral homeostasis and skeletal morphology observed in rats and people with chronic insulin deficiency (2). Experimentally, vitamin D deficiency progressively reduces insulin secretion, and this reduction soon becomes irreversible (3). It was also shown that insulin deficiency may be associated with lower vitamin D–binding …
Is persistent adenovirus 12 infection involved in coeliac disease? A search for viral DNA using the polymerase chain reaction.
Authors: J Mahon, G E Blair, G M Wood, B B Scott, M S Losowsky, P D Howdle
Journal: Gut (1991)

It has been shown that partial amino acid sequence homology between alpha gliadin and an early region protein (E1B-58 kDa) of adenovirus 12 results in immunological cross reaction. This led to the proposal that prior infection by adenovirus 12 could be associated with the development of coeliac disease. To examine this hypothesis, evidence was sought of persistent adenovirus 12 infection in the small intestinal mucosa of patients with coeliac disease. DNA isolated from biopsy samples from 24 control and 18 coeliac disease patients was analysed by the polymerase chain reaction for adenovirus 12 DNA encoding the E1B-58 kDa protein. Four of 18 coeliac disease and two of 24 control patients were positive. There is thus a low prevalence of this infection on both groups of patients but certainly no significantly increased incidence in coeliac disease. These results suggest that persistent adenovirus 12 infection is not a major element in the pathogenesis of coeliac disease.
Transmission electron microscopic identification of silicon-containing particles in synovial fluid: potential confusion with calcium pyrophosphate dihydrate and apatite crystals.
Authors: T Bardin, H R Schumacher, J Lansaman, S Rothfuss, A Dryll
Journal: Annals of the Rheumatic Diseases (1984)

Silicon-containing particles were identified by transmission electron microscopy (TEM) in thin sections of two synovial fluids, which also contained calcium pyrophosphate dihydrate (CPPD) crystals, aspirated during acute attacks of pseudogout. Such particles, which are interpreted as probably being artefacts from glassware, were electron dense and similar in appearance to some CPPD or hydroxyapatite crystals.
T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt
Authors: Vanja Lazarevic, Xi Chen, Jae-Hyuck Shim, Eun-Sook Hwang, Eunjung Jang, Alexandra N Bolm, Mohamed Oukka, Vijay K Kuchroo, Laurie H Glimcher
Journal: Nature Immunology (2010)
Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.
Authors: D T Connolly, D M Heuvelman, R Nelson, J V Olander, B L Eppley, J J Delfino, N R Siegel, R M Leimgruber, J Feder
Journal: Journal of Clinical Investigation (1989)

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis.
Properties of the COPD assessment test in a cross-sectional European study
Authors: P.W. Jones, G. Brusselle, R.W. Dal Negro, M. Ferrer, P. Kardos, M.L. Levy, T. Perez, J.J. Soler Cataluña, T. van der Molen, L. Adamek, N. Banik
Journal: European Respiratory Journal (2011)

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0–40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2±8.8; II: 16.3±7.9; III: 19.3±8.2; and IV: 22.3±8.7; I versus II, p = 0.88; II versus III, p&lt;0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ±12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2±8.3) versus those suffering an exacerbation (21.3±8.4) (p&lt;0.0001); and in patients with no (17.3±8.1) or one or two (16.6±8.2) versus three or more (19.7±8.5) comorbidities (p&lt;0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George’s Respiratory Questionnaire (r = 0.8, p&lt;0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.
A CASE OF PEMPHIGUS VEGETANS*
Authors: S. ERNEST DORE, MAURICE MITMAN
Journal: British Journal of Dermatology (1929)

Journal Article A CASE OF PEMPHIGUS VEGETANS Get access S. ERNEST DORE, M.D., F.R.C.P., S. ERNEST DORE, M.D., F.R.C.P. Physician‐in‐Charge of the Skin Departments, St. Thomas's and Westminster Hospital Search for other works by this author on: Oxford Academic Google Scholar MAURICE MITMAN, M.D., M.R.C.P MAURICE MITMAN, M.D., M.R.C.P Physician‐in‐Charge of the Skin Departments, St. Thomas's and Westminster Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 11, 1 November 1929, Pages 408–416, https://doi.org/10.1111/j.1365-2133.1929.tb09294.x Published: 01 November 1929
Use of Radical Cystectomy for Patients With Invasive Bladder Cancer
Authors: J. L. Gore, M. S. Litwin, J. Lai, E. M. Yano, R. Madison, C. Setodji, J. L. Adams, C. S. Saigal
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundEvidence-based guidelines recommend radical cystectomy for patients with muscle-invasive bladder cancer.However, many patients receive alternate therapies, such as chemotherapy or radiation.We examined factors that are associated with the use of radical cystectomy for invasive bladder cancer and compared the survival outcomes of patients with invasive bladder cancer by the treatment they received. MethodsFrom linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 3262 Medicare beneficiaries aged 66 years or older at diagnosis with stage II muscle-invasive bladder cancer from January 1, 1992, through December 31, 2002.We examined the use of radical cystectomy with multilevel multivariable models and survival after diagnosis with the use of instrumental variable analyses.All statistical tests were two-sided. ResultsA total of 21% of the study subjects underwent radical cystectomy.Older age at diagnosis and higher comorbidity were associated with decreased odds of receiving cystectomy (for those ≥80 vs 66-69 years old, odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.07 to 0.14; for Charlson comorbidity index of 3 vs 0-1, OR = 0.25, 95% CI = 0.14 to 0.45).Long travel distance to an available surgeon was associated with decreased odds of receiving cystectomy (for >50 vs 0-4 miles travel distance to an available surgeon, OR = 0.60, 95% CI = 0.37 to 0.98).Overall survival was better for those who underwent cystectomy compared with those who underwent alternative treatments (for chemotherapy and/or radiation vs cystectomy, hazard ratio of death = 1.5, 95% CI = 1.3 to 1.8; for surveillance vs cystectomy, hazard ratio of death = 1.9, 95% CI = 1.6 to 2.3; 5-year adjusted survival: 42.2% [95% CI = 39.1% to 45.4%] for cystectomy; 20.7% [95% CI = 18.7% to 22.8%] for chemotherapy and/ or radiation; 14.5% [95% CI = 13.0% to 16.2%] for surveillance). ConclusionsGuideline-recommended care with radical cystectomy is underused for patients with muscle-invasive bladder cancer.Many bladder cancer patients whose survival outcomes might benefit with surgery are receiving alternative less salubrious treatments.