tbuckley/cabot-search huggingface dataset:
Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study
Authors: C. Jeanmaire, L. Danoux, G. Pauly
Journal: British Journal of Dermatology (2001)

Non-enzymatic glycation occurring in normal human skin plays an important part in ageing. OBJECTIVES To visualize and quantify, in human subjects, the extent of glycation during human dermal intrinsic and actinic ageing, and to develop a reliable reproducible in vitro model for evaluating the efficacy of potential inhibitors of glycation.By immunohistochemistry using a monoclonal antibody recognizing carboxymethyl lysine, an advanced glycation end-product (AGE) (first objective), and by incubating dead de-epidermized dermis (DED) with glucose to simulate ageing-induced glycation in a human dermal equivalent model (second objective).We found that glycation of the dermis generally arises after 35 years, then increases rapidly with intrinsic ageing. We also noticed an enhancement of glycation by solar irradiation that occurred via glycation of the elastic fibre network or solar elastosis tissue. In the model, production of AGEs appeared in a time-dependent way, mimicking glycation observed in vivo during chronological ageing. Irradiation of DED before incubation with glucose strongly enhanced induction of AGEs, corresponding to the effect of solar irradiation on AGEs observed in vivo.These results confirm a marked increase of AGEs during intrinsic ageing in normal human skin and also suggest that glycation is enhanced in photoaged skin.
Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation
Authors: Seth B. Furgeson, Peter A. Simpson, Insun Park, Vicki VanPutten, Henrick Horita, Christopher D. Kontos, Raphael A. Nemenoff, Mary C.M. Weiser-Evans
Journal: Cardiovascular Research (2010)

AimsPhosphatase and tensin homolog (PTEN) is implicated as a negative regulator of vascular smooth muscle cell (SMC) proliferation and injury-induced vascular remodelling. We tested if selective depletion of PTEN only in SMC is sufficient to promote SMC phenotypic modulation, cytokine production, and enhanced neointima formation.
Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Philip W. Kantoff, Thomas J. Schuetz, Brent A. Blumenstein, L. Michael Glode, David L. Bilhartz, Michael Wyand, Kelledy Manson, Dennis L. Panicali, Reiner Laus, Jeffrey Schlom, William L. Dahut, Philip M. Arlen, James L. Gulley, Wayne R. Godfrey
Journal: Journal of Clinical Oncology (2010)

Therapeutic prostate-specific antigen (PSA) -targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.
Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.
Authors: E Vellenga, C A Uyl-de Groot, R de Wit, H J Keizer, B Löwenberg, M A ten Haaft, T J de Witte, C A Verhagen, G J Stoter, F F Rutten, N H Mulder, W M Smid, E G de Vries
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. PATIENTS AND METHODS One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (&lt; 0.5 x 10(9)/L) and fever (&gt; 38.5 degrees C once or &gt; 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count &gt; or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period). RESULTS Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P &lt; .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P &lt; .05). CONCLUSION These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.
GCP Data Quality for Early Clinical Development
Authors: Edwin P. Rock, Vernette J. Molloy, Jeffrey S. Humphrey
Journal: Clinical Cancer Research (2010)

Good Clinical Practice (GCP) provides an internationally accepted standard to ensure subject safety and data quality in clinical trials. Much of GCP parallels ethical considerations that have accumulated in successive versions of the World Medical Association's Declaration of Helsinki. This document advocates for preservation of rights, safety, and well-being of human study participants. By contrast, GCP data quality provisions follow from evolution in the United States drug regulatory system during the 1960s. Evidence of fraudulent or otherwise biased data-gathering ultimately led to U.S. Food and Drug Administration (FDA) data integrity regulations that were subsequently embraced as GCP principles in the Declaration of Helsinki. This manuscript summarizes GCP data quality provisions and describes practices that clinical site investigators can adopt to comply with these principles and to prevent adverse audit findings in the event of a regulatory inspection.
Specific Diagnosis of Exogenous Bronchial Asthma in Children
Authors: G. Stafanger, J. Kock Andersen, C. Koch, B. Schwartz, O. ØTerballe
Journal: Allergy (1986)

Twenty‐six children with exogenous asthma were studied by case history ((CH), skin tests (ST), allergen‐specific serum IgE (RAST), basophil histamine release (HR), and bronchial provocation tests (BPT). Nine standardized allergens were used from the following groups: house dust mite, animal dander, pollen, and mould fungi. For each allergen, the same batch was used throughout for all in vivo and in vitro studies, and the tests were carried out in a controlled, double‐blinded manner, independent of each other. Different allergen concentrations were used and die results graded on a semi‐quantitative scale. Approximately 120 comparable investigations. using; in vivo and in vitro tests were carried out, followed by calculations of the sensitivity and specificity for each test alone, as well as various combinations of tests, at various allergen‐concentrations, and compared with the result of BPT, i.e. the true diagnosis. In this way the results could be used to directly compare the diagnostic value of each test, and combination of tests. In general, a careful CH combined with ST gave the most reliable results, RAST was the most unreliable single analysis. When pollen or mite allergy was suspected, a combination of ST with either RAST or HR gave a further diagnostic reliability HR as a single: analysis did not seem to offer advantages over exiting methods. None of the tests, or combinations of tests offered 100% sensitivity and specificity. By altering the concentration of allergen, the sensitivity, or specificity could be increased, but only at the expense of a decrease in the other, BPT is still necessary in many instances when a specific diagnosis is required.
Neuroendocrine cells of nasal mucosa are a cellular source of brain-derived neurotrophic factor
Authors: L. Jornot, J. S. Lacroix, T. Rochat
Journal: European Respiratory Journal (2008)

There is growing evidence for extensive interaction between sensory neurons, immune and mucosal epithelial cells during airway inflammation and hyperreactivity. This neuro-immune cross-talk (neurogenic inflammation) involves different groups of mediators, which include the neurotrophin family (nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4). Neurotrophins modulate airway inflammation by enhancing sensory nerve excitability and production of neuropeptides, and by interaction with different immune cell types. In the present study, it was questioned whether airway epithelial cells express BDNF, and if proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma) and a glucocorticoid (budesonide) affect this expression. Primary cultures of nasal epithelial cells were used. It was found that BDNF was stored in chromogranin A-containing secretory granules of specialised epithelial cells, i.e. neuroendocrine cells, and was secreted in a polarised manner. Apical secretion appears to be constitutive, whereas basolateral secretion is markedly enhanced upon stimulation with cytokines. This enhanced basolateral secretion was not due to enhanced synthesis and was not affected by inhibitors of the processing enzymes, such as furin and the metalloproteinases involved in the maturation of BDNF, but was considerably diminished by budesonide. Therefore, airway mucosa might contribute to neurogenic inflammation through increased secretion of brain-derived neurotrophic factor by neuroendocrine cells under inflammatory conditions.
Cardiovascular Tissue Engineering Research Support at the National Heart, Lung, and Blood Institute
Authors: Martha S. Lundberg
Journal: Circulation Research (2013)

Tissue engineering aims at building 3-dimensional living substitutes that are equal to or better than the damaged tissue to be replaced. The development of such a tissue replacement requires a multidisciplinary approach and careful attention to the optimal cell source, the interactions of growth factors and extracellular milieu, and the scaffolding design. This article is a review of the tissue engineering programs of the National Heart, Lung, and Blood Institute, which support research efforts to translate novel approaches for the treatment of cardiovascular disease. Recent progress is discussed, which highlights some major questions relevant to cardiovascular tissue engineering. The National Heart, Lung, and Blood Institute has a strong interest in tissue engineering and will continue to foster the practical, clinical, and commercial development of research discoveries in this emerging field.
Control of homeostatic proliferation by regulatory T cells
Authors: S. Shen
Journal: Journal of Clinical Investigation (2005)

Homeostatic proliferation of T cells leads to the generation of effector/memory cells, which have the potential to cause harm to the host. The role of Tregs in the control of homeostatic proliferation is unclear. In this study we utilized mice that either harbor or lack Tregs as recipients of monoclonal or polyclonal T cells. We observed that while Tregs completely prevented cell division of T cells displaying low affinity for self ligands, they had a less marked, albeit significant, effect on cell cycle entry of T cells displaying higher affinity. The presence of Tregs resulted in a lower accumulation of T cells, enhanced apoptosis, and impaired differentiation to a cytokine-producing state. We conclude that Tregs play a major role in the control of homeostatic proliferation.
Randomised controlled trial of atraumatic versus standard needles for diagnostic lumbar puncture
Authors: S R. Thomas
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To compare the ease of use of atraumatic needles with standard needles for diagnostic lumbar puncture and the incidence of headache after their use. <b>Design:</b> Double blind, randomised controlled trial. <b>Setting:</b> Investigation ward of a neurology unit in a university hospital. <b>Participants:</b> 116 patients requiring elective diagnostic lumbar puncture. <b>Interventions:</b> Standardised protocol for lumbar puncture with 20 gauge atraumatic or standard needles. <b>Outcome measures:</b> The primary end point was intention to treat analysis of incidence of moderate to severe headache, assessed at one week by telephone interview. Secondary end points were incidence of headache at one week analysed by needle type, ease of use by operator according to a visual analogue scale, incidence of backache, and failure rate of puncture. <b>Results:</b> Valid outcome data were available for 97 of 101 patients randomised. Baseline characteristics were matched except for higher body mass index in the standard needle group. By an intention to treat analysis the absolute risk of moderate to severe headache with atraumatic needles was reduced by 26% (95% confidence interval 6% to 45%) compared with standard needles, but there was a non-significantly greater absolute risk of multiple attempts at lumbar puncture (14%, −4% to 32%). Higher body mass index was associated with an increased failure rate with atraumatic needles, but the reduced incidence of headache was maintained. The need for medical interventions was reduced by 20% (1% to 40%). <b>Conclusions:</b> Atraumatic needles significantly reduced the incidence of moderate to severe headache and the need for medical interventions after diagnostic lumbar punctures, but they were associated with a higher failure rate than standard needles.
Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study
Authors: Alexis Ogdie, Kevin Haynes, Andrea B Troxel, Thorvardur Jon Love, Sean Hennessy, Hyon Choi, Joel M Gelfand
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Angiokeratomas are benign vascular skin lesions characterised by proliferation of dilated blood vessels in the upper dermis. Some variants have been described that can affect different regions of the body including face and genitals. They may be isolated or clustered, and appear as small red-to-black papules, with a smooth epidermal surface. As the disease progresses, the lesions grow, reaching a diameter of 10 mm, and become dark red to black, with a verrucous surface. Depending on the characteristics of the lesions they can be treated with surgery or laser for aesthetic reasons. On the other hand, some investigators have also proved that topically applied rapamycin causes regression of facial angiokeratomas, giving better cosmetic results. <h3>Purpose</h3> To evaluate the efficacy and safety of the topical application of 0.4% rapamycin ointment in a facial angiokeratoma. <h3>Material and methods</h3> We report on a paediatric patient who presented with facial angiokeratomas. Rapamycin ointment was performed at a concentration of 0.4%, mixing with white petrolatum and petroleum jelly under safe conditions in a vertical laminar flow hood. Efficacy was measured in a paediatric judgement and through a monthly photographic examination. Safety was measured in terms of irritation and burning sensation. The patient was followed up for 1 year of treatment. <h3>Results</h3> The case of a male patient of 12 years of age (31 kg and 140 cm) is presented. After being approved the treatment in the Commission of pharmacy of our hospital, the patient started the treatment with one application every night. A photographic examination was performed, where an improvement was seen in the right malar zone, infraorbital, although the nasal area presented without changes. The patient had no irritation and burning sensation during treatment. The response of these vascular skin malformations to rapamycin, an mTOR inhibitor, suggests that activation of the PI3K/Akt/mTOR pathway in endothelial cells may play a role in the pathogenesis of angiokeratomas. <h3>Conclusion</h3> Topical rapamycin appears to be a promising and effective way of treating facial angiokeratomas. The major disadvantage is the cost of therapy, which is prohibitively expensive at the present time. <h3>References and/or Acknowledgements</h3> To my pharmacist colleagues No conflict of interest
Pleomorphic lipoma of the dermis
Authors: M.A. NIGRO, G.C. CHIEREGATO, G.QUERCI DELLA ROVERE
Journal: British Journal of Dermatology (1987)

Journal Article Pleomorphic lipoma of the dermis Get access M.A. NIGRO, M.A. NIGRO Department of Dermatology, University of Verona Medical School, Verona, Italy M.A.Nigro, Department of Dermatology, Ospedale di Borgo Trento, 37100 Verona, Italy. Search for other works by this author on: Oxford Academic Google Scholar G.C. CHIEREGATO, G.C. CHIEREGATO Department of Dermatology, University of Verona Medical School, Verona, Italy Search for other works by this author on: Oxford Academic Google Scholar G.QUERCI DELLA ROVERE G.QUERCI DELLA ROVERE Cromwell Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 5, 1 May 1987, Pages 713–717, https://doi.org/10.1111/j.1365-2133.1987.tb05906.x Published: 01 May 1987
EPITHELIAL REPAIR IN RECOVERY FROM VITAMIN A DEFICIENCY
Authors: S. Burt Wolbach, Percy R. Howe
Journal: The Journal of Experimental Medicine (1933)

1. In vitamin A deficiency, the replacement stratified keratinizing epithelium is morphologically identical in all locations. 2. All cells of the lowermost layer of the replacement epithelium have proliferative power as in the stratum germinativum of epidermis. 3. In recovery, in spite of the complete morphological masking, the epithelium in each region returns to its normal type. 4. The important histological features of repair involve removal of the layers of cells irreversibly differentiated towards keratinization and direct differentiation of the stratum germinativum into the normal type. These take place simultaneously. 5. The histological sequences observed in the removal of cells above the stratum germinativum indicate that autolysis as shown by vacuolar degeneration and heterolysis as shown by leucocytic infiltration are involved. 6. The cycle of A deficiency metaplasia and recovery affords an experimental method available for the correlation of nuclear chromatin and types of cytoplasmic activities.
Erratum. Efficacy and Safety of Dulaglutide Added Onto Pioglitazone and Metformin Versus Exenatide in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-1). Diabetes Care 2014;37:2159–2167:
Authors: Carol Wysham, Thomas Blevins, Richard Arakaki, Gildred Colon, Pedro Garcia, Charles Atisso, Debra Kuhstoss, Mark Lakshmanan
Journal: Diabetes Care (2015)

In the print version of the article cited above, a footnote was omitted with respect to antidrug antibodies (ADAs) in Table 2. Exenatide values reported in the last row in Table 2 are not treatment-emergent ADAs; they are total reported ADAs. The last three rows of Table 2 should have appeared as …
Crucial Role of Phospholipase Cε in Chemical Carcinogen-Induced Skin Tumor Development
Authors: Yunfeng Bai, Hironori Edamatsu, Sakan Maeda, Hiromitsu Saito, Noboru Suzuki, Takaya Satoh, Tohru Kataoka
Journal: Cancer Research (2004)

Abstract Mutational activation of the ras proto-oncogenes is frequently found in skin cancers. However, the nature of downstream signaling pathways from Ras involved in skin carcinogenesis remains poorly understood. Recently, we and others identified phospholipase C (PLC) ε as an effector of Ras. Here we have examined the role of PLCε in de novo skin chemical carcinogenesis by using mice whose PLCε is genetically inactivated. PLCε−/− mice exhibit delayed onset and markedly reduced incidence of skin squamous tumors induced by initiation with 7,12-dimethylbenz(a)anthracene followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the papillomas formed in PLCε−/− mice fail to undergo malignant progression into carcinomas, in contrast to a malignant conversion rate of approximately 20% observed with papillomas in PLCε+/+ mice. In all of the tumors analyzed, the Ha-ras gene is mutationally activated irrespective of the PLCε background. The skin of PLCε−/− mice fails to exhibit basal layer cell proliferation and epidermal hyperplasia in response to TPA treatment. These results indicate a crucial role of PLCε in ras oncogene-induced de novo carcinogenesis and downstream signaling from TPA, introducing PLCε as a candidate molecular target for the development of anticancer drugs.
Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria
Authors: Kai Soo Tan, Kok Onn Lee, Kee Chung Low, Akshamal Mihiranga Gamage, Yichun Liu, Gek-Yen Gladys Tan, Hui Qi Vanessa Koh, Sylvie Alonso, Yunn-Hwen Gan
Journal: Journal of Clinical Investigation (2012)

Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei–infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12–IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast, IL-12 production in diabetic cells was not affected upon Salmonella enterica infection or in response to TLR2, -3, -4, and -5 ligands. Poor IL-12 production correlated with a deficiency in intracellular reduced glutathione (GSH) concentrations in diabetic patients. Addition of GSH or N-acetylcysteine to PBMCs selectively restored IL-12 and IFN-γ production and improved bacterial killing. Furthermore, the depletion of GSH in mice led to increased susceptibility to melioidosis, reduced production of IL-12p70, and poorer disease outcome. Our data thus establish a link between GSH deficiency in diabetes and increased susceptibility to melioidosis that may open up new therapeutic avenues to protect diabetic patients against some intracellular bacterial pathogens.