tbuckley/cabot-search huggingface dataset:
Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser
Authors: L. Gao, D.M. Nadora, S. Phan, M. Chernova, V. Sun, S.M.O. Preciado, W. Jia, G. Wang, M.C. Mihm, J.S. Nelson, W. Tan
Journal: British Journal of Dermatology (2014)

The recurrence of port-wine stain (PWS) blood vessels by pulsed dye laser (PDL)-induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome.To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib.The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure.The PDL-induced increased transcriptional levels of angiogenic genes peaked at days 3-7 post-PDL exposure. Topical application of 0·5% axitinib effectively suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post-PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929·5 μm.Topical application of 0·5% axitinib can systematically suppress the PDL-induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein-1/mitogen-activated protein kinase kinase/ERK pathway cascades.
Endoscopic palliation for inoperable malignant dysphagia: long term follow up.
Authors: V Maunoury, J M Brunetaud, D Cochelard, B Boniface, A Cortot, J C Paris
Journal: Gut (1992)

This prospective non-randomised trial of 128 selected patients with unresectable oesophageal or gastrooesophageal junction cancers aims to evaluate the initial relief of malignant obstruction by means of bipolar electrocoagulation for both circumferential and submucosal strictures of Nd:YAG laser for the other patients. A limited dilatation was performed initially if a small calibre endoscope was unable to pass through the stricture. Prompt and significant relief of dysphagia without complications was achieved in 83% of patients. Improved patients were retreated monthly during the follow up period. Radiotherapy was recommended when possible. Symptomatic relief of obstruction lasted 4.2 months on average and 76% of patients remained palliated until death. Monthly retreatment using the most appropriate endoscopic procedure for the tumour configuration and radiotherapy after endoscopic relief of obstruction seems to give the best palliation for patients with unresectable cancers of the oesophagus or gastrooesophageal junction.
Slowing the Progression of Vascular Calcification in Hemodialysis
Authors: Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2003)

Hyperphosphatemia and secondary hyperparathyroidism are common complications of ESRD (chronic kidney disease stage 5) that, when untreated, may result in increased morbidity and mortality. Hyperphosphatemia and hypercalcemia have been associated with increased coronary artery calcification. Achieving control of serum phosphorus without increasing serum calcium is an important goal for patients with ESRD. Although calcium-based phosphate binders effectively reduce serum phosphorus and parathyroid hormone concentrations, these agents can lead to hypercalcemia and have been associated with increased vascular calcification. The phosphorus binder sevelamer was developed to overcome the limitations associated with the usual management of hyperphosphatemia and secondary hyperparathyroidism (i.e., mineral salts). Sevelamer, a nonabsorbable hydrogel, is as efficacious as calcium-based phosphate binders for reducing serum phosphorus but does not cause hypercalcemia or other adverse metabolic effects. Sevelamer also exhibits beneficial effects on lipids, consistently and significantly decreasing LDL cholesterol and increasing HDL cholesterol in most studies. In a head-to-head randomized clinical trial, sevelamer and calcium-based binders achieved similarly excellent phosphorus control, but the use of calcium-based binders led to significantly higher serum calcium concentrations and an increased incidence of hypercalcemia and unintended suppression of parathyroid hormone. Treatment with calcium-based binders also led to the progression of coronary artery and aortic calcification, whereas sevelamer attenuated or arrested progression. Strategies that use oral calcium and vitamin D in patients with ESRD should be reexamined, and the potential advantages of sevelamer should be considered when selecting a primary agent to reduce serum phosphorus in hemodialysis patients.
Ultrastructural study of elaunin fibres in the secretory coil of human eccrine sweat glands
Authors: G. COTTA-PEREIRA, F.GUERRA RODRIGO, S. BITTENCOURT-SAMPAIO
Journal: British Journal of Dermatology (1975)

Journal Article Ultrastructural study of elaunin fibres in the secretory coil of human eccrine sweat glands Get access G. COTTA‐PEREIRA, G. COTTA‐PEREIRA Laboratory of Cell Biology, Gulbenkian Institute of Science, Oeiras, Portugal; Department of Histology and Embryology, Faculty of Medicine, State University of Guanabara and Department of Histology and Embryology, Federal University of Rio de Janeiro, Brazil; Department of Dermatology, Faculty of Medicine, Lisbon, Portugal Search for other works by this author on: Oxford Academic Google Scholar F.GUERRA RODRIGO, F.GUERRA RODRIGO Laboratory of Cell Biology, Gulbenkian Institute of Science, Oeiras, Portugal; Department of Histology and Embryology, Faculty of Medicine, State University of Guanabara and Department of Histology and Embryology, Federal University of Rio de Janeiro, Brazil; Department of Dermatology, Faculty of Medicine, Lisbon, Portugal Search for other works by this author on: Oxford Academic Google Scholar S. BITTENCOURT‐SAMPAIO S. BITTENCOURT‐SAMPAIO Laboratory of Cell Biology, Gulbenkian Institute of Science, Oeiras, Portugal; Department of Histology and Embryology, Faculty of Medicine, State University of Guanabara and Department of Histology and Embryology, Federal University of Rio de Janeiro, Brazil; Department of Dermatology, Faculty of Medicine, Lisbon, Portugal Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue 6, 1 December 1975, Pages 623–629, https://doi.org/10.1111/j.1365-2133.1975.tb05111.x Published: 01 December 1975
Respiratory bronchiolitis associated interstitial lung disease (RB-ILD): a case of an acute presentation
Authors: D Mavridou
Journal: Thorax (2004)

Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) is a recently described clinicopathological entity that occurs almost exclusively in current heavy cigarette smokers. Few cases have been reported in the literature and no studies have been carried out on the effect of treatment, which currently consists of smoking cessation with or without corticosteroids. We report the first case of an acute presentation of histologically proven RB-ILD in a young cigarette smoker whose diagnosis and management proved to be difficult. Smoking cessation alone was found to be inadequate so management was combined with corticosteroid therapy.
Small intestinal bacterial overgrowth in patients with irritable bowel syndrome
Authors: I. Posserud, P.-O. Stotzer, E. S Bjornsson, H. Abrahamsson, M. Simren
Journal: Gut (2006)

Small intestinal bacterial overgrowth (SIBO) has been proposed to be common in irritable bowel syndrome (IBS), with altered small-bowel motility as a possible predisposing factor.To assess the prevalence of SIBO, by culture of small-bowel aspirate, and its correlation to symptoms and motility in IBS.162 patients with IBS who underwent small-bowel manometry and culture of jejunal aspirate were included. Cultures from 26 healthy subjects served as controls. Two definitions of altered flora were used: the standard definition of SIBO (>/=10(5) colonic bacteria/ml), and mildly increased counts of small-bowel bacteria (>/=95th centile in controls).SIBO (as per standard definition) was found in 4% of both patients and controls. Signs of enteric dysmotility were seen in 86% of patients with SIBO and in 39% of patients without SIBO (p = 0.02). Patients with SIBO had fewer phase III activities (activity fronts) than patients without SIBO (p = 0.08), but otherwise no differences in motility parameters were seen. Mildly increased bacterial counts (>/=5x10(3)/ml) were more common in patients with IBS than in controls (43% vs 12%; p = 0.002), but this was unrelated to small intestinal motility. No correlation between bacterial alterations and symptom pattern was observed.The data do not support an important role for SIBO according to commonly used clinical definitions, in IBS. However, mildly increased counts of small-bowel bacteria seem to be more common in IBS, and needs further investigation. Motility alterations could not reliably predict altered small-bowel bacterial flora.
The Role of STAT-3 in the Induction of Apoptosis in Pancreatic Cancer Cells by Benzyl Isothiocyanate
Authors: R. P. Sahu, S. K. Srivastava
Journal: JNCI Journal of the National Cancer Institute (2009)

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, has been reported to have anticancer properties, but the mechanism whereby it inhibits growth of human pancreatic cancer cells is incompletely understood.Human pancreatic cancer cells (BxPC-3, AsPC-1, Capan-2, MiaPaCa-2, and Panc-1) and immortalized human pancreatic cells (HPDE-6) were treated with vehicle or with BITC at 5-40 microM, cell survival was evaluated by sulforhodamine B assay, and apoptosis by caspase-3 and poly-ADP ribose polymerase cleavage or by a commercial assay for cell death. Total and activated signal transducer and activator of transcription-3 (STAT-3) protein expression in the cells were examined by western blotting, STAT-3 mRNA levels by reverse transcription-polymerase chain reaction, and STAT-3 DNA-binding and transcriptional activity by commercially available binding and reporter assays. The effects of BITC treatment on tumor growth, apoptosis, and STAT-3 protein expression in vivo were studied in xenografts of BxPC-3 pancreatic tumor cells in athymic nude mice. All statistical tests were two-sided.BITC treatment reduced cell survival and induced apoptosis in BxPC-3, AsPC-1, Capan-2, and MiaPaCa-2 cells, and to a much lesser extent in Panc-1 cells, but not in HPDE-6 cells. It also reduced levels of activated and total STAT-3 protein, and as a result, STAT-3 DNA-binding and transcriptional activities. Overexpression of STAT-3 in BxPC-3 cells inhibited BITC-induced apoptosis and restored STAT-3 activity. In mice that were fed BITC (60 micromol/wk, five mice, 10 tumors per group), growth of BxPC-3 pancreatic tumor xenografts was suppressed compared with control mice (at 6 weeks, mean tumor volume of control vs BITC-treated mice = 334 vs 172 mm3, difference =162 mm3, 95% confidence interval = 118 to 204 mm3; P = .008) and tumors had increased apoptosis and reduced STAT-3 protein expression.BITC induces apoptosis in some types of pancreatic cancer cells by inhibiting the STAT-3 signaling pathway.
B-Cell Aortic Homing and Atheroprotection Depend on Id3
Authors: Amanda C. Doran, Michael J. Lipinski, Stephanie N. Oldham, James C. Garmey, Kirsti A. Campbell, Marcus D. Skaflen, Alexis Cutchins, Daniel J. Lee, David K. Glover, Kimberly A. Kelly, Elena V. Galkina, Klaus Ley, Joseph L. Witztum, Sotirios Tsimikas, Timothy P. Bender, Coleen A. McNamara
Journal: Circulation Research (2011)

Rationale: B cells are abundant in the adventitia of normal and diseased vessels. Yet, the molecular and cellular mechanisms mediating homing of B cells to the vessel wall and B-cell effects on atherosclerosis are poorly understood. Inhibitor of differentiation-3 (Id3) is important for atheroprotection in mice and polymorphism in the human ID3 gene has been implicated as a potential risk marker of atherosclerosis in humans. Yet, the role of Id3 in B-cell regulation of atherosclerosis is unknown. Objective: To determine if Id3 regulates B-cell homing to the aorta and atheroprotection and identify molecular and cellular mechanisms mediating this effect. Methods and Results: Loss of Id3 in Apoe −/− mice resulted in early and increased atherosclerosis. Flow cytometry revealed a defect in Id3 −/− Apoe −/− mice in the number of B cells in the aorta but not the spleen, lymph nodes, and circulation. Similarly, B cells transferred from Id3 −/− Apoe −/− mice into B-cell–deficient mice reconstituted spleen, lymph node, and blood similarly to B cells from Id3 +/+ Apoe −/− mice, but aortic reconstitution and B-cell–mediated inhibition of diet-induced atherosclerosis was significantly impaired. In addition to retarding initiation of atherosclerosis, B cells homed to regions of existing atherosclerosis, reduced macrophage content in plaque, and attenuated progression of disease. The chemokine receptor CCR6 was identified as an important Id3 target mediating aortic homing and atheroprotection. Conclusions: Together, these results are the first to identify the Id3-CCR6 pathway in B cells and demonstrate its role in aortic B-cell homing and B-cell–mediated protection from early atherosclerosis.
Hypertrophy of renal mitochondria.
Authors: S Hwang, R Bohman, P Navas, J T Norman, T Bradley, L G Fine
Journal: Journal of the American Society of Nephrology (1990)

Compensatory renal hypertrophy leads to an increase in the size and metabolic capacity of renal tubular cells. Increased transport and metabolic activities must be sustained by an augmented rate of energy production, which is largely dependent on mitochondrial processes. Although previous studies have suggested that mitochondria proliferate in the hypertrophying cell, the data to support this have not been convincing. This study was designed to determine whether the mitochondria of the hypertrophied renal proximal tubular cell undergo hypertrophy or proliferation. Flow cytometric analysis of proximal tubular cells obtained from the kidneys of uninephrectomized rabbits revealed an increase in cell size and RNA content compared with control cells but showed no change in DNA content and nuclear size and no evidence of entry into the S/G2/M phases of the cell cycle. Histomorphometric analysis of cortical proximal tubules revealed that although cytoplasmic volume increased, mitochondrial density remained constant, indicating that mitochondrial volume increases in proportion to the increase in cell volume. By day 14, mitochondrial volume had increased 66% above control values. Electron microscopic examination of isolated S2 proximal tubules from 5/6 nephrectomized rabbits with maximal hypertrophy revealed mitochondrial cristae which appeared to be more densely packed than that in normal cells. The size of the functional mitochondrial pool per cell was determined by rhodamine-123 fluorescence. This increased within 24 h of uninephrectomy, peaked at approximately 80% above control levels at 5 days, and remained elevated throughout the 16 days of observation. The initial increase (days 1 and 2) occurred before a measurable increase in mitochondrial volume occurred and presumably reflects an increase in mitochondrial membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity
Authors: Renjing Liu, Yu Jin, Wai Ho Tang, Lingfeng Qin, Xinbo Zhang, George Tellides, John Hwa, Jun Yu, Kathleen A. Martin
Journal: Circulation (2013)

Smooth muscle cells (SMCs) are remarkably plastic. Their reversible differentiation is required for growth and wound healing but also contributes to pathologies such as atherosclerosis and restenosis. Although key regulators of the SMC phenotype, including myocardin (MYOCD) and KLF4, have been identified, a unifying epigenetic mechanism that confers reversible SMC differentiation has not been reported.Using human SMCs, human arterial tissue, and mouse models, we report that SMC plasticity is governed by the DNA-modifying enzyme ten-eleven translocation-2 (TET2). TET2 and its product, 5-hydroxymethylcytosine (5-hmC), are enriched in contractile SMCs but reduced in dedifferentiated SMCs. TET2 knockdown inhibits expression of key procontractile genes, including MYOCD and SRF, with concomitant transcriptional upregulation of KLF4. TET2 knockdown prevents rapamycin-induced SMC differentiation, whereas TET2 overexpression is sufficient to induce a contractile phenotype. TET2 overexpression also induces SMC gene expression in fibroblasts. Chromatin immunoprecipitation demonstrates that TET2 coordinately regulates phenotypic modulation through opposing effects on chromatin accessibility at the promoters of procontractile versus dedifferentiation-associated genes. Notably, we find that TET2 binds and 5-hmC is enriched in CArG-rich regions of active SMC contractile promoters (MYOCD, SRF, and MYH11). Loss of TET2 and 5-hmC positively correlates with the degree of injury in murine models of vascular injury and human atherosclerotic disease. Importantly, localized TET2 knockdown exacerbates injury response, and local TET2 overexpression restores the 5-hmC epigenetic landscape and contractile gene expression and greatly attenuates intimal hyperplasia in vivo.We identify TET2 as a novel and necessary master epigenetic regulator of SMC differentiation.
Impact of cigarette smoke exposure on host-bacterial pathogen interactions
Authors: J. Garmendia, P. Morey, J. A. Bengoechea
Journal: European Respiratory Journal (2011)

The human respiratory tract of individuals with normal lung function maintains a fine-tuned balance, being asymptomatically colonised by the normal microbiota in the upper airways and sterile in the lower tract. This equilibrium may be disrupted by the exposure to insults such as cigarette smoke. In the respiratory tract, the complex and noxious nature of inhaled cigarette smoke alters host–microorganism interaction dynamics at all anatomical levels, causing infections in many cases. Moreover, continuous exposure to cigarette smoke itself causes deleterious effects on the host that can trigger the development of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. COPD is an irreversible airflow obstruction associated with emphysema, fibrosis, mucus hypersecretion and persistent colonisation of the lower airways by opportunistic pathogens. COPD patients keep a stable (without exacerbation) but progressively worsening condition and suffer periodic exacerbations caused, in most cases, by infections. Although smoking and smoking-associated diseases are associated with a high risk of infection, most therapies aim to reduce inflammatory parameters, but do not necessarily take into account the presence of persistent colonisers. The effect of cigarette smoke on host–pathogen interaction dynamics in the respiratory tract, together with current and novel therapies, is discussed.
Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes
Authors: M Rollinghoff, A Starzinski-Powitz, K Pfizenmaier, H Wagner
Journal: The Journal of Experimental Medicine (1977)

Murine T lymphocytes sensitized in vitro against either allogeneic lymphocytes or syngeneic hapten-conjugated lymphocytes do differentiate into highly effective cytotoxic T lymphocytes (CTL) (1-3). In vivo immunization of T lymphocytes to the same antigens, however, results in the generation of only marginal cytotoxic activity (1,4,5). Recently we found that the weakness of in vivo generated cytotoxicity is not due to a failure of antigen-induced T-cell sensitization but rather due to suppression of the in vivo differentiation of sensitized CTL precursors into effective CTL(6). In keeping with this finding it was postulated that suppressor cells may regulate the in vivo differentiation of CTL. We now report, that cyclophosphamide-sensitive T cells suppress the in vivo differentiation of antigen-specific CTL. Thus, pretreatment of mice with a single dose of cyclophosphamide (100 mg/kg) converts their state of low responsiveness to a state of high responsiveness.
Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study
Authors: P. J. F. de Jonge, M. van Blankenstein, C. W. N. Looman, M. K. Casparie, G. A. Meijer, E. J. Kuipers
Journal: Gut (2010)

Reported incidence rates of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification is essential.To estimate the rate of malignant progression in patients with BO, all patients with a first diagnosis of BO with no dysplasia (ND) or low-grade dysplasia (LGD) between 1991 and 2006 were identified in the Dutch nationwide registry of histopathology (PALGA). Follow-up data were evaluated up to November 2007.42 207 patients with BO were included; 4132 (8%) of them had LGD. Re-evaluation endoscopies at least 6 months after initial diagnosis were performed in 16 365 patients (39%), who were significantly younger than those not re-examined (58+/-13 vs 63+/-16 years, p<0.001). These patients were followed-up for a total of 78 131 person-years, during which 666 (4%) high-grade dysplasia (HGD)/OACs occurred, affecting 4% of the surveillance patient population (mean age: 69+/-12 years, 76% male). After excluding HGD/OAC cases detected within 1 year after BO diagnosis (n=212, 32%), incidence rates per 1000 person-years were 4.3 (95% CI 3.4 to 5.5) for OAC and 5.8 (95% CI 4.6 to 7.0) for HGD/OAC combined. Risk factors for HGD/OAC were increased age (eg, >75 years HR 12; 95% CI 8.0 to 18), male sex (2.01; 1.68 to 2.60) and presence of LGD at baseline (1.91; 1.53 to 2.40).In this largest reported cohort of unselected patients with BO, the annual risk of OAC was 0.4%. Male sex, older age and LGD at diagnosis are independent predictors of malignant progression, and should enable an improved risk assessment in BO.