tbuckley/cabot-search huggingface dataset:
Capillary underperfusion in chronic venous insufficiency: a cause for leg ulceration?
Authors: O. LUETOLF, R.H. BULL, D.O. BATES, P.S. MORTIMER
Journal: British Journal of Dermatology (1993)

Dermal capillaries in the gaiter area of the lower leg were examined by video-microscopy before and after the administration of intravenous fluorescein in 13 patients with chronic venous insufficiency (CVI) who were at risk of developing leg ulceration. and in 13 normal controls. The influence of posture on capillary perfusion was determined by viewing the same area of skin with the leg in both the supine and dependent positions. Capillary density was lower in patients than in controls, irrespective of the position of the leg (P<0.01). Fluorescence angiography studies in normal controls showed a reduction in capillary density with dependency (P<0.01). but patients with CVI showed no significant change. Fluorescence angiography revealed a greater numher of capillaries than seen during native capillaroscopy (P<0.05). The decreased capillary density, and the loss of the postural vasoconstrictor reflex in patients with chronic venous incompetence may play a role in the pathogenesis of ulceration.
Serum Amyloid A Promotes Lung Neutrophilia by Increasing IL-17A Levels in the Mucosa and γδ T Cells
Authors: Desiree Anthony, Huei Jiunn Seow, Mohib Uddin, Michelle Thompson, Lovisa Dousha, Ross Vlahos, Louis B. Irving, Bruce D. Levy, Gary P. Anderson, Steven Bozinovski
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Neutrophilic inflammation is an important pathologic feature of chronic obstructive pulmonary disease (COPD) and infectious exacerbations of COPD. Serum amyloid A (SAA) promotes neutrophilic inflammation by its interaction with lung mucosal ALX/FPR2 receptors. However, little is known about how this endogenous mediator regulates IL-17A immunity.To determine whether SAA causes neutrophilic inflammation by IL-17A-dependent mechanisms.The relationship between SAA and neutrophils was investigated in lung sections from patients with COPD and a chronic mouse model of SAA exposure. A neutralizing antibody to IL-17A was used to block SAA responses in vivo, and a cell-sorting strategy was used to identify cellular sources.SAA mRNA expression was positively associated with tissue neutrophils in COPD (P < 0.05). SAA predominately promoted expression of the TH17 polarizing cytokine IL-6, which was opposed by 15-epi-lipoxin A4, a counter-regulatory mediator, and ALX/FPR2 ligand. SAA-induced inflammation was markedly reduced by a neutralizing antibody to IL-17A in vivo. Cellular sources of IL-17A induced by SAA include CD4(+) T cells, γδ T cells, and an Epcam(+)CD45(-) population enriched for epithelial cells. SAA promotes expression of IL-17A in γδ T cells and this innate cell proportionally expressed higher levels of IL-17A transcript than CD4(+) T cells or epithelial cells.The SAA-IL-17A axis represents an important innate defense network that may underlie persistent neutrophilic airway inflammation in COPD and modulating the ALX/FPR2 receptor represents a novel approach to targeting aberrant IL-17A-mediated lung immunity.
Endothelial Cells Modulate the Proliferation of Mural Cell Precursors via Platelet-Derived Growth Factor-BB and Heterotypic Cell Contact
Authors: Karen K. Hirschi, Stephanie A. Rohovsky, Laurence H. Beck, Sandra R. Smith, Patricia A. D’Amore
Journal: Circulation Research (1999)

Abstract —Embryological data suggest that endothelial cells (ECs) direct the recruitment and differentiation of mural cell precursors. We have developed in vitro coculture systems to model some of these events and have shown that ECs direct the migration of undifferentiated mesenchymal cells (10T1/2 cells) and induce their differentiation toward a smooth muscle cell/pericyte lineage. The present study was undertaken to investigate cell proliferation in these cocultures. ECs and 10T1/2 cells were cocultured in an underagarose assay in the absence of contact. There was a 2-fold increase in bromodeoxyuridine labeling of 10T1/2 cells in response to ECs, which was completely inhibited by the inclusion of neutralizing antiserum against platelet-derived growth factor (PDGF)-B. Antisera against PDGF-A, basic fibroblast growth factor, or transforming growth factor (TGF)-β had no effect on EC-stimulated 10T1/2 cell proliferation. EC proliferation was not influenced by coculture with 10T1/2 cells in the absence of contact. The cells were then cocultured so that contact was permitted. Double labeling and fluorescence-activated cell sorter analysis revealed that ECs and 10T1/2 cells were growth-inhibited by 43% and 47%, respectively. Conditioned media from contacting EC-10T1/2 cell cocultures inhibited the growth of both cell types by 61% and 48%, respectively. Although we have previously shown a role for TGF-β in coculture-induced mural cell differentiation, growth inhibition resulting from contacting cocultures or conditioned media was not suppressed by the presence of neutralizing antiserum against TGF-β. Furthermore, the decreased proliferation of 10T1/2 cells in the direct cocultures could not be attributed to downregulation of the PDGF-B in ECs or the PDGF receptor-β in the 10T1/2 cells. Our data suggest that modulation of proliferation occurs during EC recruitment of mesenchymal cells and that heterotypic cell-cell contact and soluble factors play a role in growth control during vessel assembly.
Oxygen cost of breathing and weaning process in newborn infants
Authors: JC Roze, JM Liet, V Gournay, T Debillon, C Gaultier
Journal: European Respiratory Journal (1997)

Newborn infants may have a high oxygen cost of breathing (OCB) at the time of being weaned from mechanical ventilation. We hypothesized that this increase in oxygen consumption (V'O2) could be reduced by using certain weaning ventilatory modes. We designed a study to assess V'O2 during three weaning ventilatory modes: patient triggered ventilation, synchronous intermittent mandatory ventilation (SIMV) and continuous positive airway pressure in 16 newborn infants before being weaned from mechanical ventilation In seven infants whose OCB was high. V'O2 was not significantly different between CV and PTV (8.9+/-0.6 versus 9.5+/-0.8, respectively) whereas it tended to increase to 10.8+/-1.1 mL x min(-1) x kg(-1) during SIMV and increased significantly to 11.9+/-0.8 mL x min(-1) x kg(-1). In the other nine infants whose OCB was normal, no significant variation of V'O2 was observed. Patient triggered ventilation was a weaning ventilatory mode that significantly reduced the increase in oxygen consumption observed in infants with a high oxygen cost of breathing, as compared to synchronous intermittent mandatory ventilation or continuous positive airway pressure. Further investigations in newborn infants with a high oxygen cost of breathing should be performed prior to routine use of patient triggered ventilation.
In Vivo Imaging, Tracking, and Targeting of Cancer Stem Cells
Authors: Erina Vlashi, Kwanghee Kim, Chann Lagadec, Lorenza Della Donna, John Tyson McDonald, Mansoureh Eghbali, James W. Sayre, Encrico Stefani, William McBride, Frank Pajonk
Journal: JNCI Journal of the National Cancer Institute (2009)

There is increasing evidence that solid cancers contain cancer-initiating cells (CICs) that are capable of regenerating a tumor that has been surgically removed and/or treated with chemotherapy and/or radiation therapy. Currently, cell surface markers, like CD133 or CD44, are used to identify CICs in vitro; however, these markers cannot be used to identify and track CICs in vivo. The 26S proteasome is the main regulator of many processes within a proliferating cell, and its activity may be altered depending on the phenotype of a cell.Human glioma and breast cancer cells were engineered to stably express ZsGreen fused to the carboxyl-terminal degron of ornithine decarboxylase, resulting in a fluorescent fusion protein that accumulates in cells in the absence of 26S proteasome activity; activities of individual proteases were monitored in a plate reader by detecting the cleavage of fluorogenic peptide substrates. Proteasome subunit expression in cells expressing the fusion protein was assessed by quantitative reverse transcription-polymerase chain reaction, and the stem cell phenotype of CICs was assessed by a sphere formation assay, by immunohistochemical staining for known stem cell markers in vitro, and by analyzing their tumorigenicity in vivo. CICs were tracked by in vivo fluorescence imaging after radiation treatment of tumor-bearing mice and targeted specifically via a thymidine kinase-degron fusion construct. All P values were derived from two-sided tests.Cancer cells grown as sphere cultures in conditions, which enrich for cancer stem cells (CSCs), had decreased proteasome activity relative to the respective monolayers (percent decrease in chymotryptic-like activity of sphere cultures relative to monolayers--U87MG: 26.64%, 95% confidence interval [CI] = 10.19 to 43.10, GL261, 52.91%, 95% CI = 28.38 to 77.43). The cancer cells with low proteasome activity can thus be monitored in vitro and in vivo by the accumulation of a fluorescent protein (ZsGreen) fused to a degron that targets it for 26S proteasome degradation. In vitro, ZsGreen-positive cells had increased sphere-forming capacity, expressed CSC markers, and lacked differentiation markers compared with ZsGreen-negative cells. In vivo, ZsGreen-positive cells were approximately 100-fold more tumorigenic than ZsGreen-negative cells when injected into nude mice (ZsGreen positive, 30 mice per group; ZsGreen negative, 31 mice per group), and the number of CICs in tumors increased after 72 hours post radiation treatment. CICs were selectively targeted via a proteasome-dependent suicide gene, and their elimination in vivo led to tumor regression.Our results demonstrate that reduced 26S proteasome activity is a general feature of CICs that can easily be exploited to identify, track, and target them in vitro and in vivo.
Predicting Progression of Glaucoma from Rates of Frequency Doubling Technology Perimetry Change
Authors: Daniel Meira-Freitas, Andrew J. Tatham, Renato Lisboa, Tung-Mei Kuang, Linda M. Zangwill, Robert N. Weinreb, Christopher A. Girkin, Jeffrey M. Liebmann, Felipe A. Medeiros
Journal: Ophthalmology (2013)
Fetal Pulse Oximetry and Cesarean Delivery
Authors: Steven L. Bloom, Catherine Y. Spong, Elizabeth Thom, Michael W. Varner, Dwight J. Rouse, Sandy Weininger, Susan M. Ramin, Steve N. Caritis, Alan Peaceman, Yoram Sorokin, Anthony Sciscione, Marshall Carpenter, Brian Mercer, John Thorp, Fergal Malone, Margaret Harper, Jay Iams, Garland Anderson
Journal: New England Journal of Medicine (2006)

Knowledge of fetal oxygen saturation, as an adjunct to electronic fetal monitoring, may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth. We randomly assigned 5341 nulliparous women who were at term and in early labor to either "open" or "masked" fetal pulse oximetry. In the open group, fetal oxygen saturation values were displayed to the clinician. In the masked group, the fetal oxygen sensor was inserted and the values were recorded by computer, but the data were hidden. Labor complicated by a nonreassuring fetal heart rate before randomization was documented for subsequent analysis. There was no significant difference in the overall rates of cesarean delivery between the open and masked groups (26.3% and 27.5%, respectively; P=0.31). The rates of cesarean delivery associated with the separate indications of a nonreassuring fetal heart rate (7.1% and 7.9%, respectively; P=0.30) and dystocia (18.6% and 19.2%, respectively; P=0.59) were similar between the two groups. Similar findings were observed in the subgroup of 2168 women in whom a nonreassuring fetal heart rate was detected before randomization. The condition of the infants at birth did not differ significantly between the two groups. Knowledge of the fetal oxygen saturation is not associated with a reduction in the rate of cesarean delivery or with improvement in the condition of the newborn. (ClinicalTrials.gov number, NCT00098709 [ClinicalTrials.gov].).
Drug-Resistance Patterns Assessed From Tumor Marker Analysis
Authors: J. Carl
Journal: JNCI Journal of the National Cancer Institute (1989)

We analyzed the levels of the tumor markers alpha-fetoprotein and human chorionic gonadotropin during the course of treatment in 19 patients with nonseminomatous germ cell tumors. We calculated the fractional tumor kill at each cycle using assumptions of exponential tumor growth and exponential marker decay and assumptions assuring that marker production reflects the size of the clonogenic tumor. The observed pattern of decrease was compared with three theoretical models. The first (Skipper) assumes that sensitive and resistant populations are present at the beginning of treatment. The second (Goldie and Coldman) assumes an initially sensitive population with mutation causing subsequent treatment resistance. Both models, under a wide range of parameter values, predict a much more rapid decrease in fractional tumor kill per treatment cycle than was observed. A model in which there are four clones of differing sensitivity at the start of treatment was able to adequately describe the observed time course of tumor killing.
Population Genomics of Chlamydia trachomatis: Insights on Drift, Selection, Recombination, and Population Structure
Authors: Sandeep J. Joseph, Xavier Didelot, James Rothschild, Henry J.C. de Vries, Servaas A. Morré, Timothy D. Read, Deborah Dean
Journal: Molecular Biology and Evolution (2012)

The large number of sexually transmitted diseases and ocular trachoma cases that are caused globally each year by Chlamydia trachomatis has made this organism a World Health Organization priority for vaccine development. However, there is no gene transfer system for Chlamydia to help identify potential vaccine targets. To accelerate discoveries toward this goal, here we analyzed the broadest diversity of C. trachomatis genomes to date, including 25 geographically dispersed clinical and seven reference strains representing 14 of the 19 known serotypes. Strikingly, all 32 genomes were found to have evidence of DNA acquisition by homologous recombination in their history. Four distinct clades were identified, which correspond to all C. trachomatis disease phenotypes: lymphogranuloma venereum (LGV; Clade 1); noninvasive urogenital infections (Clade 2); ocular trachoma (Clade 3); and protocolitis (Clade 4; also includes some noninvasive urogenital infections). Although the ancestral relationship between clades varied, most strains acted as donor and recipient of recombination with no evidence for barriers to genetic exchange. The niche-specific LGV and trachoma clades have undergone less recombination, although the opportunity for mixing with strains from other clades that infect the rectal and ocular mucosa, respectively, is evident. Furthermore, there are numerous occasions for gene conversion events through sequential infections at the same anatomic sites. The size of recombinant segments is relatively small (∼357 bp) compared with in vitro experiments of various C. trachomatis strains but is consistent with in vitro estimates for other bacterial species including Escherichia coli and Helicobacter pylori. Selection has also played a crucial role during the diversification of the organism. Clade 2 had the lowest nonsynonymous to synonymous ratio (dN/dS) but the highest effect of recombination, which is consistent with the widespread occurrence of synonymous substitutions in recombined genomic segments. The trachoma Clade 3 had the highest dN/dS estimates, which may be caused by an increased effect of genetic drift from niche specialization and a reduced effective population size. The degree of drift, selection, and recombination in C. trachomatis suggests that the challenge will remain to identify genomic regions that are stable and cross protective for the development of an efficacious vaccine.
Local cytokine messenger ribonucleic acid expression and in vitro allergic late phase responses in Brown-Norway rats
Authors: EM Minshall, RJ Dandurand, Q Hamid, DH Eidelman
Journal: European Respiratory Journal (1998)

The events subsequent to antigen challenge in allergic asthmatics involve the synthesis of pro-inflammatory cytokines. However, little is known how cytokine gene activation prior to allergen challenge may influence this series of events, nor how cytokine gene expression is related to antigen-induced alterations in lung function. Using a novel in vitro explant technique, we hypothesized that the local expression of cytokines influenced the development of antigen-induced late-onset airway responses, and that alterations in cytokine messenger ribonucleic acid (mRNA) expression were associated with antigen-induced changes in airway luminal area. Explants were prepared from excised lungs of ovalbumin-sensitized Brown-Norway rats. Airways were challenged by direct application of ovalbumin or an irrelevant control antigen. Cryostat sections of explants were used for in situ hybridization and mRNA for interleukin (IL)-2, IL-4 and interferon (IFN)-gamma were detected using radiolabelled probes. We found that the presence of high numbers of cells expressing IFN-gamma and IL-2 mRNA within the airways attenuated the development of antigen-induced late airway responses in sensitized rat lung explants. Furthermore, we observed that cytokine mRNA for IL-4 was significantly increased following allergen exposure in sensitized lung explants exhibiting late airway responses. This study implicates the local expression of interferon-gamma and interleukin-2 messenger ribonucleic acid in the failure of sensitized rat lung explants to exhibit late airway responses, and provides evidence linking local interleukin-4 messenger ribonucleic acid expression to the sequelae of events occurring as a result of antigen exposure within the airways.
TYLOSIS PALMARIS ET PLANTARIS WITH UNUSUAL BULLOUS LESIONS.
Authors: JOHN EVERALL
Journal: British Journal of Dermatology (1954)

Journal Article TYLOSIS PALMARIS ET PLANTARIS WITH UNUSUAL BULLOUS LESIONS. Get access JOHN EVERALL, M.R.C.P.Lond. JOHN EVERALL, M.R.C.P.Lond. Tutor in Dermatology, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 66, Issue 2, 1 February 1954, Pages 54–56, https://doi.org/10.1111/j.1365-2133.1954.tb12588.x Published: 01 February 1954
Children's coughs related to parental smoking.
Authors: A Charlton
Journal: BMJ (1984)

A survey of the smoking habits, attitudes, and background of over 15 000 8-19 year olds in northern England in December 1982 showed a positive correlation between parental smoking and the reporting of frequent coughs by children who had never smoked. This was especially pronounced in the youngest children. Thirty five per cent of boys under 11 who had never smoked and whose parents did not smoke reported frequent coughs; with one parent smoking this increased to 42%, and when both parents smoked the proportion was 48%. Girls under 11 showed the same pattern, with 32%, 40%, and 52% respectively reporting frequent coughs. Fewer older children in general reported frequent coughs. Mothers9 smoking had more influence on children9s coughs than had fathers9 smoking. Social area type had no significant effect. No significant effect of passive smoking was observed when the children themselves were smokers. These results are clear evidence of a definite link between smoking in the home and coughs in young children, which not only may present immediate problems but may also be a cause of illness in the future.
A biomimetic microfluidic chip to study the circulation and mechanical retention of red blood cells in the spleen
Authors: Julien Picot, Papa Alioune Ndour, Sophie D. Lefevre, Wassim El Nemer, Harvey Tawfik, Julie Galimand, Lydie Da Costa, Jean‐Antoine Ribeil, Mariane de Montalembert, Valentine Brousse, Bruno Le Pioufle, Pierre Buffet, Caroline Le Van Kim, Olivier Français
Journal: American Journal of Hematology (2015)

Red blood cells (RBCs) are deformable and flow through vessels narrower than their own size. Their deformability is most stringently challenged when they cross micrometer-wide slits in the spleen. In several inherited or acquired RBC disorders, blockade of small vessels by stiff RBCs can trigger organ damage, but a functional spleen is expected to clear these abnormal RBCs from the circulation before they induce such complications. We analyzed flow behavior of RBCs in a microfluidic chip that replicates the mechanical constraints imposed on RBCs as they cross the human spleen. Polymer microchannels obtained by soft lithography with a hydraulic diameter of 25 μm drove flow into mechanical filtering units where RBCs flew either slowly through 5- to 2-μm-wide slits or rapidly along 10-μm-wide channels, these parallel paths mimicking the splenic microcirculation. Stiff heated RBCs accumulated in narrow slits seven times more frequently than normal RBCs infused simultaneously. Stage-dependent retention of Plasmodium falciparum-infected RBCs was also observed in these slits. We also analyzed RBCs from patients with hereditary spherocytosis and observed retention for those having the most altered mechanical properties as determined by ektacytometry. Thus, in keeping with previous observations in vivo and ex vivo, the chip successfully discriminated poorly deformable RBCs based on their distinct mechanical properties and on the intensity of the cell alteration. Applications to the exploration of the pathogenesis of malaria, hereditary spherocytosis, sickle cell disease and other RBC disorders are envisioned.