tbuckley/cabot-search huggingface dataset:
Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines
Authors: A C Warhurst, S J Hopkins, G Warhurst
Journal: Gut (1998)

Background —Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes. Aims —To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differential modulation by interferon γ (IFN-γ), a product of activated T lymphocytes and natural killer cells. Methods and results —HT29-19A, a model of the Cl − secretory crypt cell, exhibited a parallel secretion of the α chemokines IL-8 and GROα, which could be markedly upregulated by tumour necrosis factor α (TNF-α) and IL-1β. These cells showed no significant expression of the β chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1α (macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-γ in combination with TNF-α caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-γ had no significant effect on TNF-α stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of α chemokines but secreted high levels of MCP-1 in response to IL-1β. IFN-γ did not influence α or β chemokine secretion in these cells. Conclusions —These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-γ to activate the expression of β chemokines preferentially could facilitate the development of chronic inflammatory infiltrates.
Demonstration of albumin receptors onisolated human hepatocytes by light and scanning electron microscopy
Authors: Alessandro Trevisan, Fred Gudat, Richard Guggenheim, Gunthild Krey, Ursula Dürmüller, Guido Lüond, Marcel Düggelin, Jonas Landmann, Pietro Tondelli, Leonardo Bianchi
Journal: Hepatology (1982)

The presence of albumin receptors on the plasma membrane of isolated human hepatocytes was investigated employing albumin-coupled latex minibeads. Hepatocyte-latex reaction was visualized by phase contrast and scanning electron microscopy. The experiments demonstrate that hepatocytes exhibit binding activity for polymeric and monomelic forms of glutaraldehyde-treated albumin. Additionally, the reaction was shown to be species-nonspecific. These findings support the hypothesis that polymerized albumin may act as a bridge between receptors on hepatitis B virus and human hepatocytes.
Changing the narrative on antibiotics
Authors: Fergus Shanahan
Journal: Gut (2015)

Campaigning for antibiotic conservation is a bit like the struggle against global warming. The polar ice melts while politicians, not known for long-range thinking, debate deadlines for others to meet. Similarly, new drug discovery diminishes as resistance to existing antibiotics increases. Public health officials and policy makers predict a bleak future and plead for reform of prescribing practices, but clinicians deal with individual patients, not populations, in the present. Perhaps, it is time to direct the educational narrative on antibiotics towards the consumer. Enthusiasm for antibiotic treatment, particularly for soft indications, might be tempered if the potential adverse effects on the microbiota were better known. Antibiotic-associated diarrhoea and Clostridium difficile -associated disease are well recognised but more subtle effects are less well appreciated. Few clinicians may know that antibiotics can induce an immune deficiency in experimental animals. Furthermore, increasing evidence suggests that disturbance of the indigenous microbiota by antibiotic exposure, particularly in early life, is a risk factor for later development of obesity-related metabolic disorders and several immunologically mediated disorders, such as IBD and asthma.1–,3 Concern about the adverse effects of antibiotic exposure will escalate with better understanding of host–microbe interactions in host development and homeostasis, especially when …
HILUS TUBERCULOSIS AS AN IMPORTANT CAUSATIVE FACTOR IN PULMONARY TUBERCULOSIS IN ADULTS
Authors: D. J. G. Johnston
Journal: BMJ (1929)

l'IfE tesin11 " IlillIs tuiiberuilosis " is used for )oil iieldC'e, aind ini a comnprehenisive sense, to inelude tutblelrlosis of all or, any of tlho different groups of bironchial glanids.An lmlost uniiversal distributioni of tuberculous in fection in the hulimian subject lhas been foniiid by so miiany obs;ervers i that it is iiow accepted as a proved fact.The l)lpesent inv-estigation lhas been carried out wi-itlh a view to deter- iningt, lhow far it is possible to diagcnose t1lbelrculousiifeection from cliniical signls anid symptoms only, and wlihether there is anyv direct coinllexioni betwi-Ceen such infec- tioni and l)ulimonnrv 'tuberculosis.The period of observa- tion extenided over ten years, an-d inivolved the exainina-tio11 of ov-er 20,000 childlreni between the ages of 5 andcl 14, and the re-examiiinationi at intervals of three to six milontlis of all, those showing definiite evidenice of departure from thle, niormial.The first thing that impresses itself oln thle (lise,rver wvho has examinied even a few hundred hlealtlhy chinests is that there is no fixed niormi-ial.The iiormal vIaites withinl failrly wide limits, anid a long apprenticeshil) is required to establissh confidenice in, deciding wlich czases fall wvithiln the nlormiial anld whic are definitelv outside it.The m-ciass of evidence obtainied, ofteni apparenftly verv contrad(lidtory;) w-as very perpl exinig during, the en l-liel 1)(ieiod of the inivestigationi, buit slowvly the accumuiilllated evidence of yeais tuined the minid to a more-or less definiite line of tlhought, which appeals to offer a reasoniable ex)laination for all the varyinig phases anid stages of tlle iifection.-Theplivsical examiniationi followved the uisual linies, alld does not require to be given in detail.It is aidvisable, howe%rer, to emphasize the necessity of silng the very litghtest percussion if the finier sha(des of dull- ress are to be suceessfully determiined.Tidal per'cussioni slhould always be mapped out, although, at the apices, it waIs fouind to be less valuable in' child'reni thaniin adults,
Omalizumab for chronic spontaneous urticaria: a boon for sufferers, but there are unanswered questions
Authors: M.W. Greaves
Journal: British Journal of Dermatology (2015)

Journal Article Omalizumab for chronic spontaneous urticaria: a boon for sufferers, but there are unanswered questions Get access M.W. Greaves M.W. Greaves Cutaneous Allergy Clinic St John's Institute of Dermatology St Thomas' Hospital London SE1 7EH U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Page 321, https://doi.org/10.1111/bjd.13981 Published: 01 August 2015
MyD88 But Not TRIF Is Essential for Osteoclastogenesis Induced by Lipopolysaccharide, Diacyl Lipopeptide, and IL-1α
Authors: Nobuaki Sato, Naoyuki Takahashi, Koji Suda, Midori Nakamura, Mariko Yamaki, Tadashi Ninomiya, Yasuhiro Kobayashi, Haruhiko Takada, Kenichiro Shibata, Masahiro Yamamoto, Kiyoshi Takeda, Shizuo Akira, Toshihide Noguchi, Nobuyuki Udagawa
Journal: The Journal of Experimental Medicine (2004)

Myeloid differentiation factor 88 (MyD88) plays essential roles in the signaling of the Toll/interleukin (IL)-1 receptor family. Toll–IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF)-mediated signals are involved in lipopolysaccharide (LPS)-induced MyD88-independent pathways. Using MyD88-deficient (MyD88−/−) mice and TRIF-deficient (TRIF−/−) mice, we examined roles of MyD88 and TRIF in osteoclast differentiation and function. LPS, diacyl lipopeptide, and IL-1α stimulated osteoclastogenesis in cocultures of osteoblasts and hemopoietic cells obtained from TRIF−/− mice, but not MyD88−/− mice. These factors stimulated receptor activator of nuclear factor-κB ligand mRNA expression in TRIF−/− osteoblasts, but not MyD88−/− osteoblasts. LPS stimulated IL-6 production in TRIF−/− osteoblasts, but not TRIF−/− macrophages. LPS and IL-1α enhanced the survival of TRIF−/− osteoclasts, but not MyD88−/− osteoclasts. Diacyl lipopeptide did not support the survival of osteoclasts because of the lack of Toll-like receptor (TLR)6 in osteoclasts. Macrophages expressed both TRIF and TRIF-related adaptor molecule (TRAM) mRNA, whereas osteoblasts and osteoclasts expressed only TRIF mRNA. Bone histomorphometry showed that MyD88−/− mice exhibited osteopenia with reduced bone resorption and formation. These results suggest that the MyD88-mediated signal is essential for the osteoclastogenesis and function induced by IL-1 and TLR ligands, and that MyD88 is physiologically involved in bone turnover.
Failure of consultant expansion
Authors: J. Howell, S. Ramaiah
Journal: BMJ (1995)

# Consultant expansion depends on local cooperation {#article-title-2}

EDITOR,—Surely Stephen Brearley's editorial on the failure of consultant expansion underestimates the importance of team work in producing changes in major issues at the local level.1 If people wish to move towards a consultant led service then the consultants in individual hospitals …
Update in Environmental and Occupational Lung Diseases 2013
Authors: Chris Carlsten, Steve N. Georas
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

In this update, recent publications within the field of environmental and occupational medicine, from this journal and others, are highlighted. Effects of ambient air pollution on a diverse range of airways disease continue to be discovered, reiterating the impressive potency of this near-ubiquitous and largely anthropogenic toxicant. Air pollution is now recognized as the third leading cause of disability-adjusted life years due to chronic respiratory disease globally (1). Studies in the past year have significantly strengthened the link between air pollution exposure and adverse health outcomes including mortality (2–4), lung cancer (4–6), infections (7–9), and obstructive lung disease (including asthma) (10, 11). Important underlying mechanistic details were illuminated in several animal models (12–17). The association between poor indoor air quality and lung diseases is a topic of increasing interest and was investigated in several reports in 2013 (18–21). Controlled human exposure experiments were in the spotlight, in part because of ethical concerns about the justification of this approach. An important position paper by leading researchers and a biomedical ethicist strongly supports the usefulness of controlled exposures, which continue to provide new insights into adverse health effects of different pollutants (22).

Asbestos exposure is a well-recognized risk factor for pleural mesothelioma, and two epidemiology studies were published that explored the interaction between exposure to asbestos, other mineral fibers, and cigarette smoking in mesothelioma, asbestosis, and lung cancer (23, 24). Arsenic is increasingly recognized as a groundwater contaminant, with potential effects on lung development and function. An important paper provided strong evidence that even low levels of arsenic exposure are associated with reduced lung function (25). The adverse health effects of global warming are becoming apparent, and one paper provided a sobering reminder that elevated ambient temperatures are a strong risk factor for respiratory morbidity (26). Unfortunately, the adverse effects of environmental and occupational exposures on lung health occur disproportionately in ethnic minorities and those with lower socioeconomic status, underscoring the urgent need to address these important health disparities (27). Although our understanding of the adverse effects of environmental and occupational exposures on lung health continues to expand, more research is needed to understand mechanisms involved and discover the optimal public health measures to mitigate risk.
Barium sulphate with a negative zeta potential accelerates skin permeability barrier recovery and prevents epidermal hyperplasia induced by barrier disruption
Authors: S. Fuziwara, K. Ogawa, D. Aso, D. Yoshizawa, S. Takata, M. Denda
Journal: British Journal of Dermatology (2004)

Barium sulphate, a stable inorganic material, has been used in contrast media and cosmetic products because of its stability. As a negative external electric potential accelerates the skin barrier repair after barrier disruption, we hypothesized that topical application of barium sulphate may affect the skin barrier recovery rate depending on its zeta potential.To investigate whether barium sulphate particles in aqueous solution have different zeta potentials depending on their surface structure, and to investigate the possible relation between zeta potential and skin barrier recovery rate.Mice were subjected to tape stripping to disrupt barrier function, or were treated with acetone and kept in a dry environment to induce epidermal hyperplasia. They were then treated with different forms of barium sulphate, and barrier recovery was monitored by measurements of transepidermal water loss.There was a significant correlation between the barrier recovery rate and zeta potential of barium sulphate applied topically. Barium sulphate with a negative zeta potential significantly accelerated barrier recovery, but barium sulphate with a positive zeta potential did not accelerate or even delayed barrier repair. Barium sulphate with a negative zeta potential had an X-ray diffraction pattern different from that with a positive potential. The distribution of calcium in the epidermis was also influenced by the polarity of zeta potential.These findings suggest a new pharmacological approach towards altering barrier function or epidermal hyperplasia with inorganic particles in healthy and diseased skin.
Tranexamic acid (CyklokapronR)-induced fixed-drug eruption
Authors: G.M. Kavanagh, J. E. Sansom, P. Harrison, J. A. Warwick, R. D. Peachey
Journal: British Journal of Dermatology (1993)

Journal Article Tranexamic acid (Cyklokapron®)‐induced fixed‐drug eruption Get access G.M. Kavanagh, G.M. Kavanagh Department of Dermatology, Bristol, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. E. Sansom, J. E. Sansom Department of Dermatology, Bristol, U.K. Dr J. E. Sansom Search for other works by this author on: Oxford Academic Google Scholar P. Harrison, P. Harrison Department of Nephrology, Southmead Hospital, Bristol, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. A. Warwick, J. A. Warwick Department of Pharmacy, Bristol Royal Infirmary, Bristol, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. D. Peachey R. D. Peachey Department of Dermatology, Bristol, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 2, 1 February 1993, Pages 229–230, https://doi.org/10.1111/j.1365-2133.1993.tb15161.x Published: 01 February 1993
Dose-Ranging Study of Metronomic Oral Vinorelbine in Patients with Advanced Refractory Cancer
Authors: Evangelos Briasoulis, Periklis Pappas, Christian Puozzo, Christos Tolis, George Fountzilas, Urania Dafni, Marios Marselos, Nicholas Pavlidis
Journal: Clinical Cancer Research (2009)

To determine the safe dose range and pharmacokinetics of metronomic oral vinorelbine and obtain preliminary data on biomarkers and efficacy in patients with advanced cancer.Successive cohorts of patients received escalated doses of oral vinorelbine given thrice a week until disease progression, unacceptable toxicity (UT), or consent withdrawal. UT was any grade 4 toxicity, or grade 2 or 3 toxicity that would result to longer than 2-week break during the first 2 months of treatment. Blood samples were collected for pharmacokinetics and quantification of angiogenesis regulatory proteins.Sixty-two patients (median age, 60 years) enrolled at six dose levels from 20 to 70 mg and received treatment for median 12.25 weeks (range, 2-216+). Unacceptable toxicity occurred in two of six patients treated at 60 mg (leucopenia grade 4 and epistaxis grade 2) and in one at 70 mg (leucopenia grade 2). The upper metronomic dose was 50 mg. Objective antitumor response documented in eight cases and 32% of patients experienced disease stability for minimum 6 months. Three responders (renal cancer, medullary thyroid carcinoma, and Kaposi sarcoma) received nonstop treatment for over 3 years without overt toxicity. Low pretreatment levels of circulating interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor were found predictors of efficacy. Steady-state concentrations of vinorelbine and its active metabolite ranged from 0.5 to 1.5 ng/mL.Metronomic administration of oral vinorelbine is feasible at doses up to 50 mg thrice a week and can yield sustainable antitumor activity without overt toxicity, probably through antiangiogenic mechanism. Further clinical investigation is warranted.
Traffic-related Exposures, Airway Function, Inflammation, and Respiratory Symptoms in Children
Authors: Fernando Holguin, Silvia Flores, Zev Ross, Marlene Cortez, Mario Molina, Luisa Molina, Carlos Rincon, Michael Jerrett, Kiros Berhane, Alfredo Granados, Isabelle Romieu
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Traffic-related emissions have been associated with respiratory symptoms in some studies. However, there is limited information on how traffic-related emissions relate to lung function and airway inflammation.Objectives: To determine the differential association of traffic-related exposures with exhaled nitric oxide (NO) and lung volumes and symptoms in children with and without asthma.Methods: We performed a longitudinal study of 200 children from ages 6 to 12 years of whom half had physician-diagnosed asthma. Two-week NO2 and 48-hour average levels of elemental carbon and particulate matter of less than 2.5 μm (PM2.5) were measured at participating schools. Road and traffic densities were determined at schools and at each participant's house.Measurements and Main Results: In children with asthma, an interquartile increase in road density within the 50-, 100-, and 200-m home buffer areas was associated with increased exhaled NO (50 m: 28%; P = 0.03; 95% confidence interval [CI], 3–60; 100 m: 27%; P = 0.005; 95% CI, 8–49; 200 m: 17%, P = 0.09, 95% CI, −2 to 40), and reduced FEV1 (50 m: −0.091 L; P = 0.038; 95% CI, −0.174 to −0.007; 100 m: −0.072 L, P = −0.028, 95% CI, −0.134 to −0.009; 200 m: −0.106 L, P = 0.002, 95% CI, −0.171 to −0.041]). Exposure to NO2 at schools was marginally associated with reduced FEV1 (−0.020; P = 0.060; 95% CI, −0.042 to 0.001). We did not observe significant associations with PM2.5 or elemental carbon on exhaled NO. We did not observe significant reductions in lung volumes or changes in exhaled NO among healthy children.Conclusions: Vehicular traffic exposures are associated with increased levels of exhaled NO and reduced lung volumes in children with asthma.
Daily interferon monotherapy versus daily interferon plus amantadinein the treatment of naive chronic hepatitis C patients: Short-termresponse
Authors: A. Popovic, A. Vian, U. Lorenzoni, S. Lobello, S. Pevere, E. Silverij, F. Farinati, A. Floreani, M. Chiaramonte, R. Naccarato, S. Fagiuoli
Journal: Journal of Hepatology (2000)
Testosterone concentrations, using different assays, in different types of ovarian insufficiency: a systematic review and meta-analysis
Authors: F. Janse, S.J. Tanahatoe, M.J.C. Eijkemans, B.C.J.M. Fauser
Journal: Human Reproduction Update (2012)

BACKGROUNDIncreasing age and post-menopausal status are associated with decreasing androgen concentrations in females. Women with premature loss of ovarian function, such as primary ovarian insufficiency (POI) or iatrogenic menopause may be at increased risk for diminished testosterone levels at a relatively young age. Differentiation between a hypoandrogenic or normoandrogenic state in women with premature loss of ovarian function is problematic due to trueness and precision problems using various testosterone assays. The current meta-analysis was conducted to evaluate current literature reporting serum total testosterone concentrations under these conditions, including stratification for various testosterone assays.
Addition of Omega-3 Fatty Acid to Maintenance Medication Treatment for Recurrent Unipolar Depressive Disorder
Authors: Boris Nemets, Ziva Stahl, R H Belmaker
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder. The authors studied a specific omega-3 fatty acid, the ethyl ester of eicosapentaenoic acid (E-EPA), as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy. METHOD: Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week, parallel-group, double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy. Seventeen of the patients were women, and three were men. RESULTS: Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment. CONCLUSIONS: It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own.
Inactivation of the <i>Dlc1</i> Gene Cooperates with Downregulation of <i>p15INK4b</i> and <i>p16Ink4a</i>, Leading to Neoplastic Transformation and Poor Prognosis in Human Cancer
Authors: Xiaolan Qian, Marian E. Durkin, Dunrui Wang, Brajendra K. Tripathi, Lyra Olson, Xu-Yu Yang, William C. Vass, Nicholas C. Popescu, Douglas R. Lowy
Journal: Cancer Research (2012)

Abstract The tumor suppressor gene deleted in liver cancer-1 (DLC1), which encodes a protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc42GAP activity, is inactivated in various human malignancies. Following Dlc1 inactivation, mouse embryo fibroblasts (MEF) with a conditional Dlc1 knockout allele reproducibly underwent neoplastic transformation. In addition to inactivation of Dlc1 and increased activity of Rho and Cdc42, transformation depended on the subsequent decreased expression of the Cdk4/6 inhibitors p15Ink4b and p16Ink4a together with increased expression and activation of Cdk4/6. The level of expression of these cell-cycle regulatory genes was relevant to human tumors with low DLC1 expression. Analysis of publicly available annotated datasets of lung and colon cancer with gene expression microarray profiles indicated that, in pairwise comparisons, low DLC1 expression occurred frequently together (P &amp;lt; 0.01) with downregulation of p15Ink4b or p16Ink4a or upregulation of CDK4 or CDK6. In addition, an unfavorable prognosis (P &amp;lt; 0.05) was associated with low DLC1 and low p15Ink4b in lung cancer and colon cancer, low DLC1 and low p16Ink4a in lung cancer, low DLC1 and high CDK4 in lung cancer, and low DLC1 and high CDK6 in colon cancer. Thus, several genes and biochemical activities collaborate with the inactivation of DLC1 to give rise to cell transformation in MEFs, and the identified genes are relevant to human tumors with low DLC1 expression. Cancer Res; 72(22); 5900–11. ©2012 AACR.