tbuckley/cabot-search huggingface dataset:
Different growth rates of pigmented and white hair in the beard: differentiation vs. proliferation?
Authors: W. NAGL
Journal: British Journal of Dermatology (1995)

A considerable difference in growth rates of pigmented and white anagen beard hair (0.47 mm/day vs. 1.12 mm/day, on average) was measured in three individuals over a 3-year period. Nuclear differentiation in the suprabulbar region of hair shafts revealed an earlier, and more intensive, condensation of chromatin in pigmented hair than in white hair. As other differences (diameter, presence or absence of medulla) between the two hair types could be excluded, the results suggest earlier terminal differentiation of pigmented hair compared with white hair.
Effects of Noninvasive Ventilation on Pulmonary Gas Exchange and Hemodynamics during Acute Hypercapnic Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: ORLANDO DIAZ, RAQUEL IGLESIA, MIQUEL FERRER, ELISABETH ZAVALA, CRISTINA SANTOS, PETER D. WAGNER, JOSEP ROCA, ROBERT RODRIGUEZ-ROISIN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 ± 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (1) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 ± 2 cm H2O, PEEP = 3 ± 2 cm H2O); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping Fi O2 constant (0.23 ± 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in PaO2 (from 50 ± 6 to 57 ± 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 ± 10 to 59 ± 10 mm Hg; p < 0.0001), but aaPo 2 increased (from 39 ± 13 to 48 ± 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 ± 5 to 19 ± 3 breaths/min; p < 0.0001), tidal volume increased (from 311 ± 42 to 520 ± 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 ± 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 ± 1.6 to 5.8 ± 1.3 L/min; p < 0.0025) with no impact on mixed venous Po 2. No substantial changes in V˙ a/Q˙ mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 ± 0.17 to 0.90 ± 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in V˙ a/Q˙ relationships. The increase in aaPo 2 was explained by the rise in R due to an increased clearance of body stores of CO2 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NIPPV in this type of patient.
Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?
Authors: M. Romagnoli, C. Nannini, S. Piciucchi, F. Girelli, C. Gurioli, G. Casoni, C. Ravaglia, S. Tomassetti, Ch. Gurioli, G. Gavelli, A. Carloni, A. Dubini, F. Cantini, M. Chilosi, V. Poletti
Journal: European Respiratory Journal (2011)

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.
A method to preserve sputum for delayed examination
Authors: M.M. Kelly, F.E. Hargreave, G. Cox
Journal: European Respiratory Journal (2003)

Examination of sputum cell counts is limited by the need to process samples within hours of expectoration. The validity and repeatability of a method to preserve sputum for delayed processing and examination were investigated in this study. Portions of selected sputum from 39 subjects were dispersed with dithiothreitol (routine method), or were fixed in a dithiothreitol-formaldehyde mixture for 48–72 h before dispersal with trypsin (preservation method). Total and differential cell counts using the two methods were compared; within-method repeatability of the preservation method was also examined. The intraclass correlation coefficient (ICC) for total cell counts and percentage of eosinophils, neutrophils and macrophages in sputum processed by the two methods was 0.89, 0.86, 0.91 and 0.90, respectively. Within-method repeatability (ICC) of the preservation method for the same cellular indices was 0.99, 0.94, 0.97 and 0.97, respectively. The interobserver repeatability for eosinophils, neutrophils and macrophages was 0.96, 0.97 and 0.97 using the preservation method, and 0.96, 0.99 and 0.99 using the routine method, respectively. This method of sputum preservation and dispersal is valid, reliable and convenient, and may be used for delayed processing and examination.
Influence of Sympathetic Nerve Stimulation on Ventricular Function in the Newborn Lamb
Authors: S. Evans Downing, Norman S. Talner, Alexander G. Campbell, Katherine H. Halloran, Howard B. Wax
Journal: Circulation Research (1969)

Cardiac responses to supramaximal electrical stimulation of postganglionic sympathetic nerve fibers were studied in 17 lambs, 10 hours to 3 days of age. In all lambs left ventricular contractility increased within 3 seconds and was unaltered by atropine, ganglionic blockade, or nerve sectioning proximal to the stimulating electrodes but was abolished by beta-receptor blockade. The responses were repeatedly demonstrated in two lambs subjected to bilateral adrenalectomy. Acidemia (pH 6.9) produced by lactic acid infusion failed to diminish the inotropic responses. Intravenous or leftatrial injections of tyramine produced chronotropic and inotropic responses comparable to sympathetic nerve stimulation. Glucagon, 50 to 200 µg/kg, failed to elicit cardiac responses in lambs from 1 to 60 days of age. It is concluded that sympathetic neural mechanisms may strongly influence myocardial contractility in the newborn lamb and that these responses are independent of adrenal medullary release of catecholamines. These findings further suggest that the lamb possesses a myocardial adenyl cyclase system that responds only to catecholamines and may be blocked with propranolol.
Autoimmunity Initiates in Nonhematopoietic Cells and Progresses via Lymphocytes in an Interferon-Dependent Autoimmune Disease
Authors: Alevtina Gall, Piper Treuting, Keith B. Elkon, Yueh-Ming Loo, Michael Gale, Glen N. Barber, Daniel B. Stetson
Journal: Immunity (2012)
Risk of Corticosteroid-Induced Hyperglycemia Requiring Medical Therapy among Patients with Inflammatory Eye Diseases
Authors: Joshua D. Udoetuk, Yang Dai, Gui-Shuang Ying, Ebenezer Daniel, Sapna Gangaputra, James T. Rosenbaum, Eric B. Suhler, Jennifer E. Thorne, C. Stephen Foster, Douglas A. Jabs, Grace A. Levy-Clarke, Robert B. Nussenblatt, John H. Kempen
Journal: Ophthalmology (2012)
Absence of human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus in a case of benign lymphangioendothelioma associated with periosteal haemangioma
Authors: N. Kato, K. Isu, H. Kikuta
Journal: British Journal of Dermatology (2002)

Journal Article Absence of human herpesvirus 8/Kaposi's sarcoma‐associated herpesvirus in a case of benign lymphangioendothelioma associated with periosteal haemangioma Get access N. Kato, N. Kato Departments of Dermatology and *Orthopaedics, and Clinical Research Institute, National Sapporo Hospital, Kikusui 4–2, Shiroishi‐ku, 003–0804 Sapporo, Japan †Department of Paediatrics, Hokkaido University School of Medicine, Sapporo, Japan E‐mail: kato@sap‐cc.go.jp Search for other works by this author on: Oxford Academic Google Scholar K. Isu, K. Isu Departments of Dermatology and *Orthopaedics, and Clinical Research Institute, National Sapporo Hospital, Kikusui 4–2, Shiroishi‐ku, 003–0804 Sapporo, Japan †Department of Paediatrics, Hokkaido University School of Medicine, Sapporo, Japan E‐mail: kato@sap‐cc.go.jp Search for other works by this author on: Oxford Academic Google Scholar H. Kikuta H. Kikuta Departments of Dermatology and *Orthopaedics, and Clinical Research Institute, National Sapporo Hospital, Kikusui 4–2, Shiroishi‐ku, 003–0804 Sapporo, Japan †Department of Paediatrics, Hokkaido University School of Medicine, Sapporo, Japan E‐mail: kato@sap‐cc.go.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 1, 1 January 2002, Pages 157–158, https://doi.org/10.1046/j.1365-2133.2002.04481.x Published: 01 January 2002
A Hot Spot for RAD51C Interactions Revealed by a Peptide That Sensitizes Cells to Cisplatin
Authors: Philip P. Connell, Nazli Siddiqui, Sara Hoffman, Audrey Kuang, Emir-Assan Khatipov, Ralph R. Weichselbaum, Douglas K. Bishop
Journal: Cancer Research (2004)

DNA repair via the homologous recombination pathway requires the recombinase RAD51 and, in vertabrates, five RAD51 paralogs. The paralogs form two complexes in solution, a XRCC3/RAD51C heterodimer and a RAD51B/RAD51C/RAD51D/XRCC2 heterotetramer. Mutation of any one of the five paralog genes prevents subnuclear assembly of recombinase at damaged sites and renders cells 30-100 fold sensitive to DNA cross-linking drugs. Phage display was used to isolate peptides that bind the paralog XRCC3. Sequences of binding peptides showed similarity to residues 14-25 of RAD51C protein. Point mutations in this region of RAD51C altered its interaction with both XRCC3 and RAD51B in a two-hybrid system. A synthetic peptide composed of residues 14-25 of RAD51C fused to a membrane transduction sequence [protein transduction domain 4 (PTD4)], inhibited subnuclear assembly of RAD51 recombinase, and sensitized Chinese hamster ovary cells to cisplatin when added to growth medium. These results suggest that residues 14-25 of RAD51C contribute to a "hot spot" used in both XRCC3-RAD51C and RAD51B-RAD51C interactions. Peptide-based inhibition of homologous recombination may prove useful for improving the efficacy of existing cancer therapies.
Circulating Inflammatory Endothelial Cells Contribute to Endothelial Progenitor Cell Dysfunction in Patients with Vasculitis and Kidney Involvement
Authors: Carolina Holmén, Elzafir Elsheikh, Peter Stenvinkel, Abdul Rashid Qureshi, Erna Pettersson, Sirpa Jalkanen, Suchitra Sumitran-Holgersson
Journal: Journal of the American Society of Nephrology (2005)

Impaired angiogenic function has been reported in patients with kidney failure. During vascular damage, endothelial cells may detach from the site of inflammation and be released into the peripheral blood. With the use of Wegener's granulomatosis as a study model, whether circulating inflammatory endothelial cells (IEC) can (1) be used as a disease activity marker and (2) contribute to sustained vascular damage by inducing endothelial progenitor cell (EPC) dysfunction were examined. IEC-defined as endothelial cells that express the two inflammatory-associated markers vascular-adhesion protein-1 (VAP-1) and MHC class I-related chain A (MICA)-were increased significantly in patients with active disease as compared with those in remission. IEC expressed high levels of inducible nitric oxide synthase and neutrophil-activating chemokines, such as macrophage inflammatory protein-1alpha, growth-related oncogene-alpha, epithelial neutrophil activating peptide-78, and IL-8, and induced increased neutrophil migration. IEC levels significantly correlated with C-reactive protein and extent of organ involvement. Patients with active disease had decreased numbers of EPC colony-forming units and a high expression of VAP-1 and MICA in kidney endothelium. EPC did not express VAP-1 or MICA. IEC significantly inhibited proliferation, migration, and endothelial nitric oxide synthase expression in EPC. Thus, apart from being a new disease activity marker, IEC may contribute to vascular damage by impairing the functional capacity for repair by EPC. IEC may provide a unique in vitro system to study pathogenesis of kidney and vascular diseases.
Friend disease in vitro.
Authors: T M Dexter, T D Allen, N G Testa, E Scolnick
Journal: The Journal of Experimental Medicine (1981)

In long-term marrow cultures, hemopoiesis can be maintained for several months, although erythropoiesis is normally suppressed at the most primitive level of development (the erythroid colony-forming cells). Infection of these cultures with a viral complex combining helper-independent murine leukemia virus (F-MuLV) and a spleen focus-forming virus (SFFVp) results in a productive infection of both the replication defective SFFVp and the F-MuLV. After infection, the cultures show a dramatic elevation in the numbers of late erythroid progenitor cells (CFU-E), many of which will grow in the absence of added erythropoietin, and a transient erythropoietin, independent erythropoiesis, including the production of mature, enucleated erythrocytes. Hemopoiesis eventually declines, with no evidence for the generation of Friend tumor cells. When erythropoiesis is induced in the long-term cultures by addition of anemic mouse serum before infection by polycythemia-inducing Friend virus, the generation of erythropoietin-independent CFU-E and erythrocyte formation is followed by the sustained production (greater than 40 wk) of primitive erythroid cells with low spontaneous levels (less than 5%) of hemoglobinization. Although these cells will produce spleen colonies in irradiated mice and can be cloned in soft-gel media, they do not produce autonomous, permanently growing cell lines in vitro, i.e., they retain a dependency upon the marrow-adherent layer for their continued growth. However, following a further passage on a "virgin" marrow environment, permanent cell lines can be established that are able to grow independently of environmental influences. Thus, this system is the first description of a complete in vitro system for the reproducible production and isolation of Friend virus-induced erythroid cell lines.
Dose-Dense Chemotherapy in Nonmetastatic Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: L. Bonilla, I. Ben-Aharon, L. Vidal, A. Gafter-Gvili, L. Leibovici, S. M. Stemmer
Journal: JNCI Journal of the National Cancer Institute (2010)

Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of the existing data from randomized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer. Randomized controlled trials that compared a dose-dense chemotherapy protocol with a standard chemotherapy schedule in the neoadjuvant or adjuvant setting in adult women older than 18 years with breast cancer were identified by searching The Cochrane Cancer Network register of trials, The Cochrane Library, and LILACS and MEDLINE databases (from January 1966 to January 2010). Hazard ratios (HRs) of death and recurrence and relative risks of adverse events were estimated and pooled. All statistical tests were two-sided. Ten trials met the inclusion criteria and were classified into two categories based on trial methodology. Three trials enrolling 3337 patients compared dose-dense chemotherapy with a conventional chemotherapy schedule (similar agents). Patients who received dose-dense chemotherapy had better overall survival (HR of death = 0.84, 95% confidence interval [CI] = 0.72 to 0.98, P = .03) and better disease-free survival (HR of recurrence or death = 0.83, 95% CI = 0.73 to 0.94, P = .005) than those on the conventional schedule. No benefit was observed in patients with hormone receptor–positive tumors. Seven trials enrolling 8652 patients compared dose-dense chemotherapy with regimens that use standard intervals but with different agents and/or dosages in the treatment arms. Similar results were obtained for these trials with respect to overall survival (HR of death = 0.85, 95% CI = 0.75 to 0.96, P = .01) and disease-free survival (HR of recurrence or death = 0.81, 95% CI = 0.73 to 0.88, P < .001). The rate of nonhematological adverse events was higher in the dose-dense chemotherapy arms than in the conventional chemotherapy arms. Dose-dense chemotherapy results in better overall and disease-free survival, particularly in women with hormone receptor–negative breast cancer. However, additional data from randomized controlled trials are needed before dose-dense chemotherapy can be considered as the standard of care.
Mediterranean Dietary Patterns and Cardiovascular Health
Authors: Jia Shen, Kobina A. Wilmot, Nima Ghasemzadeh, Daniel L. Molloy, Gregory Burkman, Girum Mekonnen, Maria C. Gongora, Arshed A. Quyyumi, Laurence S. Sperling
Journal: Annual Review of Nutrition (2015)

The Mediterranean dietary pattern has been linked with reduced cardiovascular disease incidence and mortality. Components of the Mediterranean diet associated with better cardiovascular health include low consumption of meat and meat products, moderate consumption of ethanol (mostly from wine), and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. Increasing evidence indicates that the synergy among these components results in beneficial changes in intermediate pathways of cardiometabolic risk, such as lipids, insulin sensitivity, oxidative stress, inflammation, and vasoreactivity. As a result, consumption of a Mediterranean dietary pattern favorably affects numerous cardiovascular disease risk factors, such as dyslipidemia, hypertension, metabolic syndrome, and diabetes. Moreover, strong evidence links this dietary pattern with reduced cardiovascular disease incidence, reoccurrence, and mortality. This review evaluates the current evidence behind the cardioprotective effects of a Mediterranean dietary pattern.
Bridging the Gap between Preclinical and Clinical Studies Using Pharmacokinetic–Pharmacodynamic Modeling: An Analysis of GDC-0973, a MEK Inhibitor
Authors: Harvey Wong, Laurent Vernillet, Amy Peterson, Joseph A. Ware, Lillian Lee, Jean-Francois Martini, Peiwen Yu, Congfen Li, Geoffrey Del Rosario, Edna F. Choo, Klaus P. Hoeflich, Yongchang Shi, Blake T. Aftab, Ron Aoyama, Sanh Tan Lam, Marcia Belvin, John Prescott
Journal: Clinical Cancer Research (2012)

GDC-0973 is a potent and selective mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor. Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to relate GDC-0973 plasma and tumor concentrations, tumor pharmacodynamics and antitumor efficacy to establish pharmacokinetic endpoints and predict active doses in the clinic.A PK-PD model was used to characterize GDC-0973 tumor disposition and in vivo potency in WM-266-4 xenograft mice. Simulations were conducted using the PK-PD model along with human pharmacokinetics to identify a target plasma concentration and predict active doses. In vivo potency and antitumor efficacy were characterized in A375 melanoma xenograft mice, and a population-based integrated PK-PD-efficacy model was used to relate tumor pharmacodynamics (%pERK decrease) to antitumor activity.GDC-0973 showed a sustained tumor pharmacodynamic response due to longer residence in tumor than in plasma. Following single doses of GDC-0973, estimated in vivo IC(50) values of %pERK decrease based on tumor concentrations in xenograft mice were 0.78 (WM-266-4) and 0.52 μmol/L (A375). Following multiple doses of GDC-0973, the estimated in vivo IC(50) value in WM-266-4 increased (3.89 μmol/L). Human simulations predicted a minimum target plasma concentration of 83 nmol/L and an active dose range of 28 to 112 mg. The steep relationship between tumor pharmacodynamics (%pERK decrease) and antitumor efficacy suggests a pathway modulation threshold beyond which antitumor efficacy switches on.Clinical observations of %pERK decrease and antitumor activity were consistent with model predictions. This article illustrates how PK-PD modeling can improve the translation of preclinical data to humans by providing a means to integrate preclinical and early clinical data.
Future Challenges to Protecting Public Health from Drinking-Water Contaminants
Authors: Eileen A. Murphy, Gloria B. Post, Brian T. Buckley, Robert L. Lippincott, Mark G. Robson
Journal: Annual Review of Public Health (2012)

Over the past several decades, human health protection for chemical contaminants in drinking water has been accomplished by development of chemical-specific standards. This approach alone is not feasible to address current issues of the occurrence of multiple contaminants in drinking water, some of which have little health effects information, and water scarcity. In this article, we describe the current chemical-specific paradigm for regulating chemicals in drinking water and discuss some potential additional approaches currently being explored to focus more on sustaining quality water for specific purposes. Also discussed are strategies being explored by the federal government to screen more efficiently the toxicity of large numbers of chemicals to prioritize further intensive testing. Water reuse and water treatment are described as sustainable measures for managing water resources for potable uses as well as other uses such as irrigation.