tbuckley/cabot-search huggingface dataset:
Diminished Immunoreactivity of <b>γ</b>-Glutamylcysteine Synthetase in the Airways of Smokers' Lung
Authors: Terttu Harju, Riitta Kaarteenaho-Wiik, Ylermi Soini, Raija Sormunen, Vuokko L. Kinnula
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Glutathione (GSH) plays a major role in protecting the airways against oxidative stress. The rate-limiting enzyme in de novo GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS), which is induced by acute exposure to GSH-depleting cytokines and oxidants, but downregulated by transforming growth factor beta and prolonged oxidant exposure, at least in vitro. Cell-specific expression or regulation of gamma-GCS may play an important role both in the defense against oxidants and in the pathogenesis of oxidant-associated airway diseases. In this study, the localizations of gamma-GCS heavy (gamma-GCS-HS) and light (gamma-GCS-LS) subunits were investigated by immunohistochemistry in 22 patients with chronic obstructive pulmonary disease (COPD), 20 smokers without COPD, and 13 lifelong nonsmokers. The ultrastructural distributions of both gamma-GCS subunits were assessed by immuno-electron microscopy. Both subunits were expressed most prominently in the large airways, and their ultrastructural localization was both cytoplasmic and along the plasma membrane. The expression of gamma-GCS-HS was stronger in the central bronchial epithelium than in the peripheral bronchioli (p = 0.020), or in alveolar macrophages (p = 0.008). The expression of gamma-GCS-HS in the central bronchial epithelium showed a tendency to be higher in nonsmokers compared with all smokers (p = 0.052). Alveolar macrophages of nonsmokers had higher levels of gamma-GCS-HS (p = 0.001) and gamma-GCS-LS (p = 0.001) than did smokers. The expression of gamma-GCS-HS in the central bronchial epithelium was more marked in nonsmokers than in patients with COPD (p = 0.015), the difference between smokers and patients with COPD was not significant. In conclusion, the heavy and light subunits of gamma-GCS are mainly expressed in the large airways. Their tendency to decrease in cigarette smokers may further predispose lung cells to ongoing oxidant stress, which contributes to the progression of lung injury.
Oxide Nanomembrane Hybrids with Enhanced Mechano‐ and Thermo‐Sensitivity for Semitransparent Epidermal Electronics
Authors: Minjoon Park, Kyungsik Do, Jaemin Kim, Donghee Son, Ja Hoon Koo, Jinkyung Park, Jun‐Kyul Song, Ji Hoon Kim, Minbaek Lee, Taeghwan Hyeon, Dae‐Hyeong Kim
Journal: Advanced Healthcare Materials (2015)

Oxide nanomembrane hybrids with enhanced mechano- and thermo-sensitivity for semitransparent epidermal electronics are developed. The use of nanomaterials (single wall nanotubes and silver nanoparticles) embedded in the oxide nanomembranes significantly enhances mechanical and thermal sensitivities. These mechanical and thermal sensors are utilized in wheelchair control and hypothermia detection, which are useful for patients with strokes.
PROLIFERATION OF DONOR MARROW AND THYMUS CELLS IN THE MYELOID AND LYMPHOID ORGANS OF IRRADIATED SYNGENEIC HOST MICE
Authors: Akikazu Takada, Yumiko Takada
Journal: The Journal of Experimental Medicine (1973)

CBA/HT(6)T(6) bone marrow cells (1 x 10(7)) or CBA/H bone marrow cells (1 x 10(7)) plus CBA/HT(6)T(6) thymus cells (5 x 10(7)) were injected intravenously into lethally (800 R) irradiated CBA/H mice. Chromosome analyses of dividing cells in the host lymphoid and myeloid organs were performed at intervals after irradiation. Donor marrow cells settled and proliferated in the host bone marrow, spleen, and lymph nodes soon after injection, but donor marrow cells did not proliferate in the host thymus until day 10; then host-type cells were quickly replaced by donor-type cells in the thymus by day 20. On the other hand, donor thymus cells settled and proliferated in the host thymus and lymph nodes soon after injection but they gradually disappeared from these organs. On day 20, a few donor-type dividing cells (of thymus origin) were found in the host lymphoid and myeloid organs.
Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children
Authors: GL Piacentini, A Bodini, S Costella, L Vicentini, P Mazzi, S Sperandio, AL Boner
Journal: European Respiratory Journal (1999)

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p&lt;0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.
KSHV- and EBV-associated germinotropic lymphoproliferative disorder
Authors: Ming-Qing Du, Tim C. Diss, Hongxiang Liu, Hongtao Ye, Rifat A. Hamoudi, José Cabeçadas, Henry Y. Dong, Nancy Lee Harris, John K. C. Chan, John W. Rees, Ahmet Dogan, Peter G. Isaacson
Journal: Blood (2002)
Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells.
Authors: E P Feener, J M Northrup, L P Aiello, G L King
Journal: Journal of Clinical Investigation (1995)

Angiotensin II (AII)- and Arg8-vasopressin (AVP)-regulated gene expression in vascular cells has been reported to contribute to vascular homeostasis and hypertrophy. In this report, AVP-induced expression of plasminogen activator inhibitor (PAI)-2 mRNA in rat microvessel endothelial (RME) cells was identified using differential mRNA display. Further characterization of vasoactive peptide effects on PAI expression revealed that AII stimulated a 44.8 +/- 25.2-fold and a 12.4 +/- 3.2-fold increase in PAI-2 mRNA in RME cells and rat aortic smooth muscle cells (RASMC), respectively. AII also stimulated a 10- and 48-fold increase in PAI-1 mRNA in RME cells and RASMC, respectively. These AII effects were inhibited by either Sar1, Ile8-angiotensin or the AT1 antagonist DuP 735, but were not significantly altered in the presence of the AT2 antagonist PD123319. AII stimulation of RASMC and RME cells also significantly increased both PAI-1 protein and PAI activity released to the culture medium. Inhibition of protein kinase C completely blocked PMA-stimulated induction of PAI-2 mRNA in both cell types and inhibited the AII-stimulated increase in RASMC by 98.6 +/- 2.8%. In contrast, protein kinase C inhibition only partially decreased the AII-stimulated PAI-2 expression in RME cells by 68.8 +/- 11.1%, suggesting that a protein kinase C-independent mechanism contributes to a 6.9 +/- 1.5-fold AII induction of PAI-2 expression in endothelial cells. AII and PMA also stimulated protein tyrosine phosphorylation in RME cells, and the tyrosine kinase inhibitor genistein partially blocked their induction of PAI-2 mRNA. These findings suggest that AII may regulate plasminogen activation in the vasculature by inducing both PAI-1 and PAI-2 expression.
Relationship between excessive erythrocytosis and acute mountain sickness: a field study
Authors: Xiao-Han Ding, Ji-Hang Zhang, Bin Cui, Lan Huang
Journal: Military Medical Research (2014)

Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness (AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and AMS following different durations of high-altitude exposure. A total of 692 healthy young Chinese men were recruited for the study in June and July of 2012 and were divided into the following five groups: I) the 24-h group (24 hours after arrival at Lhasa, 3,700 m, n = 261); II) the 7-d group (exposed at Lhasa, 3,700 m for seven days, n = 99); III) the re-exposure group (re-exposed at Yang Bajing, 4,400 m for seven days after >1 year of acclimation at 3,700 m,n = 94); IV) the acclimated group (>1 year of acclimation at 3,700 m, Lhasa, n = 42); and V) the sea-level control (control group, Chengdu, n = 196). Case report forms were used to record the subjects' demographic information and AMS-related symptoms. All of the subjects underwent routine blood tests. The red blood cell (RBC) count fell slightly but was not significant upon acute exposure to high altitude, whereas the hemoglobin concentration ([Hb]) increased significantly. After high-altitude re-exposure, both of the [Hb] and RBC count showed significant increases. The incidence of AMS was 65.1%, 26.3% and 51.1%, respectively in the 24-h, 7-d and re-exposure groups. The [Hb] (P = 0.024) and hematocrit (P = 0.017) were greater in the AMS+ individuals than in the AMS- individuals in 7-d group. A correlation analysis revealed that the [Hb] and hematocrit were closely related with AMS score in 7-d and re-exposure groups, while the RBC showed a correlation with AMS score only in the re-exposure group. The AMS incidence was lowest when the [Hb] was between 140 and 160 g/L in the 24-h and 7-d groups. AMS is associated with both [Hb] and excessive erythrocytosis. Additionally, our findings indicate the existence of an optimal [Hb] for preventing AMS.
Differentiation, phenotype, and function of interleukin-17–producing human Vγ9Vδ2 T cells
Authors: Nadia Caccamo, Carmela La Mendola, Valentina Orlando, Serena Meraviglia, Matilde Todaro, Giorgio Stassi, Guido Sireci, Jean Jacques Fournié, Francesco Dieli
Journal: Blood (2011)
Newly diagnosed cystic fibrosis in middle and later life.
Authors: B Hunt, D M Geddes
Journal: Thorax (1985)

Four patients with cystic fibrosis diagnosed in middle and later life are presented. All had chronic bronchopulmonary infection with a high sweat sodium concentration, and chest radiographic evidence of upper zone bronchiectasis. Two patients had pancreatic dysfunction. Sputum culture grew mucoid Pseudomonas aeruginosa in three patients and Haemophilus influenzae in one. Ages at diagnosis were 63, 42, 40, and 35 years. These patients confirm the possibility of occasional longevity in cystic fibrosis and emphasise the need to consider the diagnosis at all ages. They also provide encouragement for younger patients.
Engineering the cell–material interface for controlling stem cell adhesion, migration, and differentiation
Authors: Ramses Ayala, Chao Zhang, Darren Yang, Yongsung Hwang, Aereas Aung, Sumeet S. Shroff, Fernando T. Arce, Ratnesh Lal, Gaurav Arya, Shyni Varghese
Journal: Biomaterials (2011)
Transforming growth factor beta as endogenous growth inhibitor of chronic lymphocytic leukemia B cells.
Authors: M Lotz, E Ranheim, T J Kipps
Journal: The Journal of Experimental Medicine (1994)

Chronic lymphocytic leukemia (CLL) B cells are hyporesponsive or refractory to mitogens and growth factors in vitro. This study examined whether transforming growth factor beta (TGF-beta), a potent inhibitor of lymphocyte proliferation may play a role in the growth regulation of CLL B cells. CLL B cells from all donors treated expressed detectable TGF-beta 1 mRNA. In vitro release of TGF-beta by unstimulated cultures, or cultures stimulated by antibody to cell surface immunoglobulin (anti-mu) plus phorbol 12-myristate 13-acetate (PMA) was higher in CLL than in normal B cells. High levels of TGF-beta activity were also detected in plasma samples of CLL patients. The role of TGF-beta in growth regulation of CLL B cells was tested in assays using different B cell activators. Purified neoplastic B cells from most CLL patients proliferated in response to anti-mu, or the combination of anti-mu plus PMA. Levels of CLL B cell proliferation were lower than observed in normal B cells. Some CLL were refractory to these stimuli. Antibody to CD40 induced proliferation of CLL B cells from all donors tested when presented on Fc gamma RII (CDw32)-expressing L cells. Neutralizing antibodies to TGF-beta increased CLL B cell proliferation in the absence or presence of additional stimuli. These effects were dose dependent and specific. Exogenous TGF-beta completely inhibited CLL B cell proliferation induced by anti-mu, PMA, and anti-TGF-beta. CLL B cell proliferation induced by anti-CD40 was reduced by exogenous TGF-beta. However, even at high doses, TGF-beta did not completely inhibit the anti-CD40 effect. In summary, TGF-beta is overexpressed in CLL. CLL B cells are sensitive to TGF-beta and this cytokine functions as an autocrine growth inhibitor accounting at least in part for reduced proliferative responses of these leukemic cells and for the slow progression of the malignant process in vivo.
Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: An effective second-line regimen
Authors: M. Streit, U. Jaehde, S. Stremetzne, K. Ridwelski, H. Kerz, F. Strohbach, P. Hohenberger, F.M. Zwiebel, H. Hebart, R. Böthig, M. Kairies, D. Zillig, S. Schuchmann, S. Warnecke, E. Thiel, E.D. Kreuser
Journal: Annals of Oncology (1997)

A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks.From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial.In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months.This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.
Matrix Metalloproteinase-8 and -9 Are Increased at the Site of Abdominal Aortic Aneurysm Rupture
Authors: W. Richard W. Wilson, Marcus Anderton, Edward C. Schwalbe, J. Louise Jones, Peter N. Furness, Peter R.F. Bell, Matthew M. Thompson
Journal: Circulation (2006)

Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate.A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.
Aromatase Inhibitors for Breast Cancer Prevention
Authors: Jack Cuzick
Journal: Journal of Clinical Oncology (2005)

Many lines of evidence point to sex hormones as the key factors in breast carcinogenesis. Classic risk factors include age at menarche, first child birth, and menopause. Estrogens, especially estradiol, appear to be the main factor. Hormone replacement therapy increases breast cancer risk, especially when the combined pills using estrogen and progesterone are used. Weight is a risk factor for postmenopausal breast cancer,wherearomatizationofandrogens inadipose tissue is the major source of estrogen. The variability of serum oestrogen levels in postmenopausal women from the lowest to highest quintile (about a six-fold difference) is associated with a two-fold variation in breast cancer risk (Fig 1). Estrogen appears to be more closely linked with breast cancer than are the other steroid sex hormones, although theymay alsohave an independent role. Lastly, fourmajor trials using the estrogen agonist, tamoxifen, to block the activity of estrogen at the receptor have shown that about 50% of estrogen receptor (ER) -positive breast cancers (Fig 2A) can be prevented, although there appears to be little effect on ER-negative breast cancer (Fig 2B), leading to a 38% overall reduction in breast cancer. Although the use of tamoxifen has been effective in reducing the incidence of breast cancer, both in the contralateral breast for women with early breast cancer, and for those at high risk who have not had the disease, it is not without side effects, especially thromboembolic events and gynecologic symptoms, and this limits its utility in a prevention setting. Recently, the third-generation aromatase inhibitors (AIs) have been introduced into the treatment of breast cancer, and their greater efficacy compared to tamoxifen, along with a more favorable side-effect profile, make them attractive agents for use in breast cancer prevention.
Anti-IgE therapy protects against peanut allergy
Authors: N Goldsack
Journal: Thorax (2003)

▴ Leung DY, Sampson HA, Yunginger JW, et al . Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med2003;348:986–93 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Peanut induced anaphylaxis (believed to be an IgE mediated condition) may result in death. Mortality in this increasingly common illness is usually associated with accidental ingestion of the equivalent of one to two peanuts. This multicentred, double … [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa022613%26rft_id%253Dinfo%253Apmid%252F12637608%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa022613&link_type=DOI [3]: /lookup/external-ref?access_num=12637608&link_type=MED&atom=%2Fthoraxjnl%2F58%2F6%2F532.atom [4]: /lookup/external-ref?access_num=000181465200003&link_type=ISI
Anemia and Renal Insufficiency Are Independent Risk Factors for Death among Patients with Congestive Heart Failure Admitted to Community Hospitals
Authors: William M. McClellan, W. Dana Flanders, Robert D. Langston, Claudine Jurkovitz, Rodney Presley
Journal: Journal of the American Society of Nephrology (2002)

The purpose of this retrospective cohort study was to examine the associations among chronic kidney disease, anemia, and risk of death among patients with heart failure. Retrospective cohort study. Patients with a principal diagnosis of heart failure (ICD9 codes 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, and 428.xx) were included. Chronic kidney disease (CKD) was defined as a serum creatinine >1.4 mg/dl for women and >1.5 mg/dl for men. There were 665 eligible patients in the sample with a mean (SD) age of 75.7 (10.9) yr; 60% were women, 71% were white, and 38% had CKD. On admission, a hematocrit > or =40% was found for 30.3% of the patients; 22.9% had a hematocrit between 36% and 40%, 33.2% between 30% and 35%, and 13.6% had a hematocrit of <30%. The 1-yr death rates among individuals with and without CKD were 44.9% and 31.4%, respectively (relative risk [RR], 1.43; 95% confidence interval [CI], 1.17 to 1.75). The mortality at 1 yr was 31.2% for individuals with a hematocrit > or =40%; 33.8% (RR, 1.08; 95% CI. 0.79 to 1.47) for hematocrit 36 to 39%; 36.7% (RR, 1.17; 95% CI, 0.89 to 1.54) for hematocrit between 30 and 35%; and 50.0% (RR, 1.60; 95% CI, 1.19 to 2.16) for those with a hematocrit <30% (chi(2) for trend was 7.37; P = 0.007). Both hematocrit and serum creatinine were independently associated with increased risk of death during follow-up after controlling for other patient risk factors. In conclusion, CKD and anemia are frequent among older patients with heart failure and are independent predictors of subsequent risk of death.
Relationship between symptoms and ingestion of a meal in functional dyspepsia
Authors: R Bisschops, G Karamanolis, J Arts, P Caenepeel, K Verbeke, J Janssens, J Tack
Journal: Gut (2008)

A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representing a pathophysiologically homogeneous subgroup. The aim of the present study was to establish the time-course of symptoms in relation to meal ingestion, and to assess the relationship between self-reported meal-related symptoms and pathophysiological mechanisms in FD.218 FD patients (149 women, mean (SEM) age 39 (1) years) filled out a symptom questionnaire, including meal-induced aggravation. All patients underwent a gastric emptying breath test with severity (0-4) scoring of six symptoms (pain, fullness, bloating, nausea, burning and belching) at each sampling (15 min interval for 4 h). In 129 patients, gastric sensitivity and accommodation were assessed by barostat.The intensity of each FD symptom was significantly increased 15 min after the meal, compared with the premeal score, and remained elevated until the end of the measurement period (all p<0.05). The time-course of individual symptoms varied, with early peaks for fullness and bloating, intermediate peaks for nausea and belching, and late peaks for pain and burning. Meal-induced aggravation was reported by 79% of patients, and in these patients postprandial fullness, which peaked early, was the most intense symptom. In patients without self-reported meal-induced aggravation, epigastric pain, which had a delayed peak, was the most intense symptom and they had a lower prevalence of gastric hypersensitivity (27.5% vs 7.7%).Meal ingestion aggravates FD symptoms in the vast majority of patients, with symptom-specific time-courses. Postprandial fullness is the most severe symptom in patients reporting aggravation by a meal, while it is pain in those not reporting meal-related symptoms.