tbuckley/cabot-search huggingface dataset:
Effects of aging on insulin synthesis and secretion. Differential effects on preproinsulin messenger RNA levels, proinsulin biosynthesis, and secretion of newly made and preformed insulin in the rat.
Authors: S Y Wang, P A Halban, J W Rowe
Journal: Journal of Clinical Investigation (1988)

Aging in men and rodents is associated with a marked decline in glucose stimulated insulin secretion by pancreatic beta cells (B cells). Secreted insulin is the end result of a series of steps along the biosynthetic protein-secretion pathway, including insulin gene transcription, processing of transcripts to preproinsulin mRNA, translation of mRNA, segregation and processing of newly made proinsulin in secretory vesicles, proinsulin to insulin conversion, transport of vesicles to the plasma membrane, and exocytosis. We have examined the influence of age at three stages along this pathway: preproinsulin mRNA levels, proinsulin synthesis, and secretion of newly made and preformed insulin, using Fischer rats, a widely studied rodent model of aging. Pancreatic weights and total insulin contents, islet sizes, and mean insulin content per islet were the same in young adult (4-5 mo) and senescent (21-22 mo) animals. There was no effect of age on preproinsulin mRNA levels in whole pancreata of fed animals, or in isolated islets cultured for 16 h in 5.5 mM glucose. Proinsulin biosynthesis and the secretion of newly made insulin were compared in isolated islets preincubated in 5.5 mM glucose. After a pulse label at 16.7 mM glucose, proinsulin synthesis, assayed by immunoprecipitation, was decreased 16% in 7 mo islets and 39% in 21-22 mo islets, compared with 4-5 mo islets, though total protein synthesis was not reduced. When chased at 2.8 mM glucose, 4-5 month and 21-22 mo islets showed no difference in release of preformed or newly made insulin. When chased at 16.7 mM glucose, there was a significant decrease in the secretion of newly made insulin in the old islets compared with the young islets. There was preferential release of newly made insulin over preformed insulin in both young and old islets. However, since secretion of preformed insulin was decreased much more than secretion of newly made insulin in senescent islets, these displayed a two- to threefold increase in the proportion of newly made insulin relative to total immunoreactive insulin released compared with young adult islets. The differential effects of aging on these steps in the insulin synthesis-secretion pathway may be due to varying impairments in signals transducing the glucose stimulus into the wide range of B cell responses to glucose.
P2-14-05: Racial Differences in the Use of Adjuvant Chemotherapy for Breast Cancer in a Large Urban Integrated Health System.
Authors: MS Simon, L Lamerato, R Krajenta, J Booza, J Ruterbusch, S Kunz, K Schwartz
Journal: Cancer Research (2011)

Abstract Background: Despite improvements in breast cancer treatment, there continues to be a gap in survival between African American (AA) and White women with breast cancer, which may be due at least in part to racial differences in the patterns of care. In order to better understand breast cancer survival disparities, we evaluated racial differences in the receipt of adjuvant chemotherapy among women treated at a large integrated health care system in Southeastern Michigan. Materials and Methods: The study population included 2,234 women (33 % AA) with stage I through III breast cancer treated at the Henry Ford Health System (HFHS) from 1996 through 2005. Linked datasets from the HFHS, the Metropolitan Detroit Cancer Surveillance System (MDCSS) and the U.S. Census Bureau were used to obtain sociodemographic and clinical information. Co-morbidity was assessed by the Charlson co-morbidity index (CCI), and economic deprivation was categorized using a neighborhood deprivation index (DI). Results: AA women were significantly more likely than Whites to have larger tumors (40% vs. 31% &amp;gt; 2 cm), as well as more aggressive tumors (29% vs 19% estrogen and progesterone negative). AA women were also significantly more likely than Whites to have other co-morbid conditions (15 % vs. 8% with a CCI of 2+) and to reside in a more economically deprived area (45% vs. 5% reside in the most deprived area). While AA women were more likely to receive adjuvant chemotherapy (47% vs. 43%, p=0.0278), they were also more likely to have a delay in initiation of treatment (57% vs 45% delayed beyond 60 days from diagnosis, p=0.0004). After multivariable adjustment for age, DI, CCI, insurance and surgery, there were no racial differences in treatment delay (Odds Ratio 1.20, 95% confidence interval, 0.82−1.77). Discussion: In a large urban integrated health care system, racial differences in the delay in receipt of adjuvant chemotherapy for breast cancer can be explained by clinical and socioeconomic characteristics. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-05.
Association between Traffic-Related Black Carbon Exposure and Lung Function among Urban Women
Authors: Shakira Franco Suglia, Alexandros Gryparis, Joel Schwartz, Rosalind J. Wright
Journal: Environmental Health Perspectives (2008)

Although a number of studies have documented the relationship between lung function and traffic-related pollution among children, few have focused on adult lung function or examined community-based populations.We examined the relationship between black carbon (BC), a surrogate of traffic-related particles, and lung function among women in the Maternal-Infant Smoking Study of East Boston, an urban cohort in Boston, Massachusetts.We estimated local BC levels using a validated spatiotemporal land-use regression model, derived using ambient and indoor monitor data. We examined associations between percent predicted pulmonary function and predicted BC using linear regression, adjusting for sociodemographics (individual and neighborhood levels), smoking status, occupational exposure, type of cooking fuel, and a diagnosis of asthma or chronic bronchitis.The sample of 272 women 18-42 years of age included 57% who self-identified as Hispanic versus 43% white, and 18% who were current smokers. Mean +/- SD predicted annual BC exposure level was 0.62 +/- 0.2 microg/m3. In adjusted analysis, BC (per interquartile range increase) was associated with a 1.1% decrease [95% confidence interval (CI), -2.5% to 0.3%] in forced expiratory volume in 1 sec, a 0.6% decrease (95% CI, -1.9% to 0.6%) in forced vital capacity, and a 3.0% decrease (95% CI, -5.8% to -0.2%) in forced mid-expiratory flow rate. We noted differential effects by smoking status in that former smokers were most affected by BC exposure, whereas current smokers were not affected.In this cohort, exposure to traffic-related BC, a component of particulate matter, independently predicted decreased lung function in urban women, when adjusting for tobacco smoke, asthma diagnosis, and socioeconomic status.
Microalbuminuria: Invalidity of Simple Concentration-Based Screening Tests for Early Nephropathy Due to Urinary Volumes of Diabetic Patients
Authors: Timo T Kouri, Jorma S A Viikari, Kari S Mattila, Kerttu M A Irjala
Journal: Diabetes Care (1991)

To evaluate the possibility of replacing quantitative albumin excretion rate (AER) measurements with rapid screening tests for microalbuminuria.Dipstick-negative specimens from 363 consecutive insulin-dependent diabetes mellitus (IDDM) and 46 non-insulin-dependent diabetes mellitus (NIDDM) patients from primary-care and hospital clinics (11% inpatients) within the district of Turku University Hospital were studied. Albumin concentrations and 12-h nightly excretion rates (N-AER) were measured by nephelometry (sensitivity 2 mg/L).An increased N-AER (greater than 15 micrograms/min) was seen in 99 IDDM (27%) and 15 NIDDM (33%) patients. The median urinary volume was 900 ml/12 h, with a maximum of 3000 ml. At the level of 20 mg albumin/L, the sensitivity to detect elevated N-AER was 70% among IDDM patients and 60% among NIDDM patients. At a lower albumin concentration of 10 mg/L, the sensitivities were increased to 91 and 87% in IDDM and NIDDM patients, respectively, but the specificities were reduced to 77 and 71%, respectively.To evaluate incipient nephropathy, we recommend quantitative measurements of N-AER from timed urine collections only. Dipstick tests are either insensitive or nonspecific.
Sustained Improvement in Perfusion and Flow Reserve After Temporally Separated Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1 Plasmid Deoxyribonucleic Acid
Authors: Alexandra H. Smith, Michael A. Kuliszewski, Christine Liao, Dmitriy Rudenko, Duncan J. Stewart, Howard Leong-Poi
Journal: Journal of the American College of Cardiology (2012)
Diesel Exhaust Particles Enhance Lung Injury Related to Bacterial Endotoxin through Expression of Proinflammatory Cytokines, Chemokines, and Intercellular Adhesion Molecule-1
Authors: Hirohisa Takano, Rie Yanagisawa, Takamichi Ichinose, Kaori Sadakane, Shin Yoshino, Toshikazu Yoshikawa, Masatoshi Morita
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Epidemiologic studies demonstrate acute and serious adverse effects of particulate air pollution on respiratory health, especially in people who are susceptible to bacterial infection. However, the underlying mechanism remains to be elucidated. To provide experimental evidence for the epidemiologic data, we determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEPs synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEPs further activated the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-kappaB) in the lung and increased the lung expression of intercellular adhesion molecule-1, interleukin-1beta, macrophage chemoattractant protein-1, keratinocyte chemoattractant (KC), macrophage inflammatory protein-1alpha, and Toll-like receptors. DEPs given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-kappaB. The combined exposure to DEPs and endotoxin decreased nuclear localization of CCAAT/enhancer binding protein beta. These results provide the first experimental evidence that DEPs enhance neutrophilic lung inflammation related to bacterial endotoxin. The enhancement is mediated by the induction of proinflammatory molecules, likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-kappaB, such as p65/p50.
123 Impact of liver transplantation (LT) on alcohol consumption (AC) in patients with pugh B cirrhosis: A randomized study
Authors: V. Di Martino, M. Miguet, C. Vanlemmens, E. Monnet, P. Gache, M. Messner, S. Hrusovsky, A. Minello, P. Hillon, S. Bresson-Hadni, J.P. Miguet
Journal: Journal of Hepatology (2004)
Varicella and Herpes Zoster in Same Patient
Authors: F. M. B. Allen
Journal: BMJ (1944)

JOURNAL115She was x-rayed again on June 9.This showed a rather large stomach, but no sign of any recurrence of the hernia.She has remained entirely free from gastric symptoms since her discharge from the hospital, and six months after the operation had had no further trouble. COMMENTThe case is interesting on account of the condition found at operation, where the stomach was twisted and enormously distended, and by the rapid recovery of the gastric func- tions in spite of the excessive stretching of the muEcular and mucous wall of the stomach.How the torsion had occurred
Abstract B79: TIMP-2 mediated growth inhibition of human glioma U87MG is accompanied by elevated IGFBP7 and FSP-1/S100A4 expression at the tumor/stroma interface
Authors: Sandra Jensen-Taubman, Dimitra Bourboulia, Huiying Han, Laurie Shuman Moss, Beiyang Wei, William G. Stetler-Stevenson
Journal: Cancer Research (2015)

Abstract The tissue inhibitor of matrix metalloproteinase–2 (TIMP-2) belongs to a small family of multifunctional secreted proteins that inhibit matrix metalloproteases (MMPs), proteases principally associated with promoting tumor invasion and metastasis. We have previously shown that forced TIMP-2 expression inhibits human lung tumor growth through MMP-independent mechanisms including tumor cell apoptosis and upregulation of insulin growth factor binding protein-7 (IGFPB7), a protein reported to function as a potential tumor suppressor in a variety of tumor types including human glioma. In the current study, we used immunohistochemistry, TUNEL assay, and dual immunofluorescence to assess the growth inhibitory effects of TIMP-2 in human glioma xenografts generated using U87MG cells lentivirally transfected to overexpress the human TIMP-2 cDNA sequence (U87MG-T2) or vector alone (U87MG-EV). Compared to EV controls, U87MG-T2 xenografts demonstrated a significant inhibition of tumor growth, accompanied by increased tumor cell apoptosis at the tumor edge. Moreover, a dramatic increase in IGFBP7 and fibroblast specific protein-1 (FSP1)/S100A4 was detected in distinct subpopulations of non-tumor cells at the tumor/stroma interface, whereas both markers were sparsely observed in U87MG-EV controls. In an effort to determine the origin of IGFBP7 positive cells, we performed dual immunofluorescence using antibodies to the blood vessel marker CD34, FSP-1/S100A4, and human mitochondria (clone 113-1). IGFBP7 positive cells did not co-express any of the three markers analyzed, indicating that IGFBP7 positive cells are host derived and consist of cells other than blood vessels or stromal fibroblasts. We conclude that endogenous TIMP-2 significantly inhibits human glioma tumor growth in vivo through tumor cell apoptosis and tumor-host interactions involving discrete subsets of non-tumor cells in the adjacent tumor microenvironment. Citation Format: Sandra Jensen-Taubman, Dimitra Bourboulia, Huiying Han, Laurie Shuman Moss, Beiyang Wei, William G. Stetler-Stevenson. TIMP-2 mediated growth inhibition of human glioma U87MG is accompanied by elevated IGFBP7 and FSP-1/S100A4 expression at the tumor/stroma interface. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B79. doi:10.1158/1538-7445.CHTME14-B79
Endarterectomy for asymptomatic carotid artery stenosis
Authors: C. S Kase, P. A Wolf
Journal: BMJ (1996)

county demanded that "swabs" be taken of all wards.Much reassurance was needed before they agreed to continue working * A patient colonised with methicillin resistant S aureus rang up in tears.Friends and relatives had refused to visit him and accused him of spreading a lethal infection.The patient had serious medical problems, and this was putting him under severe additional stress.Although the programme made many valid points about the increased pressure that these bacteria impose on hospitals, we fear that the overall image was distorted.The message that many of the public, and health care workers, received is that people colonised with these organisms are a danger to society and must be isolated, avoided, and labelled as unclean.This perception is erroneous and dangerous.Three years of work by one of us (JH) in educating nurses and other health care workers about a rational policy regarding methicillin resistant S aureus has been at least partly undermined.The producers of the programme should think hard about the message they have impressed on the public: stories about "doomsday killer bugs" may make good copy, but they cause much needless fear, suspicion, and panic.
Conditional Expression of K-<b> <i>ras</i> </b> in an Epithelial Compartment that Includes the Stem Cells Is Sufficient to Promote Squamous Cell Carcinogenesis
Authors: Lynn Vitale-Cross, Panomwat Amornphimoltham, Galen Fisher, Alfredo A. Molinolo, J. Silvio Gutkind
Journal: Cancer Research (2004)

Ras genes are the most frequently mutated oncogenes in human cancer. However, the contribution of ras to tumor initiation still is unclear because ras expression in primary cells can cause cell cycle arrest and even cell death by apoptosis. Furthermore, when expressed in the epidermis of mice, mutant ras promotes the formation of benign papillomas, only few of which will progress into carcinomas. However, in these cases, ras-transgene expression often is restricted to suprabasal or follicular epithelial cells that may lack self-renewal capacity. Thus, it still is conceivable that expression of active ras in other epithelial compartments may exert a distinct ability to promote malignant progression. To address this possibility, transgenic mice carrying the tetracycline-inducible system (tet-on receptor) targeted to the basal layer of stratified epithelium, which includes the epithelial stem cells, were engineered and crossed with mice expressing the K-ras(G12D) oncogene under the control of tet-regulated responsive elements. On doxycycline administration, proliferative lesions ranging from hyperplasias, papillomas, and dysplasias to metastatic carcinomas developed in squamous epithelia of the skin, oral mucosa, salivary glands, tongue, esophagus, forestomach, and uterine cervix within just 10 to 20 days. The most noticeable lesions were invasive squamous carcinomas of the skin and oral mucosa. These findings suggest that the expression of oncogenes in an epithelial compartment that includes the stem cells may be sufficient to promote squamous carcinogenesis. They also provide a molecularly defined conditional animal model system in which the mechanisms responsible for cancer initiation, maintenance, and metastatic spread can be readily investigated.
Uncover, discover and the growth of ideas
Authors: K Weber
Journal: Cardiovascular Research (2000)

Scientists can be one-legged. Busy at work. Heads bowed, minds focused, captivated by today's technologies. A self-imposed exile. Digging holes, building silos. No breadth of vision. Shortsighted, without insight. No sense of history. The archaic past, obsolete ancestors.

But one leg to stand on, one foot to put forward. A …
Needs of patients with learning disabilities are not being met
Authors: M. Lakhani, J. Bates
Journal: BMJ (1999)

EDITOR—Aspray et al are right to warn of the risk of “community chaos” in the management of patients with learning disabilities.1 We are a small practice with 31 such patients. Our practice has acquired a reputation for offering a caring approach to these patients, so we have tended to attract patients, often from outside our practice area. Difficulties in finding practices willing to register patients with learning disabilities have been reported to us. Patients often find it difficult to access the …
Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor
Authors: Ablajan Mahmut, Marie-Chloé Boulanger, Rihab Bouchareb, Fayez Hadji, Patrick Mathieu
Journal: Cardiovascular Research (2015)

AimsIn this study, we sought to determine the role of ecto-nucleotidases and adenosine receptors in calcific aortic valve disease (CAVD). The expression of ecto-nucleotidases, which modify the levels of extracellular nucleotides/nucleosides, may control the mineralization of valve interstitial cells (VICs). We hypothesized that expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1), which generates AMP, and 5′-nucleotidase (CD73), an enzyme using AMP as a substrate to produce adenosine, may co-regulate the mineralization of the aortic valve.
Quality of life in 6497 Nordic patients with psoriasis
Authors: R. Zachariae, H. Zachariae, K. Blomqvist, S. Davidsson, L. Molin, C. MOrk, B. Sigurgeirsson
Journal: British Journal of Dermatology (2002)

Journal Article Quality of life in 6497 Nordic patients with psoriasis Get access R. Zachariae, R. Zachariae Psycho‐oncology Research Unit, Aarhus University Hospital, Aarhus, Denmark Professor Robert Zachariae, Psycho‐oncology Research Unit, Aarhus University Hospital, Barthsgade 5,3, DK8200 Aarhus N, Denmark. E‐mail: bzach@aaa.dk Search for other works by this author on: Oxford Academic Google Scholar H. Zachariae, H. Zachariae Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar K. Blomqvist, K. Blomqvist Department of Dermatology, Helsinki University Hospital, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar S. Davidsson, S. Davidsson Department of Dermatology, University Hospital Reykjavik, Iceland Search for other works by this author on: Oxford Academic Google Scholar L. Molin, L. Molin Department of Dermatology, Örebro Medical Centre Hospital, Sweden Search for other works by this author on: Oxford Academic Google Scholar C. MØrk, C. MØrk Department of Dermatology, Rikshospitalet, Oslo, Norway Search for other works by this author on: Oxford Academic Google Scholar B. Sigurgeirsson B. Sigurgeirsson Department of Dermatology, University of Iceland (Representing Faeroe Islands) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 6, 1 June 2002, Pages 1006–1016, https://doi.org/10.1046/j.1365-2133.2002.04742.x Published: 01 June 2002 Article history Accepted: 27 November 2001 Published: 01 June 2002
Our Experiences of Dobutamine Stress Echocardiography
Authors: Hakan Akıllı, Mehmet Kayrak, Hajrudin Alibasiç, Alpay Arıbaş, Umuttan Doğan, Mehmet Yazıcı, Hasan Gök, Kurtuluş Özdemir
Journal: Journal of the American College of Cardiology (2013)
Colchicine for Recurrent Pericarditis (CORP)
Authors: Massimo Imazio
Journal: Annals of Internal Medicine (2011)

Background: Recurrence is the most common complication of pericarditis, affecting 10% to 50% of patients. Objective: To evaluate the efficacy and safety of colchicine for the secondary prevention of recurrent pericarditis. Design: Prospective, randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov registration number: NCT00128414) Setting: 4 general hospitals in urban areas of Italy. Patients: 120 patients with a first recurrence of pericarditis. Intervention: In addition to conventional treatment, patients were randomly assigned to receive either placebo or colchicine, 1.0 to 2.0 mg on the first day followed by a maintenance dose of 0.5 to 1.0 mg/d, for 6 months. Measurements: The primary study end point was the recurrence rate at 18 months. Secondary end points were symptom persistence at 72 hours, remission rate at 1 week, number of recurrences, time to first recurrence, disease-related hospitalization, cardiac tamponade, and rate of constrictive pericarditis. Results: At 18 months, the recurrence rate was 24% in the colchicine group and 55% in the placebo group (absolute risk reduction, 0.31 [95% CI, 0.13 to 0.46]; relative risk reduction, 0.56 [CI, 0.27 to 0.73]; number needed to treat, 3 [CI, 2 to 7]). Colchicine reduced the persistence of symptoms at 72 hours (absolute risk reduction, 0.30 [CI, 0.13 to 0.45]; relative risk reduction, 0.56 [CI, 0.27 to 0.74]) and mean number of recurrences, increased the remission rate at 1 week, and prolonged the time to subsequent recurrence. The study groups had similar rates of side effects and drug withdrawal. Limitation: Multiple recurrences and neoplastic or bacterial causes were excluded. Conclusion: Colchicine is safe and effective for secondary prevention of recurrent pericarditis. Primary Funding Source: Maria Vittoria Hospital, Torino, Italy.