tbuckley/cabot-search huggingface dataset:
Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma
Authors: M. Hoshino, Y. Fujita, J. Saji, T. Inoue, T. Nakagawa, T. Miyazawa
Journal: Allergy (2005)

Background: Goblet cell metaplasia is a pathologic characteristic of asthma, associated with excess mucus secretion. Interleukin (IL)‐4 and IL‐13 plays an important role in mucus hypersecretion. Suplatast tosilate (suplatast), an antiallergic agent, is a Th2 cytokine inhibitor that suppresses the synthesis of IL‐4, IL‐5, IL‐13, and eosinophilic airway inflammation. Objective: We examined the effects of suplatast on mucus production in bronchial biopsy specimens taken from asthmatic subjects. Methods: Oral suplatast 300 mg daily, or placebo was administered for 3 months in a double‐blind, parallel‐group study in 25 patients with asthma. Biopsy specimens were evaluated at before and after treatment for alcian blue/period acid‐Schiff (AB/PAS), MUC5AC staining in bronchial epithelium and IL‐4 + , IL‐13 + cells as well as inflammatory cells in lamina propria. Results: There were significant decreases in the percentage of AB/PAS ( P &lt; 0.01) and MUC5AC ( P &lt; 0.01) stained area in the suplatast group. These changes were accompanied by significant decreases in IL‐4 + and IL‐13 + cells in suplatast‐treated subjects. Additionally, we have observed that the number of infiltrating eosinophils and CD4 + T cells significantly decreased. Conclusions: These findings suggest that suplatast prevents goblet cell metaplasia through modulation of Th2 cytokine production and the recruitment of eosinophils and CD4 + T cells in the asthmatic airways.
Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trial
Authors: R. Ramos, K. I. Kennedy, C. M Visness
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To determine the contraceptive efficacy of the lactational amenorrhoea method. <b>Design</b>: Non-comparative prospective trial. <b>Setting</b>: Urban Manila, the Philippines. <b>Subjects</b>: 485 lower income, educated women with extensive experience of breast feeding. <b>Intervention</b>: Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used. <b>Main outcome measures</b>: Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method. <b>Results</b>: The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%. <b>Conclusions</b>: The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence. <h3>Key messages</h3> Henceforth, data from clinical trials on contra-ceptives must be subject to the rigours of multiple censoring such as applied here. By excluding periods of abstinence from the calculation of risk of pregnancy, the contraceptive protection of the method cannot be attributed to postpartum or lac- tational abstinence During the first year post partum, the rate of pregnancy before the return of menses in lactating women was less than 3%
Diaphragm Unloading via Controlled Mechanical Ventilation Alters the Gene Expression Profile
Authors: Keith C. DeRuisseau, R. Andrew Shanely, Nagabhavani Akunuri, Marc T. Hamilton, Darin Van Gammeren, A. Murat Zergeroglu, Michael McKenzie, Scott K. Powers
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Prolonged controlled mechanical ventilation results in diaphragmatic inactivity and promotes oxidative injury, atrophy, and contractile dysfunction in this important inspiratory muscle. However, the impact of controlled mechanical ventilation on global mRNA alterations in the diaphragm remains unknown.In these experiments, we used an Affymetrix oligonucleotide array to identify the temporal changes in diaphragmatic gene expression during controlled mechanical ventilation in the rat.Adult Sprague-Dawley rats were assigned to either control or mechanical ventilation groups (n = 5/group). Mechanically ventilated animals were anesthetized, tracheostomized, and ventilated with room air for 6 or 18 h. Animals in the control group were acutely anesthetized but not exposed to mechanical ventilation.Compared with control diaphragms, microarray analysis identified 354 differentially expressed, unique gene products after 6 and 18 h of mechanical ventilation. In general, genes in the cell growth/cell maintenance, stress response, and nucleic acid metabolism categories showed predominant upregulation, whereas genes in the structural protein and energy metabolism categories were predominantly downregulated.We conclude that mechanical ventilation results in rapid changes in diaphragmatic gene expression, and subsequently, many of these changes may contribute to atrophy and muscle fiber remodeling associated with unloading this primary inspiratory muscle. Importantly, this study also provides new insights into why the diaphragm, after the onset of contractile inactivity, atrophies more rapidly than locomotor skeletal muscles and also highlights unique differences that exist between these muscles in the mRNA response to inactivity.
Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis
Authors: Ignacio A. Rodriguez-Brenes, Natalia L. Komarova, Dominik Wodarz
Journal: Cancer Research (2014)

Mutations associated with hematopoietic malignancies have been repeatedly identified in healthy individuals. For certain cases, such as the t(14;18) translocation and monoclonal B-cell lymphocytosis, no clear link between the presence of aberrant cells and the later development of cancer has been established. Intriguingly, longitudinal studies suggest that these abnormalities persist for long periods of time in some individuals, but in others are transient in which they disappear completely. Here, we present a mathematical model, based on cellular replication limits, that provides a possible explanation for these seemingly contradictory findings. It proposes that the transient and persistent nature of the phenotypes depends on the stage in the differentiation pathway of a given lineage in which the mutation originates. Our work suggests that cellular replication limits may not only prevent cancer by aborting clonal expansion of cells, but also by influencing the fate of altered but nonneoplastic cells in healthy tissue.
Sharing of clinical trial data among trialists: a cross sectional survey
Authors: V. Rathi, K. Dzara, C. P. Gross, I. Hrynaszkiewicz, S. Joffe, H. M. Krumholz, K. M. Strait, J. S. Ross
Journal: BMJ (2012)

<b>Objective</b> To investigate clinical trialists' opinions and experiences of sharing of clinical trial data with investigators who are not directly collaborating with the research team. <b>Design and setting</b> Cross sectional, web based survey. <b>Participants</b> Clinical trialists who were corresponding authors of clinical trials published in 2010 or 2011 in one of six general medical journals with the highest impact factor in 2011. <b>Main outcome measures</b> Support for and prevalence of data sharing through data repositories and in response to individual requests, concerns with data sharing through repositories, and reasons for granting or denying requests. <b>Results</b> Of 683 potential respondents, 317 completed the survey (response rate 46%). In principle, 236 (74%) thought that sharing de-identified data through data repositories should be required, and 229 (72%) thought that investigators should be required to share de-identified data in response to individual requests. In practice, only 56 (18%) indicated that they were required by the trial funder to deposit the trial data in a repository; of these 32 (57%) had done so. In all, 149 respondents (47%) had received an individual request to share their clinical trial data; of these, 115 (77%) had granted and 56 (38%) had denied at least one request. Respondents' most common concerns about data sharing were related to appropriate data use, investigator or funder interests, and protection of research subjects. <b>Conclusions</b> We found strong support for sharing clinical trial data among corresponding authors of recently published trials in high impact general medical journals who responded to our survey, including a willingness to share data, although several practical concerns were identified.
Zinc-finger Nucleases as a Novel Therapeutic Strategy for Targeting Hepatitis B Virus DNAs
Authors: Thomas J Cradick, Kathy Keck, Shannon Bradshaw, Andrew C Jamieson, Anton P McCaffrey
Journal: Molecular Therapy (2010)

Hepatitis B virus (HBV) chronically infects 350–400 million people worldwide and causes >1 million deaths yearly. Current therapies prevent new viral genome formation, but do not target pre-existing viral genomic DNA, thus curing only ∼1/2 of patients. We targeted HBV DNA for cleavage using zinc-finger nucleases (ZFNs), which cleave as dimers. Co-transfection of our ZFN pair with a target plasmid containing the HBV genome resulted in specific cleavage. After 3 days in culture, 26% of the target remained linear, whereas ∼10% was cleaved and misjoined tail-to-tail. Notably, ZFN treatment decreased levels of the hepatitis C virus pregenomic RNA by 29%. A portion of cleaved plasmids are repaired in cells, often with deletions and insertions. To track misrepair, we introduced an XbaI restriction site in the spacer between the ZFN sites. Targeted cleavage and misrepair destroys the XbaI site. After 3 days in culture, ∼6% of plasmids were XbaI-resistant. Thirteen of 16 clones sequenced contained frameshift mutations that would lead to truncations of the viral core protein. These results demonstrate, for the first time, the possibility of targeting episomal viral DNA genomes using ZFNs. Hepatitis B virus (HBV) chronically infects 350–400 million people worldwide and causes >1 million deaths yearly. Current therapies prevent new viral genome formation, but do not target pre-existing viral genomic DNA, thus curing only ∼1/2 of patients. We targeted HBV DNA for cleavage using zinc-finger nucleases (ZFNs), which cleave as dimers. Co-transfection of our ZFN pair with a target plasmid containing the HBV genome resulted in specific cleavage. After 3 days in culture, 26% of the target remained linear, whereas ∼10% was cleaved and misjoined tail-to-tail. Notably, ZFN treatment decreased levels of the hepatitis C virus pregenomic RNA by 29%. A portion of cleaved plasmids are repaired in cells, often with deletions and insertions. To track misrepair, we introduced an XbaI restriction site in the spacer between the ZFN sites. Targeted cleavage and misrepair destroys the XbaI site. After 3 days in culture, ∼6% of plasmids were XbaI-resistant. Thirteen of 16 clones sequenced contained frameshift mutations that would lead to truncations of the viral core protein. These results demonstrate, for the first time, the possibility of targeting episomal viral DNA genomes using ZFNs.
The Integrin-blocking Peptide RGDS Inhibits Airway Smooth Muscle Remodeling in a Guinea Pig Model of Allergic Asthma
Authors: Bart G. J. Dekkers, I. Sophie T. Bos, Reinoud Gosens, Andrew J. Halayko, Johan Zaagsma, Herman Meurs
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. The mechanisms driving these changes are, however, incompletely understood. Recently, an important role for extracellular matrix proteins in regulating ASM proliferation and contractility has been found, suggesting that matrix proteins and their integrins actively modulate airway remodeling.Objectives: To investigate the role of RGD (Arg-Gly-Asp)–binding integrins in airway remodeling in an animal model of allergic asthma.Methods: Using a guinea pig model of allergic asthma, the effects of topical application of the integrin-blocking peptide RGDS (Arg-Gly-Asp-Ser) and its negative control GRADSP (Gly-Arg-Ala-Asp-Ser-Pro) were assessed on markers of ASM remodeling, fibrosis, and inflammation induced by repeated allergen challenge. In addition, effects of these peptides on human ASM proliferation and maturation were investigated in vitro.Measurements and Main Results: RGDS attenuated allergen-induced ASM hyperplasia and hypercontractility as well as increased pulmonary expression of smooth muscle myosin heavy chain and the proliferative marker proliferating cell nuclear antigen (PCNA). No effects were observed for GRADSP. The RGDS effects were ASM selective, as allergen-induced eosinophil and neutrophil infiltration as well as fibrosis were unaffected. In cultured human ASM cells, we demonstrated that proliferation induced by collagen I, fibronectin, serum, and platelet-derived growth factor requires signaling via RGD-binding integrins, particularly of the α5β1 subtype. In addition, RGDS inhibited smooth muscle α-actin accumulation in serum-deprived ASM cells.Conclusions: This is the first study indicating that integrins modulate ASM remodeling in an animal model of allergic asthma, which can be inhibited by a small peptide containing the RGD motif.
PPARα Activators Inhibit Tissue Factor Expression and Activity in Human Monocytes
Authors: Nikolaus Marx, Nigel Mackman, Uwe Schönbeck, Nurcan Yilmaz, Vinzenz Hombach, Peter Libby, Jorge Plutzky
Journal: Circulation (2001)

Background —Tissue factor (TF), expressed on the surface of monocytes and macrophages in human atherosclerotic lesions, acts as the major procoagulant initiating thrombus formation in acute coronary syndromes. Peroxisome proliferator–activated receptor-α (PPARα), a nuclear receptor family member, regulates gene expression in response to certain fatty acids and fibric acid derivatives. Given that some of these substances reduce TF activity in patients, we tested whether PPARα activators limit TF responses in human monocytic cells. Methods and Results —Pretreatment of freshly isolated human monocytes or monocyte-derived macrophages with PPARα activators WY14643 and eicosatetraynoic acid (ETYA) led to reduced lipopolysaccharide (LPS)-induced TF activity in a concentration-dependent manner (maximal reduction to 43±8% with 250 μmol/L WY14643 [ P &lt;0.05, n=5] and to 42±12% with 30 μmol/L ETYA [ P &gt;0.05, n=3]). Two different PPARγ activators (15-deoxy _Δ12,14 -prostaglandin J 2 and BRL49653 ) lacked similar effects. WY14643 also decreased tumor necrosis factor-α protein expression in supernatants of LPS-stimulated human monocytes. Pretreatment of monocytes with WY14643 inhibited LPS-induced TF protein and mRNA expression without altering mRNA half-life. Transient transfection assays of a human TF promoter construct in THP-1 cells revealed WY14643 inhibition of LPS-induced promoter activity, which appeared to be mediated through the inhibition of nuclear factor-κB but not to be due to reduced nuclear factor-κB binding. Conclusions —PPARα activators can reduce TF expression and activity in human monocytes/macrophages and thus potentially reduce the thrombogenicity of atherosclerotic lesions. These data provide new insight into how PPARα-activating fibric acid derivatives and certain fatty acids might influence atherothrombosis in patients with vascular disease.
The Relationship Between Neutrophil / Lymphocyte Ratio and Myocardial Ischemia Detected in Dobutamine Stress Echocardiography
Authors: Hakan Akıllı, Mehmet Kayrak, Hajrudin Alibasiç, Alpay Arıbaş, Oğuzhan Yıldırım, Mustafa Karanfil, Ahmet Lütfi Sertdemir, Ufuk Tan Bayram, Kurtuluş Özdemir, Hasan Gök
Journal: Journal of the American College of Cardiology (2013)
Pollen Seasons: Forecasts of the Most Important Allergenic Plants in Finland
Authors: A. Koivikko, R. Kupias, Y. Mäkinen, A. Pohjola
Journal: Allergy (1986)

Occurrence of airborne pollen in Finland has been studied for 10 years in Turku (southern Finland), 8 years in Oulu, 4 years in Kuopio (central Finland) and 7 years at Kevo (northern Lapland). Observations on the pollen seasons of alder, birch, grasses and mugwort are presented. All these pollens occur in south and mid‐ Finland in quantities capable of causing allergy symptoms. Except for birch pollen, allergenic pollens occur in far lower concentrations than in central Europe. In northern Lapland only birch and pine pollen concentrations are high. Pollens may occur without signs of local flowering when there are southerly winds. This findings suggests that long‐distance transport is an essential contributing factor to the occurrence of pollens. There are wide year‐to‐year variations in the start of pollen seasons could very much depend on the mean temperature in April. However, a forecasting model based on this and other spring‐time temperature parameters often fails to give sufficiently accurate forecasts.
Dying and Dementia
Authors: Joanne Lynn
Journal: JAMA (1986)

Volicer et al,<sup>1</sup>in this issue ofThe Journal, report a remarkably practical, commonsense experience in limiting potentially life-extending treatments for persons with advanced senile dementia of the Alzheimer's type. Debate about forgoing life-extending treatment has recently been impaired by the irrational pretense, especially evident with "Baby Doe,"<sup>2</sup>that severe and permanent mental disability should not have a bearing on medical treatment choices. If future policy evidences more wisdom about this issue, we shall look back on this era as a temporary aberration during which it was easier to get resuscitation or extensive surgery for an older person than to provide a balanced meal or a pair of eyeglasses. On the way to that better future, caution and thoughtful reflection are essential. Although Volicer and colleagues have made significant strides, their path includes some pitfalls. For example, they present the central issue as one of refusing certain modes
CARCINOMA OF THE COLON COMPLICATING CHRONIC ULCERATIVE COLITIS
Authors: Elden C. Weckesser
Journal: JAMA (1953)

The development of carcinoma of the colon in patients suffering from chronic ulcerative colitis has been the subject of much discussion since it was reported by Bargen<sup>1</sup>in 1928. This report comprises a brief review of the literature on the subject and the experience at University Hospitals of Cleveland during a 19 year period (1932-1950). In the table is a summary of the reports in which the over-all incidence of carcinoma in patients with ulcerative colitis is given. The large number of cases reported by Lynn<sup>2</sup>constitutes a review of the literature up to 1945. Ten additional series found in the recent literature, in addition to our own cases, are also shown. The over-all incidence of carcinoma of the colon among 4,806 hospitalized patients with ulcerative colitis was 1.9%. The highest over-all incidence of carcinoma of the colon in ulcerative colitis was 6.3% among 95 children reported by
Gallium-67 for Localization of Septic Lesions
Authors: RICHARD L. LITTENBERG
Journal: Annals of Internal Medicine (1973)

Gallium-67 citrate was administered intravenously to 12 septic patients. Gamma camera scintiphotos and rectilinear scans showed focal accumulation of the gallium in 11 of the patients. In all 11 the region delineated by scan subsequently proved to be the source of the sepsis. The only patient with a negative scan had typhoid fever with hepatitis and no focal source for sepsis. These results indicate that 67Ga scanning can be a useful, noninvasive method to aid in the diagnostic evaluation of the septic patient.
Cerebral embolus after traction injury to the arm.
Authors: M. A. Edgar, M. Joyce
Journal: BMJ (1969)

BRIINsH 805 negative.Plasma calcium and potassium were normal both at the beginning and at the end of dialysis.Predialysis magnesium, how- ever, was 2 5 mg/100 ml. (normal range 1-7-21 mg./100 ml.), and this fell to 1P3 mg./100 ml. at the end of dialysis (see Table ).Magnesium Concentrations (mg./100 ml.) Present Patient Range of 6 Other Dialysis Before After
Diagnosis and Monitoring of Whipple Disease by Polymerase Chain Reaction
Authors: Nizar N. Ramzan
Journal: Annals of Internal Medicine (1997)

Background: Whipple disease is a chronic, multisystem disorder associated with infection with Tropheryma whippelii, an organism that has not yet been grown on artificial media. In some cases, the diagnosis of Whipple disease is uncertain if it is based on histology alone. Although antibiotic regimens of various durations have been used, the disease recurs in about one third of cases. No test for cure is available. Objective: To develop a test that is more sensitive and specific than histologic examination to diagnose Whipple disease and monitor the effects of antibiotic therapy. Design: Retrospective, laboratory-based evaluations of stored tissue specimens. Patients: 30 patients with clinically diagnosed, histologically confirmed Whipple disease and 8 patients in whom Whipple disease was clinically suspected but who did not have definitive histologic evidence. Measurements: Pretreatment and post-treatment biopsy specimens of the small bowel and lymph node were tested by polymerase chain reaction for the presence of T. whippelii DNA. Results: Results on PCR were positive in 29 of the 30 specimens from patients with histologically confirmed disease (sensitivity, 96.6%; specificity, 100%) and in 7 of the 8 specimens from patients in whom disease was clinically suspected. Small-bowel biopsy specimens were obtained after treatment from 17 patients (median duration of follow-up, 119 months); specimens from 12 of these patients had positive results on PCR. When these cases were correlated with therapeutic outcome, it was found that 7 of the 12 patients had clinical relapse during subsequent follow-up or had never responded to treatment (positive predictive value, 58% [95% CI, 28% to 85%]). In contrast, none of the 5 patients whose post-treatment biopsy specimens had negative results on PCR had relapse (negative predictive value, 100% [CI, 48% to 100%]; P = 0.044). No correlation was found between post-treatment histology and clinical outcome (P > 0.2). Conclusions: Polymerase chain reaction is highly sensitive and specific when used to confirm the diagnosis of Whipple disease, to identify inconclusive and suspicious cases, and to monitor response to therapy. A negative result on PCR may predict a low likelihood of clinical relapse; a positive test result that remains positive despite therapy may be associated with a poor clinical outcome. Histopathologic evaluation of post-treatment specimens does not predict clinical cure or relapse.
Oral squamous cell carcinoma and hyperkeratotic lesions with BRAF inhibitors
Authors: E. Vigarios, L. Lamant, J.P. Delord, J.C. Fricain, C. Chevreau, B. Barrés, C. Gomez-Roca, M. Boulanger, V. Sibaud
Journal: British Journal of Dermatology (2014)