tbuckley/cabot-search huggingface dataset:
Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
Authors: Ruochuan Sun, Jifeng Wu, Yuanyuan Chen, Mingdian Lu, Shangxin Zhang, Daru Lu, Yongxiang Li
Journal: Molecular Cancer (2014)

Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca2+-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer. The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan–Meier method and Cox's proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro. 85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines. Our study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer.
Treatment-Associated Musculoskeletal and Vasomotor Symptoms and Relapse-Free Survival in the NCIC CTG MA.27 Adjuvant Breast Cancer Aromatase Inhibitor Trial
Authors: Vered Stearns, Judith-Anne W. Chapman, Cynthia X. Ma, Matthew J. Ellis, James N. Ingle, Kathleen I. Pritchard, G. Thomas Budd, Manuela Rabaglio, George W. Sledge, Aurélie Le Maitre, Jessica Kundapur, Pedro E.R. Liedke, Lois E. Shepherd, Paul E. Goss
Journal: Journal of Clinical Oncology (2014)

Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA.27 anastrozole- or exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS.MA.27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6- and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with χ(2) and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity.Patients were assessable if eligible for the MA.27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P > .10) in patients with or without baseline symptoms.In MA.27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms.
Cholecalciferol Treatment to Reduce Blood Pressure in Older Patients With Isolated Systolic Hypertension
Authors: Miles D. Witham, Rosemary J. G. Price, Allan D. Struthers, Peter T. Donnan, Claudia-Martina Messow, Ian Ford, Marion E. T. McMurdo
Journal: JAMA Internal Medicine (2013)

IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension.No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people.OBJECTIVE To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension.DESIGN Parallel group, double-blind, placebo-controlled randomized trial.SETTING Primary care clinics and hospital clinics.PARTICIPANTS Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011.INTERVENTIONS A total of 100 000 U of oral cholecalciferol or matching placebo every 3 months for 1 year.MAIN OUTCOMES AND MEASURES Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months.RESULTS A total of 159 participants were randomized (mean age, 77 years).Mean baseline office systolic blood pressure was 163/78 mm Hg.Mean baseline 25-hydroxyvitamin D level was 18 ng/mL.25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001).No significant treatment effect was seen for mean (95% CI) office blood pressure (-1 [-6 to 4]/-2 [-4 to 1] mm Hg at 3 months and 1 [-2 to 4]/0 [-2 to 2] mm Hg overall treatment effect).No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance).There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24).CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension.
Phase I Open-Label Study of Continuous Treatment with BIBF 1120, a Triple Angiokinase Inhibitor, and Pemetrexed in Pretreated Non–Small Cell Lung Cancer Patients
Authors: Peter M. Ellis, Rolf Kaiser, Yihua Zhao, Peter Stopfer, Steve Gyorffy, Nasser Hanna
Journal: Clinical Cancer Research (2010)

BIBF 1120 (planned brand name Vargatef) is a novel, oral, triple angiokinase inhibitor targeting three receptor classes involved in blood vessel formation. The objectives of this phase I, open-label dose-escalation study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of BIBF 1120 with pemetrexed in patients with recurrent advanced-stage non-small cell lung carcinoma.Patients harboring a tumor of any non-small cell lung carcinoma histology, previously treated with one first-line platinum-based chemotherapy regimen, received a BIBF 1120 starting dose of 100 mg bid (days 2-21) with pemetrexed 500 mg/m2 (day 1) over a 21-day cycle. Previous pemetrexed treatment was not permitted. BIBF 1120 dose was escalated until the MTD was determined.Twenty-six patients were treated. During treatment cycle (TC) 1, dose-limiting toxicities were experienced by one patient receiving 100 mg bid, one patient receiving 150 mg bid, one patient receiving 200 mg bid, and two patients receiving 250 mg bid BIBF 1120. Two additional dose-limiting toxicities were observed in TC 1 in an expanded patient cohort receiving 200 mg bid. Gastrointestinal disorders (84.6%), general disorders, and administration site conditions (76.9%) were the most frequent drug-related adverse events. One patient had a complete response 44 days after initiating trial medication; 50% had stable disease as the best overall response. No clinically relevant pharmacokinetic interactions between BIBF 1120 and pemetrexed were observed.The MTD of BIBF 1120 in combination with standard-dose pemetrexed was 200 mg bid. Continuous daily treatment with BIBF 1120 in this combination was tolerable, with promising signs of efficacy.
Redistribution of Cortical Blood Flow during Renal VasodNatation in Dogs
Authors: JOHN L MCNAY, YOUICHI ABE
Journal: Circulation Research (1970)

We studied the distribution of cortical blood flow during renal vasodilation induced by four maneuvers; reduction of perfusion pressure, intraarterial infusion of acetylcholine, and diuresis induced by ethacrynic acid or mannitol. Dogs were anesthetized with pentobarbital and urinary losses replaced. Bloodflow of the denervated kidney was measured by an electromagnetic flowmeter,and distribution of renal cortical blood flow analyzed by the radioactive microsphere technique. Acetylcholine caused progressively greater proportional vasodilation from superficial to deep cortex. The resulting pattern of flow redistribution was nearly identical to that observed in response to reduced perfusion pressure (autoregulation). Since the same pattern of heterogeneous cortical response was elicited by two qualitatively different stimuli, we propose that it reflects differential responsiveness of individual cortex zones. Ethacrynic acid redistributed flow in a different pattern, augmenting the proportion to the middle, but not the juxtamedullary cortex. High urine flow was excluded as a nonspecific basis for this difference, since acetylcholine produced its usual pattern of redistribution during the ethacrynic acid-induced diuresis. Additionally, ethacrynic acid-induced flow redistribution was not secondary to high urine flow per se, since mannitol diuresis did not significantly alter distribution of flow.
A real occupational illness..
Authors: A Mann
Journal: BMJ (1994)

EDITOR,- Though Peter Brooks is well known in Australia for his non-conformist views concerning repetitive strain injury (a term long discarded among medical practitioners in Australia in favour of the occupational overuse syndrome), this seems a poor reason for asking him to write an editorial in the BMJ.1 I would have thought that the few, one sided references in his editorial would have alerted the editor to the possibility of …
The effects on epidermal DNA synthesis of the butyrate esters of clobetasone and clobetasol, and the propionate ester of clobetasol
Authors: ROBERT C. MARSHALL, ANTHONY VIVIER
Journal: British Journal of Dermatology (1978)

An animal model for evaluating the effects of drugs on epidermal DNA synthesis has been used to determine the time of onset, period of maximum activity and duration of effect of two topically applied proprietary glucocorticosteroids, clobetasone butyrate and clobetasol propionate. Both drugs produced maximum inhibition of epidermal DNA synthesis by 24 h after application. Clobetasol propionate exhibited a significantly earlier onset (4 1/2 h) and longer duration (36 h) of activity than clobetasone butyrate (6 and 24 h respectively). A systemic effect was not observed at any time after the application of clobetasone butyrate but was observed for up to 24 h after the application of clobetasol propionate. Clobetasol butyrate was also assayed in this system and was found to be as potent as clobetasol propionate. It is concluded that the alcoholic, as opposed to the ketonic, grouping in the 11 positions of the steroid ring profoundly alters the potentials of this molecule for systemic activity.
Persistence of the Mitochondrial Lineage Responsible for the Irish Potato Famine in Extant New World Phytophthora infestans
Authors: Michael D. Martin, Simon Y.W. Ho, Nathan Wales, Jean B. Ristaino, M. Thomas P. Gilbert
Journal: Molecular Biology and Evolution (2014)

The plant pathogen Phytophthora infestans emerged in Europe in 1845, triggering the Irish potato famine and massive European potato crop losses that continued until effective fungicides were widely employed in the 20th century. Today the pathogen is ubiquitous, with more aggressive and virulent strains surfacing in recent decades. Recently, complete P. infestans mitogenome sequences from 19th-century herbarium specimens were shown to belong to a unique lineage (HERB-1) predicted to be rare or extinct in modern times. We report 44 additional P. infestans mitogenomes: four from 19th-century Europe, three from 1950s UK, and 37 from modern populations across the New World. We use phylogenetic analyses to identify the HERB-1 lineage in modern populations from both Mexico and South America, and to demonstrate distinct mitochondrial haplotypes were present in 19th-century Europe, with this lineage initially diversifying 75 years before the first reports of potato late blight.
Respiratory irritants encountered at work.
Authors: A. J. Taylor
Journal: Thorax (1996)

Respiratory irritants cause acute lung injury.Their effects are distinguished from hypersensitivity induced lung injury by their mech- anism of action -a direct toxic effect -and the speed of onset -within minutes or hours rather than months or years.Respiratory irritants may be inhaled or transported to the lungs by the circulation.This article focuses on the long term consequences of inhaled respiratory ir- ritants on the airways.Inhaled respiratory irritants provoke an acute inflammatory response with injury to the epi- thelial cells of the lungs.Depending on the site of uptake or deposition of the irritant, these effects predominantly involve the upper res- piratory tract and airways or the gas exchanging parts of the lungs (fig 1).Irritants may be inhaled as gases or vapours, solid particles, or liquid aerosols.In general, water soluble gases and vapours and particles of aerodynamic dia- meter greater than 5,m are deposited in the upper respiratory tract and proximal airways.Water insoluble gases, vapours and fumes, and particles whose aerodynamic diameter is 05-5,m can penetrate into and be deposited or taken up in peripheral airways and the gas exchanging parts ofthe lung.Irritants deposited or dissolved in the upper respiratory tract and proximal airways may cause injury to airway mucosal cells, exaggerated physiological re- sponses, an acute inflammatory reaction, or all three of these.Exaggerated physiological responses include cough (from stimulation of Respiratory irritantsUptake prc to solubilit
Selection of Breast Cancer Patients for Adjuvant Chemotherapy
Authors: R. Andrew Packard
Journal: JAMA (1977)

To aid in the selection of breast cancer patients for adjuvant chemotherapy, 263 patients with primary breast carcinoma undergoing curative surgery at the Yale-New Haven Medical Center were examined with respect to axillary lymph node involvement and prognosis. Thirty-five percent of patients with one to three axillary nodes histologycally involved with cancer relapsed within five years, as did 61% of patients with four or more cancer-positive nodes. Equally important was the clinical stage. Stage III patients had a poor prognosis (71% relapse rate) regardless of their axillary status. Stage I patients with metastasis to one to three axillary nodes did just as well as stage I patients with no nodal involvement (13% relapse rate). Relapse rates within the nodal categories are significantly less (<i>P</i>&lt;.05) than those reported by the National Surgical Adjuvant Breast Project. (<i>JAMA</i>238:1034-1036, 1977)
Labeled lines meet and talk: population coding of somatic sensations
Authors: Qiufu Ma
Journal: Journal of Clinical Investigation (2010)

The somatic sensory system responds to stimuli of distinct modalities, including touch, pain, itch, and temperature sensitivity. In the past century, great progress has been made in understanding the coding of these sensory modalities. From this work, two major features have emerged. First, there are specific neuronal circuits or labeled lines transmitting specific sensory information from the skin to the brain. Second, the generation of specific sensations often involves crosstalk among distinct labeled lines. These features suggest that population coding is the mechanism underlying somatic sensation.
Prognosis factors of recurrent pulmonary thromboembolism
Authors: Jin Zhang, Qiu lan Xie, Hai Tan
Journal: European Respiratory Journal (2014)

Objective  To assess the factors of recurrent pulmonary thromboembolism so as to reduce the recurrence  Methods  This retrospective study admitted patients with pulmonary thromboembolism(PE) at the General Hospital of Ningxia Medical University during January 2009 and December 2012. The patients were divided into recurrent pulmonary embolism group and non-recurrent pulmonary embolism group and their medical records were reviewed and compared.  Results  Twenty five of all 846 patients diagnosed as PE were dead and 683 finished follow-up visit. Of the 683 patients, 52 were recurrent PE and the remaining 631 were not occurred. Recurrence of PE was most likely to happen in 2 years since the first episode and then show a dropping tendency by years. Univariate analysis showed that chronic diseases, history of surgery or trauma, deep venous thromboembolism (DVT)/varicose veins, short duration of anticoagulant treatment, international normalized ratio (INR) not meeting the standard and idiopathic PE were related to pulmonary embolism recurrence. While multivariate unconditional logistic regression analysis indicated that associated with chronic medical diseases, DVT/varicose veins, idiopathic PE and short duration of anticoagulant treatment were independent impact factors. Twenty seven of 52 (51.9%) recurrent pulmonary embolism cases complicated with chronic thromboembolic pulmonary hypertension(CTEPH), Four of them died.  Conclusion  The patients with PE appear to be a very high prevalence tendence of recurrence in 2 years; The chronic medical illness, DVT/varicose veins, short duration of anticoagulant treatment and idiopathic PE are a major impact factors of PE prognosis.  Keywords: Pulmonary thromboembolism; recurrence; prognosis.
General considerations on rapid desensitization for drug hypersensitivity – a consensus statement
Authors: J. R. Cernadas, K. Brockow, A. Romano, W. Aberer, M. J. Torres, A. Bircher, P. Campi, M. L. Sanz, M. Castells, P. Demoly, W. J. Pichler
Journal: Allergy (2010)

To cite this article: Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ, for the European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. General considerations on rapid desensitization for drug hypersensitivity – a consensus statement. Allergy 2010; 65 : 1357–1366. Abstract Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high‐risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE‐mediated reactions, but also in reactions where drug‐specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI‐homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.
Atherosclerotic Abdominal Aortic Aneurysm and the Interaction Between Autologous Human Plaque-Derived Vascular Smooth Muscle Cells, Type 1 NKT, and Helper T Cells
Authors: Woon Ling Chan, Nada Pejnovic, Hamish Hamilton, Tze Vun Liew, Dusan Popadic, Alessandro Poggi, Shazia M. Khan
Journal: Circulation Research (2005)

Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic, and inflammatory nature of this disease of the cardiovascular system complicates targeted cellular therapy and emphasizes the need to understand the role and interaction of immune cells with VSMCs. We characterized the immune cell subsets present in human atherosclerotic tissue derived from atherosclerotic abdominal aortic aneurysm (AAA) and expanded them to study their interaction with autologous plaque-derived VSMCs in vitro. We show here that apart from T lymphocytes, plaque infiltrates consist of lots of NK cells and significant proportions of NKT cells that express T cell receptor (TCR) αβ, CD4, and the NK markers CD56 and CD161. The infiltrates are predominantly IFN-γ–producing Type 1 lymphoid cells. When cocultured, the T and NKT cells adhere to VSMCs. CD4 + T cells enhance VSMC proliferation. VSMCs in turn enhance CD4 + CD161 + NKT but not CD4 + or CD8 + T cell proliferation. CD4 + CD161 + NKT cells inhibit VSMC proliferation by inducing apoptosis. Our results suggest that the interactions of Type 1 CD4 + T and CD4 + CD161 + NKT cells with VSMCs may regulate VSMC proliferation and death respectively in atherosclerosis and the balance of these interactions could determine plaque stability.