tbuckley/cabot-search huggingface dataset:
Abstract 297: Loss of giant obscurins expression in breast epithelium disrupts epithelial junctions and promotes cell motility and invasion.
Authors: Marey Shriver, Kimberly Stroka, Konstantinos Konstantopoulos, Aikaterini Kontrogianni-Konstantopoulos
Journal: Cancer Research (2013)

Abstract Obscurin A (∼720kDa) and B (∼870kDa) are giant multidomain proteins, encoded by the single OBSCN gene, originally shown to play important roles in the structural organization and contractile activity of striated muscles. Early studies have indicated that the OBSCN gene is highly mutated in different types of cancers. In light of this observation, our laboratory set forth to examine the expression profile and roles of giant obscurins in normal and cancer breast tissue. Obscurins are readily expressed in breast epithelial cells, but their expression is dramatically diminished in breast cancer cells. Down-regulation of obscurin A and B using small hairpin RNAs (shRNAs) in non-tumorigenic MCF10A breast epithelial cells resulted in decreased protein expression of β-catenin and E-cadherin, which are major components of adherens junctions and have been heavily implicated in the formation and metastasis of breast tumors. Specifically, β-catenin exhibited a preferential nuclear accumulation accompanied by a concomitant loss from cell-cell junctions. Additionally, loss of obscurins led to alterations in the expression levels and localization of multiple proteins associated with epithelial to mesenchymal transition (EMT). Obscurin-deficient MCF10A cells showed significantly increased motility in 2-Dimensional (2-D) substrata and confined spaces, and invasion through a matrigel coated chamber. Consistent with this, actin filaments re-distributed to extending filopodia-like protrusions where they exhibited increased dynamics. Taken together, our findings indicate that loss of giant obscurins from breast epithelium results in disruption of cell contacts and acquisition of a mesenchymal phenotype that leads to enhanced migration and invasiveness. Citation Format: Marey Shriver, Kimberly Stroka, Konstantinos Konstantopoulos, Aikaterini Kontrogianni-Konstantopoulos. Loss of giant obscurins expression in breast epithelium disrupts epithelial junctions and promotes cell motility and invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 297. doi:10.1158/1538-7445.AM2013-297
A breath for health: an exploratory study in severe asthma patients in Turkey
Authors: S. Bavbek, Z. Mısırlıgil
Journal: Allergy (2008)

Background: Severe asthma puts enormous burden on patients. To evaluate asthma‐related restrictions on patients’ daily lives along with their expectations about future asthma care. Methods: A structured questionnaire was administered to severe asthma patients at 25 centers across Turkey. The patients were divided into; uncontrolled ( n : 274) and controlled asthma ( n : 177) according to the existence of symptoms despite the GINA step 4 or 5 treatment. Results: A total of 451 patients (F/M: 337/114, mean age: 47.6 ± 13.2 years) were included; 93% were nonsmokers and 51.2% were atopic. Chronic rhino‐sinusitis, ASA/NSAID sensitivity, and osteoporosis were significantly higher in uncontrolled patients. Nearly 70% of the uncontrolled asthmatics defined asthma as disturbing with significant restrictions in daily life. The most important role for medication was symptom relief. One inhaler or one tablet a month was the most preferred form of drug usage. In addition, 30.6% of the patients had tried alternative treatment with herbal remedies. Although patients were willing to become members of an asthma association, they expected the Turkish government to provide special asthma clinics and fund research into new treatments. Controlled patients achieved or were close to achieving asthma control goals. Uncontrolled patients seemed to be more pessimistic in this respect, but they reserved significant levels of hope for the future. Two‐thirds of all the patients thought that they would receive better treatment in the next 5 years. Conclusions: In this study group, severe asthma patients face significant limitations in their daily lives, but they are optimistic about better asthma control and treatment options in the future.
Left Ventricular Structure and Function in Transthyretin-Related Versus Light-Chain Cardiac Amyloidosis
Authors: Candida Cristina Quarta, Scott D. Solomon, Imran Uraizee, Jenna Kruger, Simone Longhi, Marinella Ferlito, Christian Gagliardi, Agnese Milandri, Claudio Rapezzi, Rodney H. Falk
Journal: Circulation (2014)

Background— Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. Methods and Results— We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (−11±3% and −12±4%, respectively, P =0.54) than in ATTRm (−15±4%, P &lt;0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors. Conclusions— In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.
Medicolegal Application of Human Blood Grouping
Authors: Reuben Ottenberg
Journal: JAMA (1983)

In 1910, von Dungern and Hirschfeld<sup>1</sup>discovered that the substances A and B present in human red blood cells (on whose presence or absence the so-called blood grouping depends) are inherited according to Mendel's law. They studied 348 persons belonging to seventy-two different families. (The families were those of university professors or members of their research institute, and each family is identified in their article.) They observed that: A never occurs in a child if not present in one of the parents; the same is true of B. When one of these substances is present in both parents, it occurs in most of the children. When only one parent has one of these particular substances, some of the children inherit it. When a particular substance is absent from both parents, no child ever has it. They were forced to the conclusion that Mendel's law holds for these blood qualities, on
Reversible Chorea and Focal Dystonia in Vitamin B<sub>12</sub>Deficiency
Authors: Claudio Pacchetti, Silvano Cristina, Giuseppe Nappi
Journal: New England Journal of Medicine (2002)

To the Editor: A 71-year-old man presented in June 2000 with a two-month history of progressive right hemichorea. His medical history included a resection for gastric cancer at the age of 55 years. Neurologic examination revealed a postural, symmetric, rapid tremor of the hands; choreic movements of the right upper limb and right toes; and moderate hypopallesthesia in the four limbs. The results of laboratory tests showed a macrocytic anemia: erythrocytes, 4.15×106 per microliter (normal range, 4.7 to 6.1); mean corpuscular volume, 102.4 fl (normal range, 80 to 94); a normal hemoglobin level; and vitamin B12, 124 pg . . .
TPEAK TO TEND INTERVAL IS A SHORT TERM PROGNOSTIC FACTOR OF CARDIAC DEATH IN ACUTE HEART FAILURE SYNDROME PATIENTS WITH REDUCED EJECTION FRACTION
Authors: Soichiro Aoki, Masaki Sakakibara, Shogo Yamaguchi, Tsuyoshi Yokoi, Shinsuke Takeuchi, Naoki Iwakawa, Masaki Takenaka, Katsuhide Kitagawa, Yasushi Jinno
Journal: Journal of the American College of Cardiology (2015)
Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis
Authors: Tim O. Lankisch, Jochen Metzger, Ahmed A. Negm, Katja Voβkuhl, Eric Schiffer, Justyna Siwy, Tobias J. Weismüller, Andrea S. Schneider, Kathrin Thedieck, Ralf Baumeister, Petra Zürbig, Eva M. Weissinger, Michael P. Manns, Harald Mischak, Jochen Wedemeyer
Journal: Hepatology (2010)

Abstract Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease-specific peptide patterns in patients with choledocholithiasis (n = 16), PSC (n = 18), and CC (n = 16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis [n = 14], PSC [n = 18] and CC [n = 25]). Peptides were characterized by sequencing. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98, P = 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) in the independent cohort, resulting in an AUC value of 0.87 (95% CI: 0.73-0.95, P = 0.0001) in ROC analysis. Eight out of 10 samples of patients with CC complicating PSC were identified. Conclusion: Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC. (Hepatology 2010;)
Primary Biliary Cirrhosis -- A First Step in Prolonging Survival
Authors: Marshall M. Kaplan
Journal: New England Journal of Medicine (1994)

Primary biliary cirrhosis, a progressive cholestatic liver disease that primarily affects middle-aged women, has been called a “model autoimmune disease”1. The numerous abnormalities of the humoral and cellular immune systems include elevated serum levels of immunoglobulins, multiple circulating autoantibodies, granulomas in the liver and regional lymph nodes, and impaired regulation of both B and T lymphocytes1,2. The chronic cholestasis is due to relentless destruction of small and medium-sized bile ducts mediated by activated T lymphocytes, both CD4 and CD8 cells2. In contrast to hepatocytes, bile ducts lack the ability to regenerate when they are destroyed, or . . .
Variant Cystic Fibrosis Phenotypes in the Absence of<i>CFTR</i>Mutations
Authors: Joshua D. Groman, Michelle E. Meyer, Robert W. Wilmott, Pamela L. Zeitlin, Garry R. Cutting
Journal: New England Journal of Medicine (2002)

Cystic fibrosis is a life-limiting autosomal recessive disorder with a highly variable clinical presentation. The classic form involves characteristic findings in the respiratory tract, gastrointestinal tract, male reproductive tract, and sweat glands and is caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR ) gene. Nonclassic forms of cystic fibrosis have been associated with mutations that reduce but do not eliminate the function of the CFTR protein. We assessed whether alteration in CFTR function is responsible for the entire spectrum of variant cystic fibrosis phenotypes.
Chronic life stress and treatment outcome in agoraphobia with panic attacks
Authors: S L Wade, S M Monroe, L K Michelson
Journal: American Journal of Psychiatry (1993)

Factors associated with response to treatment for agoraphobia are as of yet poorly understood. The authors investigated the relationship between chronic forms of life stress and clinical improvement and recovery in subjects with agoraphobia.Subjects meeting the DSM-III criteria for agoraphobia with panic attacks (N = 73) completed measures of life stress, agoraphobic symptoms, and depressive symptoms at the initiation and completion of the 12-week treatment protocol. Chronic stressors were assessed during intensive structured interviews 3-5 years after the completion of treatment and were rated by using a reliable, and previously validated, contextual rating system. The contextual life stress interview was completed by 54 subjects. The relationship of chronic forms of stress to treatment response was assessed by comparing symptomatic improvement in the subjects who had and had not experienced chronic stressors.Of the 54 subjects, 23 (43%) reported chronic stressors of marked or moderate severity. Subjects experiencing chronic stressors evidenced less improvement after treatment on both self-report and objective indexes of agoraphobic symptoms. Additionally, more subjects identified as nonrecovered experienced chronic stressors than did recovered subjects.Chronic stressors appear to predict a relatively unfavorable treatment outcome, as defined by higher levels of symptoms after treatment, less improvement, and less likelihood of recovery. These results have important implications for enhancing psychotherapeutic outcomes.
Sclerotherapy of Esophageal Varices
Authors: HARVEY J. DWORKEN
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 June 1984Sclerotherapy of Esophageal VaricesHARVEY J. DWORKEN, M.D.HARVEY J. DWORKEN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-6-915_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recently published recommendation on endoscopic sclerotherapy of esophageal varices (1) presents a complete and accurate picture of the current status of this important procedure. There is, however, one omission I would like to correct, and that is the necessity for continued expert attention to patients after sclerotherapy. At times, bleeding may be aggravated by sclerotherapy, and at other times it may recur several hours afterwards. An experienced endoscopist must be available to provide further treatment. This warning is particularly relevant to hospitals where endoscopists with adequate training in sclerotherapy may not be easily available at all...Reference1. . Endoscopic sclerotherapy for esophageal varices. Ann Intern Med. 1984;100:608-10. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1984Volume 100, Issue 6Page: 915-915KeywordsHemorrhage Issue Published: 1 June 1984 PDF DownloadLoading ...
508. Development of Optimized AAV2 Vector Biosynthesis and Purification Processes To Support High Capacity Production of Clinical Vectors of High Purity and Potency
Authors: Bernd Hauck, Jitin Bajaj, Sonali Joyce, Guang Qu, Olga A. Zelenaia, Katherine A. High, J. Fraser Wright
Journal: Molecular Therapy (2006)

With the objective of establishing a capability to produce clinical grade gene transfer vectors, we have developed and implemented a novel AAV2 vector manufacturing process that enables scalable production and purification of AAV vectors of high purity, potency and safety. Biosynthesis of vector particles is achieved using transient transfection of HEK293 cells in the absence of helper virus. Our helper and packaging plasmids, in conjuction with an optimized transfection protocol, enable biosynthesis of approx. 100,000 vg per cell. The complete harvest (cells and media) is concentrated 5- fold and diafiltered by tangential flow filtration using a 100kDa NMWC membrane. Following cell lysis and clarification, AAV2 particles (vectors and empty particles) are separated from host cellular impurities by cation exchange chromatography. Highly efficient nuclease digestion is achieved by adding Benzonase to the column bound vector under conditions optimized to remove residual nucleic acids. This step was found to be highly effective for the removal of trace levels of vector-associated nucleic acids (host cellular and residual plasmid DNA) implicated in aggregation of subsequently purified vector particles. The eluate from the cation exchange resin is then subjected to a single gradient CsCl ultra-centrifugation step to separate empty capsids from the vector particles. In light of recent studies that AAV2 capsid protein contains epitopes recognized by cytotoxic T cells in a hemophilia B clinical study (Manno et al., Nat. Med. 2006), we have included the gradient step because we believe that removal of excess viral capsids reduces the potential for vector immunogenicity. A single gradient ultracentrifugation using laboratory scale equipment is sufficient to process (ie. remove empty capsid from) up to 1.0 E15 vg per centrifugation run, providing sufficient capacity to support clinical trials for current applications. A series of AAV2-hFIX vectors lots produced using this process gave a high degree of consistency in purity as assessed by SDS-PAGE silver staining analysis and potency as assessed in vitro by transduction of HepG2 cells, and in vivo by tail vein injection in C57/B6 mice. In comparison studies, the combined column / CsCl gradient purified vector demonstrated potency in vivo equal to or superior to vector purified by gradient ultracentrifugation or column chromatography alone. This combination of process steps has enabled us to initiate clinical vector production of AAV2 vectors of high safety, purity, and potency and at a capacity to meet the requirements of a range of clinical studies.
Acute effects of summer air pollution on respiratory function in primary school children in southern England.
Authors: J F Scarlett, K J Abbott, J L Peacock, D P Strachan, H R Anderson
Journal: Thorax (1996)

BACKGROUND: There is growing concern about health effects of air pollution in the UK. Studies in the USA have reported adverse effects on lung function among children but no comparable studies have been published in the UK. This study investigates the relationship between daily changes in ambient air pollution and short term variations in lung function in a panel of school children. METHODS: One hundred and fifty four children aged 7-11 attending a primary school adjacent to a major motorway in Surrey, south-east England, were studied. Bellows spirometry was performed daily on 31 schooldays between 6 June and 21 July 1994. Levels of ozone, nitrogen dioxide, and particulates of less than 10 microns in diameter (PM10) were measured continuously at the school and the pollen count was measured six miles away. Relationships between daily changes in forced expiratory volume in 0.75 seconds (FEV0.75), forced vital capacity (FVC), the FEV0.75/FVC ratio and pollutants were analysed using separate autoregressive models for each child. A weighted average of the resulting slopes was then calculated. RESULTS: There was a significant inverse relationship between daily mean PM10 levels lagged one day and FVC, with a reduction in lung function of 1% (95% CI 0.3% to 2%) across the whole range of PM10 levels (20-150 micrograms/m3). The effect on FEV0.75 was similar (-0.5%) but was not significant when weighted by 1/SE2 (95% CI -1.2% to 0.2%). There was no effect of PM10 levels on the FEV0.75/FVC ratio. No significant association was seen between FEV0.75, FVC, or the FEV0.75/FVC ratio and either ozone or nitrogen dioxide levels. There was no evidence that wheezy children were more affected than healthy children. Pollen levels on the previous day had no effect on lung function and did not change the air pollution results. CONCLUSIONS: There is a very small, but statistically significant, adverse effect of airborne respirable particulate matter, measured as PM10, on lung function in this study group. There is no evidence for an inverse association of lung function with levels of ozone or NO2 measured on the previous day.
Community Practice
Authors: Fitzhugh Mullan
Journal: JAMA (1980)

IN THE fall of 1972,I went to work as a family practitioner in a new community clinic in the barrio of Sante Fe, NM. Although I was a member of the recently established National Health Service Corps (NHSC)<sup>1,2</sup>and, therefore, a federal employee, I was assigned to the community board of<i>La Clinica de la Gente</i>as their physician. My partner (another NHSC physician) and I began to build the practice from the ground up. This included obtaining hospital privileges, joining the local medical society, establishing a medical records system, designing a treatment room, and stocking a small pharmaceutical dispensary. At the same time, we worked with the community board to determine the clinic's fee schedule, hours of operation, patient policies, and hiring policies. The final decisions in these latter areas belonged to the board. While we were generally well received, we were clearly anomalies in the medical community.
Effects of cholinergic blockade on nocturnal thyrotropin and growth hormone (GH) secretion in type I diabetes mellitus: Further evidence supporting somatostatin's involvement in GH supression
Authors: M.J. Goñi, M. Monreal, F. Goñi, M. Sopena, M.J. Gil, E. Moncada, J. Salvador
Journal: Metabolism (1997)
Physician's Assistants and Clinical Algorithms in Health Care Delivery
Authors: GERALD CHARLES
Journal: Annals of Internal Medicine (1974)

During a 3-month program in a large teaching hospital physician's assistants were trained to use clinical algorithms in seeing patients in a drop-in clinic. Evaluative studies revealed that [1] clinical algorithms can be used to deal effectively with most of the presenting complaints of patients in the drop-in clinic, [2] clinical algorithms allow control over use of institutional resources, [3] physician's assistants can be quickly trained to use clinical algorithms, [4] prior collection of data by physician's assistants reduces the amount of time physicians spend with patients, [5] physician's assistants collect and record significantly more data than do physicians, and [6] patients readily accept physician's assistants. The studies also showed that effective use of physician's assistants and clinical algorithms in institutions is hampered by problems involving professional roles, organizational structure, and managerial ability.
SENSITIVITY AND SPECIFICITY OF CMRI FOR DIAGNOSIS OF MICROVASCULAR CORONARY DYSFUNCTION IN WOMEN WITH SIGNS AND SYMPTOMS OF ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE: RESULTS FROM THE NHLBI-SPONSORED WOMEN'S ISCHEMIA SYNDROME EVALUATION (WISE)
Authors: Afsaneh Haftbaradaran Mohammadi, Puja Mehta, Melody Zaya, Megha Agarwal, B. Delia Johnson, John Petersen, Tara Sedlak, Greg Lentz, Babak Azarbal, Bruce Samuels, Chrisandra Shufelt, Piotr Slomka, Daniel Berman, Carl Pepine, C. Noel Bairey Merz, Louise Thomson
Journal: Journal of the American College of Cardiology (2013)