tbuckley/cabot-search huggingface dataset:
Abstract 11964: Circulating Levels of 2-Aminobutyric Acid Reflect Myocardial Redox State in Patients With Atrial Septal Defects
Authors: Yasuhiro Irino, Ryuji Toh, Takeshige Mori, Manabu Nagao, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Toshiro Shinke, Tatsuro Ishida, Okiko Miyata, Ken-ichi Hirata
Journal: Circulation (2014)

Heart failure (HF) is a major cause of morbidity and mortality worldwide. However, conventional biomarkers are insufficient to detect early stage of HF and identification of more sensitive markers is an urgent task. We conducted the comprehensive quantification of water-soluble metabolites in blood of atrial septal defect (ASD) patients using a gas chromatograph-mass spectrometry. We found the mean level of 2-Aminobutyric acid (2-AB) in ASD patients was significantly higher than that in healthy volunteers, and 1 month after transcatherter closure of ASD using the Amplatzer septal occluder, serum 2-AB levels in patients decreased to almost the same levels as healthy volunteers (healthy-volunteers: 15.74±1.75 μM, ASD (pre-closure): 22.38±1.99 μM, ASD (post-closure):15.50±1.50 μM, P=0.017). In contrast, serum levels of brain natriuretic peptide (BNP), frequently used as the biomarker in heart disease, did not show such relationships. In addition, 2-AB concentration had a significant correlation with tricuspid regurgitation peak gradient (TRPG) (R2=0.517, P=0.029). Because TRPG reflects right ventricular loading conditions, we examined whether mechanical stress to cardiomyocyte induces 2-AB. Mechanical stretch induced an accumulation of 2-AB, suggesting that circulating 2-AB increased in ASD patients were derived from their hearts. Next, we tried to identify the 2-AB synthesis pathway. 2-AB is known as a key molecule in the biosynthesis of ophthalmic acid that is an analogue of glutathione (GSH) and indicates GSH depletion under oxidative stress. We revealed that 2-AB was produced as the byproduct of GSH synthesis reactions. We also demonstrated that oxidative stress lead to 2-AB production by H2O2 stimulation in cardiomyocyte. Mechanical stress-induced 2-AB accumulation might be mediated by oxidative stress. In summary, circulating 2-AB levels changed before and after closure of ASD and indicated heart condition more efficiently than BNP. We also demonstrated that 2-AB reflects myocardial redox state. Thus, 2-AB monitoring may facilitate the early diagnosis strategy for HF.
REPORT OF A CASE OF BENIGN GASTRIC POLYP PRODUCING A GASTROGENIC DIARRHEA
Authors: Gordon J. Culver, Walter Westinghouse, E. C. Koenig
Journal: Annals of Internal Medicine (1942)

Case Reports1 December 1942REPORT OF A CASE OF BENIGN GASTRIC POLYP PRODUCING A GASTROGENIC DIARRHEAGORDON J. CULVER, M.D., WALTER WESTINGHOUSE, M.D., E. C. KOENIG, M.D., F.A.C.P.GORDON J. CULVER, M.D.Search for more papers by this author, WALTER WESTINGHOUSE, M.D.Search for more papers by this author, E. C. KOENIG, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-6-1015 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBenign tumors of the stomach constitute a relatively small portion of gastric lesions. According to the figures of Eusterman and Balfour they represent only 0.6 per cent of all gastric lesions seen at the Mayo Clinic. Mayo Clinic statistics show that the average age of occurrence of benign gastric lesions is 46. Twenty-six per cent occur in the body of the stomach and 69 per cent occur in the pyloric or prepyloric regions. Benign gastric lesions include leiomyomata, fibromata, lipomata, hemangiomata and adenomata. The leiomyoma is the most frequent benign gastric lesion and this usually is polypoid in structure and...References1. ALVAREZ WC: The mechanics of the digestive tract, second edition, 1928, Paul B. Hoeber, Inc., New York, p. 317. Google Scholar2. BOYD W: Text book of pathology, second edition, 1934, Lea & Febiger, Philadelphia, p. 520. Google Scholar3. CECIL RL: A text book of medicine, third edition, 1934, W. B. Saunders Co., Philadelphia and London, p. 761. Google Scholar4. EUSTERMANBALFOUR GBDC: The stomach and duodenum, 1935, W. B. Saunders Co., Philadelphia and London, pp. 547-562. Google Scholar5. WEITZEN M: Chronic gastritis caused by gastric bezoar, New York State Jr. Med., 1940, xl, 136. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Buffalo, New York*Received for publication March 12, 1941. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1942Volume 17, Issue 6Page: 1015-1020KeywordsBenign tumorsDiarrheaGastroenterology and hepatologyLesionsStomach ePublished: 1 December 2008 Issue Published: 1 December 1942 PDF downloadLoading ...
RUST AND SMUT, MAJOR CAUSES OF RESPIRATORY ALLERGY
Authors: G. L. Waldbott, M. S. Ascher
Journal: Annals of Internal Medicine (1940)

Article1 August 1940RUST AND SMUT, MAJOR CAUSES OF RESPIRATORY ALLERGYG. L. WALDBOTT, M.D., F.A.C.P., M. S. ASCHER, M.D.G. L. WALDBOTT, M.D., F.A.C.P.Search for more papers by this author, M. S. ASCHER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-2-215 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDuring the past few years we have observed that a certain number of patients manifested unusually severe asthmatic symptoms during the month of July and during the early part of August. We attributed this at first to such pollens as the plantains and lambsquarter, and to a residual effect of the timothy pollen. However, by thoroughly checking the symptoms against the daily pollen counts, by frequently retesting for the then prevailing pollens, and by administering what we felt was adequate treatment to those patients who exhibited more or less pronounced reactions to these pollens, we were unable to establish such...Bibliography1. FEINBERG SM: Seasonal hayfever and asthma due to molds, Jr. Am. Med. Assoc., 1936, cvii, 1861. CrossrefGoogle Scholar2. WALDBOTTASCHERACKLEY GLMSAB: Relation of fungi to respiratory allergy. (To be published.) Google Scholar3. CADHAM FT: Asthma due to grain rusts, Jr. Am. Med. Assoc., 1924, lxxxiii, 27. CrossrefGoogle Scholar4. WITTICHSTACKMAN FWEC: Case of respiratory allergy due to inhalation of grain smuts, Jr. Allergy, 1936, viii, 189-193. Google Scholar5. WITTICH FW: Further observations on smut sensitivity. (To be published.) Google Scholar6. DUKEDURHAM WWOC: Pollen content of the air, Jr. Am. Med. Assoc., 1928, xc, 1529. CrossrefGoogle Scholar7. DURHAM OC: Unusual shower of alternaria spores, Jr. Am. Med. Assoc., 1938, cxi, 24. CrossrefGoogle Scholar8. BROWN GT: Hypersensitiveness to fungi, Jr. Allergy, 1936, vii, 455. CrossrefGoogle Scholar9. WALDBOTTASCHER GLMS: Optimal doses in pollen therapy, Jr. Allergy, 1937, viii, 457. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan*Received for publication April 15, 1939.This investigation was made possible by a grant of Mr. J. E. Fields, Detroit, Michigan, which is gratefully acknowledged. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorn smut as a food source — perspectives on biology, composition, and nutritionFUNGI IN FACTORIES AND WORKSHOPSA study of the fungus contaminants of the air of San Diego and vicinity 1 August 1940Volume 14, Issue 2Page: 215-224KeywordsAllergy and immunologyPatientsPollen ePublished: 1 December 2008 Issue Published: 1 August 1940 PDF downloadLoading ...
Engineering liver tissue from induced pluripotent stem cells: A first step in generating new organs for transplantation?
Authors: Ira J. Fox, Stephen A. Duncan
Journal: Hepatology (2013)

A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.
Water-filtered infrared A for the treatment of chronic venous stasis ulcers of the lower legs at home: a randomized controlled blinded study
Authors: H. Schumann, T. Calow, S. Weckesser, M.L. Müller, G. Hoffmann
Journal: British Journal of Dermatology (2011)

Water-filtered infrared A (wIRA) radiation can improve the healing of acute and chronic wounds both by thermal and thermic as well as by nonthermal and nonthermic effects. wIRA increases tissue temperature, oxygen partial pressure and perfusion.Investigation of the influence of wIRA on chronic venous stasis ulcers in an investigator-initiated, randomized, controlled, blinded study.Fifty-one patients with nonhealing chronic venous stasis ulcers of the lower legs were treated with compression therapy, wound cleansing, nonadhesive wound dressings and 30 min irradiation [wIRA + visible light (VIS) or VIS alone], predominantly at home, five times per week over 9 weeks and an additional 4 weeks without irradiation.Compared with the control group with VIS alone, the group with wIRA + VIS showed better wound healing [after 9 weeks 85 vs. 67·5 on a 0-100 visual analogue scale (VAS), median difference 15, 95% confidence interval (CI) 3-30, P = 0·012], a higher percentage of patients with a healing trend [after 9 weeks 21 of 25 (84%) vs. 13 of 26 (50%), P = 0·023], better granulation (after 9 weeks 90 vs. 80 on a 0-100 VAS, median difference 10, 95% CI 0-30, P = 0·036), a trend to less exudation (after 5 weeks 30 vs. 55 on a 0-100 VAS, P = 0·075) and to faster reduction of the wound area (after 7 weeks 39% vs. 19·5% reduction of wound area, median difference 20·5%, 95% CI -4-49%, P = 0·10; for wounds with an initial area < 10 cm(2): after 13 weeks 92% vs. 47% reduction of wound area, median difference 30%, 95% CI 0-68%, P = 0·11). The main variable 'Integral of relative ulcer area for each individual patient over time, standardized to an initial size of 1' did not reach significance. The application of wIRA at home was easily manageable.For the treatment of chronic venous stasis ulcers, the application of wIRA combined with phlebological therapy, compression therapy and wound dressing can be useful and can be recommended.
Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index: characterizing disease severity and assessing responsiveness to clinical change
Authors: C.O. Anyanwu, D.F. Fiorentino, L. Chung, C. Dzuong, Y. Wang, J. Okawa, K. Carr, K.J. Propert, V.P. Werth
Journal: British Journal of Dermatology (2015)

The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment. To characterize disease severity using the CDASI and assess the responsiveness of this instrument to clinically meaningful changes in disease activity. Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n =93) and Stanford University (Stanford, n =106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales and a visual analogue scale (VAS). Data was analysed using logistic regression models and receiver operating characteristic curves to select cut‐offs. Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9·6 (median 1·1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9·7 (median 4·2) and CDASI activity scores of 14 or less characterized mild disease. When a 2‐cm change in the PGA VAS was regarded as a clinically significant improvement, a 4‐point (UPenn) or 5‐point (Stanford) change in CDASI reflected a minimal clinically significant response. The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cut‐offs may be due to differences in disease severity between the two populations or inter‐rater variations in the use of the external gold measures.
Linear IgA disease with IgA antibodies directed against 200- and 280-kDa epidermal antigens
Authors: W. Fujimoto, T. Ohtsu, Y. Toi, G. Nakanishi, J. Arata
Journal: British Journal of Dermatology (2000)

We report an 80-year-old man with the lamina lucida type of linear IgA disease, with IgA autoantibodies reactive with 200-kDa and 280-kDa epidermal proteins. The patient presented with widespread bullous lesions on his trunk and extremities without mucosal involvement. Histopathology of lesional skin showed a subepidermal blister with papillary microabscesses of neutrophils and a few eosinophils. Direct immunofluorescence microscopy of perilesional skin showed linear deposits of IgA and C3 at the basement membrane zone. The patient's serum contained IgA autoantibodies that bound exclusively to the epidermal side of 1 mol L-1 NaCl split skin as determined by indirect immunofluorescence microscopy. Circulating IgA autoantibodies to 200- and 280-kDa antigens were detected in the patient's serum by immunoblot analysis using extracts from normal human epidermis and human epidermal keratinocytes. These two antibodies, eluted from individual nitrocellulose membranes, reacted with the epidermal side of 1 mol L-1 NaCl split skin on indirect immunofluorescence microscopy, and bound to hemidesmosomes as determined by immunoperoxidase electron microscopy. This observation suggests the presence of hitherto uncharacterized 200- and 280-kDa hemidesmosomal proteins distinct from BPAG1, BPAG2 and beta4 integrin as target antigens in linear IgA disease.
Cannabis trial launched in patients with MS
Authors: Owen Dyer
Journal: BMJ (2001)

The world's biggest clinical trial of the cannabis plant got under way this week at Derriford Hospital, Plymouth; the trial is looking at the control of pain and tremors in multiple sclerosis. Twenty patients were given their first doses of capsules containing cannabis oil, tetra hydro cannabinol, or placebo. After three months, if all goes to plan, the trial will be slowly extended across the country, eventually taking in 660 participants in 40 centres.

The cannabis in multiple sclerosis (CAMS) study is sponsored by the Medical Research Council and approved by …
Abstract 1590: Expression and function of Sirt6 in muscle invasive bladder cancer
Authors: Minghui Wu, Shohreh Dickinson, Jingsong Zhang
Journal: Cancer Research (2014)

Abstract Unlike most other solid tumors, there is limited success of targeted agents in treating metastatic bladder cancer (BC), a lethal disease with a median overall survival of merely 13-15 months. No prevalent “drugable” driver mutations have been identified in muscle invasive bladder cancer (MIBC) so far. Several high profile publications in the past few years have put Sirt6, a member of the class III histone deacetylase in the center stage of cancer metabolism and DNA repair. We therefore assessed the expression and function of Sirt6 in MIBC. Inconsistent with its proposed function as a tumor suppressor in colon cancer, the gene expression datasets available in Oncomine did not reveal significant differences in Sirt6 mRNA levels among normal urothelium, superficial BC and MIBC. Compared to normal urothelium, carcinoma in situ, superficial BC, the median Sirt6 mRNA was the lowest in MIBC in the Dyrkjot bladder 3 dataset, but this was not statistically significant. We then studied Sirt6 protein expression with immunohistochemistry (IHC) in commercial tissue microarray as well as radical cystoprostatectomy samples in our total cancer care tumor bank. Sirt6 IHC were reviewed by pathologist and considered positive for Sirt6 if more than 5% of the tumor cells had at least 1+ Sirt6 nuclear staining. Positive Sirt6 IHC was detected in 33/56 (59%) of T2 (grade 1-3), 2/23 T3 (9%) and 0/3 T4 urothelial carcinoma. All the grade 3/high grade T3 urothelial carcinomas were negative for Sirt6 IHC. Negative Sirt6 IHC was also noted in 2 adenocarcinomas, 1 sarcomatoid carcinoma and 1 small cell MIBC. 1/18 (5%) lymph node metastasis had positive Sirt6 IHC. Consistent with its role of inhibiting aerobic glycolysis, bladder cancer cell lines with higher Srit6 have lower glucose uptake and lower lactate production. Knocking down Sirt6 expression in bladder cancer cell lines, however, did not sensitize bladder cancer lines to drug induced DNA damage. Among MIBC, much higher frequency of Sirt6 IHC positivity was noted in T2 urothelial carcinoma than T3, T4 and non-urothelial carcinomas. Data with bladder cancer cell lines suggest the function of Sirt6 in bladder cancer is primarily inhibiting aerobic glycolysis. Citation Format: Minghui Wu, Shohreh Dickinson, Jingsong Zhang. Expression and function of Sirt6 in muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1590. doi:10.1158/1538-7445.AM2014-1590
FAK Is required for c‐Met/β‐catenin‐driven hepatocarcinogenesis
Authors: Na Shang, Maribel Arteaga, Ali Zaidi, Jimmy Stauffer, Scott J. Cotler, Nancy J. Zeleznik‐Le, Jiwang Zhang, Wei Qiu
Journal: Hepatology (2014)

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide and most patients with HCC have limited treatment options. Focal adhesion kinase (FAK) is overexpressed in many HCC specimens, offering a potential target for HCC treatment. However, the role of FAK in hepatocarcinogenesis remains elusive. Establishing whether FAK expression plays a role in HCC development is necessary to determine whether it is a viable therapeutic target. In this study, we generated mice with hepatocyte‐specific deletion of Fak and investigated the role of Fak in an oncogenic (c‐MET/β‐catenin, MET/CAT)‐driven HCC model. We found that deletion of Fak in hepatocytes did not affect morphology, proliferation, or apoptosis. However, Fak deficiency significantly repressed MET/CAT‐induced tumor development and prolonged survival of animals with MET/CAT‐induced HCC. In mouse livers and HCC cell lines, Fak was activated by MET, which induced the activation of Akt/Erk and up‐regulated cyclin D1 and tumor cell proliferation. CAT enhanced MET‐stimulated FAK activation and synergistically induced the activation of the AKT/ERK‐cyclin D1 signaling pathway in a FAK kinase‐dependent manner. In addition, FAK was required for CAT‐induced cyclin D1 expression in a kinase‐independent fashion. Conclusion : Fak is required for c‐Met/β‐catenin‐driven hepatocarcinogenesis. Inhibition of FAK provides a potential strategy to treat HCC. (H epatology 2015;61:214–226)
Abstract 18925: Enhanced Cellular Proliferation and Altered Collagen Deposition May Accelerate Atherosclerosis in Human Peripheral Artery Disease: Implication of Morphological Predictors in Restenotic Plaque Progression
Authors: Prakash Krishnan, Purushothaman K-Raman, Meerarani Purushothaman, Jason C Kovacic, Arthur Tarricone, Miguel Vasquez, Wiley Jose, Annapoorna Kini, Samin K Sharma, Valentin Fuster, Pedro R Moreno
Journal: Circulation (2014)

Introduction: The mechanisms responsible for restenosis include cellular and extracellular matrix (ECM) overproduction mediated by vascular smooth muscle cell (SMC) migration and proliferation. However, the role of the myofibroblast is less clear.

Hypothesis: This study was designed to evaluate the role of the myofibroblast in ECM overproduction mediated by stellate cell proliferation and reparative collage III deposition in restenotic tissue from patients with symptomatic peripheral arterial disease.

Methods: Fourteen de novo and seventeen restenotic superficial femoral artery plaques were obtained in-vivo and compared for cell proliferation, SMC (α-actin), fibroblast specific protein-1 (FSP1), and vimentin by immunochemistry, type I and type III collagens by Picro-sirius red stain and polarization microscopy. Stellate cell morphology was graded by scoring. Cellular co-localization of α-actin with vimentin, FSP-1, percentage of apoptosis (active caspase 3) and percentage of cell proliferation (Ki67) were done by confocal microscopy.

Results: See figure and table. In restenotic atheroma, increased proliferation of myofibroblasts and SMCs were associated with higher content of reparative type III collagen (p= 0.0001) compared to de novo plaques. Furthermore, percent proliferative index of actin with Ki67 and percent apoptosis of actin were increased in restenotic plaques (p= 0.0001).

Conclusions: In peripheral artery disease restenosis, increased myofibroblasts, and proliferative SMC may preferentially enhance atheroma progression and may predispose to increased type III collagen deposition. This may contribute for the severity of clinical manifestation seen in PAD. The molecular pathways associated with these differences including apoptosis are under active investigation.

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Clinical Management of Keratoconus
Authors: Jonathan H. Lass, Richard G. Lembach, Steve B. Park, David L. Hom, Mary E. Fritz, Grace M. Svilar, Isaac F. Nuamah, William J. Reinhart, Eric G. Stocker, Richard H. Keates, C. Thomas Moran, L. Michael Cobo, Gary N. Foulks
Journal: Ophthalmology (1990)
Abstract 13460: Sca-1 Identifies a Monocyte-predisposed Hierarchy Of Hematopoietic Progenitor Cells In The Postnatal Murine Aorta
Authors: Peter J Psaltis, Adriana Harbuzariu, Sinny Delacroix, Tyra Witt, Laurel Kleppe, Cheryl Mueske, Rajiv Gulati, Gurpreet S Sandhu, Robert D Simari
Journal: Circulation (2011)

Peter J. Psaltis, 2011 Finalist and Presenting Author