tbuckley/cabot-search huggingface dataset:
Abstract 2940: Altered hematopoiesis and lymphomagenesis through loss of chromatin-associated protein <i>KIF4</i>
Authors: Manjari Mazumdar
Journal: Cancer Research (2010)

Abstract Hematopoiesis, the process of blood cell formation is largely dependent on specialized chromatin environment for stem cell self-renewal and multi-lineage differentiation. The kinesin motor protein KIF4 associates with chromatin during interphase, performs essential functions in mitosis and its loss causes hypercondensation of mitotic chromosomes leading to genomic instability. We have demonstrated that KIF4 is a modulator of interphase chromatin architecture. In KIF4-null mouse ES cells, heterochromatin blocks are lost, pericentormeric heterochromatin regions are decondensed in S phase and chromatin is globally decondensed. The global chromatin decondensation has functional consequences as indicated by mis-regulation of significant number of genes detected by microarray expression analysis. To understand the molecular mechanism of KIF4 function in vivo, we have developed KIF4 knockout (KIF4 KO) mouse. Here we show that in the absence of KIF4 animals develop splenomegaly, substantial populations of mice have thymic and splenic hyperplasia and ∼40% of heterozygous female mice developed Follicular B cell lymphoma similar to human Non-Hodgkin lymphoma. Flow sorting (FACS) analysis of young mice indicated that loss of KIF4 causes defects in hematopietic development and differentiation. Lymphocytes from animals lacking KIF4 exhibit chromatin defects, aneuploidy, DNA damage and slow progression of lymphocytes through cell cycle. More importantly, we find that there is an accumulation of mature B cells in the spleen in the absence of KIF4. The increased survival of germinal center B cells in the absence of KIF4 may cause the observed hyperplasia and B cell neoplasm. The mechanism of survival and expansion of lymphocytes in spite of genomic instability could be linked to the defects in chromatin organization and changes in transcriptional potential. We propose KIF4 may act as a modulator of chromatin function to regulate cell fate decision during lymphocyte development and a guardian of genome stability to prevent hematopoietic neoplasm. Hematologic malignancy via deletion of a chromatin-associated molecular motor protein is a novel paradigm both in the fields of molecular motors and cancer biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2940.
Baseline levels of plasma endothelin‐1 (ET‐1) and changes during transfusion in thalassemic patients
Authors: Vip Viprakasit, Suthida Kankirawatana, Pravit Akarasereenont, Kritvikrom Durongpisitkul, Sirikul Chotewuttakorn, Voravarn S. Tanphaichitr
Journal: American Journal of Hematology (2002)

Abstract We studied levels of plasma endothelin‐1 (ET‐1) in 25 β‐thalassemia/Hb E patients before and after blood transfusion. Baseline ET‐1 levels in these patients were significantly higher than in normal controls (10.17 ± 2.1 pg/mL vs. 8.9 ± 2.0 pg/mL, P &lt; 0.05). After blood transfusion, levels of plasma ET‐1 tend to slightly increase during the first 24 hr but significantly decline at the 7 th day to levels (8.01 ± 1.7 pg/mL) which do not differ from those of controls. This study highlights a different alteration of plasma ET‐1 in patients with β‐thalassemia compared to that of patients with sickle‐cell anemia. Am. J. Hematol. 70:260–262, 2002.© 2002 Wiley‐Liss, Inc.
Catheter-induced mechanical conduction block of right-sided accessory fibers with Mahaim-type preexcitation to guide radiofrequency ablation.
Authors: R Cappato, M Schlüter, C Weiss, J Siebels, J Hebe, W Duckeck, R U Mletzko, K H Kuck
Journal: Circulation (1994)

BACKGROUND Accessory pathways originating at the tricuspid annulus that exhibit decremental antegrade conduction properties (Mahaim-type preexcitation) are amenable to radiofrequency (RF) current catheter ablation. However, a reliable and reproducible strategy for mapping and ablation of these fibers is lacking. METHODS AND RESULTS Eleven patients with preexcited atrioventricular tachycardia involving a decrementally conducting antegrade accessory pathway underwent complete electrophysiological evaluation and subsequent attempts at RF catheter ablation. Mechanical conduction block at the subannular level of the atrial input to the accessory fiber was induced by catheter manipulation in 8 patients, in 2 of them during atrial fibrillation. RF current was delivered, after resumption of preexcitation, to the site of mechanical block during atrial pacing (n = 6) or atrial fibrillation (n = 2) and eliminated the accessory pathway in all 8 patients. In another patient, mechanical block was not observed, but ablation of the atrial accessory fiber insertion was achieved at the subannular level during atrioventricular tachycardia. The anatomic site of ablation along the tricuspid annulus was anterolateral (n = 1), lateral (n = 3), or posterolateral (n = 5). Failures were encountered in the first patient of the series in whom ablation attempts were directed at the ventricular insertion of the accessory fiber and in a patient in whom ablation of the atrial insertion was attempted at the supraannular level. Recurrence of preexcitation within 12 hours was observed in 5 of 6 patients in whom ablation had been achieved during atrial pacing. Eventually successful repeat sessions were performed the following day using a simplified ablation approach. Thus, a median of 5 RF pulses (range, 1 to 26) per accessory fiber eliminated conduction in 9 (82%) of the 11 patients in 1.9 +/- 0.9 sessions. During a follow-up of 9.5 +/- 2.3 months, preexcitation recurred in 1 patient. CONCLUSIONS The atrial origin of accessory connections with Mahaim-type preexcitation is apparently confined to the anterolateral-to-posterolateral region of the tricuspid annulus. Mechanical conduction block in the atrial input to the accessory fiber induced at the subannular level by catheter manipulation provides an optimal marker to locate the ablation site, even during atrial fibrillation. To expose early recurrence of antegrade accessory pathway conduction, intermittent atrial pacing in the 12 hours after ablation is advisable; in cases of recurrence, a repeat procedure can readily be performed using just the ablation catheter advanced to the target site at the tricuspid annulus.
Abstract 2682: Imaging prostate cancer in an orthotopic prostate model using a 68Ga-Bombesin (BB2r) radiopharmaceutical.
Authors: Kelsey Richmond, Tammy Rold, Ashley Szczodroski, Lixin Ma, Quanyu Cai, Timothy Hoffman
Journal: Cancer Research (2013)

Abstract Introduction: There continues to remain a significant need to develop molecular imaging agents for the diagnosis and staging of prostate cancer. The association of the bombesin receptor subtype 2 (BB2r) and prostate cancer is well known and several groups including our own have developed unique radiopharmaceutical targeting strategies for the delivery of BB2r agonists and antagonists. Earlier work from our group utilizing BB2r agonists and antagonists labeled with 99mTc and 111In demonstrated selective targeting of simple flank xenograft models of prostate cancer. We are now presenting a preclinical evaluation of 68Ga-BB2r PET imaging using an orthotopic prostate SCID mouse model. Methods: The BB2r antagonist, DOTA-4-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, (Eur J Nucl Med Mol Imaging 38(1):97, 2011) was synthesized commercially. 68Ga was obtained from a commercially available Ge-68/Ga-68 generator. The peptide (40ug) was radiolabeled with 10-20mCi (270-740MBq) of 68Ga using an automated radiosynthesis system. Reverse phase HPLC (C-18) was employed for quality control analysis using a combination of radiometric and UV analysis. Orthotopic prostate xenografted male SCID mice were administered ∼0.3mCi (11.1 MBq) of 68Ga labeled peptide and combined PET/CT imaging was performed 4 hours following injection. Each mouse received 100uL of Visipaque® before imaging commenced. Concurrent 7 T MRI data was obtained for anatomic verification of prostate tumor involvement. Pathologic confirmation of tumor involvement within the prostate bed was obtained. Results: The 68Ga BB2r antagonists could be readily prepared in high radiochemical yield and purity as verified by HPLC. Orthotopic prostate tumor xenografts were clearly visualized using PET/CT imaging. The predominant renal clearance of the tracer presented challenges in differentiating active tumor involvement within the prostate bed from bladder contents. These challenges could be partially addressed by employing concurrent CT contrast agent administration as an aid in accurately defining bladder contents and balder wall delineation. Conclusions: These results demonstrate that 68Ga BB2r antagonist PET/CT imaging holds the potential to accurately differentiate BB2r positive prostate tumor growth within the prostate bed as a potential screening and diagnostic tool. Citation Format: Kelsey Richmond, Tammy Rold, Ashley Szczodroski, Lixin Ma, Quanyu Cai, Timothy Hoffman. Imaging prostate cancer in an orthotopic prostate model using a 68Ga-Bombesin (BB2r) radiopharmaceutical. [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 2682. doi:10.1158/1538-7445.AM2013-2682
NADPH-diaphorase activity as a marker for nitric oxide synthase in neurons of the guinea pig respiratory tract.
Authors: T Shimosegawa, T Toyota
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Recent studies in physiology have suggested that part of the inhibitory nonadrenergic noncholinergic (iN-ANC) response of airway smooth muscle is mediated by nitric oxide (NO). To examine this point morphologically, the guinea pig respiratory tract was investigated histochemically for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d), a marker for NO synthase (NOS). In addition, coexpression of NOS and vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP) was studied using a combination of histochemistry for NADPH-d and immunohistochemistry for VIP or CGRP. Nerve fibers showing NADPH-d activity were abundantly observed in the respiratory tract. They were distributed throughout smooth-muscle bundles, lamina propria, submucosal glands, and around bronchial and pulmonary arteries. NADPH-d-containing nerve-cell bodies were occasionally found within airway ganglia. The colocalization study demonstrated that NADPH-d-containing nerve fibers frequently coincided with VIP-like immunoreactive nerve fibers but not with CGRP-like immunoreactive nerve fibers. Among nonneural tissues, NADPH-d activity was noticed in the endothelium of both bronchial and pulmonary vessels, and in the pleura. These observations indicated that NO may be produced by neurons and vascular endothelium of the guinea pig respiratory tract, and may function as a neuronal mediator as well as endothelium-derived relaxing factor (EDRF). Colocalization of NADPH-d and VIP-like immunoreactivity in nerve fibers suggested that NO and VIP may function as cotransmitters.
DEATH FROM SPINAL ANESTHESIA
Authors: A. E. ROCKEY
Journal: JAMA (1913)

In reporting this case I am prompted by a desire to place on record the dangerous side of this valuable method of anesthesia. It serves to illustrate the truth of the statement that there is no safe anesthetic. On the morning of the day when the fatality occurred I had for operation two cases of fracture which required Lane plates. The first patient was a man about 40 years of age, with an oblique fracture of the tibia which would not remain in place with an ordinary splint. Morphin, 1/6 grain, and scopolamin, 1/100 grain, were administered half an hour before the operation. Stovain was injected, and satisfactory anesthesia to the middle of the abdomen quickly followed. The Lane plate was applied, the wound dressed and splinted, and the patient returned to his bed in comfort. This operation was witnessed by the physician who had brought the second patient.
FRACTURES OF THE NECK OF THE FEMUR
Authors: P. Wiles
Journal: BMJ (1939)

Fractures of the neck of the femur are divided into two groups-intracapsular fractures of the neck proper and fractures involving the trochanters.Extracapsular frac- tures through the base of the neck belong, from a practical point of view, to the trochanteric group.The two groups are widely different as regards both prognosis and treat- ment.
BIVALIRUDIN USE AND SHORT TERM OUTCOME IN THE ERA OF NOVEL P2Y12 INHIBITORS IN REAL-LIFE PATIENTS WITH ACUTE CORONARY SYNDROME: INSIGHTS FROM THE GREEK ANTIPLATELET (GRAPE) REGISTRY
Authors: Dimitrios Alexopoulos, Ioanna Xanthopoulou, Spyridon Deftereos, Georgios Sitafidis, Ioannis Kanakakis, Michalis Hamilos, John Goudevenos, Christodoulos I. Stefanadis
Journal: Journal of the American College of Cardiology (2014)
Abstract 2033: Identification of a novel genetic abnormality, the amplification of rictor (rapamycin-insensitive companion of mTOR), in a patient with non-small cell lung cancer.
Authors: Haiying Cheng, Bilal Piperdi, Edward L. Schwartz, Changcheng Zhu, Zhenfeng Zhang, Balazs Halmos, Vincent Miller, Roman Perez-Soler
Journal: Cancer Research (2013)

Abstract Despite recent advances, clinically-relevant oncogenic drivers have not been identified in about half of lung adenocarcinormas. Here, we report rictor (rapamycin-insensitive companion of mTOR) amplification as a novel genetic abnormality in a young patient with non-small cell lung cancer. This male patient was a never smoker and was diagnosed with lung adenocarcinorma at the age of 18. He initially presented with refractory cough and persistent left lung lesions. Pathology was consistent with lung adenocarcinorma, poorly differentiated. Extensive molecular testing was negative for common genetic alterations in K-RAS, EGFR, ALK, HER2, RET, AKT, PIK3CA, BRAF and ROS1. His tumor was subsequently subjected to next generation DNA sequencing (FoundationOne, Foundation Medicine, Cambridge, MA) targeting a cohort of more than 180 cancer-related genes. This analysis identified rictor amplification of at least 6 copies as the sole DNA abnormality. Immunohistochemistry further documented rictor overexpression in the patient's lung tumor. The neoplastic lung tissue exhibited diffuse and strong cytoplasmic staining for rictor, compared to surrounding non-neoplastic tissues. Furthermore, the tumor tissue showed diffuse overexpression of phospho-S473 Akt, an essential downstream target of rictor. Rictor is a key component of mTORC2 complex, where it modifies actin cytoskeleton organization, cell proliferation and survival. Activation of rictor signaling has been suggested to play critical roles in regulating cancer cell migration, invasion and metastasis in breast, ovarian, and colorectal cancers and gliomas. To our knowledge, this is the first report of rictor amplification in lung cancer. Moreover, we found that blockade of the rictor-mTORC2 pathway by siRNA-mediated rictor knockdown or with pharmacological inhibitors led to decreased phosphorylation of S473-AKT and growth inhibition in lung cancer cell lines. Thus, rictor amplification may represent a potential novel target in lung cancer. We will perform further studies to determine whether rictor amplification is a unique molecular subtype of lung cancer. Further, we hope to identify which targeted drugs are active against tumors with rictor amplification and overexpression. Citation Format: Haiying Cheng, Bilal Piperdi, Edward L. Schwartz, Changcheng Zhu, Zhenfeng Zhang, Balazs Halmos, Vincent Miller, Roman Perez-Soler. Identification of a novel genetic abnormality, the amplification of rictor (rapamycin-insensitive companion of mTOR), in a patient with non-small cell lung cancer. [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 2033. doi:10.1158/1538-7445.AM2013-2033
Autoimmune Diseases: Drugs, Viruses, and Mechanisms.
Authors: John H. Vaughan
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Autoimmune Diseases: Drugs, Viruses, and Mechanisms.John H. Vaughan, M.D., F.A.C.P.John H. Vaughan, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-854_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe so-called autoimmune diseases are characterized by the production of autoreactive antibodies and lymphocytes capable of damaging the patients' own tissues. The damage may occur from circulating immune complexes, as in lupus nephritis; from the reaction of the autoantibodies directly with cellular elements, as in hemolytic anemias; or from attack on the tissues by autoaggressive immune lymphocytes, as in experimental thyroiditis and probably in Hashimoto's disease. Autoimmune disease can be initiated by drugs. The best understood example is pronestyl lupus, in which the data indicate that the drug probably elicits the syndrome independently of any hypothetical underlying individual predisposition to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: John H. Vaughan, M.D., F.A.C.P.Affiliations: La Jolla, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 854-854KeywordsAntibodiesAutoantibodiesAutoimmune diseasesDrugsHemolytic anemiaImmune complexLupus nephritisLymphocytesThyroid ePublished: 1 December 2008 Issue Published: 1 May 1972 PDF downloadLoading ...
F-18 FDG PET/CT in the Management of Infected Abdominal Aortic Aneurysm Due To Salmonella
Authors: Seung Jin Choi, Jin Soo Lee, Moon Hyun Cheong, Sung Su Byun, In Young Hyun
Journal: Clinical Nuclear Medicine (2008)

Mycotic aneurysm is a rare and life-threatening disorder. Computed tomography (CT) is considered to be the best diagnostic imaging modality that can detect an abdominal aortic aneurysm and changes in the surrounding structures. More recently, F-18 fluorodeoxyglucose (FDG) PET would seem to hold promise for the diagnosis of focal infection and during the follow-up after antibiotic treatment. We present a case of an infected abdominal aortic aneurysm due to Salmonella enteritidis. In this case, a combination of CT and FDG PET/CT provided accurate information for the diagnosis of the infected abdominal aortic aneurysm. Moreover, FDG PET/CT made an important contribution for monitoring response to antibiotic therapy.
Effect of indoor air pollution from biomass combustion on prevalence of asthma in the elderly.
Authors: Vinod Mishra
Journal: Environmental Health Perspectives (2002)

In this study I examined the effect of cooking smoke on the reported prevalence of asthma among elderly men and women greater than or equal to 60 years old). The analysis is based on 38,595 elderly persons included in India's second National Family Health Survey conducted in 1998-1999. Effects of exposure to cooking smoke, ascertained by type of fuel used for cooking (biomass fuels, cleaner fuels, or a mix of biomass and cleaner fuels), on the reported prevalence of asthma were estimated using logistic regression. Because the effects of cooking smoke are likely to be confounded with effects of age, tobacco smoking, education, living standard, and other such factors, the analysis was carried out after statistically controlling for such factors. Results indicate that elderly men and women living in households using biomass fuels have a significantly higher prevalence of asthma than do those living in households using cleaner fuels [odds ratio (OR) = 1.59; 95% confidence interval (95% CI), 1.30-1.94], even after controlling for the effects of a number of potentially confounding factors. Active tobacco smoking was also associated with higher asthma prevalence in the elderly, but not environmental tobacco smoke. Availability of a separate kitchen in the house and a higher living standard of the household were associated with lower asthma prevalence. The adjusted effect of cooking smoke on asthma was greater among women (OR = 1.83; 95% CI, 1.32-2.53) than among men (OR = 1.46; 95% CI, 1.14-1.88). The findings have important program and policy implications for countries such as India, where large proportions of the population rely on polluting biomass fuels for cooking and space heating. More epidemiologic research with better measures of smoke exposure and clinical measures of asthma is needed to validate the findings.
A new device for arterial blood gas sampling
Authors: T. L. Petty
Journal: JAMA (1978)

Artifacts in CO2 tension measurements owing to heparin dilution are eliminated by use of a sampling device employing crystalline heparin. The absence of a plunger and the low resistance to filling allows the use of small, 23- or 25-guage needles, thus reducing pain during arterial puncture and hematoma formation.
Book Review The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay–Sachs, Cystic Fibrosis, and Sickle Cell Disease By Keith Wailoo and Stephen Pemberton. 249 pp. Baltimore, Johns Hopkins University Press, 2006. $60.00 (cloth); $21.95 (paper). 0-8018-8325-3 (cloth); 0-8018-8326-1 (paper).
Authors: Neil A. Holtzman
Journal: New England Journal of Medicine (2006)
THE OXIDATIVE METABOLISM OF HISTAMINE IN GUINEA-PIG SKIN WITH AND WITHOUT β-BLOCKADE BY PROPANOLOL
Authors: D. W. K. COTTON, A. H. M. SUTORIUS
Journal: British Journal of Dermatology (1971)

Journal Article THE OXIDATIVE METABOLISM OF HISTAMINE IN GUINEA‐PIG SKIN WITH AND WITHOUT β‐BLOCKADE BY PROPANOLOL Get access D. W. K. COTTON, D. W. K. COTTON Department of Dermatology (Professor J. W. H. Mali), University of Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar A. H. M. SUTORIUS A. H. M. SUTORIUS Department of Dermatology (Professor J. W. H. Mali), University of Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 2, 1 February 1971, Pages 124–129, https://doi.org/10.1111/j.1365-2133.1971.tb06854.x Published: 01 February 1971 Article history Accepted: 18 September 1970 Published: 01 February 1971
Non-A, Maybe-B Hepatitis
Authors: Stephen M. Feinstone, Jay H. Hoofnagle
Journal: New England Journal of Medicine (1984)

Non-A,non-B hepatitis was described just 10 years ago.1 , 2 The deliberately vague term "non-A,non-B hepatitis" was used because the agent or agents had not been identified. Ten years later, this term is still appropriate. The transmissible agent responsible for non-A,non-B hepatitis has yet to be identified. Furthermore, there are no serologic assays for either an antigen or an antibody that can be used to detect this infection. Non-A,non-B hepatitis remains a diagnosis of exclusion.Some readers may be surprised to learn that established tests for non-A,non-B hepatitis antigens and antibodies do not exist, for in the past six years, no fewer . . .