tbuckley/cabot-search huggingface dataset:
GANGRENE OF THREE LIMBS RESULTING FROM VENOUS OCCLUSION
Authors: J R FOUNTAIN, D TAVERNER
Journal: Annals of Internal Medicine (1956)

Case Reports1 March 1956GANGRENE OF THREE LIMBS RESULTING FROM VENOUS OCCLUSIONJ. R. FOUNTAIN, M.B., M.R.C.P. (Ed.), D. TAVERNER, M.D., M.R.C.P.J. R. FOUNTAIN, M.B., M.R.C.P. (Ed.)Search for more papers by this author, D. TAVERNER, M.D., M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-44-3-549 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGangrene of the limbs resulting from venous occlusion without arterial obstruction is extremely rare. Haimovici in 19501summarized the 27 cases then reported in the literature and mentioned another. He emphasized the importance of anatomic confirmation of the patency of the arterial system in establishing the diagnosis. Gangrene was present in one limb only in 23 of the cases he reviewed, and in both lower limbs in the remaining four. Veal et al. in 19512have described 11 cases of acute massive venous occlusion, confined to one or other of the lower extremities, in which gangrene developed in two instances....Bibliography1. Haimovici H: Gangrene of the extremities of venous origin, Circulation 1: 225, 1950. CrossrefMedlineGoogle Scholar2. VealDuganJamisonBauersfeld JRTJWLRS: Acute massive venous occlusion of the lower extremities, Surgery 29: 355, 1951. MedlineGoogle Scholar3. Fontainede Souza-Pereira RA: Obliterations et resections veineuses experimentales; contributions à l'étude de la circulation collaterele veineuse, Rev. de chir., Paris 75: 161, 1937. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Leeds,*Received for publication December 17, 1954.From the Department of Medicine, General Infirmary, Leeds, England. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPhlegmasia Cerulea Dolens in the Upper ExtremityHand Gangrene Following Unsuccessful Cannulation of the Internal Jugular Vein: A Case Report and Literature ReviewUpper Extremity Compartment Syndrome in the Setting of Deep Venous Thrombosis and Phlegmasia Cerulea Dolens: Case ReportThrombosis of the inferior vena cava with gangrene of both legsUpper limb venous gangrene, a lethal conditionPain in the Extremities, Dysesthesia, PolyalgiaCase 11-1962Phlegmasia coerulea dolens: Gangrene of Venous OriginVenous GangreneCase 44172 1 March 1956Volume 44, Issue 3Page: 549-554KeywordsAnticoagulantsEdema Issue Published: 1 March 1956 PDF downloadLoading ...
Abstract 13050: Genetic Deletion of Integrin Alpha1beta1 Alleviates Aortic Rupture in Angiotensin II-induced Abdominal Aortic Aneurysm
Authors: Toru Miyoshi, Tomoko Yonezawa, Masashi Yoshida, Satoshi Akagi, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito
Journal: Circulation (2014)

Introduction: Abdominal aortic aneurysm (AAA) is a common disease characterized by chronic inflammation and degradation of extracellular matrix. Integrin alpha1beta1 is a major collagen receptor that is expressed on activated monocytes and involved as well as smooth muscle cells and fibroblasts. Integrin alpha1beta1 play an impotent role in the regulation of feedback inhibition of collagen synthesis in vessel wall. We investigated the role of integrin alpha1beta1 using murine angiotensin II-induced AAA model in which alpha1 integrin was deficient.

Methods: Apolipoprotein E -/- mice that were either alpha1 +/+ or alpha1 -/-, were infused with either saline or angiotensin II (1000 ng/kg per minute) for 28 days via mini-osmotic pumps.

Results: An increase in systolic blood pressure was observed equivalently in both groups. Deficiency in integrin aplha1 did not reduce the external diameters after 28 day (1.6 ± 0.29 mm [alpha1 +/+] vs. 1.73 ± 0.69 mm [alpha1 -/-], p=NS)(Fig A). Interestingly, Kaplan-Meier survival curves revealed that the alpha1 -/- mice (n=36) were decreased in death due to aortic rupture compared to the alpha1 +/+ mice (n=36) (p=0.04, Fig B). Next, quantitative real time PCR was performed at day 7 and at day 28. The increase in IL-6 in aortae at day 7 in the alpha1 +/+ was significantly reduced in the alpha1 -/- group. Matrix metalloproteinase (MMP)-2 and MMP-9 in aortae were increased at day both in the alpha1 -/- and the alpha1 +/+ groups similarly. Of note, increase in type 1 collagen at day 7 in the alpha1 -/- was significantly greater than that in the alpha1+/+.

Conclusions: Our results suggest that Integrin alpha1beta1 is involved in susceptibility to aortic rupture in angiotensin II-induced AAA by the suppression of inflammation and the augmentation of collagen synthesis.

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Liver stiffness as a novel marker of metabolic syndrome
Authors: E.K. Gan, J.K. Olynyk, J.A. Marsh, O.T. Ayonrinde, T.A. Mori, L.J. Beilin, L. Adams
Journal: Hepatology (2012)

Background Liver stiffness measurement by transient elastography is an attractive non-invasive method for the detection of fibrosis and cirrhosis in chronic liver diseases. Gender, obesity and metabolic syndrome are risk factors for fibrosis in chronic liver disease however their impact upon fibrosis among the general population is unclear. Aims To prospectively explore the relationship between liver stiffness and metabolic factors in a population-based cohort of young adults. Methods Liver stiffness measurements (LSM) were assessed using transient elastography in 1241 subjects from the Western Australian Pregnancy (Raine Study) Cohort from May 2010 to March 2012. Assessment included medical questionnaire, alcohol intake, anthropometric measurements, fasting serum liver function and biochemistry. Central obesity, hypertension and the metabolic syndrome (MS) were defined according to International Diabetes Federation (IDF) criteria. Linear regression was used to determine associations between log transformed LSM and components of the metabolic syndrome, BMI and sex. Results Of the 1241 subjects assessed (634 [51%] males, mean age 20 years), 265 (21%) had central obesity, 206 (17%) had systolic hypertension and 57 (4.6%) had the metabolic syndrome based on IDF definitions. LSM was reliably determined by the interquartile range (IQR)/LSM ≤ 0.3, ≥10 valid scans and success rate ≥ 60%, in 1153/1241 (93%). Median LSM was higher in males than females (5.3 kPa [IQR 4.6–6.3 kPa] vs 4.5 kPa [IQR 3.7–5.4 kPa] p < 2 × 10–16). LSM greater than 7.9 kPa, which is predictive of significant fibrosis, was more common in males than females (51 (8.6%) vs 19 (3.4%); p = 0.0002). LSM was significantly higher in obese subjects (median: 5.2 vs 4.9 kPa; p = 0.027) and subjects with raised SBP or DBP (5.4 vs 4.8 kPa, p = 2 × 10–9) and the metabolic syndrome (median: 5.7 vs 4.9 kPa, p = 0.0002). However, in the multivariate analysis, central obesity (p = 0.002) and raised SBP (p = 0.007) but not IDF MS were associated with increased log LSM. Conclusion Obesity and hypertension are associated with greater liver stiffness in the general population of young adults. These metabolic factors should be targeted to prevent the development of significant hepatic fibrosis.
Features in the Architecture of Physiological Function
Authors: Joseph Sir Barcroft
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Statins induce cell death in ovarian cancer cells through activation of the intrinsic pathway
Authors: Mauricio Cuello, Sumie Kato, Anil Sadarangani, Jorge Branes, David Mayerson, Roger Gejman, Gareth Owen
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4366 

Ovarian cancer constitutes one of the main causes of death from gynecological cancers worldwide. In spite of an excellent initial response with the use of aggressive cytoreductive surgery plus adjuvant chemotherapy the overall survival is poor. Thus, finding of new modalities of treatments remains a major challenge when dealing with advanced stages of this disease. During last years evidence has been published supporting pleitropic effects of statins beyond their better known effect, this is, the cardioprotective effect due to beneficial changes in lipid metabolism and in the inflammatory response involved in atheroma plaque formation. Statins, HMG-CoA reductase inhibitors, would induce cell death in some epithelial cancers (i.e. breast cancer) but the explanatory mechanisms are not well characterized. Objectives: We investigated if statins induce apoptosis in ovarian cancer cell lines and what are the mechanisms explaining this effect. Methods: Dose (0-10 uM) and time (0-72h) response curves were built for two statins (lovastatin and simvastatin) in two cancer cell lines (A2780 and UCI101) and in primary cultured ovarian cancer cells (established from advanced epithelial ovarian cancers). Cell viability was studied by MTS assays. Apoptosis was confirmed through DNA laddering and W-B of different proteins involved in the apoptotic cascade. Results: Both lovastatin and simvastatin induce cell death in all the ovarian cancer cells tested in a dose and time dependent manner. Statins did not affect primary cultured normal ovarian epithelial cells. W-B analysis demonstrated that statins induce caspase-mediated apoptosis through activation of the intrinsic pathway (decrease in BAD, cytochrome C release, and caspase-9 activation). The use of non-selective (ZVAD-fmk) and selective (caspase-9) caspase inhibitors almost completely reverted this effect. PI3K/AKT and MAPK signaling pathways were also involved. Active forms of both kinases (i.e. phospho-Akt) are decreased upon statin incubation. This effect was confirmed in EGFR overexpressing ovarian cancer cells in which statin preincubation (about 1h) resulted in significant decreased of Akt phosphorylation induced by EGF exposure (15 min). Conclusions: Both lovastatin and simvastatin induce cell death in ovarian cancer cells through activation of the intrinsic pathway. Further studies are prompted to discover potential uses of statins in ovarian cancer treatment. (supported by Fondecyt 1050744 and 1060495)
Abstract P447: Cellular Adhesion Molecules: Early Indicators of Subsequent Clinical Cardiovascular Disease Events in a Young Adult Population. The CARDIA Study.
Authors: Myron D Gross, Andrew O Odegaard, Suzette J Bielinski, Jose R Suarez-Lopez, J. Jeffrey Carr, Daniel A Duprez, Cora E Lewis, Leslie Lange, David R Jacobs, Alex P Reiner
Journal: Circulation (2014)

Background: Cellular adhesion molecules (CAM) have a central role in the accumulation of circulating leukocytes at sites of vascular injury, infection and/ inflammation, and have been associated with the development of atherosclerotic plaque and coronary artery disease in mature adults. Objective: To test the hypothesis that higher overall circulating CAM levels in young adults predict cardiovascular disease (CVD) events over the next 18 years. Method: We measured several circulating CAM molecules (ICAM-1, P-selectin, E-selectin and VCAM) in the Coronary Artery Risk Development in Young Adults (CARDIA) study at exam year 7 (1992-93, black and white men and women, CVD-free, mean age 32, range 25-37 years, n=2428) and monitored incident CVD events (n=70, including coronary heart disease, stroke, and heart failure, adjudicated based on medical records) through exam year 25, mean age of 50 years. We ranked each CAM in quintiles (coded 0-4) and summed the ranks across CAMs into an index to examine the association with incident CVD with Cox regression models. Results: Unadjusted cumulative CVD event rates were 1.6% (sum of CAM quartile ranks 0-8: 22 events in 1353 participants), 2.3% (sum of ranks 9-12: 29/813), and 7.3% (sum of ranks 13-16: 19/262). In proportional hazards regression analysis adjusted for year 7 age, sex, race, clinic, education, smoking, diet, physical activity, body mass index, blood pressure, blood lipids, and blood glucose, sum of ranks 13-16 were associated with a higher risk of CVD compared to the referent (rank sum 0-8) (See Table). Conclusion: High levels of circulating CAMs at an early stage of adulthood (mean age 32, range 25-37 years) were associated with an increased risk of incident CVD events. CAMs may be an early biomarker for development of subclinical CVD, even in CVD-free young adults with low atherosclerosis burden and decades prior to the development of clinical CVD.
Genotoxic effects of alpha-endosulfan and beta-endosulfan on human HepG2 cells.
Authors: Y Lu, K Morimoto, T Takeshita, T Takeuchi, T Saito
Journal: Environmental Health Perspectives (2000)

alpha-Endosulfan and ss-endosulfan are isomers of endosulfan, a pesticide used worldwide. In this study, we examined the genotoxicity of [alpha]- and ss-endosulfan in vitro with a HepG2 cell line. We used sister chromatid exchanges (SCE), micronuclei (MN), and DNA strand breaks as detected by single-cell gel electrophoresis (SCG) assays as biomarkers to judge the genotoxicity of [alpha]- and ss-endosulfan at concentrations from 1 times 10(-12) M to 1 times 10(-3) M. After treating HepG2 cells for 48 hr with ss-endosulfan, SCE showed a significant increase at concentrations from 1 times 10(-7) M to 1 times 10(-5) M, and MN showed a significant increase at concentrations from 5 times 10(-5) M to 1 times 10(-3) M. [alpha]-Endosulfan failed to show significant effects in both the SCE and MN assays. After treating HepG2 cells with [alpha]- or ss-endosulfan for 1 hr, DNA strand breaks were significantly induced by [alpha]-endosulfan at concentrations from 2 times 10(-4) M to 1 times 10(-3) M, and by ss-endosulfan at 1 times 10(-3) M. The results of this study suggest that both [alpha]- and ss-endosulfan are genotoxic to HepG2 cells and that the genotoxicity of ss-endosulfan seems stronger than that of [alpha]-endosulfan.
Life at the margins
Authors: Mary E. Moore, Thomas Borén, Jay V. Solnick
Journal: Gut Microbes (2011)

Helicobacter pylori is the primary cause of peptic ulcer disease and is estimated to account for about 60% of all cases of gastric cancer, the second most common cause of cancer death worldwide. Among the H. pylori virulence factors associated with disease, in addition to the well-known cag pathogenicity island, is the BabA adhesin, an outer membrane protein that binds with high affinity to fucosylated glycans on the gastric epithelium, such as Lewis B (Leb) and related terminal fucose residues found on the blood group O (H antigen), A and B antigens. BabA-mediated attachment to the gastric mucosa promotes chronic inflammation and gastric pathology, which from the bacterial perspective carries both risks and benefits. We recently described modulation in expression of BabA and related outer membrane proteins that occurs during colonization of experimental animals. Here we put these findings into a broader context, and speculate on their implications for the host-pathogen relationship.
Abstract 18219: TGR5 - a Novel Membrane Receptor for Bile Acids Regulates Myocardial Response to Exercise, Catecholamine and Pressure Overload Induced Stress
Authors: Moreshwar S Desai, Zina Eblimit, Saul J Karpen, David D Moore, Daniel J Penny
Journal: Circulation (2014)

Introduction: Perturbations in cardiac metabolism precede overt contractile failure and offer an early target for intervention and cure. Novel G protein coupled bile acid membrane receptor TGR5 regulates metabolism and function in brown adipose and skeletal muscles in mice. TGR5 is expressed in the hearts of mice and humans, but its role in myocardial cell biology and stress response is unknown. Hypothesis: We hypothesize that TGR5 deletion in mouse hearts impairs exercise tolerance, catecholamine response and exaggerates Transverse Aortic Constriction (TAC) induced contractile failure. Methods: Cardiomyocyte specific TGR5 deleted mice (TGR5flox/flox/cre+ [CM-TGR5del]) were generated from TGR5 floxed mice and transgenic αMHCcre mice. After confirmation of successful deletion at protein and RNA level, 12 week old male CM-TGR5del mice and their littermate (TGR5flox/flox/cre-[WT]) controls underwent baseline echocardiography (2DE), treadmill stress tests, acute catecholamine (isoprenaline [20mcg/kg i.p]) cha...
Similar repopulating capacity of mitotically active and resting umbilical cord blood CD34+ cells in NOD/SCID mice
Authors: Jannine Wilpshaar, J. H. Frederik Falkenburg, Xia Tong, Willy A. Noort, Robert Breese, Doug Heilman, Humphrey Kanhai, Christie M. Orschell-Traycoff, Edward F. Srour
Journal: Blood (2000)
Abstract 3979: NSC305787 inhibits specific protein–protein interactions involving ezrin in osteosarcoma cells
Authors: Haydar Celik, Jenny Han, Sung-Hyeok Hong, Gulay Bulut, Jeffrey Toretsky, Aykut Uren
Journal: Cancer Research (2014)

Abstract Osteosarcoma (OS) is the malignant tumor of bone that is most common in children and adolescents. OS is characterized by a high propensity for metastasis, especially to lungs, which is the main cause of death. The membrane-cytoskeleton cross-linker ezrin plays a key role in the metastatic progression of OS. In our earlier studies, we discovered that a small molecule, NSC305787, directly binds to ezrin and inhibits its function related to metastatic phenotype. In order to gain a better insight into the molecular mechanisms of NSC30787 action, an affinity pull-down coupled mass spectrometry was conducted to find the putative ezrin-interacting proteins whose interaction with ezrin is decreased or lost in the presence of NSC305787. Detailed mass spectrometry analysis identified 78 proteins after filtering for the potential background contaminants. Out of 78 proteins, 9 proteins were known ezrin-binding proteins including ezrin, radixin, moesin, polyadenylate-binding protein 1 (PABP-1), Na(+)/H(+) exchange regulatory cofactor (NHERF1/EPB-50), calpains, epidermal growth factor receptor kinase substrate 8 (EPS8), protein kinase C ioto (PKC-ioto) and focal adhesion kinase (FAK). For the remaining 69 proteins, we immunoprecipitated ezrin from K7M2 OS cells, and then western blotted for 8 selected functionally relevant proteins in order to test the validity of our approach. Of these 8 candidate proteins, Co-IP experiments verified binding of ezrin to 5 novel binding partners including DDX3 RNA helicase, caprin-1, AEG-1/MTDH/LYRIC, Rho guanine nucleotide exchange factor 2 (GEFH1) and catenin delta-1 (p120-catenin). NSC305787 effectively reduced the binding of DDX3 RNA helicase, AEG-1/MTDH/LYRIC and GEFH1 to ezrin in Co-IP experiments. Direct binding of ezrin to DDX3 RNA helicase was also demonstrated by surface plasmon resonance analysis using Biacore instrument. In conclusion, our results suggest that NSC305787 can modulate ezrin function through blocking its interaction with crucial proteins involved in adhesion, migration, invasion and survival. We also identified novel ezrin interactors that are involved in different levels of mRNA metabolism suggesting a completely new molecular function of ezrin that is independent from its classic role as a membrane cytoskeletal cross-linker at the plasma membrane. Thus, these results highlight novel molecular mechanisms for ezrin in cancer metastasis. Citation Format: Haydar Celik, Jenny Han, Sung-Hyeok Hong, Gulay Bulut, Jeffrey Toretsky, Aykut Uren. NSC305787 inhibits specific protein–protein interactions involving ezrin in osteosarcoma cells. [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 3979. doi:10.1158/1538-7445.AM2014-3979
Abstract 10625: Inflammatory Cytokines Modulate Left Ventricular Diastolic Function Through Downregulation of Sarcoplasmic Reticulum calcium Atpase
Authors: Chokai Wu, Jen-Kuang Lee, Chia-Ti Tsai, Fu-Tien Chiang
Journal: Circulation (2011)

Background  The inflammatory process is associated with cardiac diastolic dysfunction. We evaluated the mechanism from cellular models to patients with high inflammation status.   Materials and Method  An ≈1.75-kb promoter region of  SERCA2  gene was cloned to pGL3 luciferase vector. The direct effects of cytokines on  SERCA2  gene expression in HL-1 cardiomyocytes were examined by promoter activity assay, followed by western analysis, RT-PCR and also diastolic calcium decay. We further evaluated the mechanisms in 2 study groups. 101 continuous ambulatory peritoneal dialysis (CAPD) patients along with 120 controls (group 1) and 102 otherwise-healthy obese adults (group 2) were enrolled. The participants were classified as having LV diastolic dysfunction by echocardiography. In group 1, the correlation of cytokines and diastolic dysfunction were compared between CAPD patients and controls. Multivariate regression analysis was made to distinguish the interaction between cytokines and CAPD for LV diastolic dysfunction. In group 2, all participants received computerized tomography to determine central obesity. The relationship between inflammation, visceral adipose tissue (VAT) and diastolic dysfunction were evaluated by multivariate regression analysis and path analysis.   Results  Inflammatory cytokines decreased the promoter activity of the 1754-bp promoter -receptor construct of the  SERCA2  gene. The levels of  SERCA2  protein and mRNA also changed after treatment of cytokines. In study group 1, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD*TNF-α: OR: 1.45, 95% CI: 1.13 - 1.79, P=0.004). In study group 2, the relationship between VAT and LV diastolic dysfunction became insignificant when CRP was introduced into the model, although CRP itself was significantly associated with LV diastolic dysfunction (OR: 1.32, 95% CI: 1.01∼1.72, p=0.04).   Conclusions  Inflammatory cytokines may cause diastolic dysfunction through downregulation of  SERCA2  gene. Higher amounts of VAT were associated with low-grade inflammation and may lead to LV diastolic dysfunction. In CAPD patients, a synergistic effect between CAPD and inflammation would further aggravate LV diastolic dysfunction.
A Novel Program Seeks to Take Clinical Scientists Off the Endangered Species List
Authors: M J Friedrich
Journal: JAMA (2003)

NEARLY A QUARTER OF A CENtury ago, James Wyngaarden, MD, then director of the National Institutes of Health (NIH), warned that physician-scientists were becoming an endangered species (N Engl J Med. 1979;301:1254-1259). Since that time alarms have continued to sound about this disappearing breed, and especially the clinical investigator. To help reverse this disturbing trend, University of Pittsburgh School of Medicine has launched the Clinical Scientist Training Program. This novel initiative is aimed at enticing medical students to become physicianscientists by exposing them to a smorgasbord of clinical research experiences and providing mentoring and financial support to encourage their development.