tbuckley/cabot-search huggingface dataset:
Abstract 15961: Syncytial Model of Type 2 Long QT Syndrome Derived From Human iPS Cells Can Be Paced and Responds to Ikr Block and Activation
Authors: Renjun Zhu, Rosy Joshi-Mukherjee, Adriana Blazeski, Kenneth R Boheler, Gordon F Tomaselli, Leslie Tung
Journal: Circulation (2014)

Type 2 long QT (LQT2) syndrome is a cardiac disorder associated with hERG channel mutation that may lead to tachyarrhythmia and sudden death. We developed a syncytial model of cardiomyocytes (CMs) differentiated from iPS cells derived from an LQT2 patient harboring an A422T mutation. The A422T mutation has been shown to cause a marked decrease in IKr current mainly due to a trafficking defect in the hERG channel. Immunostaining of cTnI revealed that CMs were isotropically distributed with well-formed sarcomeres. Both wild type (WT) and LQT2 monolayers were stable in culture for at least 60 days with spontaneous activity, and could be paced at cycle lengths (CL) from 2000 down to 300 ms. After staining the monolayers with di-4-ANEPPS, optical mapping showed that all monolayers formed a functional syncytium that supported propagating action potentials. LQT2 monolayers had longer APD80s than WT monolayers (332±43 ms, n=6, vs. 267±46 ms, n=18, mean±SD, CL = 700 ms, p&lt;0.005), showing the delayed repolarization expected of the LQT2 phenotype. Reentrant spiral waves were observed in LQT2 (n=2), but not WT monolayers. Application of 0.2μM E-4031 (IKr blocker) slowed repolarization and prolonged APD80 in both WT and LQT2 monolayers, and slowed conduction velocity in WT monolayers (4.7±1.0 cm/s, n=6 vs. 10.4±1.4 cm/s, n=11 control, CL = 1000 ms). The slowing effect may reflect a role of IKr in setting the maximum diastolic potential in these CMs where IK1 is weakly expressed, as has been recently suggested. Application of 10μM ML-T531 (IKr activator) shortened APD80 in LQT2 monolayers (313±36 ms vs. 162±19 ms, n=4, p&lt;0.0001), showing successful reversal of the LQT phenotype. ML-T531 also shortened APD80 in WT monolayers (202±43 ms vs. 154±26 ms, n=4, p&lt;0.04). These results indicate that syncytial models of heritable cardiac disease are feasible and may be useful for studying drug effects that affect electrophysiology and arrhythmogenesis.
Abstract 243: Roles of TNF alpha and MCP-1 in Type II Diabetes-induced Endothelial Dysfunction
Authors: Jiyeon Yang, Abbott C Louise, Cuihua Zhang
Journal: Circulation (2007)

Tumor necrosis factor alpha (TNF) is reported to underlie a component of vascular inflammation and ensuing endothelial dysfunction in diabetes, but the role of inflammatory cells in these events is unknown. Because TNF reportedly induces monocyte chemoattractant protein-1 (MCP-1) expression, we hypothesized that the interaction between TNF and MCP-1 contributes to the evolution of vascular inflammation in diabetes. To test this hypothesis, expression of TNF and MCP-1, and formation of nitrotyrosine (N-Tyr, an indicator of peroxynitrite production) were determined in isolated coronary arterioles (50–100um) from genetically modified mice with Type II diabetes (Lepr db ) and the lean control heterozygotes (m Lepr db ). Protein and mRNA expression of TNF, protein expression of MCP-1, and presence of N-Tyr were significantly increased in arterioles from Lepr db mice compared to those from m Lepr db . Immunofluorescence double labeling revealed the prominent localization of MCP-1 to endothelium (Von Willebrand factor) of arterioles and venules. MCP-1 also co-localized with macrophages (CD68) in the heart tissue. To determine if MCP-1 may be key to the vascular inflammation and ensuing endothelial dysfunction, we administered anti-MCP-1 (10 μg/day, 3 days, i.p., n=4; to block MCP-1 signaling) in the mice and then determined endothelial dilation in isolated, cannulated pressurized (60 cmH2O) arterioles. Anti-MCP-1 restored dilation to acetylcholine in Lepr db mice by 35±2% (P&lt;0.05 vs Lepr db mice without treatment, 9.8±4%) but did not affect dilation in m Lepr db mice. To establish interactions between TNF and MCP-1, we administered anti-TNF (72hr treatment; 0.625mg/kg, i.p.) to block TNF signaling and determined effects on MCP-1 and oxidative stress. After anti-TNF administration, expression of MCP-1 was decreased and numbers of MCP-1 positive cells were markedly reduced in Lepr db mice. Moreover, anti-TNF prevented the formation of N-Tyr in Lepr db mice. These findings demonstrate that the endothelial dysfunction occurring in type II diabetes is the result of the effects of the inflammatory cytokine TNF and TNF related signaling, including the expression of MCP-1, which also furthers the oxidative stress.
Abstract 286: The Efficacy of Real-Time Monitoring by Regional Cerebral Oxygen Saturation During Chest Compression Cardiopulmonary Resuscitation for Avoiding Poor Neurological Outcome
Authors: Tomohiko Orita, Yukitoshi Toyoda, Yoshimi Nakamichi, Motoyasu Yamazaki, Tomohiro Funabiki, Masayuki Shimizu, Shoukei Matsumoto, Tomohiro Sato, Yousuke Kobayashi, Nao Hiroe, Taku Kazamaki, Mitsuhide Kitano
Journal: Circulation (2014)

Backgrounds and Objective: It has suggested that some real-time monitoring system during cardiopulmonary resuscitation (CPR) would need for better neurological outcomes of post cardiac arrest syndrome (PCAS) patients. Recently some studies have reported that regional cerebral oxygen saturation (rSO2) of out of hospital cardiac arrest (OHCA) patients would be one of the promising predictor for neurological outcomes of them. But it is still unclear the relationships between rSO2 level during CPR and neurological outcomes in PCAS patients. So we studied whether the rSO2 values during CPR is useful as a real-time monitoring in OHCA patients. Methods: Consecutive 121 non-traumatic OHCA patients who were admitted to our critical care unit after ROSC and could evaluate the neurological outcomes in 90th days after cardiac arrest for the latest forty-eight months were included. The level of rSO2 were monitored at three phases, Phase1; during manual chest compression, Phase2; compressing by automatic chest compress...
Improvement of glioblastoma control by combining the VEGF blocker, VEGF trap with fractionated radiotherapy: impact of scheduling
Authors: Phyllis Wachsberger, Randy Burd, Tara Strickler, Constantine Daskalakis, Jocelyn Holash, George Yancopoulos, Adam Dicker
Journal: Cancer Research (2006)

4391    Background:  VEGF Trap, an anti-VEGF angiogenesis inhibitor, was previously found to enhance the efficacy of single dose and fractionated radiotherapy in a human glioblastoma xenograft model. The objective of the present study was to determine if glioblastoma control could be optimized by examining three different scheduling protocols for VEGF Trap plus radiation therapy.  Methods:  U-87 cells were injected subcutaneously into the right hind limb of athymic NCR NUM mice. VEGF Trap was administered at two doses [high (10 mg/kg) or low (2.5 mg/kg)] every third day for up to three weeks. Radiation (RT) was administered as three daily fractions of 5 Gy each on days 0, 1 and 2. Scheduling of VEGF Trap was either (I) one week prior to, (II) concurrent with or (III) on day 3 following radiation treatment. Analysis of data was performed by using mixed-effects linear regression to model tumor volume as a function of time and treatment. Imaging of VEGF Trap-treated tumors was performed by 18-Fluorodeoxyglucose (FDG) PET analysis. Immunostaining for microvessel density (MVD) was performed using PECAM-1 antibodies.  Results:  Tumor volume in the untreated groups increased at an average rate of 27–31% per day. RT alone or VEGF Trap alone significantly reduced average tumor volume growth rate to 11-17% per day in all three experiments (p Conclusions:  Low dose VEGF Trap plus fractionated radiotherapy is superior than either treatment modality alone in U87 glioblastoma control. These data further indicate there may be an advantage to scheduling VEGF Trap prior to radiation and warrant additional investigation in other tumor models and the clinic. (This work was supported by grants from the Radiation Therapy Oncology Group, Regeneron Pharmaceuticals, Inc. and Sanofi-Aventis.)
Distribution of fluconazole-resistant Candida bloodstream isolates among hospitals and inpatient services in Israel
Authors: R. Ben-Ami, G. Rahav, H. Elinav, I. Kassis, I. Shalit, T. Gottesman, O. Megged, M. Weinberger, P. Ciobotaro, P. Shitrit, G. Weber, A. Paz, D. Miron, I. Oren, J. Bishara, C. Block, N. Keller, D.P. Kontoyiannis, M. Giladi
Journal: Clinical Microbiology and Infection (2012)
BLINDNESS FOLLOWING MASSIVE GASTROINTESTINAL HEMORRHAGE
Authors: A T HAEREM
Journal: Annals of Internal Medicine (1952)

Case Reports1 March 1952BLINDNESS FOLLOWING MASSIVE GASTROINTESTINAL HEMORRHAGEALF T. HAEREM, M.D., F.A.C.P.ALF T. HAEREM, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-3-883 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFew physicians encounter blindness as a complication of severe hemorrhage. First-hand experience with this dramatic and disastrous complication is vividly remembered. Since the medical literature contains few accounts of this complication, the following case is reported.CASE REPORTA conscientious 45 year old factory maintenance engineer held a very responsible position during World War II and was under severe nervous strain. On June 16, 1946, he attended a party and had several cocktails. The following day he had some mild indigestion but continued to work. On the morning of June 18 he awoke feeling weak, clammy and thirsty. At 9...Bibliography1. KirsnerPalmerRickettsBuserMarshall JBWLWEJWHC: Gastroenterology: a review of literature from July 1947 to July 1948, Arch. Int. Med. 83: 552-592, 677-721, 1949; 84: 321-355, 449-520, 1949. CrossrefGoogle Scholar2. Duke-Elder WS: Textbook of ophthalmology, vol. 3, 1941, C. V. Mosby, St. Louis, pp. 2556-2560. Google Scholar3. HollenhorstWagener RWHP: Loss of vision after distant hemorrhage, Am. J. M. Sc. 219: 209-219, 1950. CrossrefMedlineGoogle Scholar4. Welch CE: Treatment of acute massive gastroduodenal hemorrhage, J. A. M. A. 141: 1113-1119, 1949. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Redwood City, California*Received for publication March 24, 1950. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byVisual Loss Following Spine SurgeryIschemic Optic Neuropathy After Hemiarthroplasty for Femoral Neck FractureBilateral Retrobulbar Optic Nerve Infarctions after Blood Loss and HypotensionDissecting Aneurysm of the Aorta 1 March 1952Volume 36, Issue 3Page: 883-888KeywordsBlindnessEmotionsEngineersGastrointestinal hemorrhageHemorrhageOphthalmology ePublished: 1 December 2008 Issue Published: 1 March 1952 PDF downloadLoading ...
A memorable patient: An unmerciful end
Authors: R H Soper
Journal: BMJ (2001)

I was doing my visits when the surgery telephoned me. Ambulance Control had called—a crew were attending an 82 year old woman who had collapsed—would I go? Three weeks before, Phyllis had had a coronary event; she was treated at home by one of my partners and was doing quite well. Her daughter Diane had called to make some lunch. For the first time since she was ill, Phyllis said she would have some pudding. As she ate, she suddenly clutched her chest, gasped, gazed at her daughter, and died, falling from her chair. Diane, in her anxiety, did what most people would probably do—telephoned the emergency services.

As I drove into the quiet little cul de sac of terraced council houses, I saw, there at the end and occupying …
Abstract 17083: Assessment of Both Coronary Microvascular Damage and Left Ventricular Chamber Stiffness after Successful Percutaneous Coronary Intervention Predicts In-Hospital Cardiac Complications and Left Ventricular Remodeling in ST-Segment Elevation Myocardial Infarction
Authors: Atsushi Yamamuro, Koichi Tamita, Shuichiro Kaji, Takeshi Kitai, Yutaka Furukawa, Junichi Yoshikawa
Journal: Circulation (2014)

Background: In ST-segment elevation myocardial infarction (STEMI), the short deceleration time of left ventricular (LV) early filling by Doppler is a powerful independent predictor of clinical cardiac events. It has also been reported that the coronary flow velocity pattern in patients with microvascular obstruction is characterized by the presence of early systolic retrograde flow and a rapid diastolic deceleration time (DDT). The purpose of this study was to examine the effects of both microvascular damage and LV chamber stiffness on cardiac complications and LV remodeling after successful percutaneous coronary intervention (PCI) in STEMI patients. Methods: Two hundred and one consecutive patients with first anterior STEMI were studied following successful PCI. Microvascular damage was evaluated on the basis of coronary flow velocity patterns using Doppler guidewires. We defined the presence of microvascular obstruction as DDT ≤600 ms and the presence of systolic flow reversal. LV filling patterns were determined by LV inflow pulsed-wave Doppler examination on day 3 after STEMI. Deceleration time ≤130 ms was defined as restrictive. We classified patients into three categories: without restrictive and microvascular obstruction (group 1, n=116), with restrictive or microvascular obstruction (group 2, n= 38), and with restrictive and microvascular obstruction (group 3, n=47). Left ventriculograms were obtained immediately and 6 months after PCI. LV remodeling was defined as an increase in end-diastolic volume index ≥20%. The clinical event rate was compared among the 3 groups. Results: The in-hospital event rates for LV thrombus (2/116 [2%], 5/38 [13%] and 14/47 [30%], respectively; P &lt; 0.01) and congestive heart failure (5/116 [4%], 10/38 [26%], and 22/47 [47%]; P &lt; 0.01) were highest in group 3 and lowest in group 1. Group 3 was at the highest risk of LV remodeling, while group 1 was at the lowest (7/116 [6%], 14/38 [37%], and 39/47 [83%]; P &lt; 0.01). Conclusions: Assessment of both microvascular damage and LV chamber stiffness can accurately predict in-hospital complications and LV remodeling in STEMI patients who underwent successful reperfusion of the infarct-related coronary artery, identifying a subset of high risk patients.
Atlas der Augenkrankheiten: Sammlung typischer Krankheitsbilder mit kurzen diagnostischen und therapeutischen Hinweisen
Authors: Rudolf Thiel
Journal: JAMA (1949)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Constitutive overexpression of Nrf2-dependent HO-1 confers resistance to apoptosis by EGCG in human lung adenocarcinoma A549 cells
Authors: Mee-Hyang Kweon, Mohammad Saleem, Hasan Mukhtar
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4891 

Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea is a widely studied cancer chemopreventive and anticancer agent. The major mechanism of EGCG-mediated anticancer effects appears to be related to induce apoptosis of cancer cells. Studies have shown differential sensitivity to EGCG between tumor cells or tumor cells versus normal cells. EGCG has been shown to modulate multiple but different signal transduction pathways depending on the cell types. These may be due to the differential oxidative status imposed by EGCG or differential expression level of endogenous antioxidant defense enzymes in different cells. Heme oxygenase-1 (HO-1) is known to be induced by a variety of stress stimuli and represents a key enzyme for the protection of cells against oxidative tissue injury. However, in cancer cells HO-1 may contribute to growth advantage and cellular resistance against chemotherapy. We found that human lung adenocarcinoma A549 cells are markedly resistant to apoptosis induction by EGCG even at high concentrations (∼100 μM; 72 h). The lung cancer cells were found to express high constitutive HO-1 and Nrf2, as compared to other human epithelial cancer cells where EGCG leads to apoptosis. We investigated whether the constitutively elevated-HO-1 expression in A549 cells is associated with the observed exceptional resistance to apoptosis by EGCG. Employing two approaches: selective HO-1 inhibition with tin protoporphyrin (SnPPIX) and siRNA-mediated knockdown of HO-1 gene, we show that HO-1 blocking in A549 cells i) reduces cell proliferation; ii) upregulates p53, p21, and Bax; iii) sensitizes lung cancer cells to apoptosis induction by EGCG as well as by hydrogen peroxide and tert -butylhydroperoxide, suggesting a protective role of HO-1 against ROS-mediated apoptosis. In parallel with HO-1 upregulation, cellular Nrf2 was shown to be located in the nucleus and bound to antioxidant response element sequence, which suggests that the constitutive HO-1 expression is mediated by Nrf2 transcriptional activation. Additionally, we found that the transcriptional activation of Nrf2-targeted HO-1 mRNA and protein expression as well as cellular resistance to EGCG were decreased by inhibition of protein kinase C alpha (PKCα) and extracellular signal-regulated kinase (ERK). These effects were more profound by PKCα inhibitor, Ro317549, than by ERK inhibitor, PD98059, suggesting the involvement of an oxidative signaling pathway in the elavation of HO-1 expression. More importantly, we observed that EGCG at higher concentrations (>200 μM) could induce apoptosis and completely blocks HO-1 protein and mRNA by inhibition of PKCα phosphorylation as well as translocation and transactivation of Nrf2. Collectively, our results suggest a possibility that HO-1-, Nrf2- and PKCα-signaling pathways could be targets for lung cancer chemoprevention and chemotherapy.
Biomimetic Molecularly Imprinted Polymers as Smart Materials and Future Perspective in Health Care
Authors: Mohammad Reza Ganjali, Farnoush Faridbod, Parviz Norouzi
Journal: Advanced Healthcare Materials (2014)

This chapter contains sections titled: Molecularly Imprinted Polymer Technology Synthesis of MIPs Application of MIPs Biomimetic Molecules MIPs as Receptors in Bio-Molecular Recognition MIPs as Sensing Elements in Sensors/Biosensors MIPs as Drug Delivery Systems MIPs as Sorbent Materials in Separation Science Future Perspective of MIP Technologies Conclusion
Voriconazole N-oxide and its ultraviolet B photoproduct sensitize keratinocytes to ultraviolet A
Authors: K. Ona, D.H. Oh
Journal: British Journal of Dermatology (2015)

The antifungal agent, voriconazole, is associated with phototoxicity and photocarcinogenicity. Prior work has indicated that voriconazole and its hepatic N-oxide metabolite do not sensitize keratinocytes to ultraviolet B (UVB). Clinical observations have suggested that ultraviolet A (UVA) may be involved.To determine the photochemistry and photobiology of voriconazole and its major hepatic metabolite, voriconazole N-oxide.Voriconazole and voriconazole N-oxide were spectrophotometrically monitored following various doses of UVB. Cultured human keratinocytes were treated with parental drugs or with their UVB photoproducts, and survival following UVA irradiation was measured by thiazolyl blue metabolism. Reactive oxygen species (ROS) and 8-oxoguanine were monitored by fluorescence microscopy.Voriconazole and voriconazole N-oxide have varying UVB absorption but do not acutely sensitize cultured human keratinocytes following UVB exposure. However, sustained UVB exposures produced notable dose- and solvent-dependent changes in the absorption spectra of voriconazole N-oxide, which in aqueous solution acquires a prominent UVA absorption band, suggesting formation of a discrete photoproduct. Neither the parental drugs nor their photoproducts sensitized cells to UVB although all but voriconazole N-oxide were moderately toxic to cells in the dark. Notably, both voriconazole N-oxide and its UVB photoproduct, but not voriconazole or its photoproduct, additionally sensitized cells to UVA by greater than three-fold relative to controls in association with UVA-induced ROS and 8-oxoguanine levels.Voriconazole N-oxide and its UVB-photoproduct act as UVA-sensitizers that generate ROS and that produce oxidative DNA damage. These results suggest a mechanism for the phototoxicity and photocarcinogenicity observed with voriconazole treatment.
The hypothetical role of FoxO1 in acne is interesting, but more study is needed before any conclusions can be drawn
Authors: J.J. Leyden, H. Gollnick, D. Thiboutot, B. Dreno, V. Bettoli, S. Kang, A. Shalita, V. Torres
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, In a recent correspondence, Melnik1 proposed the hypothesis that upregulation of the Forkhead box O transcription factor (FoxO1) is the mechanism by which systemic isotretinoin exerts both its therapeutic benefit as well as its effect on triglyceride metabolism. This hypothesis is offered as an explanation for a previous hypothesis, generated by the same author, which raised the possibility that acne may be due to a deficiency of nuclear FoxO1.2 FoxOs are important regulatory proteins that modulate genes involved in acne pathophysiology including those for androgen receptors, cell proliferation, lipogenesis and inflammatory cytokines. FoxO1 levels also affect other cellular functions including DNA repair, apoptosis and glucose metabolism. However, there are no primary, experimentally derived data supporting the hypothesis that nuclear deficiency of FoxO1 has a key role in acne pathogenesis. If such a deficiency is a primary factor in acne pathophysiology, it is challenging to explain why acne resolves in most patients over time, even without treatment – the so‐called natural course of acne. Does it mean that during puberty a different response in the FoxO1 activity exists? Nuclear expression of FoxO1 could be influenced by growth factors such as elevated insulin‐like growth factor‐1 seen in growing teenagers with acne as well as by insulin levels, which, in turn, are influenced by diet. Decreased nuclear FoxO1 could influence androgen receptor expression, lipogenesis, follicular epithelial proliferation and toll‐like receptor‐induced inflammation – thus, all of the major areas of acne pathophysiology could be modulated by varying levels of this regulatory protein. While this hypothesis is certainly interesting, no primary evidence exists to permit a conclusion regarding the role of FoxO1 levels in patients with acne.