tbuckley/cabot-search huggingface dataset:
Abstract LB-400: STAT3 mediates resistance to MEK inhibitor through microRNA miR-17
Authors: Bingbing Dai, Jieru Meng, Michael Peyton, Luc Girard, William G. Bornmann, Lin Ji, John D. Minna, Bingliang Fang, Jack A. Roth
Journal: Cancer Research (2011)

Abstract AZD6244 is a small-molecule-based inhibitor targeting the MEK pathway that is currently in clinical trials. However, the mechanisms mediating intrinsic resistance to MEK inhibition remain to be completely characterized. To identify the molecular mechanism of MEK inhibitor resistance, we analyzed responses of 38 lung cancer cell lines following AZD6244 treatment and their genome-wide gene expression profiles and identified a panel of genes correlated with sensitivity or resistance to AZD6244 treatment. Ingenuity pathway analysis revealed that activation of the signal transducer and activator of transcription 3 (STAT3) pathway was associated with MEK inhibitor resistance. Inhibition of the STAT3 pathway using JSI-124, a STAT3-specific inhibitor, sensitized lung cancer cells to AZD6244 treatment and induced apoptosis in vitro and in vivo. Moreover, combining a STAT3 inhibitor with AZD6244 induced the expression of BIM and poly (ADP-ribose) polymerase (PARP) cleavage, whereas activation of the STAT3 pathway inhibited BIM expression and thus induced MEK inhibitor resistance. In addition, we found that miR-17, which is regulated by STAT3, played an important role in STAT3-mediated MEK inhibitor resistance by targeting BIM. Inhibition of miR-17 with anti-miR-17 sensitized resistant cells to AZD6244 by inducing BIM and PARP cleavage. We conclude that STAT3-mediated overexpression of miR-17 blocked BIM expression, which resulted in resistance to AZD6244. These results implicate novel alternative approaches for overcoming the MEK inhibitor resistance by combining AZD6244 with STAT3 inhibitors or miR-17 antagomirs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-400. doi:10.1158/1538-7445.AM2011-LB-400
RhoGDI-1 Modulation of the Activity of Monomeric RhoGTPase RhoA Regulates Endothelial Barrier Function in Mouse Lungs
Authors: Matvey Gorovoy, Radu Neamu, Jiaxin Niu, Stephen Vogel, Dan Predescu, Jun Miyoshi, Yoshimi Takai, Vidisha Kini, Dolly Mehta, Asrar B. Malik, Tatyana Voyno-Yasenetskaya
Journal: Circulation Research (2007)

Rho family GTPases have been implicated in the regulation of endothelial permeability via their actions on actin cytoskeletal organization and integrity of interendothelial junctions. In cell culture studies, activation of RhoA disrupts interendothelial junctions and increases endothelial permeability, whereas activation of Rac1 and Cdc42 enhances endothelial barrier function by promoting the formation of restrictive junctions. The primary regulators of Rho proteins, guanine nucleotide dissociation inhibitors (GDIs), form a complex with the GDP-bound form of the Rho family of monomeric G proteins, and thus may serve as a nodal point regulating the activation state of RhoGTPases. In the present study, we addressed the in vivo role of RhoGDI-1 in regulating pulmonary microvascular permeability using RhoGDI-1 −/− mice. We observed that basal endothelial permeability in lungs of RhoGDI-1 −/− mice was 2-fold greater than wild-type mice. This was the result of opening of interendothelial junctions in lung microvessels which are normally sealed. The activity of RhoA (but not of Rac1 or Cdc42) was significantly increased in RhoGDI-1 −/− lungs as well as in cultured endothelial cells on downregulation of RhoGDI-1 with siRNA, consistent with RhoGDI-1–mediated modulation RhoA activity. Thus, RhoGDI-1 by repressing RhoA activity regulates lung microvessel endothelial barrier function in vivo. In this regard, therapies augmenting endothelial RhoGDI-1 function may be beneficial in reestablishing the endothelial barrier and lung fluid balance in lung inflammatory diseases such as acute respiratory distress syndrome.
Keep general practice and secondary care separate
Authors: J. Fitton
Journal: BMJ (2012)

<h3>Abstract</h3> Good empirical applications of geometric morphometrics (GMM) typically involve several times more variables than specimens, a situation the statistician refers to as “high <i>p/n</i>,” where <i>p</i> is the count of variables and <i>n</i> the count of specimens. This note calls your attention to two predictable catastrophic failures of one particular multivariate statistical technique, between-groups principal components analysis (bgPCA), in this high-<i>p/n</i> setting. The more obvious pathology is this: when applied to the patternless (null) model of <i>p</i> identically distributed Gaussians over groups of the same size, both bgPCA and its algebraic equivalent, partial least squares (PLS) analysis against group, necessarily generate the appearance of huge equilateral group separations that are actually fictitious (absent from the statistical model). When specimen counts by group vary greatly or when any group includes fewer than about ten specimens, an even worse failure of the technique obtains: the smaller the group, the more likely a bgPCA is to fictitiously identify that group as the end-member of one of its derived axes. For these two reasons, when used in GMM and other high-<i>p/n</i> settings the bgPCA method very often leads to invalid or insecure bioscientific inferences. This paper demonstrates and quantifies these and other pathological outcomes both for patternless models and for models with one or two valid factors, then offers suggestions for how GMM practitioners should protect themselves against the consequences for inference of these lamentably predictable misrepresentations. The bgPCA method should never be used unskeptically — it is never authoritative — and whenever it appears in partial support of any biological inference it must be accompanied by a wide range of diagnostic plots and other challenges, many of which are presented here for the first time.
Guidelines for recertification
Authors: L. A. Brewer
Journal: JAMA (1976)

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
MECHANISM OF IMPROVEMENT IN MITRAL REGURGITATION IN THE ACUTE PHASE AFTER CARDIAC RESYNCHRONIZATION THERAPY
Authors: Michio Imai, Katsuomi Iwakura, Atsunori Okamura, Yasushi Koyama, Motoo Date, Yoshiharu Higuchi, Koichi Inoue, Ryusuke Kimura, Hiroyuki Nagai, Yuko Toyoshima, Makito Ozawa, Norihisa Ito, Yukinori Okazaki, Masahiko Shibuya, Shigemiki Omiya, Takashi Takagi, Daisuke Morisawa, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2010)
Angiosarcoma Presenting as Acute Rheumatic Pancarditis
Authors: William M. Lukash
Journal: JAMA (1965)

IT IS WELL recognized that primary cardiac tumors are rare and present with no characteristic clinical picture. The total number of primary heart tumors, benign and malignant, in the literature, now approaches 500 cases.<sup>1</sup> Crenshaw<sup>2</sup>described 12 cases of primary malignant hemangioendothelioma (angiosarcoma) of the heart. This case which presented as acute rheumatic fever with pancarditis is the 13th case of primary angiosarcoma of the heart to be reported. <h3>Report of a Case</h3> A 26-year-old white woman was transferred to the US Air Force Hospital, Marsh Air Force Base, Calif, on Oct 7, 1960, from a civilian hospital where she had been admitted one day earlier for an episode of unconsciousness. The patient had been in excellent health until one month prior to admission when she developed generalized malaise. One week prior to admission substernal pain developed that was relieved by sitting up and leaning forward. The patient
Differential Regulation of <scp>l</scp> -Arginine Transport and Nitric Oxide Production by Vascular Smooth Muscle and Endothelium
Authors: William Durante, Lan Liao, Irfan Iftikhar, William E. O’Brien, Andrew I. Schafer
Journal: Circulation Research (1996)

Abstract Since NO production is dependent on the availability of l -arginine, we examined whether l -arginine transport and NO synthesis are coregulated by vascular smooth muscle cells and endothelial cells cultured from the same vessel wall source. l -Arginine transport by both bovine aortic smooth muscle cells (BASMCs) and endothelial cells (BAECs) was primarily Na + independent (≈70%) and was mediated by both a high- and low-affinity transport system. Treatment of BASMCs with tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β) resulted in a significant increase in l -arginine transport (≈20%) and in the induction of NO release. Exposure of BASMCs to interferon gamma (IFN-γ) or lipopolysaccharide (LPS) also stimulated NO release but did not affect l -arginine transport. In contrast, incubation of BAECs with TNF-α or LPS strikingly enhanced l -arginine uptake (2.5-fold), whereas IL-1β and IFN-γ had no effect. Treatment of BAECs with any of the inflammatory mediators did not stimulate NO production. These results demonstrate that l -arginine uptake and NO synthesis by these cells are differentially regulated. In BASMCs, the coinduction of l -arginine transport and NO formation may function to provide increased levels of substrate to the cell during activation of the NO synthase enzyme. In contrast, the selective stimulation of l -arginine uptake in BAECs indicates that l -arginine transport is dissociated from NO generation in these cells.
Complement Is a Central Mediator of Radiotherapy-Induced Tumor-Specific Immunity and Clinical Response
Authors: Laura Surace, Veronika Lysenko, Andrea Orlando Fontana, Virginia Cecconi, Hans Janssen, Antonela Bicvic, Michal Okoniewski, Martin Pruschy, Reinhard Dummer, Jacques Neefjes, Alexander Knuth, Anurag Gupta, Maries van den Broek
Journal: Immunity (2015)
Recurrent Rectal Bleeding from an Appendiceal Stump Granuloma: A Rare Late Complication of Appendectomy
Authors: D. M. Kecmanovic, M. M. Bulajic, M. J. Pavlov, M. T. Micev, A. V. Sepetkovski, M. S. Ceranic, M. N. Petrovic, A. B. Stamenkovic
Journal: Endoscopy (2005)

Figure 1 A 25-year-old man underwent appendectomy for acute, gangrenous, nonperforating appendicitis; the stump was ligated with a linen suture and inverted. One year later, he developed recurrent rectal bleeding which got progressively worse and he was re-admitted to the regional hospital. After correction of his electrolyte imbalance and a blood transfusion, the bleeding stopped and he was discharged on day 6. The patient was admitted to our hospital 2 weeks later for further clinical examination and surgical treatment. Colonoscopy identified an inflammatory tumor of the cecum as the probable source of bleeding. He underwent an ileocecal resection and was discharged 5 days later, on day 12 of this hospital stay.
Relationship between plasma lipid concentrations and coronary artery disease in 496 patients.
Authors: A M Gotto, G A Gorry, J R Thompson, J S Cole, R Trost, D Yeshurun, M E DeBakey
Journal: Circulation (1977)

The relationship between fasting plasma cholesterol and triglyceride concentrations and the frequency and extensiveness of coronary artery disease (CAD) was studied in 496 subjects evaluated for chest pain by coronary arteriography at The Methodist Hospital. One hundred six of the patients had no CAD while 390 had 25% or greater stenosis of one or more major vessels. Ninety-one percent had 75% or greater stenosis of at least one major vessel. Mean age for the group with CAD was 55.7 +/- 8.7 and without disease 49.4 +/- 11.6 (P less than 0.01). Both cholesterol and triglyceride concentrations were higher (P less than 0.001) in the group with CAD. Mean cholesterol concentration in males increased from 195 +/- 36 mg/dl in the group without CAD to 219 +/- 41 in the group with three vessel disease and in females from 207 +/- 40 to 252 +/- 42. A progressive increase in triglyceride values was also detected but was less consistent. At the level of 25% and greater obstruction, the partial correlation coefficients between the number of vessels involved and the cholesterol and triglyceride concentrations, respectively, were +0.201 and +0.181.
T cells and erythroid burst forming units in chronic lymphocytic leukemia
Authors: Mark A. Socinski, William B. Ershler
Journal: American Journal of Hematology (1984)

Abstract Substantial evidence exists indicating T cell abnormalities in chronic lymphocytic leukemia (CLL). There is also evidence that the T cell is an important source of burst promoting activity (BPA) for the peripheral blood (PB) erythroid burst forming unit (BFU‐e). We studied the BPA of T cells and response of BFU‐e in normals and untreated early stage B cell CLL patients in a methylcellulose colony assay. Normal null cell cultures grew significantly more BFU‐e than CLL null cell cultures. Addition of autologous T cells to normal or CLL null cells significantly increased BFU‐e only in normals. Allogeneic coculture of T cells from CLL patients with null cells from normals yielded normal responses of BFU‐e in five of six cases. In contrast, allogeneic coculture of normal T cells with CLL null cells yielded a normal response in only one of six studies. Furthermore, adding increasing quantities of autologous or normal allogeneic T cells to CLL null cells did not augment the BFU‐e response. Accounting for the expanded lymphocyte pool in CLL, BFU‐e are decreased in concentration but the absolute number is normal or increased. The decrease in concentration could be secondary to expansion of the null cell fraction in CLL by pre‐B cells. CLL T cells appeared to augment normal allogeneic PB BFU‐e in a normal fashion, whereas, in several cases, CLL BFU‐e were hyporesponsive to autologous or normal allogeneic T cells. It is therefore apparent that in untreated early stage B cell CLL, erythroid progenitor cells are present in the peripheral blood but are diluted in an expanded null cell compartment and may, in some cases, be hyporesponsive to T cell BPA. T cell BPA of CLL T cells in this early stage of disease is preserved.
A collaborative study of infective endocarditis in the 1970s. Emphasis on infections in patients who have undergone cardiovascular surgery.
Authors: E L Kaplan, H Rich, W Gersony, J Manning
Journal: Circulation (1979)

Twenty-six major cardiovascular centers participated in a cooperative study of all cases of infective endocarditis occurring during a single calendar year to obtain an overview of infective endocarditis. The study was designed to learn which patients appear to be at highest risk to develop this infection after palliative or reparative cardiovascular surgery. Of 278 patients developing infective endocarditis during the year at these medical centers, 63 (23%) had had previous cardiovascular surgery and 215 had not. Seventy percent of the 278 patients had recognized congenital or acquired heart disease before developing the infection. Rheumatic heart disease accounted for over half of the patients with underlying structural heart disease. A majority (55%) of the 63 patients who had been operated on before developing endocarditis had prosthetic valves inserted. Of those who did not require prosthetic valves, the majority had congenital heart disease with systemic artery-to-pulmonary artery shunts. Although these data were obtained from a selected group of patients, they confirm a significant risk of endocarditis in patients with prosthetic valves and suggest that in postoperative patients with non-valvular congenital heart disease, the highest risk appears to be in cyanotic patients with palliative pulmonary artery-to-systemic artery shunts.
Sex-linked ichthyosis and placental sulphatase C deficiency
Authors: W.P. GROOT, A.C. JOBSIS, A. MARINKOVIC-ILSEN, J.G. KOPPE, H.W.A. BRUIJN
Journal: British Journal of Dermatology (1980)

Ichthyosis was diagnosed in six boys born from pregnancies in which placental steroid sulphatase deficiency was present. In four cases the diagnosis of sex‐linked ichthyosis was certain, in the other two the ichthyosis was probably of the sex‐linked type. No arylsulphatase C activity could be demonstrated histochemically either in the epidermis of these boys, or in the epidermis of adults with sex‐linked ichthyosis, whilst it was present in normal controls. In cultured skin fibroblasts steroid‐sulphatase activity was extremely low. We conclude that deficiency of steroid sulphatase C or arylsulphatase C or a third functionally linked enzyme is an important factor in the pathogenesis of sex‐linked ichthyosis.
Plantar Wart Ulcers From Radiodermatitis
Authors: Robert A. Berger
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In their article "Definitive Treatment of Intractable Plantar Ulcers" (<b>196</b>:311, 1966), Drs. Murray and Goldwyn state that "In nine cases the etiology of the ulcer was a plantar wart." Two paragraphs later, in discussing "plantar wart ulcers," the authors note that "All patients at some time had undergone local radiation therapy...." However, the authors seem more impressed by the fact that not every area of the sole which receives x-ray treatment subsequently ulcerates than by the fact that each and every patient with a so-called plantar wart ulcer in their series had received local radiation. It is misleading to consider the etiology of such intractable ulcers as being plantar warts—except in a very indirect way. The actual etiology is radiodermatitis, and this should be emphasized. In common with the series reported by Murray and Goldwyn, all of our cases of intractable plantar ulcer related to a
High‐dose cytosine arabinoside in the treatment of preleukemic disorders: A leukemia intergroup study
Authors: H. D. Preisler, A. Raza, M. Barcos, N. Azarnia, R. Larson, G. Browman, I. Walker, H. Grunwald, P. D'Arrigo, A. Stein, M. Bloom, J. Goldberg, A. Gottlieb, J. Bennett, J. Kirshner, R. Priore
Journal: American Journal of Hematology (1986)

Abstract Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high‐dose cytosine arabinoside therapy. While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status. The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset.
LIPOPROTEIN(A) AS A CARDIOVASCULAR BIOMARKER FOR LONG TERM CLINICAL OUTCOMES IN SYMPTOMATIC PATIENTS WITH CORONARY ARTERY DISEASE, IRRESPECTIVE OF CORONARY ARTERY REVASCULARIZATION STATUS
Authors: Sung Woo Kwon, Byoung Kwon Lee, Jong-Youn Kim, Eui-Young Choi, Pil-Ki Min, Young Won Yoon, Bum-Kee Hong, Se-Joong Rim, Hyuck Moon Kwon
Journal: Journal of the American College of Cardiology (2012)
Abstract 4429: Characterization of the kinesin spindle protein inhibitor AZD4877
Authors: Maria C. Pinzon-Ortiz, Alex Cao, Adam Sheehy, Lourdes Pablo, Kristen McEachern, Linda Hylander-Gans, Kaida Wu, Corinne Reimer, Deborah Morosini, Patricia McCoon, Dennis Huszar
Journal: Cancer Research (2010)

Abstract The process of mitosis is a validated point of intervention in cancer therapy and a variety of anti-mitotic drugs are successfully being used in the clinic. To date, all approved antimitotics target the spindle microtubules, thus interfering with spindle dynamics, leading to mitotic arrest and apoptosis. While effective, these drugs are also associated with a variety of side effects, including neurotoxicity. In recent years, mitotic kinesins have attracted significant attention in the search for novel, alternative mitotic drug targets. In addition, kinesin inhibitors may overcome resistance to microtubule targeting drugs. Here we describe the pharmacological evaluation of AZD4877, a selective Eg5 inhibitor. AZD4877 exhibits potent cell growth inhibition in vitro against a broad panel of both solid and hematological tumor cell lines. Efficacy is associated with formation of monoastral spindles, mitotic block and the induction of apoptosis. AZD4877 also demonstrates activity in multiple tumor xenograft models, including primary bladder tumor explants and a Rituximab-insensitive non-Hodgkin's Lymphoma model (DoHH2T53). Combination studies with a taxane agent (Docetaxel) demonstrate additive efficacy of tumor growth inhibition, with notable tumor regrowth delay in the combination arm. In summary, AZD4877 is an active Eg5 inhibitor with potent anti-tumor activities in vitro and in vivo. The efficacy observed in combination studies and in a rituximab-resistant tumor model suggests possible clinical applications for this agent. 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 4429.
Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease
Authors: Masafumi Naito, Norio Hayashi, Toyoki Moribe, Hideki Hagiwara, Eiji Mita, Yoshiyuki Kanazawa, Akinori Kasahara, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1995)

Hepatitis C virus (HCV) has been reported to conform to a quasispecies nature, which is most evident in hypervariable regions of the putative envelope 2 domain. The aim of this study was to determine the relationship between the nucleotide complexity and diversity of hypervariable region 1 and various stages of the carrier states. The subjects studied were 20 HCV carriers with normal alanine aminotransferase (ALT) levels, 50 patients with chronic hepatitis who showed elevated ALT levels, 22 with cirrhosis, and 24 with hepatocellular carcinoma. The quasispecies complexity was analyzed by means of polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP). The value of nucleotide diversity was calculated by PCR cloning and sequencing. The number of SSCP bands ranged from 1 to 7, with no significant differences in the mean numbers among the stages of HCV infection. There was no correlation between the amounts of serum HCV RNA and the numbers of SSCP bands. No significant difference was found in the values of nucleotide diversity between carriers with normal ALT levels (mean, 6.6 x 10(-2) per site) and patients with chronic hepatitis (7.7 x 10(-2). These findings suggest that the quasispecies complexity of hypervariable region 1 is independent of the stage of chronic HCV infection.