tbuckley/cabot-search huggingface dataset:
The Ankle-Brachial Index and Incident Cardiovascular Events in the MESA (Multi-Ethnic Study of Atherosclerosis)
Authors: Michael H. Criqui, Robyn L. McClelland, Mary M. McDermott, Matthew A. Allison, Roger S. Blumenthal, Victor Aboyans, Joachim H. Ix, Gregory L. Burke, Kaing Liu, Steven Shea
Journal: Journal of the American College of Cardiology (2010)
Abstract 2591: Global gene expression regulated by phenethyl isothiocyanate in human colon cancer SW480 cells.
Authors: Lixin Mi, Xiantao Wang, Xin Li, Fung-Lung Chung
Journal: Cancer Research (2013)

Abstract Phenethyl isothiocyanate (PEITC), a promising chemopreventive compound originated from cruciferous vegetables, is known to inhibit proliferation of colon cancer cells through inducing apoptosis and cell cycle arrest. Although exact mechanisms are unclear, it seems that PEITC may have multiple molecular targets and play multiple roles in a variety of events. Some of our recent studies indicate that a key mechanism of apoptosis induction by PEITC may be through covalent modification of its target proteins, such as tubulin. Numerous studies also reported that PEITC may induce apoptotic signals through gene transcriptional regulation. However, systematic studies on PEITC-induced gene expression profile, particularly in colon cancer cells, are rare. In this study, we examined overall gene expression profile of SW480 cells at different time points after PEITC treatment using cDNA microarray. Results showed that PEITC induced significant changes in expression of several apoptosis-related genes, such as BIM, DEDD2, GADD45B, HSPB8, SYK, PIK3C2A, CTNNB1, LGALS8, and NOXA. Furthermore, these changes were confirmed by real-time polymerase chain reaction at transcript level and immunoblot at protein level. Considering significant roles of these genes in signaling transduction leading to downstream events, such as apoptosis, the findings of this study may shed lights on the molecular mechanisms by which PEITC exert its anti-carcinogenic effects. (Supported by NCI grant CA100853) Citation Format: Lixin Mi, Xiantao Wang, Xin Li, Fung-Lung Chung. Global gene expression regulated by phenethyl isothiocyanate in human colon cancer SW480 cells. [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 2591. doi:10.1158/1538-7445.AM2013-2591
STENT DEGRADATION OF NOVEL FULLY BIOABSORBABLE SALICYLATE-BASED SIROLIMUS-ELUTING STENT EVALUATED BY OCT IN PIG CORONARY ARTERY
Authors: Daisuke Matsumoto, Toshiro Shinke, Sarah Geva, Nicolas Chronos, Refat Jabara
Journal: Journal of the American College of Cardiology (2010)
Abstract LB-300: Small molecule modulators of MET kinase for treatment of human malignancies
Authors: Scott C. Wise, Bryan D. Smith, Molly M. Hood, Michael D. Kaufman, Wei-Ping Lu, Daniel L. Flynn
Journal: Cancer Research (2010)

Abstract MET kinase is involved in numerous cancers including lung, melanoma and gastric. MET can not only be the oncogenic driver of the cancer cell but also is a key player in the cells ability to metastasize and invade tissues distant from the primary tumor site. It has been shown that 2 out of 3 cancers involving MET leads to a poor prognosis for patient survival. Using Deciphera Pharmaceutical's approach to kinase inhibition, compounds have been designed which effectively inhibit wild type and mutant MET kinase forms. These inhibitors are selective, including sparing of close family members AXL and RON. This presentation will highlight the attributes and development status of these compounds for treatment of human malignancy. Deciphera's MET program has afforded potent inhibitors that achieve low nanomolar inhibition of wild type MET and secondary activating mutant forms. Data will be presented on DP-4693 and DP-4756.IC50MET Kinasep-MET MKN-45MKN-45 Proliferationp-MET EBC-1EBC-1 ProliferationA549 MigrationDP-46934nM13 nM44 nM10 nM3nM260 nMDP-47566nM6nM23 nM2nM5nM21 nM DP-4693 and DP-4756 are selective, having as few as three kinases within 50 fold of MET potency. Inhibitor bound crystal structures will be shown which demonstrate the compounds mechanism of action. In addition, proliferation and MET phosphoprotein analysis performed with EBC-1 and MKN-45 cell lines have demonstrated excellent inhibitory profiles with potencies in the low nanomolar range. The compounds also inhibit HGF dependent cell motility in an A549 migration assay. In vivo evaluation of DP-4693 in an MKN-45 gastric cancer xenograft PK/PD model revealed complete target suppression at doses as low as 6 mpk. Futher studies will be presented highlighting the efficacy in both autocrine and paracrine (HGF-dependent) xenograft models. Deciphera's MET inhibitors also show acceptable ADME properties and are orally bioavailable in rat and dog using simple vehicles. These inhibitors have also been evaluated in two week toxicology studies, exhibiting excellent tolerability up to doses of 300 mpk. Further studies are ongoing to enable Development Candidate selection for progression into clinical trials. 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 LB-300.
98 DIFFERENTIAL EFFECTS OF NORUDCA AND UDCA IN THE TREATMENT OF FATTY LIVER AND ARTERIOSCLEROSIS IN WESTERN CHOW-FED APOE KNOCK OUT MICE
Authors: P. Fickert, T. Moustafa, A. Fuchsbichler, T. Claudel, E. Halilbasic, K. Zatloukal, H. Denk, M. Trauner
Journal: Journal of Hepatology (2008)
Management of massive haemoptysis with the rigid bronchoscope and cold saline lavage.
Authors: A A Conlan, S S Hurwitz
Journal: Thorax (1980)

Twelve successive patients with massive haemoptysis were treated by emergency rigid bronchoscopy and lavage of the bleeding lung with cold saline. All patients stopped bleeding during the procedure and all blood and clot was evacuated from the accessible airways. The bleeding source was localised to a lobe in seven cases, and lateralised in the remaining five patients. Five patients had a second haemorrhage during that hospital stay and cold saline lavage again terminated it. Further therapy, either surgical or medical was based on information obtained during the respite from haemorrhage achieved with this technique. There was no hospital mortality in the series.
Multidisciplinary care for poor patients with chronic kidney disease in Mexico
Authors: Guillermo Garcia-Garcia, Yolanda Martinez-Castellanos, Karina Renoirte-Lopez, Alberto Barajas-Murguia, Librado de la Torre-Campos, Laura E Becerra-Muñoz, Jaime A Gonzalez-Alvarez, Marcello Tonelli
Journal: Kidney International Supplements (2013)
Relationship between renin and intrarenal hemodynamics in hemorrhagic hypotension
Authors: A. Grandchamp, R. Veyrat, E. Rosset, J. R. Scherrer, B. Truniger
Journal: Journal of Clinical Investigation (1971)

In order to investigate the possible role of the renin-angiotensin system in the regulation of intrarenal hemodynamics in hemorrhagic hypotension (HH), seven mongrel dogs have been studied under the following conditions: (a) Control, (b) HH (mean arterial pressure 70 mm Hg), and (c) HH + alpha adrenergic blockade by phenoxybenzamine (HH + POB). The following parameters were obtained for the right kidney: Intrarenal distribution of blood flow and local blood flow rates ((133)Xe washout technique); total renal blood flow (RBF) on the basis of the clearance and extraction ratio of PAH and the arterial hematocrit; plasma renin concentrations in the renal artery and vein by the method of Boucher and his associates; and renin release into the renal circulation. Alpha adrenergic blockade reverted the typical redistribution of intrarenal blood flow observed under HH. In hemorrhage, arterial and venous renin concentrations increased by a factor of 3.4 and 4.8 respectively. A further small increase was observed during HH + POB with the respective factors increasing to 4.8 and 5.3, as compared with control values. The renin release into the circulation increased by a factor of 1.2 in HH and 4.0 in HH + POB. Whereas in HH there seemed to be a relationship between increased renin concentrations or renin release, and the redistribution of blood flow, no such correlation was found during alpha-adrenergic blockade. From these observations it is concluded that renin alone is unable to maintain the typical redistribution of RBF seen during hemorrhage. Circumstantial evidence points to a permissive role of the renin-angiotensin system in the pathogenesis of the patchy cortical hypoperfusion caused by sympathoadrenergic mechanisms during hemorrhagic hypotension.
BMA warns of arrival of genetic weapons
Authors: U. Hoang
Journal: BMJ (1999)

The BMA has warned that the possibility of developing weapons genetically targeted at different ethnic groups could be just five years away.

Dr Vivienne Nathanson, head of health policy research at the BMA, said, “It is important to emphasise that we are talking about technology and information that is becoming available now and will be available in the next few years. We have a window of opportunity before such weapons can …
Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis.
Authors: M R Wallace, F E Dwulet, E C Williams, P M Conneally, M D Benson
Journal: Journal of Clinical Investigation (1988)

In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder. We recently studied a patient of German descent with peripheral neuropathy and bowel dysfunction. Biopsied rectal tissue contained amyloid that stained with anti-human prealbumin. Amino acid sequence analysis of the patient's plasma prealbumin revealed both normal and variant prealbumin molecules, with the variant containing a tyrosine at position 77 instead of serine. We predicted a single nucleotide change in codon 77 of the variant prealbumin gene, which we then detected in the patient's DNA using the restriction enzyme SspI and a specifically tailored genomic prealbumin probe. DNA tests of other family members identified several gene carriers. This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbumin amyloidoses are more varied and prevalent than previously thought.
Multiple Atherosclerotic Plaque Rupture in Acute Coronary Syndrome
Authors: G. Rioufol, G. Finet, I. Ginon, X. André-Fouët, R. Rossi, E. Vialle, E. Desjoyaux, G. Convert, J.F. Huret, A. Tabib
Journal: Circulation (2002)

Background— To test the hypothesis of general atherosclerotic plaque destabilization during acute coronary syndrome (ACS), the present study sought to analyze the 3 coronary arteries by systematic intravascular ultrasound scan (IVUS). Methods and Results— Seventy-two arteries were explored in 24 patients referred for percutaneous coronary intervention after a first ACS with troponin I elevation. Fifty plaque ruptures (mean, 2.08 per patient; range, 0 to 6) were diagnosed by the association of a ruptured capsule with intraplaque cavity. Plaque rupture on the culprit lesion was found in 9 patients (37.5%). At least 1 plaque rupture was found somewhere other than on the culprit lesion in 19 patients (79%). These lesions were in a different artery than the culprit artery in 70.8% and were in both other arteries in 12.5% of these 24 patients. Complete IVUS examination of all 3 coronary axes in patients who had experienced a first ACS revealed that multiple atherosclerotic plaque ruptures were detected by IVUS; these multiple ruptures were present simultaneously with the culprit lesion; they were frequent and located (in three quarters of cases) on the 3 principal coronary trunks; and the multiple plaque ruptures in locations other than on the culprit lesion were less severe, nonstenosing, and less calcified. Conclusion— Although one single lesion is clinically active at the time of ACS, the syndrome seems nevertheless associated with overall coronary instability.
Response to Letter Regarding Article, “Atrial Fibrillation: Outpatient Presentation and Management”
Authors: Michael D. Ezekowitz, Timothy H. Aikens, Timothy Shapiro, Rangadham Nagarakanti
Journal: Circulation (2012)

We appreciate Drs Montone, Mollo, and Nerla's comments.The intent of this illustrative case was to present a common clinical presentation of atrial fibrillation managed by recently approved treatment options. 1 Dronedarone was prescribed to decrease the need for hospitalization and reduce the risk of cardiovascular mortality, consistent with the results of the A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 500 mg bid for the Prevention of Cardiovascular Hospitalization or Death from any cause in Patients with Atrial Fibrillation/Atrial Flutter (ATHENA) trial. 2 An added benefit was maintenance of sinus rhythm in the event of spontaneous cardioversion, given the recent onset of atrial fibrillation and the normal-sized left atrium.Anticoagulation with either dabigatran or warfarin was indicated and was independent of the decision to pursue cardioversion.The patient had normal renal function, ameliorating the risk of bleeding on Dabigatran.In addition, the risk of intracerebral bleeding on dabigatran would be reduced by 74% compared with warfarin, 3 and outpatient management was possible in a stable patient.Drs Karam and Marijon raised the important question of the effect of the outcome of the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on top of Standard Therapy (PALLAS) trial, unknown at the time that this article was published.We agree that dronedarone should not be used in patients with permanent atrial fibrillation.The patient in our publication did not have permanent atrial fibrillation.We recognize the need to monitor the patient's rhythm to ensure permanent atrial fibrillation has not developed.We were aware of the 2 patients who developed progressive liver disease of unclear causality after the prescription of dronedarone.The Food and Drug Administration has advised voluntary liver monitoring of patients prescribed dronedarone. 4,5European authorities recommend liver monitoring using identical data.We urge authorities worldwide to reach a consensus with respect to guidance.
Early steatosis and past HBV infection predict fibrosis progression inliver transplant recipients with recurrent HCV infection
Authors: M. Angelico, G. Palmieri, D. Di Paolo, E. Torri, G. Iaria, L. Baiocchi, A. Anselmo, S. Mensi, C.U. Casciani, G. Tisone
Journal: Journal of Hepatology (2000)
Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane
Authors: Jacqueline Loeper, Veronique Descatoire, Michelle Maurice, Philippe Beaune, Gerard Feldmann, Dominique Larrey, Dominique Pessayre
Journal: Hepatology (1990)

Antibodies against cytochrome P-450 are found in some children with autoimmune hepatitis (antiliver/kidney microsome 1) and in patients with ticrynafen hepatitis (antiliver/kidney microsome 2). For an immune reaction against cytochrome P-450 to possibly destroy the hepatocytes, one must assume that cytochrome P-450 is present on the plasma membrane surface of hepatocytes. In a first series of experiments, plasma membranes were prepared with a technique based on the electrostatic attachment of isolated hepatocytes to polyethyleneimine-coated beads. After vortexing, beads were coated with a very pure plasma membrane fraction. Microsomal contamination, judged from the specific activities of glucose-6-phosphatase or NADH-cytochrome c reductase, was less than 1%. Nevertheless, the specific content (per milligram of protein) of CO-binding cytochrome P-450 was 20% of that in microsomes; the specific benzo(a)pyrene hydroxylase activity was 25%, and ethoxycoumarin deethylase 11%. Immunoblots showed the presence of cytochromes P-450 UT-A, UT-H, PB-B, ISF-G and PCN-E, the last three isoenzymes being inducible by, respectively, phenobarbital, 3-methylcholanthrene and dexamethasone. In a second series of experiments, nonpermeabilized isolated hepatocytes from untreated rats were incubated with anticytochrome P-450 antibodies. Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane. In a last series of experiments, human antiliver-kidney microsomal 1 antibodies were found to react specifically with rat liver plasma membrane cytochrome P-450 UT-H (IID subfamily). We conclude that several cytochrome P-450 isoenzymes are present, active and inducible on the plasma membrane surface of hepatocytes. It is therefore conceivable that immunization against plasma membrane cytochrome P-450 might lead to the immunological destruction of hepatocytes in some patients.
Mutations in Ribonucleic Acid Binding Protein Gene Cause Familial Dilated Cardiomyopathy
Authors: Katharine M. Brauch, Margaret L. Karst, Kathleen J. Herron, Mariza de Andrade, Patricia A. Pellikka, Richard J. Rodeheffer, Virginia V. Michels, Timothy M. Olson
Journal: Journal of the American College of Cardiology (2009)
Sequential Changes in Beta-Cell Function in Insulin-Treated Diabetic Patients Assessed by C-Peptide Immunoreactivity
Authors: Marshall B. Block, Robert L. Rosenfield, Mary E. Mako, Donald F. Steiner, Arthur H. Rubenstein
Journal: New England Journal of Medicine (1973)

Assessment of beta-cell function in insulin-treated diabetes is hampered by the presence of circulating insulin antibodies, which interfere with the commonly used insulin immunoassay. The development of an immunoassay for C-peptide has enabled beta-cell secretory products, in addition to insulin, to be monitored in the circulation of such patients. Using this assay, we studied the progressive changes in beta-cell secretion in three insulin-treated diabetic patients with hyperglycemia and ketonemia. Serum C-peptide immunoreactivity increased during the remission phase of the diabetic state, suggesting that the improvement in carbohydrate tolerance was due to renewed beta-cell secretion. Eventual clinical relapse was associated with decreasing serum C-peptide immunoreactivity. These results confirm the long held clinical impression that the cause of the remission phase in diabetes is usually resumption of beta-cell secretory activity. (N Engl J Med 288:1144–1148, 1973)
SERUM REACTIVITY TO HUMAN T-CELL LEUKAEMIA/LYMPHOMA VIRUS TYPE I PROTEINS IN PATIENTS WITH LARGE GRANULAR LYMPHOCYTIC LEUKAEMIA
Authors: Gordon Starkebaum, V.S. Kalyanaraman, PamelaG. Kidd, ThomasP. Loughran, MarshallE. Kadin, JackW. Singer, FrancisW. Ruscetti
Journal: The Lancet (1987)
The efficacy of tonsillectomy on long-term renal survival in patients with IgA nephropathy
Authors: Yuansheng Xie, Shinichi Nishi, Mitsuhiro Ueno, Naofumi Imai, Minoru Sakatsume, Ichiei Narita, Yasushi Suzuki, Kouhei Akazawa, Hisaki Shimada, Masaaki Arakawa, Fumitake Gejyo
Journal: Kidney International (2003)
Antitumor Activity of GSK1904529A, a Small-molecule Inhibitor of the Insulin-like Growth Factor-I Receptor Tyrosine Kinase
Authors: Peter Sabbatini, Jason L. Rowand, Arthur Groy, Susan Korenchuk, Qi Liu, Charity Atkins, Melissa Dumble, Jingsong Yang, Kelly Anderson, Brian J. Wilson, Kyle A. Emmitte, Sridhar K. Rabindran, Rakesh Kumar
Journal: Clinical Cancer Research (2009)

Dysregulation of the insulin-like growth factor-I receptor (IGF-IR) signaling pathway has been implicated in the development of many types of tumors, including prostate, colon, breast, pancreatic, ovarian, and sarcomas. Agents that inhibit IGF-IR activity may be useful in treatment of patients with various cancers.Kinase assays were used to identify a selective small-molecule inhibitor of IGF-IR activity. The effects of this compound on IGF-IR signaling, cell proliferation, and the cell cycle were determined using a panel of cell lines. Antitumor activity was evaluated in human tumor xenografts growing in athymic mice. Inhibition of IGF-IR and the closely related insulin receptor (IR) was measured in vivo, and the effect on glucose metabolism was evaluated.GSK1904529A selectively inhibits IGF-IR and IR with IC(50)s of 27 and 25 nmol/L, respectively. GSK1904529A blocks receptor autophosphorylation and downstream signaling, leading to cell cycle arrest. It inhibits the proliferation of cell lines derived from solid and hematologic malignancies, with multiple myeloma and Ewing's sarcoma cell lines being most sensitive. Oral administration of GSK1904529A decreases the growth of human tumor xenografts in mice, consistent with a reduction of IGF-IR phosphorylation in tumors. Despite the potent inhibitory activity of GSK1904529A on IR in vitro and in vivo, minimal effects on blood glucose levels are observed in animals at doses that show significant antitumor activity.GSK1904529A is a promising candidate for therapeutic use in IGF-IR-dependent tumors.
Antibody Responses After Influenza and Pneumococcal Immunization in HIV-Infected Homosexual Men
Authors: Kuo-Liang Huang
Journal: JAMA (1987)

We conducted a study to assess the effect of human immunodeficiency virus (HIV) infection on humoral immunity. Fifty-five homosexual men and 19 heterosexual men had four- to six-week postimmunization antibody responses measured to trivalent influenza vaccine and 23-valent pneumococcal vaccine. The homosexual men were divided into three groups: 20 asymptomatic HIV-seronegative men, 10 asymptomatic HIV-seropositive men, and 25 HIV-seropositive men with persistent generalized lymphadenopathy. Antibody responses to influenza antigens in the subgroups of homosexual men did not significantly differ from those of heterosexual controls. The IgG antibody responses to pneumococcal capsular types 9N and 18C in men with lymphadenopathy, and type 18C in HIV-seronegative homosexual men, were lower than those of heterosexual controls. Otherwise, responses to other ten capsular types showed no significant differences. There was no evidence of an immunosuppressive effect of vaccination on T-cell numbers, or deterioration of clinical status associated with vaccination. This study demonstrates that HIV-infected homosexual men, asymptomatic or with persistent generalized lymphadenopathy, are able to mount appropriate antibody responses to two commonly used vaccines.