tbuckley/cabot-search huggingface dataset:
A Characteristic Precordial Repolarization Abnormality with Intermittent Left Bundle-Branch Block
Authors: Pablo Denes, Alfred Pick, Ronald H. Miller, Raymond J. Pietras, Kenneth M. Rosen
Journal: Annals of Internal Medicine (1978)

We reviewed electrocardiograms of 23 patients with intermittent left bundle-branch block. A characteristic electrocardiographic pattern consisting of right and midprecordial deep symmetrical T-wave inversions was detected during normal conduction in 19 of the 23. Of the seven patients who had cardiac catheterization, only two had findings suggestive of organic heart disease and only one had significant obstructive coronary disease. Thus we conclude that patients with intermittent left bundle-branch block frequently have T-wave inversions in right and midprecordial leads during normal conduction that do not necessarily reflect coronary disease. These T-wave changes are similar to those after termination of chronic right ventricular pacing (left bundle-branch pattern), suggesting that both patterns of abnormal ventricular activation can produce abnormal repolarization when activation returns to normal.
High density lipoprotein is not a major risk factor for ischaemic heart disease in British men
Authors: R. Peto
Journal: BMJ (1986)

of lithotripsy are therefore 3 8x£87 (inpatient) +£800 (procedure)-+£100 (other admission costs, such as investigations and records)=£1231.The costs of one stage percutaneous nephrolithotomy are 5 63 x£87 (inpatient)+£408 (procedure)+£100 (other)=£998.The appendix also omits maintenance, deprecia- tion, rates, electricity, and servicing from the calculations for open surgery and percutaneous nephrolithotomy.Lithotripsy may not be the "cheapest" pro- cedure: a controlled trial is required which must include an assessment ofbenefits for the patient (29 March, p g77).
Abstract 4321: EGFR signaling in glioblastoma regulates the expression of a brain specific isoform of <i>alphaPIX/Arhgef6</i> to promote invasion
Authors: Ivan Babic, Beatrice Gini, Kazuhiro Tanaka, Carolina Jacobs, William H. Yong, Timothy F. Cloughesy, Paul S. Mischel
Journal: Cancer Research (2012)

Abstract The gene Arhgef6 encodes the protein alphaPIX/Cool-2, a guanine nucleotide exchange factor specific for the Rho GTPases Rac1 and Cdc42. AlphaPIX is a protein of 90 kDa predominantly expressed in haemopoietic cells where it has been shown to have a role in cytoskeletal reorganization. However, Arhgef6 is also expressed in the brain and mutations in Arhgef6 have been linked to intellectual disability (ID) in humans. AlphaPIX mRNA was reported to be upregulated in glioblastoma multiforme (GBM), the most lethal form of brain cancer. We examined alphaPIX expression in several glioma cell lines and observed a smaller isoform migrating at 72 kDa. To characterize this isoform we performed 5′RACE from several glioma cell lines and show the smaller isoform is an amino-terminal truncated form of alphaPIX lacking the calponin homology (CH) domain. We demonstrate this isoform is expressed during post-natal brain development and its expression coincides with activation of mTOR. Examination of glioblastoma from both autopsy and biopsy clinical samples shows alphaPIX expression correlates with EGFR/PI3K/Akt/mTOR activation. EGF stimulation is shown to upregulate alphaPIX, and pharmacological inhibition of Akt inhibits alphaPIX expression. To examine the function of alphaPIX in glioblastoma we performed siRNA-mediated knockdown and demonstrate increased cell adhesion upon alphaPIX loss. In addition, knockdown of alphaPIX in glioma cells decreases invasive capacity and decreases the formation of invadopodia. These data demonstrate a previously uncharacterized isoform of alphaPIX is expressed during post-natal brain development, and is highly upregulated in GBM with activated EGFR signaling. A functional consequence of EGFR-mediated alphaPIX expression in glioma is increased invasion as a result of dysregulated cytoskeletal organization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4321. doi:1538-7445.AM2012-4321
Abstract 5446: FPA144: A therapeutic antibody for treating patients with gastric cancers bearing FGFR2 gene amplification
Authors: Abigael T. Gemo, Amit M. Deshpande, Servando Palencia, David I. Bellovin, Thomas J. Brennan, Namrata S. Patil, Carol Huang, Gerrit Los, Kristen L. Pierce
Journal: Cancer Research (2014)

Abstract A subset of patients with gastric cancer have an amplification of the receptor tyrosine kinase fibroblast growth factor receptor 2 (FGFR2) gene. The amplification is most common in the diffuse type of gastric cancer and its presence correlates with poor patient prognosis. Although it has been reported that there is high expression of FGFR2 protein in patients with the amplification, it has been unknown which of the two major FGFR2 isoforms, FGFR2b or 2c, is expressed. In this study, we demonstrate, by both qPCR and immunohistochemistry using FGFR2b-selective antibodies, that it is the FGFR2b isoform, and not FGFR2c, that is overexpressed in gastric cancer tumors that contain the FGFR2 amplification. Five Prime Therapeutics has developed an FGFR2b-specific antibody, FPA144, to treat patients with gastric cancers bearing amplification of the FGFR2 gene. FPA144 is glycoengineered for enhanced antibody-dependent cell cytotoxicity (ADCC). FPA144 causes tumor growth inhibition by 72% to 100% in gastric cancer xenograft models with FGFR2 gene amplification that overexpress the FGFR2b protein isoform. In the SNU-16 model, FPA144 reduces the levels of FGFR2b protein expressed in the tumors by approximately 50%, and decreases both FGFR2b phosphorylation and phosphorylation of the downstream effector, FRS2. The anti-tumor effect of FPA144 is additive with the standard of care chemotherapy regimens of 5-fluoruracil/cisplatin and paclitaxel in the OCUM-2 gastric cancer xenograft model. Since FPA144, unlike small molecule FGFR tyrosine kinase inhibitors, blocks signaling by only the FGFR2b and not the other FGFRs, we expect a favorable toxicology profile, either alone or in combination with chemotherapy. In addition, by engaging immune effector cells for direct tumor cell killing, FPA144 has a second mechanism of action that small molecule FGFR tyrosine kinase inhibitors do not have. We anticipate starting clinical trials of FPA144 in the last quarter of 2014. Citation Format: Abigael T. Gemo, Amit M. Deshpande, Servando Palencia, David I. Bellovin, Thomas J. Brennan, Namrata S. Patil, Carol Huang, Gerrit Los, Kristen L. Pierce. FPA144: A therapeutic antibody for treating patients with gastric cancers bearing FGFR2 gene amplification. [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 5446. doi:10.1158/1538-7445.AM2014-5446
Abstract 2569: Disruption of ceramide glycosylation restores p53-dependent apoptosis in p53 mutant drug-resistant cancer cells: Alternative splicing determines the feature of p53 activity
Authors: Gauri A. Patwardhan, Vineet Gupta, Shaochung Hsia, Xin Gu, Michal Jazwinski, Yong-Yu Liu
Journal: Cancer Research (2010)

Abstract Mutation of tumor suppressor p53 is frequently detected in many different types of cancers. p53 mutants acts as oncogenic proteins preventing programmed cell death and promoting cancer progression. Restoration of p53 that is to increase the expression of wild-type p53 and to eliminate mutant expression can substantially increase the efficacy of chemotherapy and stop malignant progression. However, incomplete understanding the molecular mechanism underlying p53 gene regulation limits the success in p53 restoration. We, for the first time, report that disruption of ceramide glycosylation restores p53 dependent-apoptosis in p53 mutant drug-resistant cancer cells. A lose of 21 base-pair in the mRNA of exon-5 can result in the accumulation of mutant p53 and cells insensitiveness to induced-apoptosis in human NCI/ADR-RE ovarian cancer cells. We found that treatment of mixed-backbone oligonucleotide against human glucosylceramide synthase (MBO-asGCS) increased the levels of wild-type p53 mRNA (containing the 21 bp in exon-5) and protein of wild-type p53 in dose-dependent manner (50-200 nM). In response to doxorubicin-induced DNA damage, phosphorylated p53 (Ser15 in the exon-5) was significantly increased, that in turn increased the protein levels of p21 and Bax, and apoptosis (52% vs. 3%) after MBO-asGCS treatment compared to control in NCI/ADR-RE cells. Silencing of GCS using MBO-asGCS (1 mg/kg) restored wild-type p53 expression and substantially sensitizes NCI/ADR-RE tumors to doxorubicin-induced apoptosis in vivo (10 mice per group), as compared to MBO-scramble control or other treatments. In contrast, introduction of GCS gene in NCI-ADR-RE cells reduces wild-type p53 expression and p53-depedent apoptosis. Further mechanic studies indicated that increased ceramide after GCS silencing modulates the function of SRp30a (ASF/SF2) regulating alternative pre-mRNA splicing. Increasing endogenous ceramide by inhibition of its glycosylation using PDMP or enhanced its production using sphingomylinase promoted wild-type p53 expression at the levels of mRNA, protein and phosphorylation; decreasing ceramide by inhibition of ceramide synthesis using fumonisin (FB1) repressed wild-type p53 expression. Present study indicates that cancer cells marked with mutant p53 phenotype are capable of expressing functional p53; ceramide glycosylation is one molecular mechanism that shifts expression to wild-type form of p53 at alternative splicing of post-transcription processing. MBO-asGCS, a specific agent silencing GCS restores p53-dependent apoptosis in cancer cells. 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 2569.
Spontaneous mutation in the male gamete as a cause of hemophilia A: Clarification of a case using DNA probes
Authors: Phillip L. Howard, Jennifer B. Hoag, Edwin G. Bovill, Nicholas H. Heintz
Journal: American Journal of Hematology (1988)

Abstract The carrier status of two sisters of the mother of a hemophilic boy was clarified by the use of DNA probes in a family with a single case of hemophilia A and no family history of the disease. The extragenic polymorphic site demonstrated by probe DX13 (locus DXS 15) and the intragenic polymorphic site demonstrated by Bgl I digestion and a factor VIII partial cDNA probe indicated that the mother of the index case carried a mutation in the X‐chromosome received from her nonhemophilic father rather than the X‐chromosome received from her mother. In spite of equivocal coagulation data, the mother's two sisters were shown not to be carriers of hemophilia A.
UNITY OF DIPHTHERITIC AND MEMBRANOUS CROUP.
Authors: ALEX. HARRIS
Journal: JAMA (1883)

[Read before the Section on Diseases of Children, June, 1883.] Because of the diverse views held by the profession at large, and especially the members of the district society which I have the honor to represent in part in this Association, I feel great interest in the discussion of the question, are Diphtheritic and Membranous Croup—the “Cynauche Trachialis of Cullen,” the “True Croup” of other nosologists—convertible terms, modified only by difference in local expression, or are they distinct diseases, requiring opposite site modes of treatment? In the hope, then, of eliciting a discussion of this subject, which may at least secure a uniform therapy, I will assume the affirmative. Ours does not claim to be an exact, but a progressive science. At one time vensection was regarded the “sheet anchor” in the treatment of Asiatic cholera. Some of us have cured pneumonia—the cases amenable to the<i>vis medicine</i>of that
Decorin overexpression in the arterial wall prevents neointima formation and collagen accumulation following balloon angioplasty
Authors: Asim N. Cheema, Nafiseh Nili, Alan W. Barolet, Jacek Linde, Beiping Qiang, Mohammad R. Eskandarian, Frank J. Giordano, John Sparkes, Bradley H. Strauss
Journal: Journal of the American College of Cardiology (2002)
Daunorubicin-Prednisone Treatment of Erythroleukemia
Authors: CLARA D. BLOOMFIELD
Journal: Annals of Internal Medicine (1974)

Erythroleukemia is considered a rare form of acute nonlymphocytic leukemia that is particularly resistant to chemotherapy. We have treated nine adults with erythroleukemia with daunorubicin, 1 mg/kg · day, and prednisone, 60 mg/day, for 5 days. Four (44%) complete remissions and three (33%) partial remissions were obtained. Median duration of remission was 6 months (range, 2 to 16 months). All patients who had received no prior therapy responded. Median duration of survival was 12 months (range, 4 to 27 months). We conclude that the combination of daunorubicin and prednisone may be especially useful in inducing remissions in erythroleukemia and that erythroleukemia is more responsive to chemotherapy than previously realized.
Randomized Evaluation of the Safety and Efficacy of Enoxaparin Versus Unfractionated Heparin in High-Risk Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Receiving the Glycoprotein IIb/IIIa Inhibitor Eptifibatide
Authors: Shaun G. Goodman, David Fitchett, Paul W. Armstrong, Mary Tan, Anatoly Langer
Journal: Circulation (2003)

Background— Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy. Methods and Results— We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U · kg −1 · h −1 infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180-μg/kg bolus; 2 μg · kg −1 · min −1 infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P =0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P =0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P =0.0002) and subsequent (12.7% versus 25.9%, P &lt;0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P =0.031). Conclusions— When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.
Management of Dyslipidemia in NIDDM
Authors: Abhimanyu Garg, Scott M Grundy
Journal: Diabetes Care (1990)

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial.
Authors: E J Topol, V Fuster, R A Harrington, R M Califf, N S Kleiman, D J Kereiakes, M Cohen, A Chapekis, H K Gold, M A Tannenbaum
Journal: Circulation (1994)

BACKGROUND Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. METHODS AND RESULTS Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a &gt; or = 60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P &lt; .001). Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable--the average cross-sectional area (P = .08)--as well as minimal cross-sectional area (P = .028), minimal luminal diameter (P = .029), and percent diameter stenosis (P = .07). CONCLUSIONS Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted.
No Country Is Safe without Global Eradication of Poliomyelitis
Authors: Trevor Mundel, Walter A. Orenstein
Journal: New England Journal of Medicine (2013)

In 1988, the World Health Assembly endorsed the goal of eradicating poliomyelitis worldwide. At the time, the estimated annual number of new cases of paralysis was 350,000, and poliomyelitis was considered to be endemic in 125 countries.1 In the 25 years since then, the incidence of poliomyelitis has been reduced by more than 99%, and only three countries — Pakistan, Nigeria, and Afghanistan — have never terminated indigenous transmission.1,2 Wild-type poliovirus type 2 has probably been eradicated; the last naturally occurring case was detected in 1999.2 Wild-type poliovirus type 3 appears to be close to eradication, with no new . . .
Ruptured and/or Dissecting Abdominal Aortic Aneurysms
Authors: Eugene A. Noskin
Journal: JAMA (1963)

To the Editor:  —Just as a matter of interest, I reviewed the obituary section ofThe Journalfrom June 9, 1962, until June 8, 1963, and was interested in ascertaining how many doctors die from surgically correctible diseases. The one entity that intrigued me was dissecting abdominal aortic aneurysm (medial necrosis). I, therefore, listed the number of deaths reported each week for the entire year, the number reported as dying from the above mentioned entities, and the ages of those doctors dying of aortic diseases.  Of the 3,625 deaths reported, 61 (1.68%) were deaths from ruptured and/or dissecting abdominal aortic aneurysm. The average age of these 61 doctors was 72.03, with an age range from 47 to 93. Their age distribution is presented in the Table,  together with mortality rates, by age groups, following surgery for ruptured and dissecting abdominal aortic aneurysms, as reported by DeBakey and Crawford.1Comparison
US Stem Cell Research Lagging
Authors: Tracy Hampton
Journal: JAMA (2006)

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