tbuckley/cabot-search huggingface dataset:
Abstract 5304: Dominant Negative Suppression of Rad Leads to Intracellular Ca <sup>2+</sup> Overload via Up-Regulation of Cardiac Ryanodine Receptor Activity
Authors: Mitsushige Murata, Hirotaka Yada, Hiroyuki Yamakawa, Yoshiyasu Aizawa, Shinsuke Yuasa, Daihiko Hakuno, Shinji Makino, Motoaki Sano, Mitsuru Murata, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2008)

Background: We have recently reported that the ras-related small G-protein Rad plays a critical role in generating arrhythmias via regulation of L-type Ca 2+ channel. However, it has remained unclear whether or not the mechanism for its arrhythmogenesis is attributed only to L-type Ca 2+ channel activity. This study was designed to demonstrate the role of Rad in intracellular calcium homeostasis by cardiac-specific dominant negative suppression of Rad. Methods and results: Transgenic mice that overexpress dominant negative mutant Rad (DN Rad TG) driven by α-myosin heavy chain promoter were generated. To measure intracellular Ca 2+ concentration ([Ca 2+ ] i ), we recorded [Ca 2+ ] i transients and Ca 2+ sparks from isolated cardiomyocytes by confocal microscope. The mean amplitude of [Ca 2+ ] i transient was significantly increased in DN Rad TG cardiomyocytes, compared with WT littermate mouse cells (F/F 0 3.3 ± 0.2, n = 25, in DN Rad TG cells vs. 2.4 ± 0.1, n = 30, in WT cells, P&lt;0.05). The frequency of Ca 2+ sparks was significantly higher in TG cells than in WT cells (5.2 ± 0.6 sparks•100 μm −1 •s −1 , n = 45 in TG cells vs. 1.9 ± 0.3 sparks•100 μm −1 •s −1 , n = 45, in WT controls, P&lt;0.05), although there were no significant differences in their amplitudes. Furthermore, SR Ca 2+ content was not altered in TG cells, as assessed by caffeine-induced [Ca 2+ ] i transient. These results suggested that the properties of fundamental SR Ca 2+ release units might have been affected by the inhibition of endogenous Rad activity. To elucidate the mechanism for the increased frequency of SR Ca 2+ release channel, phosphorylation of Ser 2809 on cardiac ryanodine receptor (RYR2) was examined. The phosphorylation of RYR2 at Ser 2809 was significantly enhanced in TG mouse hearts compared with WT mice, implicating the upregulation of RYR2 activity in TG mice. Additionally, this Rad-mediated phosphorylation of RYR2 was regulated by protein kinase A (PKA) activity. Conclusions: Our results provided the first evidence that Rad regulated RYR2 activity via PKA signaling pathway. Thus, Rad might play a critical role in cellular Ca 2+ homeostasis via its inhibitory effects on RYR2 as well as L-type Ca 2+ channel.
Reduction of suicidality during clozapine treatment of neuroleptic- resistant schizophrenia: impact on risk-benefit assessment
Authors: H Y Meltzer, G Okayli
Journal: American Journal of Psychiatry (1995)

Suicide has been reported to occur in 9%-13% of schizophrenic patients. It has been suggested that neuroleptic-resistant or neuroleptic-intolerant schizophrenic patients are at higher risk for suicide than neuroleptic-responsive patients. Clozapine is the treatment of choice for neuroleptic-resistant patients, but its use has been greatly limited because of its ability to cause potentially fatal agranulocytosis. The purpose of this study was to compare the suicidality of neuroleptic-resistant and neuroleptic-responsive patients and to determine if clozapine treatment decreased suicidality in the former group.Prior episodes of suicidality were assessed in a total of 237 neuroleptic-responsive and 184 neuroleptic-resistant patients with schizophrenia or schizoaffective disorder. Eighty-eight of the neuroleptic-resistant patients were treated with clozapine and prospectively evaluated for suicidality for periods of 6 months to 7 years.There was no significant difference in prior suicidal episodes between neuroleptic-responsive and neuroleptic-resistant patients. Clozapine treatment of the neuroleptic-resistant patients during the follow-up period resulted in markedly less suicidality. The number of suicide attempts with a high-probability of success decreased from five to zero. This decrease in suicidality was associated with improvement in depression and hopelessness.These results suggest a basis for reevaluation of the risk-benefit assessment of clozapine, i.e., that the overall morbidity and mortality of patients with neuroleptic-resistant schizophrenia are less with clozapine treatment than with typical neuroleptic drugs because of less suicidality. This conclusion also has implications for increasing the use of clozapine with neuroleptic-responsive patients.
UNBS4209: A bilactosylated steroid with anti-galectin-1 activity
Authors: Laurent Ingrassia, Véronique Mathieu, Véronique Megalizzi, Florence Lefranc, Francis Darro, Robert Kiss
Journal: Cancer Research (2007)

4857  Galectins are a family of carbohydrate binding proteins with an affinity for β-galactosides which are differentially expressed by various normal and diseased tissues and appear to be functionally multivalent, with a wide range of biological activity. The carbohydrate recognition domain is responsible for the specificity of galectins for saccharides. Galectin-1 expression or over-expression in tumors or surrounding tissues, is considered a sign of malignant tumor progression that often relates to the dissemination of tumoral cells (metastasis) into the surrounding normal tissues or to remoter sites (see Camby et al., Glycobiology 2006 for review). Furthermore, galectin-1 helps tumor cells to escape attack by the immune system (Rubinstein et al., Cancer Cell 2004) and it also displays potent pro-angiogenic effects (Thijssen et al., PNAS 2006). Thus, the targeted inhibition of galectin-1 expression should offer therapeutic potential against cancer progression. A series of glycosylated steroids, including lactosylated ones have been developed (Ingrassia et al., J Med Chem 2006) and data from the present study show that UNBS4209, a bilactosylated steroid from this series that displays binding affinity for galectin-1 in the µM range, was associated in vitro with non-cytotoxic but anti-migratory activity in human PC3 prostate, A549 NSCLC, HT144 melanoma and U373 glioblastoma cell populations. Anti-migratory activity was quantitatively determined by means of computer-assisted cellular imaging (Decaestecker et al., Med Res Rev 2006). UNBS4209 disorganized the tubular networking of human HUVEC cells cultured onto Matrigel®. It also impaired vasculogenic mimicry processes of HT144 and U373 cancer cells cultured on Matrigel®. Glioblastoma cells are resistant to apoptosis (Lefranc et al., J Clin Oncol 2005) but UNBS4209 increased the sensitivity of U373 cells to the cytotoxic effects of pro-apoptotic agents, as it also did in HT144 melanoma cells. These effects were determined by means of the scratch wound assay (Decaestecker et al., Med Res Rev 2006). The genes targeted by UNBS4209 to sensitise apoptosis-resistant tumor cells to the cytotoxic effects of pro-apoptotic agents, are in part currently being deciphered. For this purpose the effects of UNBS4209 on the full U373 cell genome using an Affymetrix approach is being undertaken. The in vivo anti-tumor effects of combining cytotoxic agents with UNBS4209 in orthotopic xenograft models of human glioblastomas and melanomas will be undertaken shortly.
THE SOCIAL RESPONSIBILITIES OF MEDICINE
Authors: John P. Peters
Journal: Annals of Internal Medicine (1938)

Article1 October 1938THE SOCIAL RESPONSIBILITIES OF MEDICINEJOHN P. PETERSJOHN P. PETERSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-4-536 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe social responsibility of medicine, as I see it, is to provide to all classes of the population medical care of the highest quality. A lesser adjective like adequate is so indefinite that it can be argued out of all meaning. It is hardly necessary to say that any program that professes to provide the highest quality of medical care must include measures for its continuous improvement.This premise may be challenged on the grounds that members of the medical profession have no greater moral responsibility to the public than do men and women in other walks of life; that... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Haven, Connecticut*Read before the American College of Physicians, New York, N. Y., April 4, 1938. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byJohn P Peters (1887–1955): McCarthyism and the Unfinished Revision of Quantitative Clinical Chemistry 1 October 1938Volume 12, Issue 4Page: 536-543KeywordsHealth care quality ePublished: 1 December 2008 Issue Published: 1 October 1938 PDF downloadLoading ...
BALL THROMBUS IN THE HEART
Authors: David M. Spain
Journal: Annals of Internal Medicine (1943)

Case Reports1 July 1943BALL THROMBUS IN THE HEARTDAVID M. SPAIN, M.D.DAVID M. SPAIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-19-1-144 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBall thrombus in the heart is a frequently mentioned complication in the course of mitral stenosis. However, reviews of the literature by Abramson (1914)1 and Aronstein and Neuman (1939)2 revealed reports of only 31 authentic cases. Recently, Garvin (1941)3 reported three additional cases. Ball thrombus of the heart is rare, and in only a few cases has the correct antemortem diagnosis been made or even considered.In the laboratories of pathology at Bellevue Hospital during the past year, I have encountered a ball thrombus in which the correct clinical diagnosis was made.CASE REPORTThe patient, (V. K.), a 33...Bibliography1. ABRAMSON JL: Ball thrombi of the heart, Ann. Clin. Med., 1924, iii, 327. Google Scholar2. ARONSTEINNEUMAN CGL: Ball thrombus of the heart: report of a case with review of the literature, Arch. Path., 1939, xxvii, 907. Google Scholar3. GARVIN CF: Ball thrombi in the heart, Am. Heart Jr., 1941, xxi, 371. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication June 13, 1941.From the Laboratories of Pathology, Bellevue Hospital, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRight atrial thrombi with ball-valve actionBall thrombus of the right auricleBALL THROMBUS OF THE HEARTMASS THROMBUS OF THE LEFT AURICLEBall thrombus in the right auricle of the heart, with a description of the symptoms produced 1 July 1943Volume 19, Issue 1Page: 144-146KeywordsClinical pathologyHeartMitral stenosisThrombosis ePublished: 1 December 2008 Issue Published: 1 July 1943 PDF downloadLoading ...
SICKLE CELL ANEMIA AND CARCINOMA OF THE BREAST COMPLICATED BY PREGNANCY
Authors: Ferdinand Fetter, John C. Howell
Journal: Annals of Internal Medicine (1950)

Case Reports1 March 1950SICKLE CELL ANEMIA AND CARCINOMA OF THE BREAST COMPLICATED BY PREGNANCYFERDINAND FETTER, M.D., F.A.C.P., JOHN C. HOWELL, M.D.FERDINAND FETTER, M.D., F.A.C.P.Search for more papers by this author, JOHN C. HOWELL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-3-548 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe literature contains records of pregnancy complicating sickle cell anemia in only 21 patients. This combination is therefore sufficiently rare that an additional case is in itself worth reporting. Besides sickle cell anemia and pregnancy, the patient we are reporting had carcinoma of the breast, and eventually died of metastatic lesions nine and one-half months after radical mastectomy. To the best of our knowledge, no patient has been previously reported with this unusual combination of diseases.Sickle Cell Anemia and Pregnancy. In 1941, Kobak, Stein, and Daro1reviewed the existing literature on sickle cell anemia and pregnancy and added six...Bibliography1. KobakSteinDaro AJPJAF: Sickle cell anemia in pregnancy: a review of the literature and report of six cases, Am. J. Obst. and Gynec. 41: 811-823, 1941. CrossrefGoogle Scholar2. van der Sar A: Sickle-cell anemia in pregnancy, Rev. Policlin. Caracas 12: 1-12, 1943. Google Scholar3. Spivack M: Sickle-cell anemia complicated by pregnancy, Am. J. Obst. and Gynec. 50: 442-446, 1945. CrossrefGoogle Scholar4. Noyes RW: Sickle cell anemia in pregnancy: report of case with autopsy, Am. J. Obst. and Gynec. 52: 469-473, 1946. CrossrefMedlineGoogle Scholar5. Grover V: The clinical manifestations of sickle cell anemia, Ann. Int. Med. 26: 843-851, 1947. LinkGoogle Scholar6. Geschickter CF: Diseases of the breast, 2nd Ed., 1945, J. B. Lippincott, Philadelphia, pp. 175 and 482. Google Scholar7. Harrington SW: Carcinoma of the breast, Ann. Surg. 106: 690-700, 1937. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Received for publication October 16, 1947.From the Department of Radiology of the Philadelphia General Hospital, Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1950Volume 32, Issue 3Page: 548-553KeywordsAnemiaDiagnostic radiologyLesionsPregnancy Issue Published: 1 March 1950 PDF downloadLoading ...
Meningoencephalitis due to primary HIV infection
Authors: M. Melzer
Journal: BMJ (2003)

Editor—Newton et al describe how meningoencephalitis was caused by primary HIV infection, and we agree with them that a high index of suspicion is required for diagnosis.1 A more common presentation in unconfused patients is a maculopapular rash or a glandular fever type illness, which provides an opportunity for early counselling and HIV testing without ethical constraints.1,2 In south London we recently showed that primary HIV infection remains undiagnosed in patients with a rash or a glandular fever type illness caused by HIV.

Between May 1998 and April 1999, with ethics approval, we retrospectively and anonymously tested 268 stored serum samples for HIV. The samples had been sent to the virology laboratory at St Thomas's Hospital and were from patients aged 16 years and over who had clinical details of a maculopapular rash or fever, sore throat, and lymphadenopathy. Patients with other diagnoses and previous positive results on HIV testing were excluded. Patient confidentiality was maintained by unlinking clinical details from name, hospital, and laboratory numbers.

Of the 268 serum samples tested, eight (3%) were positive for HIV antibody and six (2%) gave results consistent with long standing infection. Two samples (1%) had Western blot profiles compatible with primary HIV infection. HIV RNA was not detectable by nucleic acid sequence based amplification (NASBA, Organon-Teknika) in the samples without HIV antibodies.

Being able to diagnose primary HIV infection provides an opportunity to prevent the spread of HIV when patients are highly infectious, start prophylaxis against opportunistic infection, and start treatment with highly active antiretroviral therapy (HAART) before the immune system is irreparably damaged. Like Newton et al, we believe that more risk assessments and HIV testing is required if patients living in areas such as south London are to receive early diagnosis and benefit from current and future treatments.
Abstract 3734: Glucose-Insulin-Potassium Infusion in Patients with Acute Myocardial Infarction treated with Reperfusion Therapy Does Not Reduce the Risk of Cardiovascular Events: A Pooled Meta-analysis of Randomized Controlled Trials
Authors: Srikanth Katragadda, Sandeep A Saha, Rohit R Arora
Journal: Circulation (2007)

Background: Metabolic modulation of ischemic myocardium using a glucose-insulin-potassium (GIK) infusion has been studied in patients with acute myocardial infarction treated with reperfusion therapy, but the results have been conflicting. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials evaluating the utility of GIK in the prevention of adverse cardiovascular outcomes in patients with acute myocardial infarction who underwent reperfusion therapy. Methods: A total of 19,222 patients from 6 randomized placebo-controlled clinical trials were analyzed using pooled meta-analysis techniques, and relative risks at the end of one month were computed for various adverse cardiovascular outcomes. Statistical significance was determined using the z -test (two-sided alpha-error &lt;0.05). Results: The use of GIK did not significantly reduce the risk of death within the first month among patients with acute myocardial infarction treated with reperfusion therapy (p=0.40), and did not differ among those treated with thrombolytic agents (p=0.54) or those treated with primary coronary angioplasty (p=0.38). The risk of re-infarction within the first month was also not significantly reduced (p=0.32), nor were the risk of development of heart failure (p=0.40) or the need for invasive coronary revascularization (p=0.76). Conclusions: Among patients with acute myocardial infarction who are treated with reperfusion therapy, the use of GIK infusion has no significant effect on mortality or the occurrence of adverse cardiovascular events within the first month.
Targeting Pre-B Cell Receptor and BCL6 In TCF3-PBX1 B-Lineage Acute Lymphoblastic Leukemia
Authors: Huimin Geng, Christian Hurtz, Zhengshan Chen, Wei-Yi Chen, Erica Ballabio, Gang Xiao, Soo-mi Kweon, Rahul Nahar, Seyedmehdi Sojaee, Lai N. Chan, Behzad Kharabi Masouleh, David B. Sykes, Ari Melnick, Robert Roeder, Thomas Milne, Markus Muschen
Journal: Blood (2013)
Abstract 17873: Neurocognitive Improvement after Carotid Artery Stenting Is Persistent Up to 1 Year in Patients with Chronic Occlusion or Critical Stenosis
Authors: Ching-Chang Huang, Mao-Shin Lin, Ying-Hsien Chen, Chi-Chao Chao, Ming-Jang Chiu, Hsien-Li Kao
Journal: Circulation (2010)

Backgorund: Carotid artery stenting might improve 3-month neurocognitive function post-procedurally in patients with severe carotid artery stenosis (CAS) or occlusion (CAO), but the long-term effec...
Efficacy and Tolerance of Carvedilol in Combination with a Thiazide Diuretic in the Treatment of Essential Hypertension
Authors: Minoru Yasujima, Yuichiro Goto, Kaoru Yoshinaga, Yuichi Kumahara, Osamu Iimura, Masao Ishii, Eiji Murakami, Tadanao Takeda, Tatsuo Kokubu, Kikuo Arakawa, Masao Ikeda
Journal: Drugs (1988)
Regional metabolic rate of glucose (CMRglu) evaluation and clinical assessment in idiopathic normal-pressure hydrocephalus (iNPH) patients before and after ventricular shunt placement. A prospective analysis
Authors: Maria Lucia Calcagni, Silvia Taralli, Annunziato Mangiola, Luca Indovina, Maria Dea Lavalle, Pasquale De Bonis, Carmelo Anile, Alessandro Giordano
Journal: Clinical Nuclear Medicine (2013)
Kozhikode doctors plan court action over claims by homeopaths
Authors: S. Bagcchi
Journal: BMJ (2015)

The Kozhikode branch of the Indian Medical Association (IMA) is planning to take legal action against the Indian Homeopathic Medical Association in response to misleading information about treating communicable diseases, The Hindu has reported.1

A 19 June article in the newspaper said that the IMA’s complaint followed a recent report in a “popular Malayalam daily” in which the homeopathic association claimed that “excess use of medicines was a major reason for the increase in fever deaths” in …
Abstract 327: Mitochondrial Functional Variation Contributes to Endothelial Cell Activation
Authors: David M Krzywanski, Bing Cheng, Xinggui Shen, Christopher Kevil
Journal: Circulation Research (2014)

Vascular oxidant stress contributes to endothelial dysfunction and plays a critical role in early stage cardiovascular disease (CVD) development. Changes in endothelial function due to oxidant stress may contribute to CVD initiation and progression through the development of a pro-inflammatory environment. Differences in mitochondrial function may contribute to this process and provide insight into why age of onset and clinical outcomes differ amongst individuals form distinct ethnic groups; but no reports demonstrate distinct mitochondrial functional parameters between normal cells. Consequently, we hypothesized that significant variations in normal mitochondrial function and oxidant production exist between endothelial cells from donors representing different ethnic groups. Aspects of mitochondrial oxygen utilization and oxidant production were assessed under basal and inflammatory conditions in human aortic endothelial cells (HAECs) isolated from African Americans (AA) and Caucasians (CA). Bioenergetic analysis indicates that compared to CA, AA HAEC utilized significantly less oxygen for ATP production, possess a lower maximal respiratory capacity, and have reduced electron leak. Significant differences in mitochondrial membrane potential, decreased expression of endothelial nitric oxide synthase, and increased levels of superoxide were also observed and AA HAEC supporting a pro-inflammatory phenotype. As a marker of endothelial cell activation, AA HAEC expressed increased levels of intercellular cell adhesion molecule-1 under both basal and inflammatory conditions that could be partially mitigated but treatment with the mitochondrially targeted antioxidant MitoTEMPO. These data demonstrate that fundamental differences exist in mitochondrial oxygen utilization and oxidant production between CA and AA HAEC and that these changes may affect endothelial cell activation. These findings are consistent with the hypothesis that differences in “normal” mitochondrial function amongst ethnic groups could influence individual susceptibility by contributing to vascular inflammation, providing important insights into the mechanisms that contribute human CVD development.