tbuckley/cabot-search huggingface dataset:
Impact of High Glucose/High Insulin and Dichloroacetate Treatment on Carbohydrate Oxidation and Functional Recovery After Low-Flow Ischemia and Reperfusion in the Isolated Perfused Rat Heart
Authors: Peipei Wang, Steven G. Lloyd, John C. Chatham
Journal: Circulation (2005)

It is believed that increasing cardiac glucose metabolism in the setting of ischemia and reperfusion is protective because of the resulting decrease in fatty acid oxidation, which improves cardiac efficiency and increases glucose oxidation relative to glycolysis; however, these conclusions are based primarily on studies in which glucose is the only carbohydrate provided. The goal of this study was to examine the effect of stimulating myocardial carbohydrate use either by increasing glucose and insulin levels or by using dichloroacetate on the response to ischemia and reperfusion in hearts perfused with physiological concentrations of lactate and pyruvate plus glucose and fatty acids.Metabolic fluxes were determined in hearts from male Sprague-Dawley rats perfused with 13C-labeled substrates using 13C/1H-NMR isotopomer analysis after 30 minutes of low-flow ischemia (0.3 mL/min) and 60 minutes of reperfusion. Measurements were made under control conditions: 5 mmol/L glucose, 1 mmol/L lactate, 0.1 mmol/L pyruvate, 0.3 mmol/L palmitate, and 50 microU/mL insulin plus dichloroacetate 5 mmol/L or glucose and insulin increased to 30 mmol/L and 1000 microU/mL, respectively. Dichloroacetate increased carbohydrate oxidation and the ratio of glucose oxidation to glycolysis but did not improve functional recovery or cardiac efficiency; however, elevated glucose and insulin levels improved functional recovery and cardiac efficiency but did not increase carbohydrate oxidation or the ratio of glucose oxidation to glycolysis.These data support the notion that increasing myocardial glucose use is beneficial in the setting of ischemia and reperfusion; however, the protective effect appears not to be mediated by shifting the balance between carbohydrate and fatty acid oxidation.
Gift at Bar Mitzvah
Authors: Charles W. Frank
Journal: Annals of Internal Medicine (1993)

Ad Libitum15 November 1993Gift at Bar MitzvahCharles W. Frank, MDCharles W. Frank, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-10-199311150-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This brings up the subject of THE THIRD LECH LECHA. This one is from Saba to you, Tavi. Go forth on the journey you described in your autobiography, and get your school records in acceptable shape. With good college grades and your high rating in character, you should be entering the Albert Einstein College of Medicine in 1999. If Hashem and the Dean will permit, I will be there to greet you as you start your medical studies.This evening, after Havdala, I will give you the stethoscope that I have used for many years. Take good care of it. ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1993Volume 119, Issue 10Page: 1049KeywordsHeartHeart diseasesLongitudinal studiesMagnetic resonance imagingScientists ePublished: 15 August 2000 Issue Published: 15 November 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Can the Reliance of Hormone Receptor Assays of Surgical Specimens Be Explained by the Fluctuation of Estrogen Receptor, Progesterone Receptor, and HER-2 Protein Expression in Tumor Samples of Premenopausal Breast Cancer Patients?
Authors: Andrea Alimonti, Gianluigi Ferretti, Francesco Cognetti
Journal: Journal of Clinical Oncology (2005)
A screen in mice uncovers repression of lipoprotein lipase by microRNA‐29a as a mechanism for lipid distribution away from the liver
Authors: Aras N. Mattis, Guisheng Song, Kelly Hitchner, Roy Y. Kim, Andrew Y. Lee, Amar D. Sharma, Yann Malato, Michael T. McManus, Christine C. Esau, Erich Koller, Suneil Koliwad, Lee P. Lim, Jacquelyn J. Maher, Robert L. Raffai, Holger Willenbring
Journal: Hepatology (2014)

Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo , we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase ( Lpl ), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy‐dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR‐29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR‐29a levels causes lipids to accumulate in mouse livers. Conclusion : Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR‐29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR‐29a's known antifibrotic effect, suggest miR‐29a is a therapeutic target in fatty liver disease. (H epatology 2015;61:141–152)
Inhibition of Hsp90 Compromises the DNA Damage Response to Radiation
Authors: Hideaki Dote, William E. Burgan, Kevin Camphausen, Philip J. Tofilon
Journal: Cancer Research (2006)

Inhibitors of the molecular chaperone Hsp90 have been shown to enhance tumor cell radiosensitivity. To begin to address the mechanism responsible, we have determined the effect of the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) on the DNA damage response to radiation. Exposure of MiaPaCa tumor cells to 17DMAG, which results in radiosensitization, inhibited the repair of DNA double-strand breaks according to gammaH2AX foci dispersal and the neutral comet assay. This repair inhibition was associated with reduced DNA-PK catalytic subunit (DNA-PKcs) phosphorylation after irradiation and a disruption of DNA-PKcs/ErbB1 interaction. These data suggest that the previously established 17DMAG-mediated reduction in ErbB1 activity reduces its interaction with DNA-PKcs and thus accounts for the attenuation of radiation-induced DNA-PK activation. 17DMAG was also found to abrogate the activation of the G(2)- and S-phase cell cycle checkpoints. Associated with these events was a reduction in radiation-induced ataxia-telangiectasia mutated (ATM) activation and foci formation in 17DMAG-treated cells. Although no interaction between ATM and Hsp90 was detected, Hsp90 was found to interact with the MRE11/Rad50/NBS1 (MRN) complex. 17DMAG exposure reduced the ability of the MRN components to form nuclear foci after irradiation. Moreover, 17DMAG exposure reduced the interaction between NBS1 and ATM, although no degradation of the MRN complex was detected. These results suggest that the diminished radiation-induced activation of ATM in 17DMAG-treated cells was the result of a compromise in the function of the MRN complex. These data indicate that Hsp90 can contribute to the DNA damage response to radiation affecting both DNA repair and cell cycle checkpoint activation.
Clinical Impact of Checkpoint Inhibitors as Novel Cancer Therapies
Authors: Kent Shih, Hendrik-Tobias Arkenau, Jeffrey R. Infante
Journal: Drugs (2014)

Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibitory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing understanding of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhibitory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among the first to be tested in the clinic, and ipilimumab was the first immune checkpoint inhibitor approved for an anticancer indication. Agents targeting the programmed death 1 (PD-1) pathway, either PD-1 or one of its ligands, programmed death ligand 1, are in active clinical development for numerous cancers, including advanced melanoma and lung cancer. Understanding the different mechanisms of action, safety profiles, and response patterns associated with inhibition of the CTLA-4 and PD-1 pathways may improve patient management as these therapies are moved in to the clinical practice setting and may also provide a rationale for combination therapy with different inhibitors. Additional immune checkpoint molecules with therapeutic potential, including lymphocyte activation gene-3 and glucocorticoid-induced tumor necrosis factor receptor-related gene, also have inhibitors in early stages of clinical development. Clinical responses and safety data reported to date on immune checkpoint inhibitors suggest these agents may have the potential to markedly improve outcomes for patients with cancer.
Cefotaxime Is More Effective Than Is Ampicillin–Tobramycin in Cirrhotics With Severe Infections
Authors: Josefina Felisart, Antoni Rimola, Vicente Arroyo, Rosa M. Perez-Ayuso, Enrique Quintero, Pere Gines, Joan Rodes
Journal: Hepatology (1985)

We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection. Most of these patients had spontaneous peritonitis and/or bacteremia. Patients were randomly allocated into two groups. Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime. Patients from both groups were similar with respect to clinical data, standard liver and renal function tests, types of infection and isolated organisms. Ninety-two per cent of bacteria isolated in Group I and 98% of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime, respectively. Ampicillin-tobramycin cured the infection in 56% of Group I patients, and cefotaxime in 85% of Group II patients (p less than 0.02). Five patients treated with ampicillin-tobramycin, and none treated with cefotaxime developed superinfections (p = 0.024). Nephrotoxicity (impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter) occurred in two patients in Group I and none in Group II. These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections.
Myositis ossificans of the chest wall
Authors: JF Nisolle, L Delaunois, JP Trigaux
Journal: European Respiratory Journal (1996)

We report the unusual case of a young man with progressive pain in the thoracic wall. The radionuclide bone scan revealed an increased uptake, and the bone roentgenogram, a calcified soft-tissue mass. Based on computed tomography findings, biopsy was avoided, and evolution was favourable for myositis ossificans. Although rare, myositis ossificans is one of the potential causes of thoracic pain, not to be mistaken for a malignant or infectious lesion.
Serum level of interleukin‐16 in multiple myeloma patients and its relationship to disease activity
Authors: Michael G. Alexandrakis, Freda H. Passam, Despina S. Kyriakou, Anna V. Christophoridou, Kostas Perisinakis, Aria Hatzivasili, Andreas Foudoulakis, Elias Castanas
Journal: American Journal of Hematology (2004)

Abstract Interleukin‐16 (IL‐16) is a chemoattractant of CD4(+) lymphocytes, and it has been implicated in the pathogenesis of various inflammatory diseases. There is evidence that it may have a role in multiple myeloma (MM). In the present study, we determined the serum level of IL‐16 both before and after treatment of MM and related it to inflammatory markers and survival. Forty‐eight newly diagnosed MM patients were included in the study. Disease stage was defined using the Durie–Salmon classification system (10 patients were in stage I, 19 in stage II, and 19 in stage III). After standard treatment, 22 patients reached the plateau phase and were re‐evaluated. The following serum parameters were measured: IL‐16, IL‐6, α‐1 antitrypsin (α1AT), and C‐reactive protein (CRP). Survival was determined as the number of months elapsed since original diagnosis. The mean ± SD of serum IL‐16 was 343 ± 195 pg/ml in the pre‐treatment MM group and 101 ± 30 pg/ml in the control group. All measured parameters were higher in the patient group compared to healthy controls. Furthermore, IL‐16, IL‐6, α1AT, and CRP were significantly increased with increasing stage of disease, from stage I to stage III ( P &lt; 0.01). All parameters decreased significantly following effective chemotherapy ( P &lt; 0.002). Patients with a high level of IL‐16 (&gt;430 pg/ml) displayed an inferior survival time in comparison to those with lower levels of IL‐16. In the pre‐treatment group, IL‐16 correlated with α1AT and IL‐6 ( r = 0.374, P &lt; 0.01 and r = 0.454, P &lt; 0.002, respectively). IL‐16 may play a role in multiple myeloma; however, further functional studies are required. Am. J. Hematol. 75:101–106, 2004. © 2004 Wiley‐Liss, Inc.
Use of Plasma Products With Whole Blood and Packed RBCs
Authors: Richard A. Kahn
Journal: JAMA (1979)

During the past five years, there has been a sharp increase in the use of packed RBCs (PRBCs) and plasma products, whereas whole blood (WB) transfusions have steadily decreased. In order to determine whether plasma and its derivatives were being used to "reconstitute" whole blood from PRBCs, we performed a retrospective evaluation of all transfusion episodes in ten representative regional hospitals during a five-month period. Our results indicate that PRBCs were transfused 2.5 times more frequently than WB. Plasma products were administered with PRBCs less often than with WB: 14% of all PRBCs vs 24% of all WB units tranfused. The likelihood of a patient receiving plasma was found to correlate with the total amount of blood transfused and the frequency of transfusion. This study provides evidence that, at most, only a small percentage of PRBCs are given in conjunction with plasma as "reconstituted" WB.
Appendicectomy in children.
Authors: R J Brereton
Journal: BMJ (1993)

different outcomes of our trial and Grethe St0a-Birketvedt's trial3 could be explained by a difference in weight loss before randomisation.The weight of all the patients in our trial, however, remained stable within a few kilograms during the month before the trial, and most patients were at their maximum weight.We did not show our data on the number of previous attempts at slimming.There was no difference, however, in the mean number of such attempts between the cimetidine and placebo groups.We agree that the different numbers of previous attempts in the cimetidine and the placebo groups in St0a-Birketvedt's trial cannot explain the remarkable weight loss reported.
TRANSPORTATION OF INJURED EMPLOYES.
Authors: FRANK H. CALDWELL
Journal: JAMA (1896)

The preliminary treatment given the employe or passenger at the time of accident, resulting in injury, and before the patient is removed to his home or to the hospital, is a service of vital importance; but the scope of this paper will not permit its discussion. The writer intends to confine himself strictly to the subject, as outlined for him by your committee. Considering the importance of transportation of persons injured it would be natural to suppose that there exists some literature on the subject, but a careful search has failed to reveal any material which could be utilized. The writer is forced, therefore, to give you his experience, trusting that in the discussion of his brief paper, new and valuable ideas will be brought out, which will prove of benefit to those unfortunates, who are often compelled to travel long distances while suffering intense agony from injuries. It has
SEASONAL VARIATION IN THE INCIDENCE OF SEVERELY CRIPPLING MENTAL DISORDERS II. ALCOHOLISM
Authors: NELSON J. BRADLEY, RUBEL J. LUCERO
Journal: American Journal of Psychiatry (1959)

Four thousand, one hundred consecutive alcoholic admissions over a 3-year period to the Willmar State Hospital were studied in an attempt to discover whether external stresses occurring within the framework of different times of the year played a part in frequency of admissions.
Increased levels of serum IgM antibody to staphylococcal enterotoxin B in patients with rheumatoid arthritis.
Authors: T Origuchi, K Eguchi, Y Kawabe, I Yamashita, A Mizokami, H Ida, S Nagataki
Journal: Annals of the Rheumatic Diseases (1995)

To investigate the role of superantigen in rheumatoid arthritis (RA) by assaying the serum levels of staphylococcal enterotoxin B (SEB) antibodies. Serum IgG and IgM SEB antibodies were measured using an enzyme linked immunosorbent assay (ELISA), and confirmed by Western blot analysis. The T cell receptor V beta (TCR V beta) repertoire was analysed using the reverse transcriptase polymerase chain reaction. RA patients had increased levels of serum IgM SEB antibody compared with normal subjects, patients with systemic lupus erythematosus, Sjögren's syndrome, and Behçet's disease. The titres of rheumatoid factor (RF) showed no correlation with the levels of IgM SEB antibodies, and the levels of SEB antibodies were not inhibited by the addition of human immunoglobulin, or after absorption of RF. RA patients whose disease duration was less than 10 years had greater levels of serum IgM SEB antibodies than those with disease duration more than 10 years. The levels of IgM and IgG SEB antibodies in synovial fluid from RA patients were correlated with those in their sera. Western blot analysis detected IgM and IgG SEB antibodies as a band of approximately 30 kDa molecular size. The percentage of TCR V beta 2, V beta 5.2, and V beta 12 in phytohaemagglutinin stimulated peripheral T cells correlated significantly with the levels of serum IgM SEB antibody in RA patients. These results suggest that SEB, one of the superantigens, may have a critical role in the pathogenesis of RA.
Atrial natriuretic peptide, arginine vasopressin and renal function during percutaneous transvenous mitral valvuloplasty
Authors: Rong-Chi Tsai, Tohru Yamaji, Miyuki Ishibashi, Fumimaro Takaku, Morgan Fu, Wen-Jin Cherng, Kanji Inoue, Jui-Sung Hung
Journal: Journal of the American College of Cardiology (1990)
Hypothesis: Vasa Vasorum and Neovascularization of Human Coronary Arteries
Authors: A. Clifford Barger, Reinier Beeuwkes, Lewis L. Lainey, Kenneth J. Silverman
Journal: New England Journal of Medicine (1984)

ALTHOUGH the vasa vasorum, the nutrient vessels in the wall of the human aorta, have been studied in some detail,1 there has been disagreement concerning the presence or extent of vasa vasorum in the coronary arteries. As early as 1876 Köster2 suggested that the intimal proliferation and medial hypertrophy of "arteriitis" was related to the presence of vasa vasorum in the media and intima. In 1938 Winternitz et al.3 injected India ink into the wall of cleared coronary arteries and demonstrated the "presence of rich vascular channels surrounding and penetrating sclerotic lesions." They suggested that "here, undoubtedly, was the source . . .
Rheumatology gone global
Authors: D. H Solomon, A. Tyndall, S. E Gabriel, M. Dougados
Journal: Annals of the Rheumatic Diseases (2008)

We read about the effects of globalisation everyday in the pages of our newspapers; now read about them here in the pages of your rheumatology journal—the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) have agreed to collaborate.

The two organisations have been discussing collaboration for over 3 years and in this issue of both the Annals of the Rheumatic Diseases and Arthritis & Rheumatism ( Arthritis Care & Research ), the first fruits of that collaboration are blossoming. Aletaha and colleagues from Europe and North America have developed recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis (RA), and this paper (as well as this Editorial) is published simultaneously in the two journals (see …
Are Stem Cells Drugs?
Authors: Michael R. Rosen
Journal: Circulation (2006)

Stem cell research and its clinical application have become political, social, and medical lightning rods, polarizing opinion among members of the lay community and among medical/scientific professionals. A potpourri of opinion, near-anecdotal observation, and scientifically sound data has sown confusion in ways rarely seen in the medical arts and sciences. A major issue is regulation, with different aspects of stem cell research falling within the purview of different government agencies and local offices. An overarching clearinghouse to review the field and recommend policy is lacking. In the following pages, I touch on the societal framework for regulation, the known and potential risks and benefits of cardiovascular stem cell therapies, whether stem cells should be regulated as drugs or in analogy to drugs, and if there is to be regulation, then by whom. In so doing, I refer to the stem cell literature only as it relates to the discussion of regulation because this is not a review of stem cell research; it is an opinion regarding regulation.
The Electrocardiogram in Patients with Both Great Vessels Arising from the Right Ventricle Combined with Pulmonary Stenosis
Authors: M. MIROWSKI, ALI MEHRIZI, HELEN B. TAUSSIG
Journal: Circulation (1963)

IN the past decade several cases of both great vessels arising from the right ven- tricle combined with pulmonary stenosis have been reported.1-5This condition has been de- scribed as complete dextroposition of the aorta, pulmonary stenosis, and ventricular septal defect' and also as double outlet right ventricle.2During life this malformation has frequently been confused with the tetralogy of Fallot and the correct diagnosis has usu- ally not been made until autopsy.Recently, in this clinic and elsewhere," various angiocardiographic procedures have proved to be of diagnostic aid in the recog- nition of both great vessels arising from the right ventricle combined with pulmonary ste- nosis.Surgical correction of this malformation, although difficult, has been successfully performed*," emphasizing the necessity of a correct antemortem diagnosis.Inasmuch as the hemodynamics of this entity differ in many aspects from those of a tetralogy of Fallot and since the alteration in the work required of the heart is usually reflected in the cardiac electrical activity,7-9 it was thought that the electrocardiogram might show specific changes in this malformation.Indeed, we have seen a few patients in whom the electrocardiogram suggested that the con-
Selection of patients for haemodialysis. Who best to make the choice?
Authors: J. D. Nabarro
Journal: BMJ (1967)

Selection of Patients for HaemodialysisIn the past few months there has been much debate on the ethical difficulties in selecting patients for haemodialysisincluding a Ciba Symposium' and statements by the Sheffield Regional Hospital Board' and by the Minister of Health."To discuss various aspects of this problem we have invited contributions from four doctors in different fields-a general physician, a consultant in clinical renal physiology, a professor of urology, and a family doctor.