tbuckley/cabot-search huggingface dataset:
Randomized phase II study of epirubicin (E) plus cyclophosphamide (C) vs. weekly paclitaxel (P) as primary systemic therapy (PST) in patients (pts) with stage II and III breast cancer (BC)
Authors: M. Miyashita, N. Kohno, S. Takao, K. Wakita, M. Konishi, M. Kubota, H. Yoshimura, Y. Kasahara, Y. Sumi, I. Kokufu
Journal: Journal of Clinical Oncology (2005)

720 Background: Response and survival rates achieved by anthracycline and P (q 3 weeks (W)) pts with metastatic BC are comparable (ECOG1193). Weekly P is expected to produce higher response rates and lower hematological toxicity than tri-weekly P for PST (MDACC2002). The aim of this study was to evaluate the activity and toxicity of weekly P therapy compared with EC therapy for stage II and III BC with PST. Methods: Pts with histologically confirmed BC, stage II or III, performance status 0–2, and absence of prior chemotherapy were randomized to either Arm A (EC: E 75mg/m2 and C 600 mg/m2 every 3 W for 4 cycles) or Arm B (weekly P: P 80 mg/m2 weekly for 12 W). Pts received PST for 12 W, then underwent surgery. All pts received a cross-over regimen as adjuvant chemotherapy after surgery. Results: As of Nov 2004, 114 pts have been recruited. Ninety-seven pts (Arm A: n=50, Arm B: n=47) were evaluable. The clinicopathological characteristics of pts (age, tumor size, stage, hormone receptor (HR) and HER2 status) were well balanced in the two arms. Overall response rate (OR) was 65.6% in Arm A and 67.9% in Arm B. OR in HER2-positive pts was 80.0% in Arm A and 91.7% in Arm B, but there was no significant difference. OR in HR negative pts or in tumors measuring more than 3 cm were equal in both arms. The incidence of grade3/4 neutropenia (46.7% vs 3.1%, p<.001) and leukopenia (43.3% vs 0%, p<.001) were lower in Arm B than in Arm A, while that of vomiting (45.5% vs 12.0%, p<.01) was higher in Arm A. Nausea (28.3% vs 12.0%) and mucositis (38.1% vs 16.0%) were more frequently seen in Arm A than in Arm B, but there was no significant difference. The incidence of neuropathy (3.0% vs 27.2%, p<.01) was higher in Arm B. Conclusions: Interim analysis of 97 pts suggested that weekly P was associated with less toxicity than EC therapy, but more frequently induced neuropathy. OR was similar in both therapies. Therefore, induction of PST by weekly P therapy seems to be promising. We are further investigating the pathological response and accrual is still proceeding until the planned sample size of 200 pts is achieved. No significant financial relationships to disclose.
Decreasing galectin-1 expression in human experimental glioblastomas impairs the endoplasmic reticulum stress (ERS) response and increases temozolomide anti-tumor effects.
Authors: Marie Le Mercier, Yasuko Kondo, Veronique Mathieu, Isabelle Camby, Christine Decaestecker, Robert Kiss, Florence Lefranc
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1967 

Malignant gliomas, and especially glioblastomas (GBMs) are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells with reduced levels of apoptosis (Type I programmed cell death (PCD)), and consequent resistance to the cytotoxic insults of pro-apoptotic drugs (Lefranc et al., J Clin Oncol 2005). In contrast, GBM cells display sensitivity to autophagy, i.e. Type II PCD (Kanzawa et al., Cell Death Differ 2004), a fact that can at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 plays a number of vital roles in Ras signaling, which in turn is pivotal to GBM development and resistance to apoptosis (see Camby et al., Glycobiology, 2006, for review). The stable inhibition of galectin-1 expression in human U87 GBM cells alters the expression of a number of genes that either directly or indirectly influences the adhesion, the motility and the invasive ability of human glioblastoma cells, and additionally, immunocompromized mice intracranially grafted with human GBM cells constitutively expressing low levels of galectin-1 had longer survival periods than mice grafted with GBM cells expressing normal levels of galectin-1 (see Camby et al., Glycobiology, 2006, for review).

The data in the present study reveal that treating Hs683 human GBM cells with temozolomide increases galectin-1 expression, suggesting therefore a cytoprotective role for galectin-1. Reducing galectin-1 expression in human Hs683 GBM cells using a specifically designed anti-galectin-1 siRNA does not induce apoptotic or autophagic features. In contrast, this galectin-1 depletion decreases the levels of expression of several genes involved in the response to endoplasmic reticulum stress; including DUSP5, HERP, DNAJB9/MDG1/ERdj4 and HYOU1/ORP150, the latter of which modulates angiogenesis via the processing of VEGF. Reduced galectin-1 expression in Hs683 tumor cells also leads to sustained decreases in VEGF expression, with severe in vivo impairment of angiogenesis in Hs683 orthotopic xenografts. Furthermore, the in vivo delivery of a non-viral infusion of anti-galectin-1 siRNA into the ventricular system of the brains of adult mice orthotopically grafted with Hs683 GBM cells increases the anti-tumor effects of temozolomide. This novel facet of galectin-1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.
Urinary Concentration in the Papillary Collecting Duct of the Rat
Authors: Richard E. Oliver, Denis R. Roy, Rex L. Jamison
Journal: Journal of Clinical Investigation (1982)

Urine was observed to flow intermittently in the collecting ducts of the extrarenal papilla of antidiuretic rats. The purpose of this investigation was to test Reinking and Schmidt-Nielsen's hypothesis that intermittent flow plays an important role in the production of maximally concentrated urine. Samples of collecting duct fluid were obtained from the base and tip of the papilla by micropuncture through the intact ureter. Fluid osmolality rose sharply from base, 894±120 mosmol/kg H2O−1 (mean±SE), to tip, 1,667±114 (P<0.001), a distance of only 2 mm, and was due exclusively to reabsorption of water. After excision of the ureter, which abolished intermittent flow, osmolality fell modestly at the base to 723±82 mosmol/kg H2O−1 (P < 0.02), but strikingly at the tip to 1,012±103 (P < 0.001). The pelvic ureter was paralyzed by topical verapamil and dimethylsulfoxide, which abolished intermittent flow. Osmolality of urine at the tip was not changed (1,959±184 mosmol/kg H2O−1 before, vs. 1,957±126 after paralysis). The ureter was severed just beyond the papillary tip, a maneuver which preserved intermittent flow but abolished urinary reflux over the papilla. Urinary osmolality fell from 1,876±134 mosmol/kg H2O−1 to 1,284±115 (P < 0.005). These findings demonstrate that when the ureter is intact, over half of the increase in urinary osmolality above isotonicity occurs in the terminal one-fourth of the medullary collecting duct and is due exclusively to water reabsorption (no net solute addition). It is the continuity of the ureter, rather than intermittent flow due to ureteral peristalsis, which is essential for the formation of a maximally concentrated urine.
Abstract 331: Recovery of Mitochondrial Bioenergetics after Hypoxia via Regulating Pyruvate Dehydrogenase Kinase and Adenosine Monophosphate-activated Kinase
Authors: Jessica M Toli, Minzhen He, Carolyn Suzuki, Maha Abdellatif
Journal: Circulation Research (2014)

Mitochondrial quality control is critical for the survival of cardiac myocytes during stress. The purpose of this study was to examine the effect of metabolic substrates and regulators of metabolism on mitochondrial bioenergetics, as an indicator of mitochondrial quality, and how these factors might influence the recovery of the cell’s bioenergetics after hypoxia/ischemia. By monitoring oxygen consumption rates (OCR), in real-time, in live neonatal rat myocytes and human cardiac myocyte-differentiated induced pluripotent stem cells, we found that both cell types can maintain basal OCR efficiently with any metabolic substrate; however, the neonatal cells require both glucose and fatty acid, while the human adult cells require fatty acid only, for mounting maximum reserve respiratory capacity (RRC). Our data also show that subjecting cardiac myocytes to hypoxia results in a reduction of the cells’ basal OCR and oxidative phosphorylation, and exhausts the RRC, which is accompanied by an increase in pyruvate dehydrogenase kinase (Pdk) 1 and 4. Except for normalization of Pdk1 levels, there was little or no recovery of these parameters after reoxygenation. We, thus, hypothesized, that inhibition of Pdks may help recovery of the cell’s bioenergetics. Indeed, our results show that by inhibiting Pdks with dichloroacetate (DCA) before or after hypoxia, the cells’ bioenergetics, including OCR, oxidative phosphorylation, and RRC in neonatal myocytes, and RRC in the human myocytes fully recover within 24 h. On the other hand, activating AMP-activated kinase (AMPK) resulted in delayed (96 h) improvement of the cells’ RRC that was accompanied by an increase in peroxisome proliferator-activated receptor gamma, coactivator 1α (3.5x), peroxisome proliferator-activated receptor-α (2x), and mitochondrial number (2x). These results led us to conclude that compromised mitochondrial quality can be rescued through mechanisms that regulate glucose or fatty acid oxidation by either inhibiting Pdks or activating AMPK, respectively, in rodent and human myocytes.
Abstract 1373: Site Specific Correlation of Pericardial Fat With Cardiac Function in Metabolic Syndrome
Authors: Ning Hua, Zhongjing Chen, Sherman Bigornia, Alkystis Phinikaridou, Ye Qiao, Caroline Apovian, Hernan Jara, James Hamilton, Frederick Ruberg
Journal: Circulation (2009)

The total volume of pericardial fat has been associated with increased coronary artery plaque calcification and reduced left ventricular (LV) function; however, it is not known whether these advers...
History of the Great War. Based on Official Documents. Medical Services: Pathology.
Authors: W. G. Macpherson, W. B. Leishman, S. L. Cummins
Journal: JAMA (1923)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Effects of Sodium Tetraiodophenolphthalein On Some Vital Organs
Authors: C. K. Hsieh
Journal: Annals of Internal Medicine (1927)

Article1 August 1927Effects of Sodium Tetraiodophenolphthalein On Some Vital OrgansC. K. HSIEH, M.D.C. K. HSIEH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-2-96 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe remarkable Graham method for visualization of gall bladder since its discovery in 1923 (1) is now widely used as a routine procedure in the Roentgen diagnosis of gall bladder conditions. The high toxicity of the tetrahalogenophenolphthaleins employed in this test is well known as evidenced by the reports of some marked constitutional reactions after the administration of the drug sometimes observed in the earlier days of the development of this method of diagnosis. With the improvement of technique of administration and of purer preparation of the salts, however, any untoward effect has been eliminated. The substitution for the tetrabromphenolphthalein...References(1) GRAHAMCOLE EAWH: Roentgenological examination of the gall bladder; preliminary report of a new method utilizing the intravenous injection of tetrabromphenolphthalein. J. Am. M. Ass., Feb. 23, 1924, lxxxii, 613. CrossrefGoogle Scholar(2) WHITAKERMILLIKEN LRG: A comparison of sodium tetrabromphenolphthalein with sodium tetraiodophenolphthalein in gall bladder radiography. Surg., Gynec. and Obst., Jan., 1925, xl, 17. Google Scholar(3) GRAHAMCOLECOPHER EAWHGH: Cholecystography: its development and application. Am. J. Roentgenol. and Rad. Therapy, December, 1925, xiv, 487. Google Scholar(4) OTTENBERGABRAMSON RHA: Production of liver necrosis by tetrachlorphenolphthalein and tetrabromphenolphthalein. J. Am. M. Ass., March 14, 1925, lxxxlv, 800. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Peking, China*From the Departments of Pathology and Roentgenology, University of Michigan, Ann Arbor, Michigan, and the Department of Roentgenology, Peking Union Medical College, Peking, China. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1927Volume 1, Issue 2Page: 96-107KeywordsAdverse reactionsBladderDrug administrationSaltsSodiumToxicity ePublished: 1 December 2008 Issue Published: 1 August 1927 PDF downloadLoading ...
β-d-Glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis
Authors: Estrella Martín-Mazuelos, Ana Loza, Carmen Castro, Desirée Macías, Ismail Zakariya, Pedro Saavedra, Sergio Ruiz-Santana, Elena Marín, Cristóbal León
Journal: Intensive Care Medicine (2015)
Abstract 43: Mice With Cardiac-Specific Inactivation Of Ppap2b (Lipid Phosphate Phosphatase 3) Validates Genome-Wide Association Studies.
Authors: Manikandan Panchatcharam, Sumitra Miriyala, Natalie D Hendrix, Diana Escalante-Alcalde
Journal: Circulation Research (2014)

A recent meta-analysis of Genome-Wide Association Studies (GWAS) of coronary artery disease (CAD) involving over 86,000 individuals identified PPAP2B (encodes lipid phosphate phosphatase-3; LPP3) as a new loci (SNP rs17114036; P= 3.81 X 10 −19 ) that independently predicts CAD. LPP3 is an integral membrane enzyme that dephosphorylates lysophosphatidic acid, sphingosine-1-phosphate and related bioactive lipids. Strikingly, we found that targeted inactivation of LPP3 in endothelial cells results in early embryonic lethality, in part to due to vascular patterning defects. In addition, we found that constitutive inactivation of LPP3 in the myocardium results in cardiac dysfunction, indicating that dysregulation of LPP3-dependent cardiomyocyte cell function. Heart rate was significantly higher in conditional Ppap2b Δ mice (P&lt;0.001), which may indicate a role for LPP3 in regulating heart rate and/or function. Further, we found that myocardial LPP3 levels are altered following myocardial infarction in mice and these results are in accord with our myocardial infarct data from patient that had down-regulated myocardial LPP3 levels. The major rs17114036A allele was associated with a 1.17 odds ratio for CAD. This SNP is located in the final intron of the six exon PPAP2B gene. At least seven SNPs are in robust linkage disequilbrium (r2&gt;0.9) with rs17114036. The sequence surrounding the SNP rs17114036 matches a U1 spliceosome recognition sequence, and the variant base is located at the final position of a sequence with high homology to a U1 spliceosome 5’ spice site recognition motif. Binding of the U1 spliceosome may alter mRNA stability or processing, perhaps by masking cryptic splice sites, thus enabling efficient splicing or promoting polyadenylation of the mature message. To address the polymorphism, we transfected MDA MB 453 cells, which are homozygous for the “T’ allele of rs17114036 SNP, with a short synthetic 2’-O-methyl phosphorothioate RNA. We found a dramatic decrease in both LPP3 protein expression and LPP3 mRNA levels. These results imply that the region containing the rs17114036 SNP may be important for proper processing and/or stability of the LPP3 transcript thereby functionally validating the GWAS study.
Venous Pressure in Pneumonia
Authors: George J. Kastlin, W. W. G. Maclachlan
Journal: Annals of Internal Medicine (1931)

Article1 February 1931Venous Pressure in PneumoniaGEORGE J. KASTLIN, M.D., W. W. G. MACLACHLAN, M.D.GEORGE J. KASTLIN, M.D.Search for more papers by this author, W. W. G. MACLACHLAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-8-959 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the study of the circulation in the normal individual, Eyster, Hooker, Clark and others have placed particular emphasis on the variations and importance of the venous pressure. The results of these investigations have given evidence that the venous pressure is altered greatly by varied demands on the circulatory mechanism. It has been observed that the venous return of blood to the heart apparently regulates in large part the arterial output. The venous pressure determines the degree of filling of the ventricular chambers in diastole, and this determines the amount of blood expelled at each contraction of the ventricles. An...Bibliography1 EYSTERMIDDLETON JAWS: Clinical Studies of Venous Pressure. Arch. Int. Med., 34:228, 1924. CrossrefGoogle Scholar2 EYSTERMIDDLETON JAWS: Venous Pressure as a Guide to Venesection in Congestive Heart Failure. Am. J. M. Sc., 174:486, 1927. Google Scholar3 EYSTER JA: Venous Pressure in Cardiac Decompensation. J.A.M.A., 89: 428, 1927. CrossrefGoogle Scholar4 EYSTER JA: "Clinical Aspects of Venous Pressure." The Macmillan Co. N.Y. 1929. Venous Pressure." The Macmillan Co., as a Method of Functional Measurement of Heart in the Human. Deut. Arch. f. kl. Med., 108,537, 1912. CrossrefGoogle Scholar6 FUCHS L: Measurement of Venous Pressure and Its Clinical Significance. Deut. Arch. f. kl. Med., 134-35.68, 1920-21. Google Scholar7 HOOKEREYSTER DRJA: An Instrument for the Determination of Venous Pressure in Man. John-Hop. Hos. Bull., 19:274, 1908. Google Scholar8 CLARK AH: Study of Diagnostic and Prognostic Significance of Venous Pressure Observations in Cardiac Disease. Arch. Int. Med., 16:587, 1915. CrossrefGoogle Scholar9 HEINTZELMAN JH: To be published. Google Scholar10 MACLACHLANKASTLINLYNCH WWGJR: The Use of Dextrose in Pneumonia. Am. J. M. Sc., 179:93, 1930. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Pa.*From the Medical Clinic of Mercy Hospital, Pittsburgh, and Department of Medicine, University of Pittsburgh. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe measurement of venous pressure by the direct method 1 February 1931Volume 4, Issue 8Page: 959-968KeywordsBloodDiastoleHeartHospital medicinePneumonia ePublished: 1 December 2008 Issue Published: 1 February 1931 PDF downloadLoading ...
Another Agent for Obesity — Will This Time Be Different?
Authors: Elias S. Siraj, Kevin Jon Williams
Journal: New England Journal of Medicine (2015)

Over the past few decades, obesity has become a global epidemic that affects diverse societies across developed and developing countries. Obesity rates correlate well with recent developments such as incessant enticements to sit and an unprecedented availability, at low or no cost, of foods and beverages rich in poorly satiating calories. These rapid environmental changes interact with preexisting genetic tendencies, yet in a timescale so brief as to outstrip evolution.What is wrong with obesity? Extra weight once indicated prosperity and was considered to be attractive. But now we know that overnutrition and underexertion beget a cluster of seemingly unrelated . . .
Abstract P109: Alteration in Intracellular Calcium During Cardiac Arrest
Authors: Satoshi Takeda, Hiroshi Yoshida, Takeki Ogawa
Journal: Circulation (2008)

AIM: A cytosolic free calcium is an important regulator of cardiac metabolism and contractility, and an increased [Ca2+]i has been implicated in irreversible cell injury and contractile dysfunction. We investigated intracellular calcium ([Ca2+]i) dynamics during cardiac arrest, especially in pulseless electrical activity (PEA) and asystole. METHODS: Rat hearts (n=18) were perfused with a Langendorff system and loaded with Fura-2/AM, as a [Ca2+]i marker, and BCECF/AM, as a pHi marker. Surface fluorescence of the heart was recorded with an intracellular ion analyzer. A latex balloon was inserted into the left ventricle to monitor left ventricular pressure. Sustained normo-thermic cardiac arrest was induced for 20 min by clamping the aortic cannula. RESULTS: After clamping (cardiac arrest), the left ventricular developed pressure decreased significantly, from 84.3±11 mmHg to 3.88±0.7 mmHg (p&lt;0.01) at 2min. The rhythm was PEA in all cases in this period, followed by asystole. The amplitude of the [Ca2+]i transient (0.30±0.03) was maintained at 2 min, but further significant increases were observed in both systolic (1.14±0.04, p&lt;0.01) and diastolic levels of [Ca2+]i (0.84±0.04, p&lt;0.05), when compared with pre-arrest levels. The [Ca2+]i transient disappeared 4.7±0.6 min. The diastolic [Ca2+]i increased gradually after 5 min to 20 min. This diastolic [Ca2+]i increase was parallel with the increase in left ventricular end diastolic pressure (indicated ischemic contracture). The pHi increased (to 7.6±1.0) immediately after clamping. Thereafter pHi decreased rapidly and remained steady (at pH 6.6±0.6). CONCLUSIONS: The change in the [Ca2+]i-pressure relationship rather than change in the amplitude of the [Ca2+]i transient was the main contributor in the early cardiac arrest phase. The diastolic [Ca2+]i increase might induce irreversible cell injury in the late cardiac arrest phase.
Clinical Teaching with Special Reference to Bedside Study of Disease
Authors: L. J. Moorman
Journal: Annals of Internal Medicine (1932)

Article1 August 1932Clinical Teaching with Special Reference to Bedside Study of DiseaseL. J. MOORMAN, M.D., F.A.C.P.L. J. MOORMAN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-6-2-289 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe word "clinical" means to lie in bed. Clinical medicine in its broadest sense means that part of medicine which has to do with the bedside investigation of disease in the living body. Clinical medicine is not a school of dogma; it is a school of method. Progress in clinical medicine is not hedged about by fixed limits, but may go as far as the individual's methods of observation and investigation can carry him.The medical student should be impressed with this fact early in the course of his studies, because there can be no better preparation of the soil... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oklahoma City, Oklahoma*Received for publication, November 7, 1931.†From the Department of Clinical Medicine, University of Oklahoma. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1932Volume 6, Issue 2Page: 289-292 ePublished: 1 December 2008 Issue Published: 1 August 1932 PDF downloadLoading ...