tbuckley/cabot-search huggingface dataset:
In Vivo Enzymatic Assay Reveals Catalytic Activity of the Human Renin Precursor in Tissues
Authors: Danielle Methot, David W. Silversides, Timothy L. Reudelhuber
Journal: Circulation Research (1999)

Abstract —The aspartyl protease renin is secreted into the circulation of mammals in 2 forms: the proteolytically processed active form of the enzyme and the precursor form, prorenin. Prorenin has no detectable enzymatic activity in the circulation, but it is the exclusive form of the enzyme produced by several tissues that also produce the other components of the renin enzymatic cascade (renin-angiotensin system). To test whether prorenin might be enzymatically active in these tissues, transgenic mice expressing the human renin substrate (angiotensinogen) exclusively in the pituitary gland were mated to mice expressing either active human renin or prorenin in the same tissue. Measurement of in vivo product formation in pituitary glands of double-transgenic mice revealed that human prorenin was enzymatically active, and Western blot analysis demonstrated that this prorenin was in the precursor form with its prosegment attached. This in vivo enzymatic assay demonstrates for the first time that human prorenin can be activated within tissues by nonproteolytic means, where it could contribute to the activity of a localized renin-angiotensin system.
Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary World
Authors: Benjamin Djulbegovic
Journal: Annals of Internal Medicine (2009)

Letters3 February 2009Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary WorldBenjamin Djulbegovic, MD, PhDBenjamin Djulbegovic, MD, PhDFrom University of South Florida, Tampa, FL 33620.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-3-200902030-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with great interest the article by Vickers and colleagues (1), in which they note the problem of diagnosis caused by difficulties in classification of borderline cases: One individual or very small differences in the quantities of interest may completely change categorization and consequent actions. Unfortunately, the risk prediction alternative recommended by the authors is unlikely to attenuate the problem of diagnosing diseases that are defined on a continuum. The problem described by the authors is not trivial and has preoccupied philosophers since ancient times. It is commonly referred to as the sorites paradox (from the ...References1. Vickers AJ, Basch E, Kattan MW. Against diagnosis. Ann Intern Med. 2008;149:200-3. [PMID: 18678847] LinkGoogle Scholar2. Williamson T. Vagueness. London: Routledge; 1994. Google Scholar3. Hyde D. Sorites Paradox. In: Stanford Encyclopedia of Philosophy. Accessed at plato.stanford.edu/entries/sorites-paradox/ on 11 December 2008. Google Scholar4. Sorenson R. Vagueness. In: Stanford Encyclopedia of Philosophy. Accessed at plato.stanford.edu/entries/vagueness/ on 11 December 2008. Google Scholar Author, Article, and Disclosure InformationAffiliations: From University of South Florida, Tampa, FL 33620.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAgainst Diagnosis Andrew J. Vickers , Ethan Basch , and Michael W. Kattan Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary World Gregory Patrick Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary World Robert A. Swerlick Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary World Andrew J. Vickers , Ethan Basch , and Michael Kattan Risk Prediction Versus Diagnosis: Preserving Clinical Nuance in a Binary World Jeremy L. Warner Metrics 3 February 2009Volume 150, Issue 3Page: 223KeywordsBlood pressureConflicts of interest ePublished: 3 February 2009 Issue Published: 3 February 2009 CopyrightCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Monitoring of sodium: Proton exchange in isolated hepatocytes by electronic cell sizing
Authors: David J. Stewart
Journal: Hepatology (1989)

To investigate volume-regulating processes in the hepatocyte, a rapid and precise method of measuring cell volume in isolated hepatocytes was devised which uses a Coulter Counter equipped with a Channelyzer. Isolated hepatocytes exhibit a volume-decreasing mechanism (potassium channel) which is triggered by cell volume increases as small as 10%. Cell volume increases in the hepatocyte may be mediated by activity of the Na:H exchanger. To examine Na:H exchange-mediated cell volume increases, without apparent interference by the volume-decreasing mechanism, acetate was substituted for chloride in the incubation medium. Hepatocytes placed in a medium containing sodium acetate at an acidic pH exhibit a continuous amiloride-sensitive swelling. A simple procedure was devised for estimating Na:H exchanger set-point by electronic cell sizing. In a sodium acetate medium, the internal pH equilibrates with the external pH. By placing cells in sodium acetate medium of various pH values and measuring the rate of amiloride-sensitive swelling, an estimate of Na:H exchanger set-point can be obtained. By this method, the exchanger was estimated to cease activity above an intracellular pH of 7.2. This method could be useful for identification of stimuli that might promote cell enlargement by raising the exchanger set-point. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate tetraacetic acid raises the set-point of the exchanger in the isolated hepatocytes, resulting in exchanger activity at normal cellular pH, and at the same time promotes hepatocyte swelling. Exchanger activation via a kinase C-mediated mechanism is one possible way that hepatocyte enlargement may occur.
A NOTE ON THE PURIFICATION AND ADMINISTRATION OF INSULIN
Authors: N. F. FISHER
Journal: JAMA (1923)

In view of the work recently reported by Mills on absorption of insulin from the intestine, and the work by Best and Scott on the recovery of insulin from urine, it was thought best to report a summary of the results obtained with insulin in a similar type of experiments during the past year. The details of the work will be left for a later communication. The Doisy-Somgyri-Shafer method of preparing insulin was modified and used with great success. One of the modifications was to precipitate with one volume of 95 per cent. alcohol, whereas the workers mentioned used nine volumes to precipitate the final product. This precipitate, thrown down by one volume of 95 per cent, alcohol, raised the blood sugar of animals when injected subcutaneously. When a small amount was given intraperitoneally to rats or guinea-pigs, death invariably resulted within fifteen minutes. The injection of this substance subcutaneously
CHRONIC RETENTION OF URINE ARISING FROM PROSTATIC DISORDER: ITS CAUSE, AND TREATMENT BY THE PRACTITIONER WITHOUT OPERATION
Authors: H. T. Herring
Journal: BMJ (1921)

UR1E DUE TO PROSTATIC DISORDER.-I As,arSJm an excitiug dose, or a curative dose, we may well be puzzled in finding thie correct dose in a sensitive patient.Stmrnarzi.1.By the skin reactions half the cases of asthma can be proved to be due to some foreign protein.2. If these causes can then be removed the patients are relieved of their asthma at onice.3. iM:uch can be done to relieve or even cure other cases which do not give positive sliin reactions, by the usage of variouLs proteins, as antigens, to desensitize them with.4. Asthma, hay fever, urticaria, eczema, migraines, epilepsy, and paroxysmal haemoglobinuria, have many common traits an(d will probably all be proved eventually to be symptoms of anaphylaxis and not separate diseases at all.This list will most likely be considerably enlarged.In conclusion I wish to thank those many gentlemen whose patients I have tested and treated, but especially my friend Dr. Latham, through whose interest my atten- tion and work have been so fully turned to tllis matter.This new advance in medicine may be only a matter of inches, but it does allow us to see round a fresh corner and to obtain a view, and a direct view, of great possibilities in connexion witli these chronic complaints, the cause and cure of wlhich have so long baffled explanation.
Gas Physiology in Space Operations
Authors: Emanuel M. Roth
Journal: New England Journal of Medicine (1966)

What is the frequency of bends to be expected after decompression in space operations? From the previous consideration of the pressure and oxygen factors one can assume that a space-cabin atmosphere containing inert diluent should have about 3.5 psia (180 mm. of mercury) of oxygen and a total pressure of 5 to 7 psia. This would allow for 1.5 to 3.5 psia of inert gas. From the point of view of decompression, the lower the equilibrium pressure level of inert gas, the lower the bends hazard upon subsequent decompression to a lower pressure. This would make the cabin with 50 . . .
Osteoporosis And Fluorides
Authors: Daniel S. Bernstein
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The letter of Dr. Saville has raised some pertinent points. It is difficult to define "bias" in any population sample. The studies of Vincent and Urist and Gershon-Cohen et al may be expected to represent the picture in the institutions they studied, but these people undoubtedly vary in ethnic origin, previous dietary history, occupation, and many other characteristics. There is no reason to believe that they represent a random sample of the population at large. Indeed it may be assumed that they do represent a "biased" sample. The groups we studied were individuals who consulted their physician for some purpose and who consented to participate in the study. There is indeed reason to believe that such samples are "biased" since they are people who, for some reason, consult their physician. One might expect such a sample to have a higher proportion of osteoporosis than a random sample
Cadmium accumulation and protein binding patterns in tissues of the rainbow trout, Salmo gairdneri.
Authors: J Kay, D G Thomas, M W Brown, A Cryer, D Shurben, J F Solbe, J S Garvey
Journal: Environmental Health Perspectives (1986)

Rainbow trout were exposed to defined levels of cadmium in their aquarium water for differing periods at a variety of near-lethal concentrations that ensured the survival of the majority of the fish. The gills, liver and kidney together accounted for 99% of the accumulated load of body cadmium in the fish under these conditions. Although the proportion of total cadmium present in the liver remained relatively constant throughout, the distribution of the remainder between gill and kidney altered with the time of exposure. The cadmium in all three organs was bound by two low molecular weight proteins distinct in character from metallothionein. The isoforms of metallothionein were also present but were found to bind only zinc and copper. By contrast, when trout were injected with cadmium intraperitoneally, most of the metal accumulated in the liver where it was sequestered by the two isoforms of metallothionein. Pre-exposure of the trout to either a low concentration of cadmium (for several months) or to an elevated concentration of zinc (for 5 days) allowed the animals to survive a subsequent exposure to a high, otherwise lethal concentration of cadmium. The proteins responsible for sequestration of the two metals were identified, but two different mechanisms seemed to be involved in the protection of the animals. The significance of these observations in terms of the induction of proteins and the prevention of the toxic effects of cadmium is considered.
Abnormal left ventricular contraction pattern in the systolic click-late systolic murmur syndrome.
Authors: D G Mathey, P R Decoodt, H N Allen, H J Swan
Journal: Circulation (1977)

A contraction abnormality of the left ventricle has previously been described in patients with systolic click-late systolic murmur syndrome. To determine if the contraction abnormality is present in the preprolapse period, LV dimensions and the instantaneous velocity of circumferential fiber shortening (VCF) were studied in 18 patients with the mitral valve prolapse and 16 normal subjects using computer analysis of echocardiograms. VCF attained its maximum (max VCF) during the preprolapse period an average of 94 msec before the mid-systolic click. Max VCF was significantly reduced in patients with mitral valve prolapse (2.06 vs 2.55 circ/sec in normal subjects, P less than 0.001). Despite the reduction in max VCF, no difference in the extent and percentage of diameter shortening was found between patients and normal subjects. This discrepancy is explained by a sustained rate of mid-to-late systolic diameter shortening in the presence of mitral valve prolapse as manifested by a typical VCF profile (P less than 0.001) and a longer duration of diameter shortening (353 vs 306 msec in normal subjects, P less than 0.01). The decrease of max VCF in patients with mitral valve prolapse suggests a reduction in LV contractility. Since the abnormality is present in the preprolapse period, it is unrelated to a direct mechanical effect of the prolapse itself. Additional fiber shortening in mid-to-late systole indicates that the sudden displacement of the mitral leaflets may have an unloading effect on the left ventricle.
Empyema Incised Antiseptically: Death from Pericarditis
Authors: G. H. Philipson
Journal: BMJ (1881)

a milliner, first complained of feel- inig ill and generally out of sorts; she had slight headache, and loss of flesh and appetite; the bowels were constipated.She was a thin medium-sized uwoman, of a nervous anxious temperament.After talkilng a couple of colocynth pills, she was attacked by severe enteritis, with vomniting, purging, tenderness on pressure, and great tenesmus.At the end of a fortnight, the dliarrhoea having ceased, the patient was somewhat improved; but the emaciation continued, and at last was extreme.In the beginning of September, she had slight jaundice, and complaineed of pain in the right side and in the epigastrium.On Septem)ber i8th, a tumour was felt by palpation in the right hypochondriac region, tender to the touch, and giving an indefinite feeling of fluctua- tioni.The swelling began below the costal cartilages, descending about two and a half inches, extending)back; to about an inch beyond the
Pseudomembranous necrotising bronchial aspergillosis complicating chronic airways limitation.
Authors: A G Nicholson, K M Sim, B F Keogh, B Corrin
Journal: Thorax (1995)

Pseudomembranous necrotising bronchial aspergillosis is a variety of invasive aspergillosis found in immunosuppressed patients. A case is presented of a 66 year old woman whose only underlying disease was chronic airways limitation. The pathological findings and clinical implications are discussed.
The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Induces Growth Inhibition and Enhances Gemcitabine-Induced Cell Death in Pancreatic Cancer
Authors: Nichole Boyer Arnold, Nohea Arkus, Jason Gunn, Murray Korc
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Pancreatic cancer is an aggressive human malignancy that is generally refractory to chemotherapy. Histone deacetylase inhibitors are novel agents that modulate cell growth and survival. In this study, we sought to determine whether a relatively new histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), inhibits pancreatic cancer cell growth. Experimental Design: The effects of SAHA on the growth of three pancreatic cancer cell lines (BxPC3, COLO-357, and PANC-1) were examined with respect to cell cycle progression, p21 induction and localization, and interactions with the nucleoside analogue gemcitabine. Results: SAHA induced a G1 cell cycle arrest in BxPC-3 cells and COLO-357 cells but not in PANC-1 cells. This arrest was dependent, in part, on induction of p21 by SAHA, as p21 was not induced in PANC-1 cells, and knockdown of p21 using small interfering RNA oligonucleotides nearly completely suppressed the effects of SAHA on cell cycle arrest in COLO-357 and partly attenuated the effects of SAHA in BxPC-3. COLO-357 and BxPC-3 cells, but not PANC-1 cells, were also sensitive to gemcitabine. In the gemcitabine-resistant PANC-1 cells, a 48-h cotreatment with SAHA rendered the cells sensitive to the inhibitory and proapoptotic effects of gemcitabine. An additive effect on growth inhibition by SAHA and gemcitabine was observed in COLO-357 and BxPC-3 cells. Moreover, analysis of p21 distribution in COLO-357 cells revealed that SAHA induced the cytoplasmic localization of both p21 and phospho-p21. Conclusions: These data indicate that SAHA exerts proapoptotic effects in pancreatic cancer cells, in part, by up-regulating p21 and sequestering it in the cytoplasm, raising the possibility that SAHA may have therapeutic potential in the treatment of pancreatic cancer.
Serologic Markers of Effective Tumor Immunity against Chronic Lymphocytic Leukemia Include Nonmutated B-Cell Antigens
Authors: Ovidiu Marina, Ursula Hainz, Melinda A. Biernacki, Wandi Zhang, Ann Cai, Jonathan S. Duke-Cohan, Fenglong Liu, Vladimir Brusic, Donna Neuberg, Jeffery L. Kutok, Edwin P. Alyea, Christine M. Canning, Robert J. Soiffer, Jerome Ritz, Catherine J. Wu
Journal: Cancer Research (2010)

Patients with chronic lymphocytic leukemia (CLL) who relapse after allogeneic transplant may achieve durable remission following donor lymphocyte infusion (DLI), showing the potency of donor-derived immunity in eradicating tumors. We sought to elucidate the antigenic basis of the effective graft-versus-leukemia (GvL) responses associated with DLI for the treatment of CLL by analyzing the specificity of plasma antibody responses developing in two DLI-treated patients who achieved long-term remission without graft-versus-host disease. By probing high-density protein microarrays with patient plasma, we discovered 35 predominantly intracellular antigens that elicited high-titer antibody reactivity greater in post-DLI than in pre-DLI plasma. Three antigens-C6orf130, MDS032, and ZFYVE19-were identified by both patients. Along with additional candidate antigens DAPK3, SERBP1, and OGFOD1, these proteins showed higher transcript and protein expression in B cells and CLL cells compared with normal peripheral blood mononuclear cells. DAPK3 and the shared antigens do not represent minor histocompatibility antigens, as their sequences are identical in both donor and tumor. Although ZFYVE19, DAPK3, and OGFOD1 elicited minimal antibody reactivity in 12 normal subjects and 12 chemotherapy-treated CLL patients, 5 of 12 CLL patients with clinical GvL responses were serologically reactive to these antigens. Moreover, antibody reactivity against these antigens was temporally correlated with clinical disease regression. These B-cell antigens represent promising biomarkers of effective anti-CLL immunity.
Linear double-stranded DNA that mimics an infective tail of virus genome to enhance transfection
Authors: Takahisa Anada, Ryouji Karinaga, Kazuya Koumoto, Masami Mizu, Takeshi Nagasaki, Yoshio Kato, Kazunari Taira, Seiji Shinkai, Kazuo Sakurai
Journal: Journal of Controlled Release (2005)
The Transcription Factor IRF8 Counteracts BCR-ABL to Rescue Dendritic Cell Development in Chronic Myelogenous Leukemia
Authors: Tomoya Watanabe, Chie Hotta, Shin-ichi Koizumi, Kazuho Miyashita, Jun Nakabayashi, Daisuke Kurotaki, Go R. Sato, Michio Yamamoto, Masatoshi Nakazawa, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Akira Nishiyama, Zenro Ikezawa, Michiko Aihara, Yoshiaki Ishigatsubo, Tomohiko Tamura
Journal: Cancer Research (2013)

Abstract BCR-ABL tyrosine kinase inhibitors (TKI) have dramatically improved therapy for chronic myelogenous leukemia (CML). However, several problems leading to TKI resistance still impede a complete cure of this disease. IFN regulatory factor-8 (IRF8) is a transcription factor essential for the development and functions of immune cells, including dendritic cells. Irf8−/− mice develop a CML-like disease and IRF8 expression is downregulated in patients with CML, suggesting that IRF8 is involved in the pathogenesis of CML. In this study, by using a murine CML model, we show that BCR-ABL strongly inhibits a generation of dendritic cells from an early stage of their differentiation in vivo, concomitant with suppression of Irf8 expression. Forced expression of IRF8 overrode BCR-ABL (both wild-type and T315I-mutated) to rescue dendritic cell development in vitro, indicating that the suppression of Irf8 causes dendritic cell deficiency. Gene expression profiling revealed that IRF8 restored the expression of a significant portion of BCR-ABL–dysregulated genes and predicted that BCR-ABL has immune-stimulatory potential. Indeed, IRF8-rescued BCR-ABL–expressing dendritic cells were capable of inducing CTLs more efficiently than control dendritic cells. Altogether, our findings suggest that IRF8 is an attractive target in next-generation therapies for CML. Cancer Res; 73(22); 6642–53. ©2013 AACR.
Dihydroxyacetone Naphthoquinone Sunscreen
Authors: Ramon M. Fusaro
Journal: JAMA (1972)

<h3>To the Editor.—</h3> During the past decade, we have successfully used a sunscreen containing dihydroxyacetone/ naphthoquinone (lawsone) for patients with all types of cutaneous photosensitivity.<sup>1</sup>An advantage of this sunscreen is its capacity to induce a broad "ultraviolet shield" (290 to 405 nm) in the uppermost layer of the skin. In order to induce ultraviolet protection, the patient's skin must have an intact keratin layer. The amount of photoprotection achieved by a patient depends upon the following: (1) the chemical reactivity of the skin with the sunscreen; (2) the thickness of the keratin layer; (3) the number of applications of the sunscreen per day; (4) the degree of the patient's photosensitivity; and (5) the quanta of light per unit time received by the patient. Because of these variables, there is a wide spectrum of protective responses in our study<sup>1</sup>from less than one hour to more than eight
Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression
Authors: Hitoshi Yoshiji, Shigeki Kuriyama, Ryuichi Noguchi, Junichi Yoshii, Yasuhide Ikenaka, Koji Yanase, Tadashi Namisaki, Mitsuteru Kitade, Masaharu Yamazaki, Tsutomu Masaki, Hiroshi Fukui
Journal: Journal of Hepatology (2005)
DIFFERENTIAL USE BETWEEN PRASUGREL AND TICAGRELOR IN PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PERCUTANEOUS CORONARY INTERVENTION IN ROUTINE PRACTICE
Authors: Mark B. Effron, Cliff Molife, Swapna Karkare, Cynthia Larmore, Yajun Zhu, Won Chan Lee, Feride Frech-Tamas, Hsiao Lieu, Mitch DeKoven
Journal: Journal of the American College of Cardiology (2014)
Information Sources in the Medical Sciences
Authors: Ann C. Weller
Journal: JAMA (1985)

This text acquaints the researcher, clinician, medical school student, and information specialist with all aspects of accessing and using the information available in a medical library. The first five chapters are instructive for those unfamiliar with library resources. Chapter 1 summarizes the major medical libraries of Great Britain and North America and outlines cataloging schemes of the National Library of Medicine and the Dewey decimal system. An overview of primary sources tells how to obtain information on journals, research reports, theses, and translation facilities. This is followed by a well-annotated summary of indexing and abstracting services, encyclopedias, yearbooks, annuals, handbooks, directories, and dictionaries. There is an especially informative discussion on locating statistics. A section on developments and trends in biomedical communication, touching on such topics as the value of medical periodicals, the review process, the growth of journal literature, and the significance of citation analysis, is a welcome addition to