tbuckley/cabot-search huggingface dataset:
Abstract 4626: The mechanism and structure localization relationship studies of a small organic molecule as a fluorescent tumor marker
Authors: Chi-Chih Kang, Ta-Chau Chang
Journal: Cancer Research (2010)

Abstract BMVC, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide, is a novel organic molecule with special tumor recognition characteristic. BMVC appears bright fluorescence in the nucleus of cancer cells while only weak fluorescence in the cytoplasm of normal cells. The strong fluorescence of BMVC in the nucleus is mainly due to significant enhancement of BMVC fluorescence upon binding to DNA. Therefore, these distinct properties of BMVC in cells allow us to differentiate cancer cells from normal cells. It appears that BMVC is a potential fluorescent tumor marker. It is of interest to elucidate the reason why BMVC can act as a potential fluorescence tumor marker. Confocal microscopic images by merging with organelle trackers suggested that BMVC mainly localizes in the nucleus and mitochondria of cancer cells, but in the lysosome of normal cells. Several leading experiments suggested that the major pathway for BMVC uptake is endocytosis. In addition, the carbonyl-cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) and microinjection experiments showed that the destination of endocytosed BMVC is trapped in the lysosome of normal cells. However, it is not clear why BMVC is not trapped in the lysosome of cancer cells. Since the lysosomal membrane permeabilization (LMP) could sensitize cancer cell to death, we performed the cathepsin immunofluorescence and vacuolization experiments to elucidate whether there is LMP difference between cancer and normal cells. Our results showed that the LMP indeed plays an important role for trapping BMVC in the lysosome of normal cells, but releasing BMVC to the nucleus and mitochondria of cancer cells. Furthermore, the structure localization relationship (SLR) studies show that BMVC derivatives with large hydrogen bonding capacity (HBC) are less lysosomal membrane permeable in normal cells. In addition, we found the more lipophilic of BMVC derivatives the more mitochondria localization in cancer cells. It is likely that the HBC and the lipophilicity are two important characters in determining intracellular localization of BMVC derivatives in cells. In summary, the LMP and SLR studies of BMVC and its derivatives demonstrated a new direction for further design and synthesis of better fluorescent tumor markers and also provided a new platform for cancer selective drug through the combination of a cancer targeting molecule and anticancer drug. Reference: [1] C. C. Kang, C. C. Chang, T. C. Chang, L. J. Liao, P. J. Lou, W. Xie, E. S. Yeung, Analyst 2007, 132, 745. [2] L. J. Liao, C. C. Kang, I. S. Jan, H. C. Chen, C. L. Wang, P. J. Lou, T. C. Chang, Analyst 2009, 134, 708. [3] N. Fehrenbacher, M. Jaattela, Cancer Res 2005, 65, 2993. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4626.
Which Test to Replace Diagnostic ERCP - MRCP or EUS?
Authors: C. L. Kay
Journal: Endoscopy (2003)

Choledocholithiasis coexists with cholelithiasis in a significant number of patients (15 - 20 %) [1], and is present in 1 - 5 % of patients who have undergone cholecystectomy [2]. As clinical and biochemical abnormalities associated with this condition are neither sufficiently accurate nor specific, transcutaneous ultrasound (TUS) remains the initial imaging test in the evaluation of patients with suspected bile duct calculi. TUS, although it is noninvasive, quick, cheap, and readily available, has a widely variable sensitivity for the detection of choledocholithiasis of 20 - 80 % [2], not least because of its highly operator-dependent nature. Endoscopic retrograde cholangiopancreatography (ERCP) has been widely used for the detection of common bile duct (CBD) calculi, and serves not only as an accurate diagnostic modality, but also as a therapeutic manoeuvre. ERCP is, however, invasive, operator-dependent, and is associated with significant morbidity and mortality rates of 1 - 6 % and 0.1 - 0.6 %, respectively [3] [4] [5], as a result of pancreatitis, sepsis, perforation, and haemorrhage. While such complication rates may be acceptable in therapeutic ERCP, as an alternative to the higher risks of surgical management, these levels of morbidity and mortality are not acceptable when only diagnostic ERCP is necessary. Consequently, the need for safe, noninvasive imaging of the pancreaticobiliary tree has resulted in the development of magnetic resonance cholangiopancreatography (MRCP).
Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, l-amino acid-defined diet, accelerates motility of hepatoma cells
Authors: Masaaki Onaga, Akio Ido, Satoru Hasuike, Hirofumi Uto, Akihiro Moriuchi, Kenji Nagata, Takeshi Hori, Katsuhiro Hayash, Hirohito Tsubouchi
Journal: Journal of Hepatology (2003)
Eli Lilly violates patients' privacy
Authors: G. Yamey
Journal: BMJ (2001)

The drug company Eli Lilly, which manufactures fluoxetine (Prozac), has admitted that it violated its own policy on patient confidentiality by publicising the email addresses of over 700 patients taking the drug.

For the past two years the company has offered patients taking fluoxetine an email reminder service (Medi-messenger). Patients decided what kind of reminder they wanted, …
Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters
Authors: Bence György, Károly Módos, Éva Pállinger, Krisztina Pálóczi, Mária Pásztói, Petra Misják, Mária A. Deli, Áron Sipos, Anikó Szalai, István Voszka, Anna Polgár, Kálmán Tóth, Mária Csete, György Nagy, Steffen Gay, András Falus, Ágnes Kittel, Edit I. Buzás
Journal: Blood (2010)
Comparison of M-mode and cross-sectional echocardiography in infective endocarditis.
Authors: L S Wann, C C Hallam, J C Dillon, A E Weyman, H Feigenbaum
Journal: Circulation (1979)

Cross-sectional and M-mode echocardiograms were performed on 23 consecutive patients with infective endocarditis. Both M-mode and cross-sectional echocardiography identified vegetations in 18 patients, 10 of whom required valve replacement within 1 month of presentation. Cross-sectional echocardiography alone identified a vegetation in one patient with a prosthetic valve. Neither technique identified vegetations in five instances. The size and shape of a vegetation on cross-sectional echocardiography did not accurately predict the need for early valve replacement of the incidence of major peripheral emboli.
In vivo production of different chloroform metabolites: effect of phenobarbital and buthionine sulfoximine pretreatment.
Authors: S Gemma, M Sbraccia, E Testai, L Vittozzi
Journal: Environmental Health Perspectives (1994)

The regioselective attack on microsomal phospholipid (PL) polar heads (PH) and fatty acyl chains (FC) demonstrated in vitro has been exploited for the selective quantitation in vivo of the biochemical damages produced by the oxidation and reduction products of CHCl3 metabolism. Five hours after CHCl3 injection (60 mg/kg body weight, ip) to control Sprague-Dawley rats, most of the label covalently bound in the liver was associated to PH, indicating a predominant production of COCl2. The levels of radioactivity bound to both PL moieties increased proportionally when 180 mg/kg body weight 14CHCl3 was administered. Buthionine sulfoximine (BSO) pretreatment resulted in a further increase of binding either to PH or FC. The pretreatment of rats with phenobarbital (PB) reduced the PH/FC binding ratio to 3.4, still indicating the predominance of the oxidative metabolism, but giving some indication of the simultaneous presence of CHCl3 reduction. When reduced glutathione (GSH) was depleted by BSO in PB-induced animals prior to 14CHCl3 administration, only the level of radioactivity associated with oxidative intermediates was increased six times. The present results confirmed that GSH is able to exert an efficient protection mainly toward 14CHCl3 oxidation intermediates. Furthermore, they indicate that in the liver of the Sprague-Dawley rat the major pathway of CHCl3 biotransformation is its oxidation and that pretreatment of rats with a GSH-depleting agent (such as BSO) is more relevant than PB induction in enhancing the biochemical damages produced by CHCl3.
Localisation of apoptosis and expression of apoptosis related proteins in the synovium of patients with rheumatoid arthritis.
Authors: M Sugiyama, T Tsukazaki, A Yonekura, S Matsuzaki, S Yamashita, K Iwasaki
Journal: Annals of the Rheumatic Diseases (1996)

To investigate whether apoptosis occurs in the synovium of rheumatoid arthritis (RA), and the intermediate molecules operating in this process.DNA fragmentation was detected by in situ nick end labelling (ISNEL) in the synovium of patients with RA (n = 11) and control patients with femoral neck fracture (n = 5). The expression of proteins p53, p21WAFI/CIPI, c-myc, proliferating cell nuclear antigen (PCNA), and Bcl-2 was also examined by immunohistochemistry.ISNEL positive synovial cells with apoptosis specific morphology were detected in extremely limited areas in only two RA synovial tissue specimens. Proteins p53, p21WAFI/CIPI, and c-myc, known inducers of apoptosis or cell cycle arrest or both, were expressed in the sublining cells independent of ISNEL positive cells. PCNA, a marker for cell proliferation, was observed in the synovial lining cells. Bcl-2, an inhibitor of apoptosis, was expressed mainly in infiltrated lymphocytes and in parts of the sublining layer cells of RA; it also did not correspond with ISNEL staining.Our findings indicate that RA synovial cells undergo apoptosis in addition to cell proliferation, but the frequency of apoptosis was very low. We suspect that the apoptotic process in the RA synovium may be suppressed by over-expression of Bcl-2. Although expressed proteins p53, p21WAFI/CIPI, and c-myc were present in the RA synovium, these protooncogenes are probably not implicated in the apoptotic process.
Too Many Sensitivity Data
Authors: RICHARD H. GLEW
Journal: Annals of Internal Medicine (1981)

Letters and Correction1 February 1981Too Many Sensitivity DataRICHARD H. GLEW, M.D.RICHARD H. GLEW, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-2-281_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the October issue, Peacock and associates (1) presented results of qualitative and quantitative antibiotic sensitivity testing on 34 isolates of methicillin-resistant Staphylococcus aureus obtained during an outbreak of nosocomial transmission of this organism. In these studies, each isolate was evaluated for antibiotic sensitivity as though it represented a unique organism. The authors state, however, that at least 22 of the isolates were linked by common phage type and roommate-to-roommate transmission of the organism and suggested that perhaps all but four of the isolates represented repeated isolation of an identical organism.Because epidemiology and phage typing indicate...Reference1. PEACOCK J, MARSIK F, and WENZEL R. Methicillin-resistant Staphylococcus aureus: introduction and spread within a hospital. Ann Intern Med. 1980;93:526-32. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: RICHARD H. GLEW, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1981Volume 94, Issue 2Page: 281-282KeywordsAntibioticsBacteriophagesEpidemiologyMethicillin-resistant staphylococcus aureus ePublished: 1 December 2008 Issue Published: 1 February 1981 PDF downloadLoading ...
Nutrition in sepsis
Authors: M. Planas, M. A. Arbós, S. Schwartz, E. García, J. López, A. Andreu, G. Gängen, G. Sganga, P. Carducci, S. Lippa, A. DeGaetano, E. Landolfi, M. Castagneta, F. Crucitti, G. I. Carlson, P. Gray, J. Arnold, R. A. Little, M. I. L. Irving, Th. Schricker, K. Träger, G. Braun, B. Kugler, M. Georgieff, C. Chiarla, I. Giovannini, J. H. Siegel, M. Castagneto, B. Morlion, E. Toryesten, K. Lessire, T. N. N. Nguyen, C. Feldmarm, G. Sturm, M. Pfisterer, P. Stehle, C. Puchstein, P. Fürst
Journal: Intensive Care Medicine (1992)
Variable effect of nifedipine on myocardial blood flow at three grades of coronary occlusion in the dog.
Authors: W S Weintraub, S Hattori, J Agarwal, M M Bodenheimer, V S Banka, R H Helfant
Journal: Circulation Research (1981)

The effect of nifedipine on myocardial blood flow at various grades of coronary stenosis is unknown, Thus 22 open-chest dogs underwent carotid to left anterior descending perfusion with flow and perfusion pressure monitoring. Grades of coronary occlusion were defined by minimum diastolic perfusion pressure. six dogs (group 1) underwent moderate occlusion to 50 to 55 mm Hg diastolic perfusion pressure; (group 2), severe occlusion to 40 mm Hg perfusion pressure; and six (group 3), more severe occlusion at 25 mm Hg. Regional myocardial blood flow was measured with radioactive microspheres before and after the intracoronary injection of 10 microgram of nifedipine. In group 1, nifedipine induced epicardial hyperemia and little change in endocardial flow in the ischemic zone. In group 2, nifedipine induced epicardial hyperemia from 1.06 to 1.39 mg/g per min, but endocardial flow decreased from 0.70 to 0.60 ml/g per min. In group 3, there was no change in blood flow. Thus the effect of nifedipine on myocardial blood flow depends on the extent of occlusion. Furthermore for certain degrees of occlusion, redistribution of blood flow from endocardium to epicardium has been shown to occur.
Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes
Authors: Peter J. Stubbs, Mohamed K. Al-Obaidi, Ronan M. Conroy, None MusB, Paul O. Collinson, None MRCPath, Ian M. Graham, None FRCPI, Mark I. M. Noble
Journal: Circulation (2000)

Background —Although a raised plasma homocysteine is a risk factor for vascular disease, it is not known whether it is associated with an adverse cardiac outcome in patients admitted with acute coronary syndromes. We evaluated the relationship between plasma homocysteine and short-term (28 days) and long-term (median 2.5 years) prognosis in acute coronary syndromes. Methods and Results —We evaluated the relationship of quintiles of homocysteine to fatal and nonfatal coronary disease early (28 days) and late (29 days to a median of 2.5 years) after admission to a single unit of patients with unstable angina (n=204) and myocardial infarction (n=236). The end points studied were cardiac death (n=67) and/or myocardial (re)infarction (n=30). Cox regression and logistic regression were used to estimate the relationship of homocysteine to coronary events. The event rate within the first 28 days (22 cardiac deaths and 5 nonfatal infarctions) was not related to the admission homocysteine level. In the 203 unstable angina and 214 myocardial infarction survivors, an apparent threshold effect was seen on long-term follow-up, with a significant step-up in the frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11 nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal events). Patients in the upper 2 quintiles (&gt;12.2 μmol/L) had a 2.6-fold increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P &lt;0.001). Conclusions —Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.
The prevalence of peripheral arterial disease in a defined population.
Authors: M H Criqui, A Fronek, E Barrett-Connor, M R Klauber, S Gabriel, D Goodman
Journal: Circulation (1985)

Because patients with peripheral arterial disease (PAD) may be asymptomatic or may present with atypical symptoms or findings, the true population prevalence of PAD is essentially unknown. We used four highly reliable, sophisticated noninvasive tests (segmental blood pressure, flow velocity by Doppler ultrasound, postocclusive reactive hyperemia, and pulse reappearance half-time) to assess the prevalence of large-vessel PAD and small-vessel PAD in an older (average age 66 years) defined population of 613 men and women. A total of 11.7% of the population had large-vessel PAD on noninvasive testing, and nearly half of those with large-vessel PAD also had small-vessel PAD (5.2%). An additional 16.0% of the population had isolated small-vessel PAD. Large-vessel PAD increased dramatically with age and was slightly more common in men and in subjects with hyperlipidemia. Isolated small-vessel PAD, by contrast, was essentially unrelated to sex, hyperlipidemia, or age, although it was somewhat less common before age 60. Intermittent claudication rates in this population were 2.2% in men and 1.7% in women, and abnormalities in femoral or posterior tibial pulse were present in 20.3% of men and 22.1% of women compared with the noninvasively assessed large-vessel PAD rate of 11.7%. Thus assessment of large-vessel PAD prevalence by intermittent claudication dramatically underestimated the true large-vessel PAD prevalence and assessment by peripheral pulse examination dramatically overestimated the true prevalence.
3,3′,5-Triiodothyronine Administration In Vivo Modulates the Hormone-sensitive Adenylate Cyclase System of Rat Hepatocytes
Authors: Craig C. Malbon, Michael L. Greenberg
Journal: Journal of Clinical Investigation (1982)

The ability of 10 μM epinephrine or isoproterenol to stimulate cyclic AMP accumulation was decreased in hepatocytes isolated from hyperthyroid (triiodothyronine treated) as compared to euthyroid rats. In the presence of methylisobutylxanthine, epinephrine or isoproterenol-stimulated cyclic AMP accumulation was ∼65% lower in hyperthyroid as compared with euthyroid rat hepatocytes. The ability of glucagon to stimulate a cyclic AMP response was also decreased in the hyperthyroid state, when assayed in either the absence or presence of a methyl xanthine. The character of the catecholamine-stimulated cyclic AMP response was beta adrenergic in both the hyperand euthyroid states. No evidence for an alpha2 adrenergic mediated component of catecholamine action on cyclic AMP levels was noted. Cyclic AMP phosphodiesterase activity of hepatocyte homogenates was not altered in the hyperthyroid state. Hormone-stimulated, guanine nucleotide- and fluoride-activatable adenylate cyclase activity was reduced in subcellular fractions obtained from hyperthyroid as compared with euthyroid rat hepatocytes. Beta adrenergic receptor binding was reduced ∼35% and glucagon receptor binding reduced ∼50% in the hyperthyroid as compared with euthyroid rat hepatocyte membrane fractions. The status of the regulatory components of adenylate cyclase were examined by in vitro treatment of subcellular fractions with cholera toxin. The ability of cholera toxin to modulate adenylate cyclase was not altered by hyperthyroidism. Cholera toxin catalyzed AD[32P]ribosylation of hyperthyroid and euthyroid rat hepatocyte proteins separated electrophoretically displayed nearly identical autoradiograms. Studies of the reconstitution of adenylate cyclase activity of S49 mouse lymphoma cyc− mutant membranes by detergent extracts from rat hepatocyte membranes, indicated that hyperthyroidism was associated with a reduced capacity of regulatory components to confer fluoride, but not guanine nucleotide activatability to catalytic cyclase. Thyroid hormones regulate the hormone-sensitive adenylate cyclase system of rat hepatocytes at several distinct loci of the system.
Old docs and new tricks
Authors: Graeme M Mackenzie
Journal: BMJ (2005)

Editor—In British general practice, where everyday demand exceeds capacity, the efficient general practitioner is king. That is one thing that experience should bring. If all general practitioners followed every guideline the system would collapse, and although a few patients would have exemplary care, many would have no care at all as they would just not get seen because they would find the wait intolerable. Perhaps this is what happens now in secondary care, where care delivered is often very good but access is less and less.

Accepted practice is often developed for a “one issue patient.” Reality means multi-issue patients, who themselves have limited ability to follow all the investigation and “treatment” recommended by the single issue academic establishment. Many indications for treatment are immediately met with contraindications. Experience allows general practitioners to cut back on too much excess investigation and treatment while still striving to meet the guidelines.

Protecting the patient from the iatrogenic harm of excess health care used to be a core skill of the general practitioner. Is this being taken away from us as well?

A system that fails to value the soft end points and often efficient and effective care that experience brings will have to restructure to meet the demand and that inevitably will lead to a hugely expanded system with resource implications. I am not disputing the findings of the paper reported by Spurgeon, that the standard of care may drop with years spent in practice,1 but the immediate common sense illogically of its hypothesis and conclusions make me advise to proceed down this route with caution. Being a doctor is already a difficult job. Being advised that all your thoughtful patient experience has actually made you a worse doctor is demotivating. Perhaps experienced doctors and patients would have a different set of criteria about what good care is?
Retinal Input Directs the Recruitment of Inhibitory Interneurons into Thalamic Visual Circuits
Authors: Bruno Golding, Gabrielle Pouchelon, Camilla Bellone, Sahana Murthy, Ariel A. Di Nardo, Subashika Govindan, Masahuro Ogawa, Tomomi Shimogori, Christian Lüscher, Alexandre Dayer, Denis Jabaudon
Journal: Neuron (2014)
326 LEPTIN IS A GROWTH FACTOR FOR CHOLANGIOCARCINOMA: AN IN VIVO EXPERIMENTAL STUDY
Authors: G. Fava, G. Alpini, G. Svegliati-Baroni, C. Rychlicki, S. Saccomanno, L. Trozzi, C. Candelaresi, A. Di Sario, M. Marzioni, A. Benedetti
Journal: Journal of Hepatology (2008)
A VEST POCKET OPHTHALMOSCOPE CASE.Read in the Section of Ophthalmology at the Forty-first Annual Meeting of the American Medical Association, held at Nashville, Tenn., May, 1890.
Authors: FRANK TRESTER SMITH
Journal: JAMA (1890)

I present to the Section an ophthalmoscope case made for me by Meyrowitz Bros, in 1886, and which I have had in constant use ever since. It is made like a spectacle case, the open end being closed with a tightly fitting lid, or like a flattened pencil case such as is used by school-children. It is made of stiff pasteboard, or other light material, covered with morocco. It presents the following advantages over the form in ordinary use: 1. Size. This is such that it can be carried in the vest pocket. The thickness is about half that of the wooden case. 2. Weight. Being smaller and made of lighter material, it is not as heavy as the ordinary form. 3. Shape. There are no corners and the edges are rounded off. 4. As a result of the shape we have another advantage: It is dust-proof. The lenses are