tbuckley/cabot-search huggingface dataset:
Reversal of different drug-resistant phenotypes by an autocatalytic multitarget multiribozyme directed against the transcripts of the ABC transporters MDR1/P-gp, MRP2, and BCRP
Authors: Petra Kowalski, Pawel Surowiak, Hermann Lage
Journal: Molecular Therapy (2005)

A "multitarget multiribozyme" (MTMR) was constructed. It consists of three trans-acting hammerhead ribozymes directed against the transcripts of the ABC transporters MDR1/P-gp, BCRP, and MRP2; three cis-acting MDR1/P-gp-specific ribozymes; and three MDR1/P-gp-homologous spacer sequences. The trans-acting hammerhead ribozymes are liberated from the MTMR through autocatalytic self-cleavage by the cis-acting ribozymes. The MTMR was characterized with regard to its kinetic parameters. Comparison of the MTMR-specific kinetic values with those of the corresponding monoribozymes demonstrated that MTMR fragments could cleave their specific substrates without loss of efficiency. The MTMR was applied to three cell models, each overexpressing another ABC transporter, i.e., the gastric carcinoma cell line EPG85-257RDB expresses MDR1/P-gp, the cell variant EPG85-257RNOV synthesizes BCRP, and the ovarian carcinoma line A2780RCIS produces MRP2. In all cellular systems, the MTMR could specifically decrease the expression of the respective ABC transporter at the mRNA level (97% decrease in the MDR1/P-gp mRNA, 80% decrease in the BCRP mRNA, 96% decrease in the MRP2 mRNA) and the protein level. Resistance against the selection drug was reversed completely (100% in EPG85-257RDB) or by 94 (EPG85-257RNOV) or 63% (A2780RCIS). Thus, the MTMR technology provides a novel tool for gene therapeutic applications to reverse different ABC-transporter-dependent drug-resistant phenotypes.
Hightlights from this issue
Authors: Emad El-Omar, William Grady, Alexander Gerbes, Thomas Rösch
Journal: Gut (2013)

### Overall burden of Helicobacter pylori on mortality

H pylori colonisation has been associated with increased risk of peptic ulcer disease and gastric cancer, and reduced risk of asthma and allergy, while the association with cardiovascular disease and lung cancer is inconsistent. In this issue of Gut, Chen et al report their interesting data on the influence of H pylori on total and category-specific mortality. They conducted prospective cohort analyses in a nationally representative sample of 9895 participants enrolled in the National Health and Nutrition Examination Survey III (NHANES III) to assess the association of H pylori status with all-cause and cause-specific mortality. The authors found that H pylori status was not related to overall all-cause mortality. H pylori colonisation was associated with reduced risk of death due to stroke and increased risk of death due to gastric cancer. The data also suggest an inverse association with lung cancer. The authors conclude that H pylori colonisation may have new possibly protective effects (see page 1262) .

### A little chilli for oropharyngeal dysphagia

Oropharyngeal dysphagia (OD) is a major complaint among the elderly and sadly has no pharmacological treatment. Afferent areas that trigger a swallowing response are sensitive to mechanical stimuli, to changes in temperature and to chemical stimuli, and express the polymodal …
UNUSUAL EXPOSURE TO LIGHT FOLLOWED BY SEBORRHEIC KERATOSIS
Authors: DOUGLASS W. MONTGOMERY
Journal: JAMA (1913)

Seborrheic keratosis is a common cutaneous disease which most frequently occurs in elderly people, and especially, as its name implies, in those who have a seborrheic skin. Light, especially the actinic rays of light, is now considered to be in many cases the exciting cause of the trouble. There is no direct evidence in support of this view, but there are a number of phenomena difficult to interpret in any other way: 1. Patches of seborrheic keratosis begin very frequently as small pigmented spots, and the formation of pigment is a well-known effect of the action of light. 2. Seborrheic patches occur most commonly and most profusely in persons exposed to light. 3. They appear almost exclusively on the exposed surthefaces of the face, ears, neck and back of the hands, and der 0Slofls' as a whole, are analogous to those of xeroma pigmentosum, a disease in which light is
Renal Amyloidosis, Nephrotic Syndrome, and Impaired Renal Tubular Reabsorption of Bicarbonate
Authors: ANTHONY SEBASTIAN
Journal: Annals of Internal Medicine (1968)

A 29-year-old man with renal amyloidosis, nephrotic syndrome, and chronic renal failure had the classic physiologic features of the Fanconi syndrome and hyperchloremic acidosis associated with inappropriately alkaline urine and striking bicarbonaturia. Sodium bicarbonate loading studies demonstrated that the maximal renal tubular reabsorption of bicarbonate (Tm HCO3 -) was reduced by some 20 to 30%; tubular reabsorption of bicarbonate (T HCO3 -) at normal plasma bicarbonate concentrations was reduced by more than 15%. Such reductions of Tm HCO3 - and T HCO3 - at normal plasma bicarbonate concentration characterize a renal acidification defect physiologically distinct from that of adult patients with classic renal tubular acidosis or that described in patients with uremic acidosis. The magnitude of reduction of Tm HCO3 - and T HCO3 - at normal plasma bicarbonate concentrations suggests that the impairment in renal bicarbonate reabsorption involves the acidification process of the proximal nephron.
Drug-Induced Heat-Shock Preconditioning Improves Postischemic Ventricular Recovery After Cardiopulmonary Bypass
Authors: Nilanjana Maulik, Richard M. Engelman, Zongjie Wei, Xuekun Liu, John A. Rousou, Joseph E. Flack, David W. Deaton, Dipak K. Das
Journal: Circulation (1995)

Background Heat-stress preconditioning of mammalian heart has been found to confer protection against ischemic reperfusion injury. Heat shock is generally provided by warming the animal by mechanical means, which is often impractical in a clinical setting. Amphetamine, a sympathomimetic drug, can elevate the body temperature as a result of enhanced endogenous lipolysis. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial recovery in a setting of coronary revascularization for acute myocardial infarction. Methods and Results Adult Yorkshire swine were injected with amphetamine (3 mg/kg IM) (n=12), and body temperature was continuously monitored. For control studies, the pigs were injected with saline (n=12). Five swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs in each group were placed on cardiopulmonary bypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery followed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dP/dt, myocardial segment shortening, and coronary blood flow. Cellular injury was examined by measurement of creatine kinase release. The antioxidant enzymes superoxide dismutase and catalase were also assayed. Amphetamine treatment was associated with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital organs, including heart, lung, liver, kidney, and brain. Amphetamine also enhanced superoxide dismutase and catalase activities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV developed pressure (61% versus 52%), LV dP/dt max (52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase release in the amphetamine group. Conclusions The results demonstrate that amphetamine can induce whole-body heat shock that can precondition the heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditioning.
307. The Tumor-Selective Viral Protein Apoptin Is a Potential Gene Therapeutic Agent for Prostate Cancer Therapy
Authors: Xiang Liu, Ahmed El-Zawhry, David Holman, Saeed Elojeimy, Alicja Bielawaska, Jacek Bielawaska, Mahvash Tavassoli, James S. Norris
Journal: Molecular Therapy (2005)

Prostate cancer is currently the most common cancer in American males and the second leading cause of cancer-related death. It is now clear that many oncogenic mutations, particularly in the p53 tumor suppressor pathway disrupt apoptosis leading to tumor progression and metastasis and reduced sensitivity to radiation or chemotherapy. The chicken anemia virus-derived protein, Apoptin, induces apoptosis in a wide range of human tumor cells but not in primary cells and its action appears to be p53 and Bcl-2 independent. In this study, we examined whether Apoptin was capability to kill prostate cancer cells. Expression of Apoptin from a Tet amplified adenoviral vector caused effectively cell killing in Du145, PC-3, and LnCap tumor cells, three independent cell lines which represent different types of prostate cancer. We compared the internal expression of p53, Bcl-2, Bcl-xl, Bax, Survivin, Flips, XIAP and CIAP in all three cell lines, and found that there was no obvious correlation between Apoptin-induced cell death and the status of these pro- and anti-apoptotic molecules. p21waf-1 was observed upregulated after cells was infected with Ad-GFPApoptin, as reflected by increased accumulation of G2-M-phase cells. Interestingly, following treatment of cells with Ad-GFPApoptin, we detected an increase in ceramide level 16 hours post-infection which reached a maximum at 24 hours. Application of the cell-permeable ceramide analog (C6) after Ad-Apoptin infection resulted in a significant increase in apoptosis. This is a previously undescribed effect of Apoptin and could reasonably be expected to lead to programmed cell death by the pathways described for ceramide. Activating transcription factor-2 (ATF-2) was found to become phosphorylated in the Apoptin treated group, which indicated that SAPK/JUK kinase pathway might also be involved in Apoptin's function. This is consistent with our ceramide elevation observation. Experiments in mice demonstrated that Ad-GFPApoptin could be safely administered by tail vein, and intratumoral injection in Du145 xenograft bearing nude mice resulted in a significant reduction of tumor growth. Taken together, our data demonstrated that tumor specific death protein-Apoptin might be use as an attractive therapeutic agent to treat prostate cancer. Induction of ceramide by Apoptin is a previously undescribed event and may have relevance to the mechanism of cell death induced by Apoptin.
“Listen to the People”: Public Deliberation About Social Distancing Measures in a Pandemic
Authors: Nancy M. Baum, Peter D. Jacobson, Susan D. Goold
Journal: The American Journal of Bioethics (2009)

Public engagement in ethically laden pandemic planning decisions may be important for transparency, creating public trust, improving compliance with public health orders, and ultimately, contributing to just outcomes. We conducted focus groups with members of the public to characterize public perceptions about social distancing measures likely to be implemented during a pandemic. Participants expressed concerns about job security and economic strain on families if businesses or school closures are prolonged. They shared opposition to closure of religious organizations, citing the need for shared support and worship during times of crises. Group discussions elicited evidence of community-mindedness (e.g., recognition of an extant duty not to infect others), while some also acknowledged strong self-interest. Participants conveyed desire for opportunities for public input and education, and articulated distrust of government. Social distancing measures may be challenging to implement and sustain due to strains on family resources and lack of trust in government.
Adrenal Pseudocyst Demonstrated with Radionuclide Blood Pool Imaging
Authors: WILLIAM H. MCCARTNEY, ROBERT L. TAYLOR, JEROME A. WALISZEWSKI, JERRY L. PRATHER, MARTIN L. NUSYNOWITZ
Journal: Clinical Nuclear Medicine (1977)

An adrenal pseudocyst was visualized as a persistent “cold” suprarenal mass on a radionuclide renal angiography study using 99mTc-Sn-DTPA. A 99mTcpertechnetate blood pool study performed shortly after the renal study again showed an avascular mass, and visualization of vascular abdominal structures was striking. This prolonged and excellent visualization of blood pools is attributable to pertechnetate labeling of red cells from the residual small amounts of circulating Sn (II) derived from the 99mTc-Sn-DTPA given shortly before. Experiments confirmed that over 95% of pertechnetate may label red cells when as little as .001 mg Sn per kg of body weight is given (here, in the DTPA preparation) 45 minutes prior to pertechnetate administration. This in vivo labeling of red cells may be turned to advantage in visualizing blood pools during the study of abdominal masses.
ANTIBODIES TO INTESTINAL MICROVILLOUS MEMBRANES
Authors: Iain L. Mackenzie, Robert M. Donaldson, William L. Kopp, Jerry S. Trier
Journal: The Journal of Experimental Medicine (1968)

Microvillous membranes isolated from the distal, but not proximal, half of hamster small bowel induced in rabbits the formation of antisera which inhibited intrinsic factor-mediated uptake of vitamin B(12) by hamster brush borders. The extent of inhibition was directly proportional to the concentration of antiserum, and an excess of IF-bound vitamin B(12) could overcome the inhibitory effect. The inhibitory factor was absorbed from antisera by brush borders isolated from the distal, but not proximal, half of the hamster intestine. Fractionation of antisera by gel filtration and DEAE-cellulose chromatography established that immunoglobulin G contained the inhibitory factor. Antisera capable of completely blocking uptake of IF-bound vitamin B(12) did not react with hamster IF or with the IF-vitamin B(12) complex, did not inhibit brush border disaccharidase activity and did not impair glucose transport by everted sacs of hamster intestine. These results demonstrate that an antibody to distal microvillous membranes competes with the IF-vitamin B(12) complex for a specific binding site or receptor located on the surface of distal hamster intestine.
Something for the weekend?
Authors: D. Lockington, P. Cauchi, E. Kemp
Journal: BMJ (2012)

Removal of an eye—whether by evisceration, enucleation, or exenteration—can have a devastating impact on a patient’s life and social confidence. These procedures are often performed at the end of a chronic disease process, such as removing a shrunken (phthisical), painful, blind eye, or to address pathology, such as ocular malignancy, so patients are relatively accepting of this surgical decision. In order to facilitate rehabilitation, an appropriate conformer …
Neoplastic circulating endothelial cells in multiple myeloma with 13q14 deletion
Authors: Gian Matteo Rigolin, Chiara Fraulini, Maria Ciccone, Endri Mauro, Anna Maria Bugli, Cristiano De Angeli, Massimo Negrini, Antonio Cuneo, Gianluigi Castoldi
Journal: Blood (2005)
Medicine's living death
Authors: D. Spence
Journal: BMJ (2008)

On Sunday afternoons we shuffle around IKEA’s one way system with the identikit couples. Children whine and occasionally escape to bounce on a sofa. Eventually we find the various flat packs we need for the wardrobe. Then more queuing and the spontaneous purchase of lavender aromatherapy candles. At home we pore over the instructions and find that we need, seemingly, only a small Allen key. Six angry hours later we beat the unrecognisable, pulverised plywood ball with a hammer, and decide that the …
PEGylation of interleukin-10 improves the pharmacokinetic profile and enhances the antifibrotic effectivity in CCl4-induced fibrogenesis in mice
Authors: Adriana Mattos, Alie de Jager-Krikken, Marianne de Haan, Leonie Beljaars, Klaas Poelstra
Journal: Journal of Controlled Release (2012)
THE USE OF ANTISEPTICS IN PUERPERAL CASES.
Authors: MADISON REECE
Journal: JAMA (1884)

[Read before the Military Tract Medical Association.] During one of the hottest days of the month of July, 1881, I was called to see Mrs. W., near London Mills, in consultation with Dr. Wilson, of that place. I found her in a small bed-room, only large enough for the bed upon which she was lying, with but one window in the room. She had been confined a week previously. Her pulse was 160, her temperature 106°, the tongue dry, abdomen distended to the size of a woman at full term, the secretion of milk suppressed. She was delirious, and an odor filled the room like that of a body far gone in putrefaction. The husband was informed that there was no probability whatever for the recovery of his wife, every symptom indicating a speedy dissolution. However, I suggested a thorough washing out of the uterus with antiseptics. A half gallon
OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma
Authors: Akihisa Ueno, Yohei Masugi, Ken Yamazaki, Mina Komuta, Kathryn Effendi, Yutaka Tanami, Hanako Tsujikawa, Akihiro Tanimoto, Shigeo Okuda, Osamu Itano, Yuko Kitagawa, Sachio Kuribayashi, Michiie Sakamoto
Journal: Journal of Hepatology (2014)
Mind Matters in Cancer Survival
Authors: David Spiegel
Journal: JAMA (2011)

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 Journals 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Effect of Cimetidine on Exogenous Histamine Inhibition of Histamine Release in Vivo
Authors: Stanislaus Ting, Burton Zweiman, Robert M. Lavker, Eliot H. Dunsky
Journal: Allergy (1983)

We previously reported that exogenous histamine inhibits in vivo histamine release and eosinophil accmulation in ragweed‐challenged skin sites of sensitive human subjectes. The mechanism(s) involved were unclear. In this study, we repeated similar approaches in of the same subjects pretreated for 3 days with cimetidine, an H 2 receptor antagonist. The pattern of exogenous histamine effects was now different in that local exogenous histamine (50 ug/ml) did not significantly alter ragweed‐induced mast cell alteration, histamine release, or the degree of eosinophil accumulation in skin challenge sites. These findings suggest that the observed exogenous histamine inhibitory effects may be mediated through the H 2 receptor.
Book: Small Wars: The Cultural Politics of Childhood
Authors: ME Black
Journal: BMJ (1999)

Nancy Scheper-Hughes, Carolyn Sargent University of California Press, £13.95, pp 429 ISBN 0 520 2 918 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The words blister off the pages, and I have been unable to put this book down. At once compelling and uneven, these 18 pieces cross the world. Spirits of aborted fetuses in Japan, the cultural history of neonatal jaundice, mothers who kill their children, the Catholic church and sex abuse … the tiny details of each are teased out and explained. Almost all written by anthropologists, with … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Surface expression of only gamma delta and/or alpha beta T cell receptor heterodimers by cells with four (alpha, beta, gamma, delta) functional receptor chains.
Authors: T Saito, F Hochstenbach, S Marusic-Galesic, A M Kruisbeek, M Brenner, R N Germain
Journal: The Journal of Experimental Medicine (1988)

Surface expression of TCR dimers by cells synthesizing three or four distinct types of receptor chains was analyzed. Cells containing intact gamma, alpha, and beta chains had only gamma delta dimers on the cell surface. In human PEER cells, addition of a functional alpha chain led to the loss of gamma delta dimer expression and expression of only alpha beta dimers. This result was not due to transcriptional down-regulation of the gamma or delta loci. In murine cells expressing all four chains, both gamma delta and alpha beta dimers could be demonstrated on a single cell. No other chain combinations (alpha gamma, alpha delta, beta gamma, or beta delta) were detected. Thus, there is stringent control of assembly and/or transport of TCR heterodimers, such that functional receptors consist only of alpha beta and gamma delta pairs, and no additional repertoire diversity is generated by cross pairing.
Long term care of patients who have had a laryngectomy
Authors: M Gleeson, P Jani
Journal: BMJ (1994)

Each year almost 2000 people in England and Wales develop either laryngeal or hypopharyngeal cancer.1 Radiotherapy controls or cures this disease in many patients, but those with advanced tumours or disease that has failed to respond to radiotherapy require surgery for any hope of cure.

Partial laryngectomy may be suitable for a few patients, who are left with a compromised, but often satisfactory, oral airway. Some patients may also require a permanent tracheostomy. For these fortunate patients speech is retained, but even if altered it is at least immediately understandable. Many more patients lose their larynx completely; to preserve any part would compromise their chance of survival. For them, no matter how well counselled before operation, there is the intense frustration of waking from their surgery aphonic and able to express themselves only by gestures, writing, or mouthing messages. The rehabilitation of voice was discussed fully in a previous editorial,2 but for these patients this represents just one of many problems that they have to contend with, and they justifiably feel that few, even their general practitioners, fully comprehend the extent of their disability.

If there are no complications patients are discharged home 10 to 14 days after their laryngectomy with a plastic stent or metal cannula to maintain the patency of their tracheostome. After …
Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF
Authors: I Ricca, M Compagno, M Ladetto, A Rocci, M Dell'Aquila, P Omedè, F De Marco, S D'Antico, D Caracciolo, D Ferrero, C Carlo-Stella, C Tarella
Journal: Leukemia (2005)