tbuckley/cabot-search huggingface dataset:
Abstract 3694: Activation of ASK1 by capsaicin mediates apoptosis in pancreatic cancer cells
Authors: Kartick C. Pramanik, Sanjay K. Srivastava
Journal: Cancer Research (2011)

Abstract Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) kinase kinase family plays an essential role in reactive oxygen species (ROS) induced cellular response. Thioredoxin (Trx), a redox sensitive protein binds to ASK1 and inhibits its activation. In our previous study, we have shown that capsaicin induced apoptosis in pancreatic cancer cells was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. In the present study, we evaluated the interaction of thioredoxin/ASK1 in pancreatic cancer cells. In a concentration dependent study, we observed that capsaicin treatment down regulated thioredoxin and increased the phosphorylation (activation) of ASK1 at Thr845 in AsPC-1 and BxPC-3 cells. ASK1 has been shown to activate JNK, which in turn activates MKK4/7 resulting in the cleavage of caspase-9, and caspase-3. In agreement, our results reveal that capsaicin treatment activated JNK, MKK4/7, caspase-9 and caspase-3. Interestingly, treatment of cells with antioxidants such as tiron or catalase blocked the activation of ASK1 cascade by capsaicin and protected the cells from apoptosis indicating the involvement of ROS in the activation of ASK1. To confirm the interaction of Trx/ASK1 and the dissociation of ASK1 by capsaicin in our model, BxPC-3 cell were transiently transfected with contructs encoding ASK1 fused to C-terminal hemaggutinin (HA) and flag tagged Trx. Our results reveal that Trx over expression suppressed the effects of capsaicin whereas ASK1 over expression enhanced the apoptosis-inducing effects of capsaicin. Taken together, our results suggest that ROS generated by capsaicin reduce Trx expression resulting in the activation of ASK1 and downstream effectors leading to apoptosis in pancreatic cancer cells. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3694. doi:10.1158/1538-7445.AM2011-3694
NEW INSTRUMENTS FOR THE REMOVAL OF THE FAUCIAL TONSILS.
Authors: CHARLES M. ROBERTSON
Journal: JAMA (1902)

The methods of tonsillotomy that have been in use in the past having proven unsatisfactory and incomplete, it seems an opportune time to present, not a new operation, but a new method of operation. We are fast coming to realize that enlarged or diseased conditions of the tonsil are a detriment to the economy and nearly all of us agree at the present time that, when a diseased condition of a gland exists, the entire gland should be extirpated. For the past five or six years it has been my custom to remove the entire tonsil when diseased or chronically enlarged. For this purpose I have devised instruments which make the operation complete. It is almost universally conceded that if any procedure is adopted at all, it is to the end of destroying the gland, whether this be by a shrinking process, by cautery or by operative means. For the
Fat Hypertrophy in a Pharyngeal Reconstruction Flap Presenting as an Enlarging Neck Mass: Demonstration of Benign Changes With PET/CT
Authors: Michael C. Roarke, Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2005)

The patient is a 73-year-old man with a history of radioresistant recurrent squamous cell carcinoma of the larynx, treated with total laryngectomy/pharyngectomy and rectus abdominis deep inferior epigastric perforator flap reconstruction, who presented with a painless enlarging neck mass. Physical examination revealed increased neck bulk and fiberoptic nasopharyngolaryngoscopy was negative. The clinician was concerned about underlying recurrent neoplasm or adenopathy displacing the flap outward and referred the patient for PET/CT.
Staging of Breast Cancer and Survival Rates
Authors: Carl M. Sutherland
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We read the article by Ferguson and associates in the Sept 17 issue entitled "Staging of Breast Cancer and Survival Rates" (1982;248:1337). The authors are to be congratulated for providing us with valuable information in this difficult area of evaluating the long-term effects of breast cancer. However, we must question the use of relative survival rates to determine the long-range effects of breast cancer. The relative survival rate at time X is given by the following equation: Probability of Surviving in Study Population to Time X/ Probability of Surviving in Control Population to Time X This ratio is then the proportion of the population escaping the<i>excess</i>(not absolute) risk of death caused by breast cancer if the risk of death by other causes is equal in both the study and the general population. It is known that patients from higher socioeconomic conditions have lower death rates
Neurosenpsychologische Untersuchungen zum Effort-Syndrom
Authors: C. Drunkenmölle
Journal: Psychotherapy and Psychosomatics (1973)

A psychological investigation was conducted into the neurotic features of 28 male and 25 female patients with functional cardiac disorders (effort syndrome). The aim was to determine the proportion of neurotics in a selected group of patients. Significant differences were found in comparison with a control group of neurotics in respect of the present complaints, the symptoms remembered from childhood, the family climate, family consitution, trigger situations and scale 7 of the MMPI. In 42 out of 50 patients, it was possible to delineate the neurotic structure objectively by means of the MMPI. Effort syndrome is thus not a pathogenetic entity. In one fifth of the patients, there was no MMPI evidence of a neurosis. Attention is drawn to the necessity for detecting cardiac neuroses in patients with cardiac disorders, by the appropriate use of psychodiagnostic methods so that they can receive proper treatment.
Functional Consequences of Sulfhydryl Modification in the Pore-Forming Subunits of Cardiovascular Ca <sup>2+</sup> and Na <sup>+</sup> Channels
Authors: Nipavan Chiamvimonvat, Brian O’Rourke, Timothy J. Kamp, Roland G. Kallen, Franz Hofmann, Veit Flockerzi, Eduardo Marban
Journal: Circulation Research (1995)

Abstract The structure and function of many cysteine-containing proteins critically depend on the oxidation state of the sulfhydryl groups. In such proteins, selective modification of sulfhydryl groups can be used to probe the relation between structure and function. We examined the effects of sulfhydryl-oxidizing and -reducing agents on the function of the heterologously expressed pore-forming subunits of the cloned rabbit smooth muscle L-type Ca 2+ channel and the human cardiac tetrodotoxin-insensitive Na + channel. The known sequences of the channels suggest the presence of three or four cysteine residues within the putative pores of Ca 2+ or Na + channels, respectively, as well as multiple other cysteines in regions of unknown function. We determined the effects of sulfhydryl modification on Ca 2+ and Na + channel gating and permeation by using the whole-cell and single-channel variants of the patch-clamp technique. Within 10 minutes of exposure to 2,2′-dithiodipyridine (DTDP, a specific lipophilic oxidizer of sulfhydryl groups), Ca 2+ current was reduced compared with the control value, with no significant change in the kinetics and no shift in the current-voltage relations. The effect could be readily reversed by 1,4-dithiothreitol (an agent that reduces disulfide bonds). Similar results were obtained by using the hydrophilic sulfhydryl-oxidizing agent thimerosal. The effects were Ca 2+ -channel specific: DTDP induced no changes in expressed human cardiac Na + current. Single-channel Ba 2+ current recordings revealed a reduction in open probability and mean open time by DTDP but no change in single-channel conductance, implying that the reduction of macroscopic Ca 2+ current reflects changes in gating and not permeation. In summary, the pore-forming (α 1 ) subunit of the L-type Ca 2+ channel contains functionally important free sulfhydryl groups that modulate gating. These free sulfhydryl groups are accessible from the extracellular side by an aqueous pathway.
A tale of two blisters
Authors: M G Jacoby
Journal: BMJ (2002)

In 1924, when I was 4 years old, there was an outbreak of smallpox in Sunderland, my home town. Everyone was getting vaccinated with three inoculations of cowpox vaccine scratched into the skin over the deltoid area on the left arm. After a few days three blisters would appear, while the surrounding area became red and inflamed. To avoid pain, those who had been vaccinated wore red ribbons on their …
Leukopenia — A New Immune Mechanism?
Authors: Albert LoBuglio
Journal: New England Journal of Medicine (1976)

The mechanisms involved in producing a clinical state of leukopenia with recurrent infection in man have been difficult to elucidate clearly. Certain drugs and other environmental factors can produce total marrow aplasia or selective absence of marrow leukocyte precursors, with resultant production deficit and leukopenia that is frequently of lethal severity. However, more often, patients have reduced leukocytes in the presence of marrow precursors, and ability to define the pathophysiologic process has been hindered by a variety of problems unique to the granulocyte, including cumbersome radioactive-labeling technics, tendency to clumping and other artifactual lesions, short circulation time (four to 12 . . .
Regeneration of Liver and Kidney
Authors: Richard L. Wood
Journal: JAMA (1971)

This brief and well-written volume reviews the current knowledge of compensatory growth (regeneration) in liver and kidney after partial removal of organ mass. The authors enhance the value of their presentation by surveying basic concepts in molecular biology, as a background for comparing growth phenomena in the two organs. Much of the material appeared in a series of reviews in the<i>New England Journal of Medicine</i>. Superficially liver and kidney appear to react rather differently to major loss of tissue mass; in the liver the main response is hyperplastic growth, and that in the kidney, cellular hypertrophy. Drs. Bucher and Malt point out, however, that the fundamental difference may, in fact, be largely one of degree. Cellular hypertrophy precedes cell proliferation after partial hepatectomy, and cell proliferation does occur in compensatory growth of kidney under extreme conditions. The underlying question which has stimulated broad interest in compensatory growth relates to
TWO-DIMENSIONAL STRAIN: A USEFUL TOOL FOR THE ASSESSMENT OF RIGHT VENTRICULAR DYSFUNCTION IN PULMONARY HYPERTENSION
Authors: Ines Garcia Lunar, Susana Mingo Santos, Vanessa Moñivas Palomero, Daniela Cristina Mitroi, Gonzalo Guzzo Merello, Miguel Angel Cavero Gibanel, Luis Alonso Pulpon
Journal: Journal of the American College of Cardiology (2011)
In-Vivo and In-Vitro Conversion of Angiotensin I to Angiotensin II in Dog Blood
Authors: SUZANNE OPARIL, CHARLES A. SANDERS, EDGAR HABER
Journal: Circulation Research (1970)

The conversion of angiotensin I to angiotensin II was studied in vivo in the intact anesthetized dog and in vitro in whole blood and plasma treated with various anticoagulants by fractionation of radioactively labeled peptides and by radioimmunoassay. After injection of angiotensin I into the pulmonary artery at 10,000 times the physiologic level, approximately 50% of the injected material was recovered in the aorta. Fifty three percent of the material recovered had been converted to angiotensin II, as measured both by peptide release and by radioimmunoassay. Following injection of 1000 to 10,000 times physiologic levels of angiotensin I into the renal artery, 7 to 10% of the immunoreactive material in the venous effluent after a single circulation time was angiotensin II. There was no evidence of conversion in the liver or hindlimb. Conversion in vitro was far slower than in vivo, the half-life in fresh blood being 3 minutes, with longer times observed in anticoagulated plasmas. The major metabolite of in-vivo conversion was leucine, of in-vitro conversion, histidyl leucine. These observations indicate that the major site of conversion of angiotensin I to angiotensin II is in the pulmonary capillary bed. The kidnev may participate as a secondary site. Conversion in plasma probably plays no important physiologic role. The mechanism of organ and plasma conversion may differ, as indicated by the different metabolites.
Assessment of Atrioventricular Junction Ablation and DDDR Mode-Switching Pacemaker Versus Pharmacological Treatment in Patients With Severely Symptomatic Paroxysmal Atrial Fibrillation
Authors: Michele Brignole, Lorella Gianfranchi, Carlo Menozzi, Paolo Alboni, Giacomo Musso, Maria Grazia Bongiorni, Maurizio Gasparini, Antonio Raviele, Gino Lolli, Nelly Paparella, Simonetta Acquarone
Journal: Circulation (1997)

Background The purpose of the study was to evaluate the effect of AV junction ablation and pacemaker implantation on quality of life and specific symptoms in patients with paroxysmal atrial fibrillation (AF) not controlled by drugs. Methods and Results We performed a multicenter, randomized, 6-month evaluation of the clinical effects of AV junction ablation and DDDR mode-switching pacemaker (Abl+Pm) versus pharmacological treatment in 43 patients with intolerable, recurrent paroxysmal AF of three or more episodes in the previous 6 months not controlled with three or more antiarrhythmic drugs. Before completion of the study, 3 patients in the drug group withdrew because of the severity of their symptoms and 1 patient assigned to the Abl+Pm group in whom the ablation procedure failed. At the end of the 6 months, the 21 patients of the Abl+Pm group who completed the study showed, in comparison with the 18 of the drug group, lower scores in the Living with Heart Failure Questionnaire (−51%, P =.0006), palpitations (−71%, P =.0000), effort dyspnea (−36%, P =.04), exercise intolerance score (−46%, P =.001), and easy fatigue (−51%, P =.02). The scores for rest dyspnea, chest discomfort, and NYHA functional classification were also lower (−56%, −50%, and −17%, respectively) in the Abl+Pm group, although not significantly. At the end of the study, palpitations were no longer present in 81% of the Abl+Pm group and in 11% of the drug group ( P =.0000). AF was documented in 31 of 122 visits (25%) in the Abl+Pm group and in 9 of 107 examinations (8%) in the drug group ( P =.0005); chronic AF developed in 5 (24%) and 0 (0%) in the two groups, respectively ( P =.04). Conclusions In patients with paroxysmal AF not controlled by pharmacological therapy, Abl+Pm treatment is highly effective and superior to drug therapy in controlling symptoms and improving quality of life. The discontinuation of drug therapy exposes patients to further recurrences of paroxysmal AF and the risk of developing permanent AF.
Transrectal Ultrasound in the Diagnosis and Management of Inflammatory Bowel Disease
Authors: Ü. Dağli, H. Över, A. Tezel, A. Ülker, G. Temuçin
Journal: Endoscopy (1999)

Background and Study Aims: To aim of the present study was to determine the value of transrectal ultrasonography (TRUS) in the assessment of disease activity in ulcerative colitis patients, and in differentiating between mucosal inflammation and transmural inflammation.
THE VALUE OF THE PULMONIC SECOND SOUND.
Authors: J. N. HALL
Journal: JAMA (1896)

My object in presenting this paper is to call attention to a well-known but much neglected subject, the investigation, in diseases of the chest especially, of the character of the second sound at the orifice of the pulmonary artery. It appears to me that many physicians, although gauging quite accurately the tension in the systemic circulation, by means of the pulse and the character of the aortic second sound, pass over as almost unworthy of notice the examination of the pulmonic area. And yet, in a few seconds, with the stethoscope as much may be learned of the conditions of the circulation in the lungs as has been learned, at the aortic area, of the systemic circulation. In diseases of the mitral valve, whether obstructive or regurgitant, all authorities agree as to the importance of the accentuation of the pulmonic second sound, in deciding as to the degree of obstruction
The Hour of Our Death
Authors: D. Healy
Journal: BMJ (2003)

Philippe Ariés Oxford University Press 1991 (Alfred A Knopf 1981), pp 651 ISBN 0 19 507364 9 This classic book is currently out of print, but may be available from libraries and online secondhand bookshops Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Philippe Ariés was one of the most highly regarded social historians of the second half of the 20th century. His first essays on the history of death appeared in 1975, just when emerging medical capacities to keep people alive on ventilators to the end of the tax year had given a whole new meaning to the biblical adage to render unto Caesar what is Caesar's and to God what is God's. Aware of changing attitudes to death, and wondering if we were facing a radical break with … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Study associates viral infection with some childhood brain tumours
Authors: S. Mayor
Journal: BMJ (2002)

An epidemiological study carried out in the north west of England has shown for the first time that some types of childhood brain tumours may be associated with viral infection.

The study analysed 1045 cases of brain tumour in children, all from the Manchester Children's Tumour Registry and dating from 1954 to 1998. Results showed that more children who lived nearer to each other than would be expected by chance were diagnosed with two types of brain cancer—astrocytoma and ependymoma—than would have been expected by chance.

This pattern—known as “space-time clustering”—resulted …
Molecular evolution and mosaic structure of alpha, beta, and gamma intimins of pathogenic Escherichia coli
Authors: E. A. McGraw, J. Li, R. K. Selander, T. S. Whittam
Journal: Molecular Biology and Evolution (1999)

Two types of pathogenic Escherichia coli, enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC), cause diarrheal disease by disrupting the intestinal environment through the intimate attachment of the bacteria to the intestinal epithelium. This process is mediated by intimin, an outer membrane protein that is homologous to the invasins of pathogenic Yersinia. The intimin (eae) gene is part of a pathogenicity island, a 35-kb segment of DNA that has been acquired independently in different groups of pathogens. Nucleotide sequences of eae of three EPEC and four EHEC strains representing distinct clonal lineages revealed an exceptionally high level of divergence (15%) in the amino acid sequences of alpha, beta, and gamma intimin molecules, most of which is concentrated in the C-terminal region. The gamma intimin sequences from E. coli strains with serotypes O157:H7, O55:H7, and O157:H- are virtually identical, supporting the hypothesis that these bacteria belong to a single clonal lineage. Sequences of beta intimin of EPEC strains of serotypes O111:H2 and O128:H2 show substantial differences from alpha and gamma intimins, indicating that these strains have evolved independently. Strong nonrandom clustering of polymorphic sites indicates that the intimin genes are mosaics, suggesting that protein divergence has been accelerated by recombination and diversifying selection.
INTUBATION OF THE LARYNX, WITH PERSONAL REMINISCENCES.
Authors: F. E. WAXHAM
Journal: JAMA (1901)

March 20, 1885, it was my privilege to present a paper on the intubation of the larynx to the Chicago Medical Society, and to illustrate the operation on the cadaver. Through the courtesy of Dr. Joseph O'Dwyer, of New York, now deceased, who was experimenting with this, operation in the hospitals of that city, I was provided with the crude and primitive instruments then in use. My first operation was performed April 19, 1885, on a child 2 years old, choking to death with diphtheritic croup. My assistants were an old lady, who held the patient on her lap, and a boy 12 years old, who held the gag and steadied the head. I had never seen the operation done, yet, with these poor and untrained assistants, the tube was successfully introduced on the third attempt, giving prompt and immediate relief. This was the first intubation performed west of New
Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to &lt;18 years) with chronic hepatitis B
Authors: Maureen M. Jonas, Deirdre Kelly, Henry Pollack, Jacek Mizerski, Jeff Sorbel, David Frederick, Elsa Mondou, Franck Rousseau, Etienne Sokal
Journal: Hepatology (2008)

This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to &lt;7 years; &gt;7 to &lt;12 years; &gt;12 to &lt;18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to &lt;18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA &lt;1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA &lt;1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to &lt;18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. Conclusion: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.