tbuckley/cabot-search huggingface dataset:
Expression of SPARC in normal and fibrotic livers
Authors: Edward Frizell, Shu-Ling Liu, Ann Abraham, Iwata Ozaki, Mahboubeh Eghbali, Helene E. Sage, Mark A. Zern
Journal: Hepatology (1995)

SPARC (secreted protein, acidic and rich in cysteine)--also known as osteonectin, BM-40, and 43K glycoprotein--is secreted by endothelial cells and fibroblasts in response to culture shock. SPARC has been found in association with tissues undergoing cell proliferation, migration, and extracellular matrix remodeling. We demonstrate that normal livers from humans, rats, and mice express substantial levels of SPARC messenger RNA (mRNA). Moreover, when compared with control specimens, significantly increased levels of SPARC mRNA were found in fibrotic livers from two animal models of liver disease: murine schistosomiasis and carbon tetrachloride-induced fibrosis in rats. Fibrotic human livers also had markedly increased levels of SPARC mRNA in comparison with normal livers. We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocytochemical analysis, SPARC protein was apparent in freshly isolated Ito cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibited traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstrate the increased expression of SPARC--a protein that modulates cell shape and disrupts cell-matrix interactions--during the initial stages of hepatic fibrosis.
Liver injury following normothermic ischemia in steatotic rat liver
Authors: Ai-Min Hui, Seiji Kawasaki, Masatoshi Makuuchi, Jun Nakayama, Toshihiko Ikegami, Shinichi Miyagawa
Journal: Hepatology (1994)

The influence of normothermic ischemia on steatotic liver was compared with that on healthy liver in rats. Steatotic liver was induced with 4 wk of a cholinedeficient diet. We used a procedure of subcutaneous spleen transposition to develop portosystemic collaterals to avoid splanchnic stasis during total hepatic vascular occlusion. One–week survival rates after 30, 45, and 60 min of normothermic ischemia were 75%, 20% and 0% in the steatotic liver group and 100%, 90% and 70% in the control group, respectively. Significantly poor restoration of energy metabolism was observed in the steatotic liver group. After 1 hr of reflow following 45 and 60 min of ischemia, ATP was restored to 74% and 50%, respectively, of the preischemic level in healthy liver but to only 44% and 27% respectively, in steatotic liver. Microscopically, focal hemorrhage, disruption of the sinusoidal microvasculature and occasional spotty necrosis of hepatocytes were demonstrated after 1 hr of reflow following ischemia in steatotic liver, but no significant changes were evident in healthy liver. This microcirculatory alteration seems to be responsible for the loss of organ viability in steatotic liver. We suggest that steatotic liver is more vulnerable than healthy liver to normothermic ischemia in the rat. (Hepatology 1994;20:1287-1293).
GW25-e2264 Antegrade Recanalisation of Coronary Chronic Total Occlusions with the Child-in-mother Catheter
Authors: Jiang Chaohui, Jia Chunwen, Wu Shujin, Wu Xinseng, Ye Shenyi, Dou Xuekai, Chen Ruijuan, Chaohui Jiang
Journal: Journal of the American College of Cardiology (2014)
A MULTI‐CENTRE TRIAL OF POLLEN‐TYROSINE ADSORBATE
Authors: W. R. PALMER, A. BALACESCU
Journal: Allergy (1977)

We report the results of a multi-centre trial involving 433 hay fever patients treated in 1975 with a 3-injection tyrosine-adsorbed vaccine containing glutaraldehyde-modified grass pollens and cultivated rye. Despite the high pollen counts recorded in Germany in 1975, treatment was considered to be effective in 73 per cent of the patients, irrespective of their age, sex or past history. Side effects were normally mild although the incidence of local reactions was relatively high. Only six patients discontinued treatment due to untoward reactions and there were no cases of anaphylactic shock. This paper adds further evidence to support the view that this vaccine offers a safe, effective and convenient method of treatment for grass pollen allergy.
Treatment with danazol and plasma glucagon concentration.
Authors: G Williams, F Lofts, H Fuessl, S Bloom
Journal: BMJ (1985)

The association between treatment with danazol and hyperglucagonaemia was studied. Plasma glucagon concentrations were measured during an oral glucose tolerance test in seven women taking danazol and six healthy controls not taking danazol. Results showed that treatment with danazol is associated with severe hyperglucagonaemia, and in three patients glucagon concentrations reached the range suggestive of glucagonoma. It is important to recognise that this increasingly used drug may cause severe hyperglucagonaemia to prevent patients treated with danazol undergoing unnecessary investigations to localise glucagonoma.
Disulfiram—Alcohol Side Effects
Authors: Jordan Scher
Journal: JAMA (1968)

<h3>To the Editor:—</h3> I certainly do agree with the tenor of what Dr. Fox says regarding the use of disulfiram and would like to state very clearly that I continue to use it and strongly believe in it as an adjunct in the treatment of alcoholism. I reported the reaction since I felt that it was quite a striking one and because the reaction occurred in an individual who was not by any means otherwise psychotic. The individual on which I reported had functioned well in the community prior to that episode, which was the first and only one of its kind for him. There have been none since. As a matter of fact, I am not sure that he could have been classified as an alcoholic in the usual sense, but instead as a "heavy drinker." More recently, I have been using disulfiram with people who are not alcoholics,
Adenovirus i-Leader Truncation Bioselected Against Cancer-associated Fibroblasts to Overcome Tumor Stromal Barriers
Authors: Cristina Puig-Saus, Alena Gros, Ramon Alemany, Manel Cascalló
Journal: Molecular Therapy (2011)

Tumor-associated stromal cells constitute a major hurdle in the antitumor efficacy with oncolytic adenoviruses. To overcome this biological barrier, an in vitro bioselection of a mutagenized AdwtRGD stock in human cancer-associated fibroblasts (CAFs) was performed. Several rounds of harvest at early cytopathic effect (CPE) followed by plaque isolation led us to identify one mutant with large plaque phenotype, enhanced release in CAFs and enhanced cytotoxicity in CAF and several tumor cell lines. Whole genome sequencing and functional mapping identified the truncation of the last 17 amino acids in C-terminal end of the i-leader protein as the mutation responsible for this phenotype. Similar mutations have been previously isolated in two independent bioselection processes in tumor cell lines. Importantly, our results establish the enhanced antitumor activity in vivo of the i-leader C-terminal truncated mutants, especially in a desmotic fibroblast-embedded lung carcinoma model in mice. These results indicate that the i-leader truncation represents a promising trait to improve virotherapy with oncolytic adenoviruses. Tumor-associated stromal cells constitute a major hurdle in the antitumor efficacy with oncolytic adenoviruses. To overcome this biological barrier, an in vitro bioselection of a mutagenized AdwtRGD stock in human cancer-associated fibroblasts (CAFs) was performed. Several rounds of harvest at early cytopathic effect (CPE) followed by plaque isolation led us to identify one mutant with large plaque phenotype, enhanced release in CAFs and enhanced cytotoxicity in CAF and several tumor cell lines. Whole genome sequencing and functional mapping identified the truncation of the last 17 amino acids in C-terminal end of the i-leader protein as the mutation responsible for this phenotype. Similar mutations have been previously isolated in two independent bioselection processes in tumor cell lines. Importantly, our results establish the enhanced antitumor activity in vivo of the i-leader C-terminal truncated mutants, especially in a desmotic fibroblast-embedded lung carcinoma model in mice. These results indicate that the i-leader truncation represents a promising trait to improve virotherapy with oncolytic adenoviruses.
NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human
Authors: Jianhua Yu, Takeki Mitsui, Min Wei, Hsiaoyin Mao, Jonathan P. Butchar, Mithun Vinod Shah, Jianying Zhang, Anjali Mishra, Christopher Alvarez-Breckenridge, Xingluo Liu, Shujun Liu, Akihiko Yokohama, Rossana Trotta, Guido Marcucci, Don M. Benson, Thomas P. Loughran, Susheela Tridandapani, Michael A. Caligiuri
Journal: Journal of Clinical Investigation (2011)

IL-15 may have a role in the development of T cell large granular lymphocyte (T-LGL) or NKT leukemias. However, the mechanisms of action and the identity of the cell subset that undergoes leukemic transformation remain elusive. Here we show that in both mice and humans, NKp46 expression marks a minute population of WT NKT cells with higher activity and potency to become leukemic. Virtually 100% of T-LGL leukemias in IL-15 transgenic mice expressed NKp46, as did a majority of human T-LGL leukemias. The minute NKp46+ NKT population, but not the NKp46– NKT population, was selectively expanded by overexpression of endogenous IL-15. Importantly, IL-15 transgenic NKp46– NKT cells did not become NKp46+ in vivo, suggesting that NKp46+ T-LGL leukemia cells were the malignant counterpart of the minute WT NKp46+ NKT population. Mechanistically, NKp46+ NKT cells possessed higher responsiveness to IL-15 in vitro and in vivo compared with that of their NKp46– NKT counterparts. Furthermore, interruption of IL-15 signaling using a neutralizing antibody could prevent LGL leukemia in IL-15 transgenic mice. Collectively, our data demonstrate that NKp46 identifies a functionally distinct NKT subset in mice and humans that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. Thus, IL-15 signaling and NKp46 may be useful targets in the treatment of patients with T-LGL or NKT leukemia.
People's willingness to accept overdetection in cancer screening: population survey
Authors: A. Van den Bruel, C. Jones, Y. Yang, J. Oke, P. Hewitson
Journal: BMJ (2015)

To describe the level of overdetection people would find acceptable in screening for breast, prostate, and bowel cancer and whether acceptability is influenced by the magnitude of the benefit from screening and the cancer specific harms from overdetection.Online survey. Women were presented with scenarios on breast and bowel cancer, men with scenarios on prostate and bowel cancer. For each particular cancer, we presented epidemiological information and described the treatment and its consequences. Secondly, we presented two different scenarios of benefit: one indicating a 10% reduction in cancer specific mortality and the second indicating a 50% reduction.Online survey of the population in the United Kingdom.Respondents were part of an existing panel of people who volunteer for online research and were invited by email or online marketing. We recruited 1000 respondents, representative for age and sex for the UK population.Number of cases of overdetection people were willing to accept, ranging from 0-1000 (complete screened population) for each cancer modality and each scenario of benefit.There was large variability between respondents in the level of overdetection they would find acceptable, with medians ranging from 113 to 313 cases of overdetection per 1000 people screened. Across all scenarios, 4-7% of respondents indicated they would accept no overdetection at all compared with 7-14% who thought that it would be acceptable for the entire screened population to be overdetected. Acceptability in screening for bowel cancer was significantly lower than for breast and prostate cancer. People aged 50 or over accepted significantly less overdetection, whereas people with higher education levels accepted more; 29% of respondents had heard of overdetection before.Acceptability of overdetection in cancer screening is variable. Invitations for screening should include clear information on the likelihood and consequences of overdetection to allow people to make an informed choice.
Minimal Brain Dysfunction-Reply
Authors: Sydney S. Gellis
Journal: JAMA (1976)

In Reply.—  I do not see how Dr Wright's statements take issue with my arguments. I am opposed to the term minimal brain dysfunction because it is a wastebasket diagnosis and because of its connotation to parents and teachers. It is, to my mind, similar to labeling every child with seizures as having epilepsy and failing to investigate metabolic or other possible causes. The desire to eliminate the term minimal brain dysfunction is not an argument to end research into causes, but rather to enhance it. It is too easy to decide that the child of normal intelligence is having school problems or is hyperactive because he has minimal brain dysfunction and then to prescribe that he have a one-to-one relationship with an excellent teacher or start drug therapy. It is entirely conceivable that hyperactivity may be due to a metabolic error, whereas inability to read or clumsiness in writing
Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome.
Authors: W Shimizu, T Ohe, T Kurita, H Takaki, N Aihara, S Kamakura, M Matsuhisa, K Shimomura
Journal: Circulation (1991)

Several recent experimental and clinical studies have shown that early afterdepolarizations (EADs) are important in the genesis of QTU prolongation and ventricular tachyarrhythmias (VTs) in patients with long QT syndrome. On the other hand, sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and VTs in patients with congenital long QT syndrome. The present study was performed to examine the influence of isoproterenol on the genesis of EADs and on the action potential durations and QTU intervals in patients with congenital long QT syndrome.We recorded monophasic action potentials (MAPs) with a contact electrode during right atrial pacing at a constant cycle length of 500 msec before and after continuous isoproterenol infusion (1 microgram/min). MAPs were obtained from the right and left ventricular endocardium in six patients with congenital long QT syndrome (LQT group, 18 recording sites) and in eight control patients (control group, 19 recording sites). Although no EADs were recorded from either group during the control state, MAP duration at 90% repolarization (MAPD90) was significantly longer in the LQT group (n = 18) than in the control group (n = 19) (275 +/- 36 versus 231 +/- 22 msec; p less than 0.0005). Isoproterenol induced EADs in four of the six LQT patients (five of 18 recording sites) but not in the eight control patients (zero of 19 recording sites). The appearance of EADs in the LQT group was associated with an increased amplitude of the late component of the TU complex, and the corrected QT (QTc) interval was prolonged by isoproterenol from 543 +/- 53 to 600 +/- 30 msec 1/2 (n = 6; p less than 0.05). Isoproterenol also prolonged the MAPD90 from 275 +/- 36 to 304 +/- 50 msec in the LQT group (n = 18; p less than 0.005), whereas it shortened the MAPD90 from 231 +/- 22 to 224 +/- 25 msec in the control group (n = 19; p less than 0.05). Moreover, isoproterenol increased the dispersion of MAPD90 (difference between the longest MAPD90 and the shortest MAPD90 in each patient) from 30 +/- 5 to 62 +/- 35 msec in the LQT group (n = 6; p = 0.08), whereas it did not change the dispersion of MAPD90 in the control group (n = 8; 25 +/- 14 versus 27 +/- 14 msec).These results suggest that patients with congenital long QT syndrome have primary repolarization abnormalities and that EADs induced by isoproterenol play an important role in the exaggeration of these repolarization abnormalities.
Electric fire burn.
Authors: A. Gunn
Journal: BMJ (1967)

Electric fires are of three types: silica-sheathed, fireclay mounted, and exposed rod. Children who grasp the heating element of electric fires of the exposed-rod type sustain severe burns of the hand. Wynn Williams (1955) reviewed 100 cases of children with burnt hands and noted that 36% were due to electric fires. Muir (1958) described and illustrated the electric bar fire burn of the hand, separating it from electric current burns and defining it as a thermal injury. Clarkson and Pelly (1962) also described it as a severe and specific injury of the hand in children. Evans (1962) recorded the impression that the injury was happening more often. This paper reviews the incidence and results of this burn and discusses prevention.
Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.
Authors: M J Monaghan, G Jackson, D E Jewitt
Journal: BMJ (1987)

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.
USE OF ATROPIN SULPHATE AS A MEANS OF DIAGNOSIS IN CERTAIN PERSISTENT HEADACHES.
Authors: OTTO LANDMAN
Journal: JAMA (1900)

This paper deals with the determination of the etiology of some forms of persistent headaches. The method under consideration will save time, is coupled with a great degree of accuracy, and requires no special knowledge of refraction and its correction by glasses. It will enable us to exclude other conditions as causes of certain persistent headaches, and consists simply in the use of a solution of sulphate of atropin instilled into the eyes. The method should be employed to determine the cause of persistent headaches. It is probable that the results obtained are due to the effect of the drug on the innervation of the ciliary muscle, for after the accommodative power returns the headaches often reappear. Concerning the explanations of headaches we may say that, in general, they are produced by some kind of irritation of the filaments of the fifth nerve, which supplies the dura mater. The following
A thermoreversible hydrogel as a biosynthetic bandage for corneal wound repair
Authors: Chayanin Pratoomsoot, Hidetoshi Tanioka, Kuniko Hori, Satoshi Kawasaki, Shigeru Kinoshita, Patrick J. Tighe, Harminder Dua, Kevin M. Shakesheff, Felicity Rosamari A.J. Rose
Journal: Biomaterials (2007)
The effect of astemizole on bronchial hyperresponsiveness and exercise‐induced asthma in children
Authors: V. Backer, N. Bach‐Mortensen, U. Becker, L. Brink, P. Howitz, K. Kaae Hansen, D. Wendelboe Jensen, E. Mosfeldt Laursen
Journal: Allergy (1989)

The ability of the new generation H 1 ‐receptor antagonist, astemizole, to prevent histamine‐induced airway obstruction and exercise‐induced asthma (EIA) was studied in 20 children with asthma. The study was a randomised clinically controlled trial of oral astemizole versus placebo in a cross‐over study. In each of the two treatment periods the children were tested at days 0, 6, 15 and 22 of therapy. The two treatment periods were separated by a washout period of 50 days, and at each visit a bronchial challenge with increasing concentrations of histamine followed by an exercise test was performed, and peak flow and asthmatic symptom score were recorded daily. The children tolerated significantly higher mean concentrations of histamine when treated with astemizole compared with placebo ( P &lt; 0.001). Astemizole postponed the response to exercise, but no change in the maximal response was found. No differences between the treatment periods were found regarding frequency of asthmatic symptoms or the daily recording of peak flow.
Small elevations of glucose concentration redirect and amplify the synthesis of guanosine 5'-triphosphate in rat islets.
Authors: S A Metz, M Meredith, M E Rabaglia, A Kowluru
Journal: Journal of Clinical Investigation (1993)

Recent studies suggest a permissive requirement for guanosine 5'-triphosphate (GTP) in insulin release, based on the use of GTP synthesis inhibitors (such as myocophenolic acid) acting at inosine monophosphate (IMP) dehydrogenase; herein, we examine the glucose dependency of GTP synthesis. Mycophenolic acid inhibited insulin secretion equally well after islet culture at 7.8 or 11.1 mM glucose (51% inhibition) but its effect was dramatically attenuated when provided at < or = 6.4 mM glucose (13% inhibition; P < 0.001). These observations were explicable by a stimulation of islet GTP synthesis derived from IMP since, at high glucose: (a) total GTP content was augmented; (b) a greater decrement in GTP (1.75 vs. 1.05 pmol/islet) was induced by mycophenolic acid; and (c) a smaller "pool" of residual GTP persisted after drug treatment. Glucose also accelerated GTP synthesis from exogenous guanine ("salvage" pathway) and increased content of a pyrimidine, uridine 5'-triphosphate (UTP), suggesting that glucose augments production of a common regulatory intermediate (probably 5-phosphoribosyl-1-pyrophosphate). Pathway-specific radiolabeling studies confirmed that glucose tripled both salvage and de novo synthesis of nucleotides. We conclude that steep changes in the biosynthesis of cytosolic pools of GTP occur at modest changes in glucose concentrations, a finding which may have relevance to the adaptive (patho) physiologic responses of islets to changes in ambient glucose levels.
Favorable Prognosis of Upper-Gastrointestinal Bleeding in 1041 Older Patients: Results of a Prospective Multicenter Study
Authors: S NAHON, O NOUEL, H HAGEGE, P CASSAN, A PARIENTE, R COMBES, A KERJEAN, S DOUMET, P COCQVEZILIER, G TIELMAN
Journal: Clinical Gastroenterology and Hepatology (2008)
Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: Combined results of two double-blind investigations
Authors: Donald P. Lookingbill, Dan K. Chalker, Jane S. Lindholm, Harry Irving Katz, Stephen E. Kempers, Christopher J. Huerter, James M. Swinehart, Donald J. Schelling, Harry C. Klauda
Journal: Journal of the American Academy of Dermatology (1997)