tbuckley/cabot-search huggingface dataset:
Evidence for altered mast cell proliferation and apoptosis in cutaneous mastocytosis
Authors: K. Hartmann, B. Hermes, K. Rappersberger, N. Sepp, Y.A. Mekori, B.M. Henz
Journal: British Journal of Dermatology (2003)

Mastocytosis presents as a focal or generalized increase of mast cells, particularly in the skin, but also in other organs. Activating mutations of KIT (formerly c-kit), the receptor of the mast cell growth factor stem cell factor (SCF), appear to play a key role in the pathogenesis of sporadic adult onset mastocytosis. However, these mutations are not present in childhood-onset and familial mastocytosis and also fail to explain the heterogeneity of adult-onset disease. Other factors such as prolonged survival of mast cells may therefore participate in causing and modulating the pathological increase of mast cells in mastocytosis.To examine the expression of proliferation and apoptosis markers in the mast cells of cutaneous mastocytosis lesions in order to gain further insight into the pathogenesis of mastocytosis.Lesional cutaneous biopsies from eight infants with solitary mastocytomas, five children with multiple mastocytomas, 11 children with generalized urticaria pigmentosa, 12 adults with urticaria pigmentosa, and skin from seven normal controls were used in this study. Serial sections were stained with toluidine blue to quantify mast cell numbers and with antibodies against the proliferation marker Ki67 protein, the tumour suppressor protein p53, and the inhibitor of cyclins and cyclin-dependent kinases p21WAF1/CIP1, using the alkaline phosphatase antialkaline phosphatase technique. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method was used to assess apoptosis.Cutaneous mast cell counts were significantly increased in all patient sections, particularly in childhood lesions, and similarly, a small but significant increase of proliferation was found in the lesional mast cells of all patients. Enhanced mast cell numbers and proliferation was associated with a significant decrease of TUNEL staining, particularly in mastocytomas. p53 expression was highly variable, with an overall significant increase in all patient skin mast cells, whereas p21 expression was barely observed at all.These findings further support the concept that an imbalance of mast cell proliferation and apoptosis is prevalent in mastocytosis lesions that may account in part for the increased focal mast cell accumulation in this condition.
Poor countries lack relevant health information, says Cochrane editor
Authors: Tessa Richards
Journal: BMJ (2004)

Although access to health information in developing countries has steadily improved over the past decade its local relevance is limited because most it is generated in developed countries. This was the key message froma seminar held last week in London by the Health Information Forum, a group set up to improve access to health information for developing countries. The meeting was organised by The International Network for the …
Olympics' public health surveillance scheme will be retained after games, agency says
Authors: A. Gulland
Journal: BMJ (2012)

The health surveillance scheme to be used for the Olympic Games will remain after the event finishes, it has been announced. 

Brian McCloskey, the London regional director of the Health Protection Agency, told a recent meeting at the London School of Hygiene and Tropical Medicine that the public health surveillance system, which has previously been used on a one-off basis for such events as the G20 summit in 2009, the Ryder Cup in Wales, and the visit of Pope Benedict XVI, will for the first time remain in place after the crowds disperse.

Twenty five hospital emergency departments and a sentinel group of GP out of hours and walk-in centres around the country will monitor and record any …
CONTEMPORARY CONVERSION REACTIONS: A CLINICAL STUDY
Authors: FREDERICK J. ZIEGLER, JOHN B. IMBODEN, EUGENE MEYER
Journal: American Journal of Psychiatry (1960)

1. Our operational criteria for the diagnosis of conversion reactions are discussed, and an analysis of a series of 134 consecutive patients so diagnosed is presented. 2. From our contemporary point of view, 4 clinical aspects of the conversion reaction phenomenon are discussed and illustrated. These clinical aspects are : a) "classical" symptom patterns of "loss of function" and "hystero-epilepsy," b) simulation of known organic disease entities with varying degrees of expertness, c) symptom patterns in which bodily pain is a predominant feature, and d) symptom aggregates in which conversion symptoms are intermingled with those of an organic and/or psychophysiological nature. 3. In addition to patients evidencing the well-known relationship between conversion mechanisms and neurotic anxiety, in our conversion series there was a group of 40 patients with clinically evident features of depression, a group of 19 patients with clinical features of incipient schizophrenia, and a group of adolescents with characteristic ego identity problems. These subgroups were not randomly distributed within the parent group, but had significantly different parameters. We conclude that conversion reactions serve to reduce or avoid less tolerable depression, neurotic anxiety, the threat of psychotic disorganization, and the painful affects associated with adolescent ego identity problems. 4. Less than one-half of our conversion patients could be considered so call "hysterical personalities." We prefer the term "histrionic personality" to "hysterical personality," since the former calls attention to the essential characterological feature, i.e., a propensity for transparent dramatization. 5. It was found that a significantly greater proportion of our patients had occupied the position of the youngest child, or the youngest child of one sex in the family than would have been expected by chance alone. It is postulated that these and other "special person" relationships within the family group in early life may lead to difficulties in role stabilization in later life. 6. The majority of our patients regarded themselves as organically ill and a direct recommendation of psychotherapy was usually rejected. A more oblique therapeutic approach was sometimes effective. The potential therapeutic usefulness of a convalescent ward in a general hospital is suggested.
Phase I Study of Ombrabulin in Combination with Paclitaxel + Carboplatin Administered Every 3 Weeks to Japanese Patients
Authors: K. Matsumoto, K. Fujiwara, M. Tanioka, T. Onoe, S. Negoro, K. Shimada, S. Saji, Y. Sasaki, K. Noguchi
Journal: Annals of Oncology (2013)
Health status and health‐related quality of life associated with von Willebrand disease
Authors: Ronald D. Barr, Julia Sek, John Horsman, William Furlong, Mahassen Saleh, Mohan Pai, Irwin Walker
Journal: American Journal of Hematology (2003)

Abstract Von Willebrand disease (VWD) is the commonest inherited disorder of hemostasis and the majority of women with this disorder experience excessive uterine bleeding. Yet very little information is available on the health‐related quality of life (HRQL) in individuals with VWD. To test the a priori hypotheses that these individuals will have poorer HRQL than members of the general population, and that this burden of morbidity will correlate with the severity of VWD, a cross‐sectional study was undertaken of a population‐based cohort in a regional hemophilia program in Ontario, Canada. A survey was made of individuals over 13 years of age with VWD who self‐reported their health status using a standard 15 item questionnaire. The responses were converted to levels in the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems to form multi‐element vectors from which single attribute morbidity and overall HRQL utility scores were determined. As a group, individuals with VWD were shown to have poorer HRQL than members of the general population and those with Type 2 disease carried a greater burden of overall morbidity than those with Type 1 disorder. Morbidity was evident mainly in the attributes of emotion, cognition with pain. A striking difference was observed between males and females, with the latter having overall HRQL utility scores similar to those reported previously for HIV positive, severe hemophiliacs. It is possible that this remarkable burden of morbidity reflects chronic iron deficiency associated with menorrhagia. A national study has been proposed to address this likelihood as it offers an opportunity for effective therapeutic intervention (iron supplementation) with a concomitant gain in health status and HRQL. Am. J. Hematol. 73:108–114, 2003. © 2003 Wiley‐Liss, Inc.
Doctors in the private sector should report adverse events after immunisation to complete dataset
Authors: S. Bhaumik
Journal: BMJ (2013)

The Indian Academy of Pediatrics has called for doctors working in the private sector to report adverse events after immunisations to the national surveillance system to ensure more complete vaccine safety data. 

In a position paper published in Indian Pediatrics , the academy said that the adverse event following immunization (AEFI) surveillance system run by the government needed to be strengthened by including reports from the private sector.1

India has one of the largest universal immunisation programmes in the world, with 26 million babies born every year. Approximately …
Perioperative outcome of colorectal cancer and validation of CR-POSSUM in a Caribbean country
Authors: Seetharaman Hariharan, Deryk Chen, Anushka Ramkissoon, Nicholas Taklalsingh, Chevonne Bodkyn, Ryon Cupidore, Amit Ramdin, Akash Ramsaroop, Videsh Sinanan, Siara Teelucksingh, Sumit Verma
Journal: International Journal of Surgery (2009)
Treatment of Sporotrichosis
Authors: Richard B. Hornick
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In the article "Pulmonary Sporotrichosis" (<b>210</b>:1741, 1969), a statement was made about therapy which I would like to question: "Improvement has been noted with use of Griseofulvin...." A reference was given. This disease responds to amphotericin, and it is important to have available secondary drugs which may be useful in treating the disease. Unfortunately, there is no evidence that griseofulvin does affect this disease, and, indeed, the reference listed also correctly states that this antifungal has no effect on sporotrichosis in mice.
Reduction in Myocardial Ischemia/Reperfusion Injury in Group X Secretory Phospholipase A <sub>2</sub> –Deficient Mice
Authors: Daisuke Fujioka, Yukio Saito, Tsuyoshi Kobayashi, Toshiaki Yano, Hideo Tezuka, Yoshikazu Ishimoto, Noriko Suzuki, Yasunori Yokota, Takamitsu Nakamura, Jyun-ei Obata, Masaki Kanazawa, Ken-ichi Kawabata, Kohji Hanasaki, Kiyotaka Kugiyama
Journal: Circulation (2008)

Background— Group X secretory phospholipase A 2 (sPLA 2 -X) has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid among several types of sPLA 2 . sPLA 2 -X is expressed in neutrophils, but its pathogenic role remains unclear. Methods and Results— We generated mice that lack sPLA 2 -X and studied their response to myocardial ischemia/reperfusion. The sPLA 2 -X −/− mice had a significant reduction in myocardial infarct size and a decrease in myocardial myeloperoxidase activity compared with sPLA 2 -X +/+ mice. Myocardial infarct size was also significantly reduced in lethally irradiated sPLA 2 -X +/+ mice reconstituted with sPLA 2 -X −/− bone marrow compared with sPLA 2 -X +/+ bone marrow. The extent of myocardial ischemia/reperfusion injury was comparable between sPLA 2 -X −/− and sPLA 2 -X +/+ mice in Langendorff experiments using isolated hearts and blood-free perfusion buffer, supporting a potential role of sPLA 2 -X in blood in myocardial ischemia/reperfusion injury. In the infarcted myocardium of sPLA 2 -X +/+ mice, sPLA 2 -X was released from neutrophils but not myocardial tissues and platelets and was undetectable in the peripheral serum. The sPLA 2 -X −/− mice had lower accumulation of neutrophils in ischemic myocardium, and the isolated sPLA 2 -X −/− neutrophils had lower release of arachidonic acid and attenuated cytotoxic activities including respiratory burst compared with sPLA 2 -X +/+ neutrophils. The attenuated functions of sPLA 2 -X −/− neutrophils were reversible by the exogenous addition of sPLA 2 -X protein. Furthermore, administration of a sPLA 2 inhibitor reduced myocardial infarct size and suppressed the cytotoxic activity of sPLA 2 -X +/+ neutrophils. Conclusions— Myocardial ischemia/reperfusion injury was attenuated in sPLA 2 -X −/− mice partly through the suppression of neutrophil cytotoxic activities.
Normotriglyceridemic abetalipoproteinemia. absence of the B-100 apolipoprotein.
Authors: M J Malloy, J P Kane, D A Hardman, R L Hamilton, K B Dalal
Journal: Journal of Clinical Investigation (1981)

In the two genetic forms of abetalipoproteinemia described previously, recessive abetalipoproteinemia and homozygous hypobetalipoproteinemia, all lipoproteins that normally contain apolipoprotein B are absent from plasma. We describe here a new disorder in which normal low density and very low density lipoproteins are absent, but in which triglycerides are absorbed from the intestine and chylomicrons are present in plasma. The underlying molecular defect appears to be selective deletion of the hepatogenous B-100 apolipoprotein. The B-48 apolipoprotein found in chylomicrons is spared. These findings suggest that the two species of apolipoprotein B are under separate genetic control and that low density lipoproteins are not normally derived from chylomicrons.
Abstract 5439: A novel drug sensitivity assay method for 3D cultured cell using an imaging device
Authors: Ruriko Sakamoto, Noriko Sakemura, Manami Shimomura, Noboru Hirakawa, Hirotada Watanabe, Satoru Tanaka, Kaori Yoshida, Tetsuya Nakatsura
Journal: Cancer Research (2011)

Abstract Three-dimensional (3D) cultured cells are useful for the physiological study of tumor cells owing to their similar characteristics. Currently, the popular methods for 3D cell culture-for example, collagen gel or the matrix method-involve complicated procedures that often result in experimental errors. We attemted to develop a novel technique for the use of 3D cell culture in a novel drug sensitivity assay using an imaging technique. We used a NanoCulture® plate (NCP) for 3D cell culture of the human breast cancer cell lines BT474 and T47D for forming multicellular spheroids and used these in a drug sensitivity assay for trastuzumab and paclitaxel by employing the imaging device BioStation CT. The NCP has a fine pattern carved on the surface of the wells’ bottoms, which provides scaffolding for cells with expanding pseudopodia. Thus, the cells can move and aggregate to form uniform spheroids on the NCP. These spheroids further migrate and fuse each other during culture. The effects of anticancer drugs-i.e., a decrease in the migration velocity of spheroids and suppression of spheroid fusion in a dose-dependent manner-were estimated using NCP-cultures spheroids analyzed using sequential BioStation CT images. These results were compared to the conventional assay method of ATP quantification with a good agreement. We confirmed the antitumor effect of the drugs on cells seeded in a single well of the 96-well plate by this technique. We expect this method to be useful in research on new antitumor agents and in drug sensitivity tests for individually tailored cancer treatments. 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 5439. doi:10.1158/1538-7445.AM2011-5439
Comparative Imaging
Authors: JOHN R. STY, ROBERT G. WELLS, BRUCE A. SCHROEDER
Journal: Clinical Nuclear Medicine (1987)

Bile-plug syndrome (inspissated bile syndrome) is a correctable cause of obstructive jaundice in infants. Formerly thought to be a common cause of neonatal jaundice, the presence of thick bile in the extrahepatic ducts is now usually felt to represent a result of a hepatic disorder (hepatitis) rather than the primary cause of the abnormality. Operative cholangiography has shown, however, occasional cases of neonatal jaundice with a definite obstructing bile-plug. Bile-plug syndrome usually occurs in neonates with sepsis (as in this case), acute dehydration, and massive hemolysis due to Rh or ABO incompatibility. A three-week-old infant with this syndrome who presented with a direct bilirubin of 5 mg/dl is reported. Antibiotic therapy and hydration resulted in complete improvement in five days.
S115 Magnitude of cough response to inhaled capsaicin differentiates between health and disease
Authors: E. C. Young, H. Sumner, A. Kelsall, A. A. Woodcock, J. A. Smith
Journal: Thorax (2010)

<h3>Background</h3> Patients with chronic cough (CC) have substantially higher 24-h cough rates compared to patients with asthma (A) or healthy controls (HC). CC patients also have a more sensitive cough reflex, when measured as the ‘<i>threshold</i>’ dose of a tussive agent (eg, capsaicin) inducing at least two or five coughs (C2/C5), although there is substantial overlap between CC and HC. We aimed to investigate if the ‘<i>magnitude’</i> of cough response to inhaled capsaicin would better differentiate CC patients from A and HC subjects. <h3>Methods</h3> We devised a cough challenge technique, with increasing doubling concentrations of capsaicin (0.48–1000 μMol) extended beyond the C5 threshold, up to the maximum tolerated dose. At each capsaicin concentration four single-breath inhalations were administered from a dosimeter 30 s apart. After each inhalation, the number of coughs in the first 15 s was counted. Using Generalised Estimating Equations (GEE), we explored the effect of group and gender on average cough response to increasing concentrations of capsaicin. <h3>Results</h3> We studied 20 treatment resistant CC, 18 stable mild/moderate A and 20 HC subjects, matched for age and gender; (M:F 10:10, 9:9,10:10, respectively), age [mean (±SD) 57.1 years (±15.7), 51.7 years (±13.5), 58.8 years (±13.5); p=0.17], and lung function [3.02L (±0.98), 2.96L (±1.10), 3.20L (±0.99); p=0.72]. CC (vs HC p&lt;0.001) and females (vs males, p&lt;0.001) cough significantly more after capsaicin (see Abstract S115 Figure 1). There was no significant difference between A and HC (p=0.407). <h3>Conclusions</h3> <i>Magnitude</i> of cough responses to inhaled capsaicin, beyond the standard endpoints: clearly discriminates chronic cough from healthy controls, demonstrates gender differences, may be valuable for investigation of physiological mechanisms and anti-tussive agents. In addition to a reduced cough threshold, these findings are consistent with a failure of inhibitory mechanisms to prevent coughing to repetitive and potent stimuli in chronic cough.
An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells.
Authors: D Jaraquemada, M Marti, E O Long
Journal: The Journal of Experimental Medicine (1990)

The recognition of virus-infected cells by class I MHC-restricted cytotoxic T cells requires endogenous processing of antigen for presentation. It is still unclear whether endogenous processing of antigen can be utilized by class II MHC molecules for presentation. To test this possibility, a human B cell line expressing HLA-A2 and HLA-DR1 was infected with a recombinant vaccinia virus expressing the Influenza A virus M1 matrix protein (VAC-M1) and was assayed for lysis by different M1-specific cytolytic T cell lines, restricted by either HLA-A2 or by HLA-DR1. Class II-restricted lysis of VAC-M1-infected cells did occur. This lysis required de novo M1 synthesis and was not due to exogenous antigen. Several properties of the endogenous processing pathway for class II-restricted presentation were different from those of the pathway utilized by class I molecules. First, class II-mediated recognition of VAC-M1 infected cells was less efficient, requiring higher doses of virus and longer infection times, than the class I-mediated recognition. Second, chloroquine completely blocked presentation of endogenous M1 to class II-restricted T cells but had no effect on the class I-restricted presentation. Third, the class II-restricted presentation of M1 was only mildly affected by Brefeldin A, a drug that prevents transport from the endoplasmic reticulum to the Golgi, whereas the class I-restricted presentation of M1 was completely abrogated by this drug. These data demonstrate the existence of an endogenous processing pathway for the presentation of cytosolic antigen by class II molecules and show that this pathway is distinct from the one used for presentation by class I molecules.
Tumor Angiogenesis
Authors: David A. Cheresh, Dwayne G. Stupack
Journal: Circulation Research (2014)

We and others have demonstrated that antagonists of αv integrins target and suppress pathological angiogenesis, resulting in decreased tumor growth, 9,10 inflammatory disease, 9,11 and retinal disease. 5In glioblastoma patients treated with these agents, some clinical efficacy was noted, 12 although overall survival was not significantly impacted in recently announced phase III trials.Studies by Hynes et al showed that mice deficient in either αv or β3 showed robust blood vessel development. 13,14In fact, these animals displayed enhanced endothelial cell VEGF receptor (VEGFR) expression associated with increased tumor angiogenesis.This led the authors to conclude that αvβ3 plays a negative role in angiogenesis.How, then, can one reconcile the fact that αvβ3 antagonists suppress angiogenesis in mice and humans?In an elegant series of studies, Steri et al 7 examined the effects of acute depletion of endothelial cell integrin αvβ3 on neovascularization via Cre-mediated inactivation of a floxed β3 gene.Complementary approaches were used in this multicenter tour de force of mouse genetics, including Tie2-driven expression of Cre and hydroxytamoxifen-inducible expression of Cre driven by platelet-derived growth factor b promoters.The finding by Steri et al 7 that αvβ3 is required for angiogenesis is consistent with previous studies by Byzoya and et al,15 Tumor Angiogenesis Putting a Value on Plastic GEMMs