tbuckley/cabot-search huggingface dataset:
Contribution of general practice to NHS patients
Authors: A. Elliott
Journal: Journal of the Royal Society of Medicine (2006)

I commend the article by Wilson et al. (January 2006 JRSM1).

Regarding the equity of general practitioner provision, the authors correctly point out the under provision in some working class areas. Government policy is to introduce non-NHS providers, including multinational private health corporations. No mention is made of the former Medical Practices Committee, which stopped GPs practising in over-doctored areas, like Kensington, and gave financial incentives to doctors setting up in under-doctored areas.
Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy
Authors: Hironori Ishibashi, Takashi Suzuki, Satoshi Suzuki, Hiromichi Niikawa, Liangying Lu, Yasuhiro Miki, Takuya Moriya, Shin-ichi Hayashi, Masashi Handa, Takashi Kondo, Hironobu Sasano
Journal: Cancer Research (2005)

Abstract A possible involvement of gender-dependent factors has been postulated in development of human non–small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptor–positive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumor-node-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptor–positive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptor–positive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dose-dependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptor–positive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor–positive NSCLC patients.
Characterization of Familial Non-<i>BRCA1/2</i>Breast Tumors by Loss of Heterozygosity and Immunophenotyping
Authors: Rogier A. Oldenburg, Karin Kroeze-Jansema, Hanne Meijers-Heijboer, Cristi J. van Asperen, Nicoline Hoogerbrugge, Inge van Leeuwen, Hans F.A. Vasen, Anne-Marie Cleton-Jansen, Jaennelle Kraan, Jeanine J. Houwing-Duistermaat, Hans Morreau, Cees J. Cornelisse, Peter Devilee
Journal: Clinical Cancer Research (2006)

Since the identification of BRCA1 and BRCA2, there has been no major breast cancer susceptibility gene discovered by linkage analysis in breast cancer families. This has been attributed to the heterogeneous genetic basis for the families under study. Recent studies have indicated that breast tumors arising in women carrying a BRCA1 mutation have distinct histopathologic, immunophenotypic, and genetic features. To a lesser extent, this is also true for breast tumors from BRCA2 carriers. This indicates that it might be possible to decrease the genetic heterogeneity among families in which BRCA1 and BRCA2 have been excluded with high certainty (BRCAx families) if distinct subgroups of BRCAx-related breast tumors could be identified.Loss of heterozygosity (LOH) analysis with at least one marker per chromosomal arm (65 markers) was used to characterize 100 breast tumors derived from 92 patients from 42 selected BRCAx families. In addition, the immunophenotype of 10 markers was compared with that of 31 BRCA1- and 21 BRCA2-related breast tumors.The BRCAx-related tumors were characterized by more frequent LOH at 22q relative to sporadic breast cancer (P < 0.02), and differed significantly from BRCA1- and BRCA2-related tumors in their positivity for Bcl2. However, cluster analyses of the combined data (LOH and immunohistochemistry) did not result in subgroups that would allow meaningful subclassification of the families. On chromosomes 2, 3, 6, 12, 13, 21, and 22, we found markers at which LOH occurred significantly more frequent among the tumors from patients belonging to a single family than expected on the basis of overall LOH frequencies. Nonetheless, linkage analysis with markers for the corresponding regions on chromosomes 12, 21, and 22 did not reveal significant logarithm of the odds.
The murine lymphocyte receptor for IgE. II. Characterization of the multivalent nature of the B lymphocyte receptor for IgE.
Authors: W T Lee, D H Conrad
Journal: The Journal of Experimental Medicine (1984)

The murine B lymphocyte Fc epsilon R is functionally multivalent. Radiolabeled rat IgE, when bound to the B cell Fc epsilon R will co-isolate with the Fc epsilon R on a rat IgE affinity column; examination of the affinity column eluate by SDS-PAGE reveals the component previously identified as the Fc epsilon R as well as E and L chains from IgE. At low levels of Fc epsilon R saturation, up to 30% of the Fc epsilon R bound IgE becomes bound to IgE-Affi-Gel. By using a biotin-avidin system, the coprecipitation of non-haptenated IgE with haptenated IgE was examined and the results suggest (but do not prove) a divalent receptor.
Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy
Authors: J. Bellmunt, L. Paz-Ares, M. Cuello, F.L. Cecere, S. Albiol, V. Guillem, E. Gallardo, J. Carles, P. Mendez, J.J. de la Cruz, M. Taron, R. Rosell, J. Baselga
Journal: Annals of Oncology (2007)
Rhinitis-asthma and aeroallergen pattern in the last five year at the outpatient clinic of the institute of immunology, Caracas, Venezuela
Authors: J.V. Garmendia, P. Tassinari, O. Aldrey, L. Davila, B. Durante, D. Galante, N.E. Bianco
Journal: Journal of Allergy and Clinical Immunology (2003)
Chronic bronchitis--measurements and observations over 10 years.
Authors: R N Johnston, R S McNeill, D H Smith, J S Legge, F Fletcher
Journal: Thorax (1976)

A total of 111 patients with chronic bronchitis were selected for study in 1963. By 1974 only 54 patients were available for clinical examination, chest radiography, and pulmonary function measurements. There was a significantly higher mortality compared with men of the same age and in the same locality, and this was due to cardiorespiratory failure and bronchial carcinoma. Reduction of cigarette smoking, declining atmospheric pollution, and antibiotic treatment have reduced the 24-hour sputum volume of these patients. The initial one-second forced expiratory volume (FEV1) and vital capacity were significantly lower in those patients who later died from cardio-respiratory failure. The duration of antibiotic treatment and the smoking record have not significantly affected the decline of the FEV1 with advancing age. The transfer factor (diffusing capacity) for carbon monoxide (TF) has declined more in those who continued to smoke. Of the 54 patients 14 had radiological evidence of emphysema initially. This has shown little change over 10 years.
Role of right and left atria in natriuresis and atrial natriuretic factor release during blood volume changes in the conscious rat.
Authors: R Garcia, M Cantin, G Thibault
Journal: Circulation Research (1987)

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)
Use of Lung Transplantation Survival Models to Refine Patient Selection in Cystic Fibrosis
Authors: Theodore G. Liou, Frederick R. Adler, David Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Lung transplantation in cystic fibrosis may improve survival for patients with low 5-year predicted survival. Identifying characteristics that affect post-transplantation survival may improve patient selection and survival benefit. Using Cystic Fibrosis Foundation Patient Registry and United Network for Organ Sharing data, we identified 845 lung transplant recipients from 1991-2001, and 12,826 control patients from 1997. We used Cox proportional hazards models to identify variables that influence post-transplantation survival. To estimate the survival benefit of transplantation for patients affected by identified variables, we compared Kaplan-Meier survival curves of transplanted and control patients stratified by 5-year predicted survival. Post-transplantation survival improved annually. Youth, Burkholderia cepacia, and cystic fibrosis-related arthropathy increased the post-transplantation hazard of death. Compared with control subjects, transplanted adults with a 5-year predicted survival of less than 50% without B. cepacia or arthropathy have improved survival. Transplanted adults with B. cepacia, arthropathy, or a 5-year predicted survival of greater than 50% have decreased survival. Transplantation never improves survivorship for pediatric patients. Patients with arthropathy, B. cepacia infection, or younger age derive no aggregate survival benefit and must appraise carefully the high risk of decreased post-transplantation survival. Adult patients with low 5-year predicted survival without B. cepacia infection should receive priority for lung transplantation.
Horse chestnut <i>(Aesculus hippocastanum)</i> pollen: a frequent cause of allergic sensitization in urban children
Authors: W. Popp, F. Horak, S. Jäger, K. Reiser, C. Wagner, H. Zwick
Journal: Allergy (1992)

We investigated the incidence of allergic sensitization and the risk factors underlying sensitization in 214 urban children exposed to horse chestnut pollen. By means of the Phadezym RAST, we found IgE specific to horse chestnut pollen in 12.6% of the urban children, whereas it occurred in only 1.9% of control subjects recruited from a rural area. Reports of allergic symptoms in spring during the horse chestnut pollen load coincided with the presence of specific IgE in 5.1% of the urban group as against 1.4% of that recruited from the rural area. Environmental factors other than those related to urban living and higher horse chestnut pollen counts had no significant impact on allergic sensitization. Increased total IgE levels (&gt; 100 kU/1), however, and the sensitization to pollen of other species significantly raised the odds for sensitization to chestnut pollen. They were highest in highly atopic children with sensitization to pollen, especially to that of plane trees (OR = 73.9). These results suggest the relevance of horse chestnut pollen because of the high allergic sensitization rate among urban children, and they should also be borne in mind when it comes to the planting of trees in urban areas.
Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study
Authors: Sabino De Placido, Giovanni Scambia, Giovanni Di Vagno, Emanuele Naglieri, Alessandra Vernaglia Lombardi, Rosalbino Biamonte, Marco Marinaccio, Giacomo Cartenì, Luigi Manzione, Antonio Febbraro, Andrea de Matteis, Gianpietro Gasparini, Maria Rosaria Valerio, Saverio Danese, Francesco Perrone, Rossella Lauria, Michele De Laurentiis, Stefano Greggi, Ciro Gallo, Sandro Pignata
Journal: Journal of Clinical Oncology (2004)

Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown.To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP.Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP.The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.
The autonomic nervous system in functional bowel disorders
Authors: G Tougas
Journal: Gut (2000)

Communications along the brain-gut axis involve neural pathways as well as immune and endocrine mechanisms.The two branches of the autonomic nervous system are integrated anatomically and functionally with visceral sensory pathways, and are responsible for the homeostatic regulation of gut function.The autonomic nervous system is also a major mediator of the visceral response to central influences such as psychological stress and other central factors.As presently defined, functional disorders represent a constellation of symptoms, some of which suggest the presence of altered perception while other symptoms point to disordered gastrointestinal function as the cause of the symptoms.2][3] While a number of diVerent methods were used to assess autonomic function, they generally point to decreased vagal (parasympathetic) outflow or increased sympathetic activity in conditions usually associated with slow or decreased gastrointestinal motility.Other studies found either increased cholinergic activity or decreased sympathetic activity in patients with symptoms compatible with increased motor activity. 3 4Under certain conditions, altered autonomic balance (including low vagal tone and increased sympathetic activity) may also alter visceral perception.Autonomic dysfunction could also represent the physiological pathway accounting for many of the extraintestinal symptoms seen in irritable bowel syndrome (IBS) patients, and for some of the frequent gastrointestinal complaints reported by patients with disorders such as chronic fatigue and fibromyalgia.
Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia
Authors: Alessia Omenetti, Lee M. Bass, Robert A. Anders, Maria G. Clemente, Heather Francis, Cynthia D. Guy, Shannon McCall, Steve S. Choi, Gianfranco Alpini, Kathleen B. Schwarz, Anna Mae Diehl, Peter F. Whitington
Journal: Hepatology (2011)

Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and may be profibrogenic. We examined the hypothesis that in BA excessive Hh activation impedes ductular morphogenesis and enhances fibrogenesis by promoting accumulation of immature ductular cells with a mesenchymal phenotype. Livers and remnant extrahepatic ducts from BA patients were evaluated by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) and immunostaining for Hh ligands, target genes, and markers of mesenchymal cells or ductular progenitors. Findings were compared to children with genetic cholestatic disease, age-matched deceased donor controls, and adult controls. Ductular cells isolated from adult rats with and without bile duct ligation were incubated with Hh ligand-enriched medium ± Hh-neutralizing antibody to determine direct effects of Hh ligands on epithelial to mesenchymal transition (EMT) marker expression. Livers from pediatric controls showed greater innate Hh activation than adult controls. In children with BA, both intra- and extrahepatic ductular cells demonstrated striking up-regulation of Hh ligand production and increased expression of Hh target genes. Excessive accumulation of Hh-producing cells and Hh-responsive cells also occurred in other infantile cholestatic diseases. Further analysis of the BA samples demonstrated that immature ductular cells with a mesenchymal phenotype were Hh-responsive. Treating immature ductular cells with Hh ligand-enriched medium induced mesenchymal genes; neutralizing Hh ligands inhibited this. Conclusion : BA is characterized by excessive Hh pathway activity, which stimulates biliary EMT and may contribute to biliary dysmorphogenesis. Other cholestatic diseases show similar activation, suggesting that this is a common response to cholestatic injury in infancy. (HEPATOLOGY 2011;)
New Mouse Models Mimic Biology of Human Cancer
Authors: S. Charlie
Journal: JNCI Journal of the National Cancer Institute (2015)

Scientists always try to develop mouse models that better represent human cancer and therapy. With two recent developments, those efforts have turned a corner. In one, investigators have published proof-of-principle findings with a highly outbred mouse that shows diverse responses to benzene, which causes human leukemia. This diversity outbred (DO) mouse represents an advanced model to derive human exposure limits for carcinogens. In the other development, clinical trials are expanding the array of decision-making tools by incorporating patient-derived xenograft (PDX) models that can grow human tumors.
Selective down-regulation of high-affinity IgE receptor (FcεRI) α-chain messenger RNA among transcriptome in cord blood–derived versus adult peripheral blood–derived cultured human mast cells
Authors: Makoto Iida, Kenji Matsumoto, Hisashi Tomita, Toshiharu Nakajima, Akira Akasawa, Noriko Yuyama Ohtani, Ning Lu Yoshida, Keiko Matsui, Akiko Nakada, Yuji Sugita, Yuji Shimizu, Shunichi Wakahara, Toru Nakao, Yasuyuki Fujii, Chisei Ra, Hirohisa Saito
Journal: Blood (2001)
CellMiner: A Web-Based Suite of Genomic and Pharmacologic Tools to Explore Transcript and Drug Patterns in the NCI-60 Cell Line Set
Authors: William C. Reinhold, Margot Sunshine, Hongfang Liu, Sudhir Varma, Kurt W. Kohn, Joel Morris, James Doroshow, Yves Pommier
Journal: Cancer Research (2012)

Abstract High-throughput and high-content databases are increasingly important resources in molecular medicine, systems biology, and pharmacology. However, the information usually resides in unwieldy databases, limiting ready data analysis and integration. One resource that offers substantial potential for improvement in this regard is the NCI-60 cell line database compiled by the U.S. National Cancer Institute, which has been extensively characterized across numerous genomic and pharmacologic response platforms. In this report, we introduce a CellMiner (http://discover.nci.nih.gov/cellminer/) web application designed to improve the use of this extensive database. CellMiner tools allowed rapid data retrieval of transcripts for 22,379 genes and 360 microRNAs along with activity reports for 20,503 chemical compounds including 102 drugs approved by the U.S. Food and Drug Administration. Converting these differential levels into quantitative patterns across the NCI-60 clarified data organization and cross-comparisons using a novel pattern match tool. Data queries for potential relationships among parameters can be conducted in an iterative manner specific to user interests and expertise. Examples of the in silico discovery process afforded by CellMiner were provided for multidrug resistance analyses and doxorubicin activity; identification of colon-specific genes, microRNAs, and drugs; microRNAs related to the miR-17-92 cluster; and drug identification patterns matched to erlotinib, gefitinib, afatinib, and lapatinib. CellMiner greatly broadens applications of the extensive NCI-60 database for discovery by creating web-based processes that are rapid, flexible, and readily applied by users without bioinformatics expertise. Cancer Res; 72(14); 3499–511. ©2012 AACR.
The hormonal response to exercise in asthma
Authors: JM Kallenbach, V Panz, MS Girson, BI Joffe, HC Seftel
Journal: European Respiratory Journal (1990)

The hormonal responses to exercise of 10 asthmatic patients and 12 normal subjects were compared by studying the changes in the plasma levels of growth hormone, prolactin, adrenocorticotropic hormone (ACTH) and cortisol induced by treadmill running. The asthmatic patients demonstrated absence of the plasma cortisol response to exercise (peak increment -15 +/- 21 (SEM) vs 108 +/- 34 nmol.l-1 p less than 0.02). None of these patients were being treated with systemic corticosteroids and there was no difference between the responses of users and non-users of beclomethasone dipropionate. The results suggest the presence of an impaired adrenocortical response to the stress of physical exercise in asthma and indicate the need for detailed evaluation of hypothalamic-pituitary-adrenal function in patients with the disease.