tbuckley/cabot-search huggingface dataset:
Nuclear Hormone Receptor Activity of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Metabolites in Transactivation Assays Using Chinese Hamster Ovary Cells
Authors: Hiroyuki Kojima, Shinji Takeuchi, Naoto Uramaru, Kazumi Sugihara, Takahiko Yoshida, Shigeyuki Kitamura
Journal: Environmental Health Perspectives (2009)

An increasing number of studies are reporting the existence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (HO) and methoxylated (MeO) metabolites in the environment and in tissues from wildlife and humans.Our aim was to characterize and compare the agonistic and antagonistic activities of principle PBDE congeners and their HO and MeO metabolites against human nuclear hormone receptors.We tested the hormone receptor activities of estrogen receptor alpha (ERalpha), ERbeta, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor alpha(1) (TRalpha(1)), and TRbeta(1) against PBDE congeners BDEs 15, 28, 47, 85, 99, 100, 153, and 209, four para-HO-PBDEs, and four para-MeO-PBDEs by highly sensitive reporter gene assays using Chinese hamster ovary cells.Of the 16 compounds tested, 6 and 2 showed agonistic activities in the ERalpha and ERbeta assays, respectively, and 6 and 6 showed antagonistic activities in these assays. 4'-HO-BDE-17 showed the most potent estrogenic activity via ERalpha/beta, and 4'-HO-BDE-49 showed the most potent anti estrogenic activity via ERalpha/beta. In the AR assay, 13 compounds showed antagonistic activity, with 4'-HO-BDE-17 in particular inhibiting AR-mediated transcriptional activity at low concentrations in the order of 10(-8) M. In the GR assay, seven compounds, including two HO-PBDEs and two MeO-PBDEs, showed weak antagonistic activity. In the TRalpha(1) and TRbeta(1) assays, only 4-HO-BDE-90 showed weak antagonistic activity.Taken together, these results suggest that PBDEs and their metabolites might have multiple endocrine-disrupting effects via nuclear hormone receptors, and para-HO-PBDEs, in particular, possess more potent receptor activities compared with those of the parent PBDEs and corresponding para-MeO-PBDEs.
841-2 Periadventitial fat inflammation correlates with plaque inflammation in patients with coronary plaque ruptures: New marker of plaque vulnerability?
Authors: Deborah Vela, Allen Burke, Alireza Zarrabi, Morteza Naghavi, Mohammad Madjid, Ward Casscells, Renu Virmani, James T Willerson, Silvio Litovsky
Journal: Journal of the American College of Cardiology (2004)
The performance of e23(Fv)PEs, recombinant toxins targeting the erbB-2 protein
Authors: C. Richter King, Paul H. Fischer, Robert F. Rando, Ira Pastan
Journal: Seminars in Cancer Biology (1996)

The overexpression of the erbB-2 (HER-2, neu) gene has attracted significant interest as a molecular target for the rational design of cancer therapies. This review examines the design and preclinical testing phase for one such experimental therapy, recombinant toxins targeted to the erbB-2 protein, termed e23(Fv)PEs.
PTU-064 Increased Mucosal Expression Of Insoluble Keratins 8, 18 And 19 In Long-standing Ulcerative Colitis In Comparison To Recent-onset Ulcerative Colitis: Validation Of Mass Spectrometry Data
Authors: A Assadsangabi, C Evans, D Majumdar, BM Corfe, AJ Lobo
Journal: Gut (2014)

<h3>Introduction</h3> Intermediate filaments (IF) are one of the main components of the human cell cytoskeleton with keratins (K) being the largest component. K8, K18 and K19 constitute the main keratins in the intestinal epithelial cells. Keratin alteration may play a role in the pathophysiology of ulcerative colitis (UC). K8 -/- mice develop chronic colitis. K8 and K18 play a role in TNF-α induced-apoptosis. We have previously shown increased expression of insoluble K8, K18 and K19 in long-standing UC relative to recent – onset ulcerative colitis (≤5 years) using mass spectrometry (MS) in the IF fraction of pooled patient samples. The aim of this study was to use antibody-based relative quantification of K8, K18, K19 in individual patient samples to validate MS results and describe variation in expression across the cohort. <h3>Methods</h3> IF proteins were extracted from individual biopsies in patients with long-standing pan-colitis (LSPC) in clinical, endoscopic and histological remission (n = 10) and with recent onset ulcerative colitis (ROUC) also in remission (n = 8). Each sample was dot-blotted on a membrane followed by immunoblotting for identification and quantification of keratins (8, 18 and19) sequentially. MCF-7 cell line was used as control in each experiment. Relative Keratins concentration for each dot- blotted sample was inferred by determining its signal intensity relative to the MCF-7 keratins signal intensity measured in turn by densitometry. Statistical analysis to compare the two groups was made separately for K8, K18, K19 using Mann-Whitney U test. <h3>Results</h3> Median relative IF protein levels in patients with LSPC were 1.54, 0.41 and 2.12 for K8, K18 and K19, respectively were significantly higher than those with ROUC: 0.03, 0.05 and 0.07 for K8 (p = 0.001), K18 (p = 0.002) and K19 (p = 0.021), respectively. Median Baron’s endoscopy score in patients with LSPC and ROUC were 0 (range 0–1) and 1 (range 0–1), respectively. Median histological activity index in both groups were 0 (range 0–1). <h3>Conclusion</h3> This study confirms increased expression of insoluble keratins in colonic epithelial cells during LSPC in remission relative to the levels in ROUC and validate our previous MS observations. Restoration of keratins in quiescent LSPC may be a protective mechanism against recurrent inflammation and colorectal cancer. <h3>Disclosure of Interest</h3> None Declared.
The Role of Human Epidermal Growth Factor Receptor 2 as a Prognostic Factor in Lung Cancer: A Meta-Analysis of Published Data
Authors: Lingxiang Liu, Xiaoyan Shao, Wen Gao, Jianling Bai, Rongsheng Wang, Puwen Huang, Yongmei Yin, Ping Liu, Yongqian Shu
Journal: Journal of Thoracic Oncology (2010)
Death Due to Swelling of Ball Component of Aortic Ball-Valve Prosthesis
Authors: Eugene G. Laforet
Journal: New England Journal of Medicine (1967)

ALTHOUGH implantable vascular prostheses of a conduit type – such as arterial grafts – have a long and fairly honorable history, that of cardiac valvular prostheses is much shorter and, it would seem, somewhat less honorable. Perhaps the major difficulty, once the valve has been successfully inserted, has been the tendency to thrombus formation, frequently with embolic sequelae. The incidence of actual mechanical failure of the prosthetic device has not been high. The purpose of this note is to describe a patient who died twenty months after an aortic ball-valve prosthesis had been implanted to correct aortic regurgitation. At autopsy . . .
Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical outcome at one year.
Authors: A. G. Jolley, S. R. Hirsch, A. McRink, R. Manchanda
Journal: BMJ (1989)

A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse. The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared. Fifty four stable, remitted outpatients meeting the American Psychiatric Association's DSM-III criteria for schizophrenia were randomised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections. Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up. Eight (30%) of the patients given placebo injections and only 2 (7%) of the controls, however, had a recurrence of schizophrenic symptoms. Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia. Dysphoric and neurotic symptoms were identified before eight out of 11 relapses, and these symptoms were more frequent in patients given placebo depot injections. These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill, chronic, stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse.
Epidemiological study of HLA and GM in rheumatoid arthritis and related symptoms in an open Dutch population.
Authors: B.M de Jongh, L.K van Romunde, H.A Valkenburg, G.G de Lange, J.J van Rood
Journal: Annals of the Rheumatic Diseases (1984)

This report deals with the question of whether or not the established association of HLA-DR4 with rheumatoid arthritis (RA) can also be detected in cases of RA as diagnosed in a population survey. For this purpose 6584 persons older than 19 years living in a single community in The Netherlands were investigated for the presence of rheumatoid arthritis and related abnormalities. After five years 83 patients with RA, 30 with only erosive abnormalities on radiological examination (Rad), and 48 with only rheumatoid factor (RF) were reinvestigated and typed for HLA and allotypes of immunoglobulin G heavy chain (GM). On the classification of the initial survey no significant association of HLA-DR4 or GM could be detected in any of the three categories. When the information of the follow-up investigation was taken into account, a reappraisal of the classification resulted in 53 cases with RA, 18 with Rad only, and 35 with RF only. The frequencies of HLA-DR4 and GM in the three categories were also about the same as those in normal controls. However, an increase in the frequency of HLA-DR4 was observed in cases of RA positive for Rad, RF, or both. We found no evidence for an interaction between HLA-DR4 and GM. Our results suggest that rheumatoid arthritis is a heterogeneous disorder, only a fraction of which is associated with HLA-DR4. At present no single determinant of RA such as Rad or RF can characterise the HLA-DR4-associated, and most probably more severe, type of RA.
Prednisolone in Treatment of Pulmonary Tuberculosis: A Controlled Trial
Authors: N. W. Horne
Journal: BMJ (1960)

The Research Committee of the Tuberculosis Society of Scotland (1957) published a preliminary account of the results of a controlled trial of the use of prednisolone in the treatment of pulmonary tuberculosis.That report was an analysis of the results attained in 110 patients who had completed six months' treatment.This present report is concerned with the results achieved in all patients 213 in number admitted to the trial between February, 1956, and December, 1957.The patients were studied for a period of 12 months from the beginning of treatment.The physicians participating in the trial were: Aberdeen:
Ototoxicity from Aminoglycoside Antibiotics
Authors: D. Mansel-Jones
Journal: BMJ (1970)

MDICJOUL 227 also been examined.This has a differently designed blood port gasket, and we found that although this is a loose gasket system bacteria tend to collect and survive beneath the blood port gasket in considerable numbers.This gasket was much more difficult to remove than the other type and was probably not-removed so regularly when the boards were disinfected.The use of loose gaskets has largely removed the sequestration of bacteria in the gasket channels.Thus there is a reduction in the bacterial challenge to the disinfection techniques, and, as these techniques will always suffer from the possibility of incomplete access of disinfectant either to the dismantled boards or to the assembled dialyser, there follows an improvement in the bacteriological state of the prepared dialyser and a reduction in the likelihood of bacterial proliferation during the subsequent dialysis.
The low molecular weight heparin, enoxaparin, limits infarct size at reperfusion in the dog
Authors: Danielle Libersan, Ahmad Khalil, Pierre Dagenais, Eric Quan, Fernand Delorme, André Uzan, Jean-Gilles Latour
Journal: Cardiovascular Research (1998)

Objective: Heparin (HEP) is used in the post-thrombolytic state to prevent vessel reocclusion, thereby aiding myocardial salvage. Side effects limit its benefits, but besides anticoagulant activity HEP has diffuse actions that may be potentially beneficial to jeopardized reperfused myocardium. This study compares the effect of therapeutic doses of HEP and enoxaparin (ENOX), a low molecular weight heparin, and to streptokinase (SK), on infarct size. Methods: The left anterior descending coronary artery was occluded in dogs for 90 min, followed by 6 h of reperfusion with a residual critical stenosis in place. Five min before reperfusion, HEP (2800 IU) was injected i.v., and perfused at 500 IU/h until sacrifice in group 2, while groups 3 and 4 received ENOX (2128 anti-Xa IU i.v.) followed by 380 anti-Xa IU/h. Group 4 was also given 500 000 IU SK over 30 min before reperfusion beginning at 55 min of occlusion (ENOX+SK), while group 5 received only SK. Controls (CON, group 1) received saline. P-selectin mediated platelet–neutrophil rosettes formation was also tested in vitro in the presence of HEP and ENOX. Results: The area at risk delimited by dye perfusion was statistically similar among groups. Covariance analysis between infarct size (% of area at risk) delimited with triphenyltetrazolium and collateral flow measured with radioactive microspheres confirmed that groups given ENOX (21.6±5.5%) and ENOX+SK (24.9±3.9%) developed smaller infarcts (P<0.05) than CON (48.1±4.5%), as opposed to HEP (32.2±3.6%) and SK (46.8±3.4%) groups. 111In-platelet counts in the infarct were reduced significantly by 64% in the ENOX group as compared to CON, and to a lesser extent (42%, n.s.) in the ENOX+SK group, but were not reduced by HEP and SK treatments. Neutrophil accumulation in the infarcts was decreased significantly and by more than 75% in the ENOX and ENOX+SK groups versus CON, but not in the HEP and SK groups. Also, only ENOX (10–100 μg/ml) significantly inhibited platelet–neutrophil rosettes formation in a plasmatic milieu. Conclusions: The ENOX treatment, as opposed to that of HEP, reduces myocardial platelet and neutrophil accumulations, and limits infarct size when given just before and during reperfusion. The benefits of ENOX on infarct size were not modified by SK, and may be related, at least in part, to an interaction with P-selectin-mediated cell adhesion.
FDA oversight of drug company promotion of off-label use is poor, US watchdog says
Authors: J. H. Tanne
Journal: BMJ (2008)

The US Food and Drug Administration does a poor job of monitoring drug companies’ promotion of unapproved or “off-label” uses of their drugs, says a report by the US Government Accountability Office, the investigative arm of Congress.

Charles Grassley, an Iowa senator who is the senior Republican member of the Senate Committee on Finance, asked the accountability office to review the FDA’s effectiveness in monitoring drug companies’ efforts to promote off-label uses. He said he was concerned about the possible effects of such promotion on doctors’ prescribing practices and on patients’ safety.

Although doctors may prescribe drugs off label for indications that have not been approved by the FDA, drug companies are forbidden from promoting such unapproved uses.

The accountability office’s report said the FDA’s …
Care in hospitals often lacks compassion, says report
Authors: Z. Kmietowicz
Journal: BMJ (2008)

The quality of care in hospitals around the country is patchy, and staff often fail to provide the compassionate care that patients seek, says a report from a health policy think tank.

The report from the Point of Care programme of the King’s Fund found that although surveys of patients show high levels of satisfaction with hospital care, more detailed studies that include patients’ own stories show that the quality of care varies and that staff members often fail to see the person in the patient. The charity set up the Point of Care programme to improve the experience of care in hospitals for patients and their …
THE STAPHYLOCOCCUS-SPRAY TREATMENT OF DIPHTHERIA CARRIERS
Authors: A.M. ALDEN
Journal: JAMA (1913)

The presence of diphtheria bacilli in the throats and nasal passages of patients convalescing from the disease long after all clinical symptoms have disappeared constitutes one of the most prolific sources of infection the health officer has to deal with in combating this disease. Just what the average period of persistence in virulent cases of diphtheria is it is hard to say. Graham Smith and Cobbett's<sup>1</sup>tables give it as 31.6 days and estimate that one-third of the cases exceed this time. Our experience, however, has been that according to the cultural method the average period of persistence in Iowa is about sixteen days. Henry Albert<sup>2</sup>says: Unfortunately, however, there are some in whom the bacteria remain so persistently that they can still be found for from five to seven weeks, in one of our cases for seven weeks and in one case on record for twenty-three weeks
Breaking the allergic response by disrupting antibody glycosylation
Authors: Max Crispin
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental Medicine Monocytes are a heterogeneous population of phagocytic cells that are generated in the bone marrow and released into the bloodstream.There are two main monocyte subsets in mice: "inflammatory" monocytes that are Ly6C hi CCR2 hi CX 3 CR1 low and "alternative" or "patrolling" monocytes that are Ly6C low CCR2 low CX 3 CR1 hi .The process of monocyte recruitment and differentiation is still a matter of controversy.In this issue, Dal-Secco et al. report in situ monocyte reprogramming in the liver, from proinflammatory CCR2 hi CX 3 CR1 low cells into reparative CCR2 low CX 3 CR1 hi cells and show, for the first time, that this occurs at the site of injury.Dal-Secco et al. harnessed the power of imaging technology and fluorescent reporter mice to track monocytes in a model of sterile inflammation in the liver (induced after a 30 µm 3 burn by a thermal probe).In this model, the recruitment of monocytes is dependent on CCR2 present on CCR2 hi CX 3 CR1 low monocytes.Some of these cells were observed patrolling the liver sinusoids in the steady state.Within 24-48 hours, CCR2 hi CX 3 CR1 low monocytes extravasated and formed a ring structure surrounding the necrotic tissue at the site of the injury.These extravascular monocytes started to differentiate and, by 48-72 hours, had lost CCR2 expression and gained CX 3 CR1 and MHC class II expression (CCR2 low CX 3 CR1 hi CD11b hi MHCII hi CD64 hi F4/80 -).Blocking IL-10 and IL-4 delayed this phenotypic transition and impaired wound healing as shown by failure to clear necrotic hepatocytes and failure to deposit collagen.
Posterior Cingulate Hypoperfusion in Alzheimerʼs Disease, Senile Dementia of Alzheimer type, and Other Dementias Evaluated by Three-Dimensional Stereotactic Surface Projections Using Tc-99m HMPAO SPECT
Authors: Koichiro Kaneko, Yasuo Kuwabara, Masayuki Sasaki, Koji Ogomori, Atsushi Ichimiya, Hirofumi Koga, Makoto Nakagawa, Kazutaka Hayashi, Hiroshi Honda
Journal: Clinical Nuclear Medicine (2004)

Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.
Dendritic Spikes Induce Ripples in Parvalbumin Interneurons during Hippocampal Sharp Waves
Authors: Balázs Chiovini, Gergely F. Turi, Gergely Katona, Attila Kaszás, Dénes Pálfi, Pál Maák, Gergely Szalay, Mátyás Forián Szabó, Gábor Szabó, Zoltán Szadai, Szabolcs Káli, Balázs Rózsa
Journal: Neuron (2014)
Late complications of surgery for coarctation of the aorta.
Authors: J K Ross, J L Monro, C G Sbokos
Journal: Thorax (1975)

The problem of the patient who has had one operation for coarctation of the aorta and who then requires another because of a late complication at or near the coarctation site is a demanding one. The safety of aortic cross-clamping at the second operation depends on the adequacy or otherwise of the collateral circulation, and this in turn depends on the presence or absence of residual or recurrent aortic obstruction. Three illustrative cases are described in which there was complete, incomplete, and no aortic obstruction respectively at the time of reoperation, two of the cases presenting the additional complication of local aneurysm formation. The various aspects of management of such individuals are discussed, and the relevant literature has been reviewed in an attempt to provide a systematic approach to these difficult patients. The methods for assessing collateral circulation are both clinical and radiological with trial clamping of the aorta and pressure measurement as the most reliable ultimate test. A pressure of 50 mmHg in the distal aorta is accepted as indicating an adequate peripheral circulation, but it is recommended that the trial clamping should always include both the left subclavian artery and any particularly large local collaterals. The use of a perfusion technique to sustain the distal tissues is also recommended, although local bypass shunts have a place when their use is dictated in the interests of safety for the patient.
Context effects equally applicable in generalization and similarity
Authors: Emmanuel M. Pothos
Journal: Behavioral and Brain Sciences (2001)

Shepard's theoretical analysis of generalization is assumed to enable an objective measure of the relation between objects, an assumption taken on board by Tenenbaum &amp; Griffiths. I argue that context effects apply to generalization in the same way as they apply to similarity. Thus, the need to extend Shepard's formalism in a way that incorporates context effects should be acknowledged. [Shepard; Tenenbaum &amp; Griffiths]
REGRESSION OF TRANSPLANTED LYMPHOMAS INDUCED IN VIVO BY MEANS OF NORMAL GUINEA PIG SERUM
Authors: John G. Kidd
Journal: The Journal of Experimental Medicine (1953)

In the experiments here described transplanted lymphomas of two kinds regularly regressed following repeated injections of normal guinea pig serum intraperitoneally into mice carrying them, the animals meanwhile remaining lively and devoid of signs of illness or wasting. The lymphomas of untreated control mice, by contrast, usually grew progressively and killed their hosts within 20 to 30 days, and the same was true of the growth of other mice given repeated injections of horse serum or rabbit serum. In similar experiments, the cells of a transplanted lymphosarcoma of rats were temporarily kept from proliferating by repeated intraperitoneal injections of guinea pig serum, though the cells of two transplanted mammary carcinomas of mice, and those of fibrosarcoma, grew unimpeded in hosts likewise treated. Additional experiments related to the phenomenon here described, and a discussion of the findings as a whole, are given in an associated paper.