tbuckley/cabot-search huggingface dataset:
Effects of adrenaline during treatment with propranolol and metoprolol.
Authors: C L van Herwaarden, R A Binkhorst, J F Fennis, A van t'Laar
Journal: BMJ (1977)

<h3>Abstract</h3> Cross-orientation suppression is a classic form of contextual normalization in visual cortex, yet the degree to which cortical circuits participate in the normalization computation is unclear. We visualized orientation maps of individual ferrets, and provided patterned optogenetic stimulation to both excitatory and inhibitory cells in orientation columns that either matched or were orthogonal to the preferred visual orientation of neurons recorded with electrodes. When visual or optogenetic stimulation of columns preferring one orientation was combined with optogenetic stimulation of columns preferring the orthogonal orientation, we observed less suppression than when orthogonal stimulation was provided visually, suggesting that cortical circuits do not provide a large fraction of visual cross-orientation suppression. Integration of visual and optogenetic signals was linear when neurons exhibited low firing rates and became sublinear when neurons exhibited higher firing rates. We probed the nature of sublinearities in cortex by examining the influence of optogenetic stimulation of cortical interneurons. We observed a range of responses, including evidence for paradoxical responses in which interneuron stimulation caused a decrease in inhibitory firing rate, presumably due to the withdrawal of recurrent excitation. These results are compatible with cortical circuits that exhibit strong recurrent excitation with stabilizing inhibition that provides normalization, albeit normalization that is too weak across columns to account for cross-orientation suppression.
Insulin-like growth factor-1 and myocyte growth: the danger of a dogma. Part I. Postnatal myocardial development: normal growth
Authors: Piero Anversa, Jan Kajstura, Wei Cheng, Krzysztof Reiss, Elena Cigola, Giorgio Olivetti
Journal: Cardiovascular Research (1996)

The possibility that the human heart may respond to an increase in pressure and volume loads not only by hypertrophy of pre-existing myocytes but also by myocyte cellular hyperplasia has been a matter of controversy for several decades. The critical heart weight theory introduced by Linzbach in the late 1940s and early 1950s [l] has suggested that in the presence of a cardiac weight of nearly 500 g or greater, hyperplasia of myofibers begins and this cellular process constitutes the prevailing form of myocyte growth in the heart. These initial findings were restricted to the left ventricle, but similar adaptations subsequently have been shown at the level of the right ventricle [2], indicating that the entire heart may react to a sustained increase in workload by the generation of new myocytes through mitotic division of the stressed muscle cells. In contrast, experimental studies have demonstrated that short-term cardiac hypertrophy in the adult heart results from an enlargement of myocytes with little DNA synthesis in myocyte nuclei, possibly representing the formation of polyploid cells [3-51. Thus, it has become a general belief that no proliferation of myocytes occurs once cell division has ceased immediately after birth in the mammalian myocardium. These studies in the pressure-overloaded rat heart have examined thymidine incorporation early after the imposition of the overload and the lack of autoradiographic labeling in myocytes has been interpreted as a definitive indication of the terminally differentiated
Rare and More Prevalent Cancers May Have Much in Common at Gene Level
Authors: Beverly Merz
Journal: JAMA (1988)

CANCER FAMILIES, which have long been a source of information on rare inherited malignancies, are beginning to provide insights into the development of common cancers as well. What investigators are finding is that, at the level of the gene, rare and common forms of cancer have a great deal in common. Many apparently result from the same aberrations in the genome. The difference is basically one of timing. Persons with inherited forms of cancer are born with at least one aberration transmitted from the parent; those with sporadic forms of the disease develop these aberrations later in life. Through studying the familial forms of the disease, investigators have attained a better idea of how a cell becomes malignant. Most now agree with the multi-hit hypothesis propounded in 1971 (to explain familial carcinogenesis) by Alfred Knudsen, PhD, Fox Chase Cancer Center, Philadelphia. Knudsen proposed that carcinogenesis requires more than one genetic
Over-diagnosis in breast cancer screening
Authors: Henrik Møller, Elizabeth Davies
Journal: BMJ (2006)

the cumulative rate at first but at the end a not statistically significant 8% higher incidence in the former invited group.In other trials almost no excess incidence was shown when the control group was invited, which is to be interpreted as similar rates of over-diagnosis in both groups. 14 Exclusion of prevalent casesWe found a reduced, but remaining, excess incidence after exclusion of prevalent cases (the first two screening rounds).This shows that the excess incidence is not just related to prevalent cases in a population exposed to screening.Two screening rounds correspond to four years, and the average lead time has been estimated to be two to four years depending on age. 11 12Most of the prevalent cases in the invited group and their corresponding controls should therefore have been accounted for. Factors influencing over-diagnosisAttendance rates for screening decrease with age, as shown in both the Malmö mammographic screening trial and in the subsequent service screening programme. 15 16 On the other hand, women who had been screened in the Malmö trial were more likely to attend the service screening programme 16 and probably also to undergo mammography after screening had ended.Furthermore, mammography of asymptomatic women outside the trial in the control groups may lead to underestimation of over-diagnosis.It is widely agreed that screening using mammography can reduce mortality in breast cancer.The rate of over-diagnosis is another issue to be considered in the discussion on implications of breast cancer screening.
Free retroviral drugs could save up to 1.7 million South Africans
Authors: P. Sidley
Journal: BMJ (2003)

By offering free antiretroviral drugs to the six million people with HIV/AIDS who can't afford them the South African government could save or prolong the lives of about 1.7 million people, a new study says.

The study was commissioned by the ministers of health and finance in the South African government, but its results were leaked this week by the Treatment Action Campaign, frustrated by the government's lack of action.

The campaign is an AIDS activist group calling for antiretroviral treatment for people with HIV/AIDS in South Africa. It has risen to prominence because of the government's ambivalent attitude towards the disease and antiretroviral drugs.

The …
363 Activin secreted from hepatocytes plays a key role in liver fibrogenesis
Authors: N KITAMURA, T AZUMA, Y ETO, K TOMITA, S INOKUCHI, T NISHIMURA, H ISHII
Journal: Hepatology (2003)

Epidermal growth factor receptor (EGFR) transactivation induced by angiotensin II (Ang II) participates in the progression of various diseases. A disintegrin and metalloproteinase 17 (ADAM17) is thought to promote renal fibrosis, cardiac hypertrophy with fibrosis and atherosclerosis by activation of the EGFR through secretion of EGFR ligands. The purpose of this study was to investigate whether Ang II-induced EGFR transactivation occurs on hepatic stellate cells (HSCs) and whether the reaction is mediated via ADAM17.Ang II-induced EGFR transactivation and cellular proliferation of the human HSC line LI90 were investigated using Western blotting and ATP assay, respectively. Ang II-induced secretion of mature amphiregulin into the cell culture medium was evaluated by enzyme-linked immunosorbent assay (ELISA).An inhibitor of ADAM17, TAPI-1, as well as antagonists of EGFR and angiotensin II type-1 receptor (AT1), attenuated Ang II-induced EGFR transactivation and proliferation of LI90 cells. Furthermore, silencing of ADAM17 inhibited Ang II-induced secretion of mature amphiregulin in addition to EGFR transactivation.These results indicate that ADAM17 mediates Ang II-induced EGFR transactivation on HSCs, and that this process may participate in the progression of liver fibrosis.
Transforming growth factor-/Smad3 signalling regulates inflammatory responses in a murine model of contact hypersensitivity
Authors: M. Anthoni, N. Fyhrquist-Vanni, H. Wolff, H. Alenius, A. Lauerma
Journal: British Journal of Dermatology (2008)

Background Transforming growth factor (TGF)‐β is an important modulator of immune functions and cellular responses, such as differentiation, proliferation, migration and apoptosis. The Smad proteins, which are intracellular TGF‐β signal transducers, mediate most actions of TGF‐β. Objectives This study examines the role of Smad3 in a murine model of contact hypersensitivity (CHS). Methods The CHS response to oxazolone was studied in Smad3‐deficient mice. The ear swelling response was measured and skin biopsies from oxazolone‐sensitized skin areas were obtained for RNA isolation, immunohistochemical analyses and histology. Ear draining lymph nodes were collected for RNA isolation and proliferation tests. Quantitative real‐time polymerase chain reaction was used to quantify mRNA expression of cytokines, chemokines and transcription factors. Results The expression of proinflammatory [interleukin (IL)‐1β, tumour necrosis factor‐α, IL‐6], Th2 (IL‐4) and Th17 type cytokines (IL‐17), as well as regulatory components (TGF‐β, Foxp3) increased significantly at the mRNA level in the skin of oxazolone‐treated Smad3−/− mice when compared with wild‐type controls. The expression of the Th1 type cytokine IFN‐γ and the chemokines CXCL9 and CXCL10 was, however, unaffected by the lack of Smad3. The number of neutrophils and expression of the chemokines CCL3 and CXCL5, which are both involved in neutrophil recruitment, were increased in mice lacking Smad3. Also Th2 type chemokines CCL24, CCL3 and CXCL5 were increased in the skin of Smad3−/− mice compared with wild‐type mice. In the lymph nodes, mRNA of IL‐1β and IL‐17, but not IL‐4, TGF‐β or Foxp3, was increased in Smad3−/− mice during the CHS response. Conclusions The lack of intact TGF‐β signalling via Smad3 results in an increased proinflammatory, Th2 and Th17 type response in the skin, as well as increased expression of regulatory elements such as TGF‐β and Foxp3. Understanding the role of Smad3 in the CHS response may offer treatment and prevention strategies in this often disabling disease.
Prognostic Predictive Value of Total Lesion Glycolysis From 18F-FDG PET/CT in Post-Surgical Patients With Epithelial Ovarian Cancer
Authors: Shanshan Liao, Xiaoli Lan, Guoxiang Cao, Hui Yuan, Yongxue Zhang
Journal: Clinical Nuclear Medicine (2013)

The aim of this study was to determine an optimal threshold method for the segmentation of malignant lesions from (18)F-FDG PET/CT images and to evaluate the prognostic value of the total lesion glycolysis in post-surgical patients with epithelial ovarian cancer.We retrospectively reviewed 47 patients with pathologically proven epithelial ovarian cancer who underwent (18)F-FDG PET/CT imaging after surgery. The follow-up time was 26.6 ± 19.8 months (ranged from 4 to 89 months). For each patient, every lesion was segmented by 2 thresholds with 3D-area growing algorithm, standard uptake value (SUV) 2.5, and background method. The detection rates were compared. The optimal threshold method was then used to calculate whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG). The prognostic significance of SUV(max), WBMTV, WBTLG, and other pathological variables for overall survival were assessed by Cox proportional hazards regression analysis and Kaplan-Meier survival analysis.A total of 142 metastatic lesions of 47 patients were confirmed by long-term clinical follow-up or pathological findings. The detection rates of the threshold SUV 2.5 and background methods were 37.32% (53/142) and 96.48% (137/142), respectively, which showed significant difference between the 2 methods (P < 0.005). In multivariate analysis, WBTLG, obtained from the background method, was an independent predictive factor associated with the prognosis (HR 1.043, 95% CI 1.01-1.078, P = 0.011), and none of the other factors had statistical association. Survival analysis also showed that the survival time was clearly shortened with WBTLG increasing (P < 0.001).In this group of post-surgery patients with epithelial ovarian cancer, the background method could segment much more malignant lesions than SUV = 2.5 method, and WBTLG, obtained from this method, could be used as an independent prognostic factor.
214. HVJ-E/Importin β Hybrid for Efficient Gene Delivery
Authors: Takeshi Nagasaki, Takeshi Kawazu, Seiji Shinkai
Journal: Molecular Therapy (2005)

Over the past decade great deal of effort has been directed towards the development of effective non-viral vectors. Because the transfection efficiency of non-viral vectors is much lower than that of viral vectors, often due to the limited nuclear import of the transgene, many studies have focused on overcoming this problem.
Organ-specific roles for transcription factor NF-κB in reovirus-induced apoptosis and disease
Authors: Sean M. O’Donnell, Mark W. Hansberger, Jodi L. Connolly, James D. Chappell, Melissa J. Watson, Janene M. Pierce, J. Denise Wetzel, Wei Han, Erik S. Barton, J. Craig Forrest, Tibor Valyi-Nagy, Fiona E. Yull, Timothy S. Blackwell, Jeffrey N. Rottman, Barbara Sherry, Terence S. Dermody
Journal: Journal of Clinical Investigation (2005)

Reovirus induces apoptosis in cultured cells and in vivo. In cell culture models, apoptosis is contingent upon a mechanism involving reovirus-induced activation of transcription factor NF-κB complexes containing p50 and p65/RelA subunits. To explore the in vivo role of NF-κB in this process, we tested the capacity of reovirus to induce apoptosis in mice lacking a functional nfkb1/p50 gene. The genetic defect had no apparent effect on reovirus replication in the intestine or dissemination to secondary sites of infection. In comparison to what was observed in wild-type controls, apoptosis was significantly diminished in the CNS of p50-null mice following reovirus infection. In sharp contrast, the loss of p50 was associated with massive reovirus-induced apoptosis and uncontrolled reovirus replication in the heart. Levels of IFN-β mRNA were markedly increased in the hearts of wild-type animals but not p50-null animals infected with reovirus. Treatment of p50-null mice with IFN-β substantially diminished reovirus replication and apoptosis, which suggests that IFN-β induction by NF-κB protects against reovirus-induced myocarditis. These findings reveal an organ-specific role for NF-κB in the regulation of reovirus-induced apoptosis, which modulates encephalitis and myocarditis associated with reovirus infection.
SOS: time to reclaim the air we breathe
Authors: A. Jain
Journal: BMJ (2014)

Asking for a history of smoking is an integral part of a medical consultation. But has the day arrived when we routinely ask patients about outdoor exposure to air pollutants ? Or given the frenetic pace of urbanisation, do we just assume that most of the population is at high risk? And that the future generation is in for a lifetime’s exposure to potentially lethal toxins, completely beyond their control? When living and breathing come to be, well, risk factors for living and breathing.

Inexcusably, we have abused and disregarded the air we breathe, points out a recent study conducted by the Centre for Science and Environment (doi:10.1136/bmj.g1597). The levels of atmospheric particulate matter and noxious gases in Delhi have risen exponentially in the past decade, …
Maximal erythrocyte and hemoglobin catabolism
Authors: Ronald F. Coburn, Peter B. Kane
Journal: Journal of Clinical Investigation (1968)

A series of experiments were performed on anesthetized dogs in which varying quantities of normal canine erythrocytes damaged by incubation with N-ethylmaleimide were injected into the circulation. Cell sequestration and catabolism of hemoglobin to carbon monoxide remained normal after injections that contained from 0.058 to 0.154 g of hemoglobin per kg of body weight. After administration of larger quantities of these cells, from 0.154 to 0.364 g of hemoglobin per kg of body weight, sequestration remained normal but the rate of catabolism of hemoglobin to carbon monoxide reached a maximum. Large quantities of hemoglobin entered the plasma in these experiments at a time when cell sequestration in the reticuloendothelial system appeared to be virtually complete. After injection of even larger quantities of damaged erythrocytes, 0.545 and 0.552 g of hemoglobin per kg, sequestration became slightly delayed, but was complete. These data appear to indicate that (a) the maximal rate of hemoglobin catabolism in normal anesthetized dogs averages approximately 0.07 g/kg of body weight per hr; (b) hemoglobinemia can result from "overloading" the reticuloendothelial system with damaged sequestered cells and, therefore, may not always indicate "intravascular" hemolysis; and (c) the sequestering function of the reticuloendothelial system appears not to limit the maximal rate of catabolism of hemoglobin. The limiting parameter or parameters were not defined in these studies.
Chronotype Is Independently Associated With Glycemic Control in Type 2 Diabetes
Authors: Sirimon Reutrakul, Megan M. Hood, Stephanie J. Crowley, Mary K. Morgan, Marsha Teodori, Kristen L. Knutson, Eve Van Cauter
Journal: Diabetes Care (2013)

To examine whether chronotype and daily caloric distribution are associated with glycemic control in patients with type 2 diabetes independently of sleep disturbances.Patients with type 2 diabetes had a structured interview and completed questionnaires to collect information on diabetes history and habitual sleep duration, quality, and timing. Shift workers were excluded. A recently validated construct derived from mid-sleep time on weekends was used as an indicator of chronotype. One-day food recall was used to compute the temporal distribution of caloric intake. Hierarchical linear regression analyses controlling for demographic and sleep variables were computed to determine whether chronotype was associated with HbA1c values and whether this association was mediated by a higher proportion of caloric intake at dinner.We analyzed 194 completed questionnaires. Multiple regression analyses adjusting for age, sex, race, BMI, insulin use, depressed mood, diabetes complications, and perceived sleep debt found that chronotype was significantly associated with glycemic control (P = 0.001). This association was partially mediated by a greater percentage of total daily calories consumed at dinner.Later chronotype and larger dinner were associated with poorer glycemic control in patients with type 2 diabetes independently of sleep disturbances. These results suggest that chronotype may be predictive of disease outcomes and lend further support to the role of the circadian system in metabolic regulation.
More Blood for the Anticoagulant Battle
Authors: Alvan R. Feinstein
Journal: New England Journal of Medicine (1975)

And now, under the aegis of the editor who has helped assemble two anthologies of Controversy in Internal Medicine, 1 , 2 the Journal presents a pair of papers (pp. 1359 and 1362) that can evoke almost enough new controversy to fill a third volume.One of the prime disputes will produce a revival of the quiescent old battle over the use of anticoagulants for patients with acute myocardial infarction. The pro-anticoagulant arguments, which had dominated therapeutic decisions for almost two decades, had recently begun to wane after failing to be confirmed in several randomized, concurrently controlled clinical trials. The publication of these . . .
The Metabolic Basis of Human Atherosclerosis
Authors: FREDERICK H. EPSTEIN
Journal: Annals of Internal Medicine (1967)

Editorial Notes1 May 1967The Metabolic Basis of Human AtherosclerosisFREDERICK H. EPSTEIN, M.D., LEON D. OSTRANDER JR., M.D., F.A.C.P.FREDERICK H. EPSTEIN, M.D., LEON D. OSTRANDER JR., M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1019 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA national symposium under the auspices of the Heart Association of Southeastern Pennsylvania on The Metabolic Basis of Human Atherosclerosis was held in Philadelphia in February. Dr. Peter T. Kuo and his program committee deserve the greatest praise for having organized this meeting at this time because, as it turned out, a variety of exciting developments over the past few years suddenly seemed to fall into place.The first session of the symposium dealt with "Errors of Metabolism in Human Atherosclerosis," with papers on genetic factors (E. A. Murphy), genetic types of hyperlipidemia (D. S. Fredrickson), disturbances in carbohydrate metabolism...Reference1. FREDRICKSONLEVYLEES DSRIRS: Fat transport in lipoproteins. New Eng. J. Med. 276: 148, 1967. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: FREDERICK H. EPSTEIN, M.D.; LEON D. OSTRANDERJR., M.D., F.A.C.P.Affiliations: Department of Epidemiology School of Public Health University of Michigan Department of Internal Medicine University of Michigan Medical School Ann Arbor, Mich. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySPECIAL ARTICLE 1 May 1967Volume 66, Issue 5Page: 1019-1021KeywordsAtherosclerosisCarbohydrate metabolismFallsGeneticsHeartHyperlipidemia ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Higher mortality in deprived areas: community or personal disadvantage?
Authors: A. Sloggett, H. Joshi
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To investigate the association between level of social deprivation in electoral wards and premature mortality among residents, before and after allowing for levels of personal deprivation. <b>Design</b>: Longitudinal study of the Office of Population Censuses and Surveys. <b>Setting</b>: England. Subjects—Random sample of nearly 300 000 people aged between 16 and 65 at the 1981 census and followed up for nearly nine years. Main outcome measure—Death from all causes between ages of 16 and 70. <b>Results</b>: Without allowance for personal disadvantage, both sexes showed a clear, significant, and roughly linear positive relation between degree of deprivation of the ward of residence in 1981 and premature death before 1990. For men, this association was effectively explained away once allowance was made for individual socioeconomic circumstances. For women living in wards of above average deprivation, the association was also effectively removed, but the situation for other women was less clear. <b>Conclusion</b>: The excess mortality associated with residence in areas designated as deprived by census based indicators is wholly explained by the concentration in those areas of people with adverse personal or household socioeconomic factors. Health policy needs to target people as well as places.