tbuckley/cabot-search huggingface dataset:
Low-Level Human Equivalent Gestational Lead Exposure Produces Supernormal Scotopic Electroretinograms, Increased Retinal Neurogenesis, and Decreased Retinal Dopamine Utilization in Rats
Authors: Donald A. Fox, Subbarao V. Kala, W. Ryan Hamilton, Jerry E. Johnson, James P. O’Callaghan
Journal: Environmental Health Perspectives (2008)

Postnatal lead exposure in children and animals produces alterations in the visual system primarily characterized by decreases in the rod-mediated (scotopic) electroretinogram (ERG) amplitude (subnormality). In contrast, low-level gestational Pb exposure (GLE) increases the amplitude of scotopic ERGs in children (supernormality).The goal of this study was to establish a rat model of human equivalent GLE and to determine dose-response effects on scotopic ERGs and on retinal morphology, biochemistry, and dopamine metabolism in adult offspring.We exposed female Long-Evans hooded rats to water containing 0, 27 (low), 55 (moderate), or 109 (high) ppm of Pb beginning 2 weeks before mating, throughout gestation, and until postnatal day (PND) 10. We measured maternal and litter indices, blood Pb concentrations (BPb), retinal Pb concentrations, zinc concentrations, and body weights. On PND90, we performed the retinal experiments.Peak BPb concentrations were < 1, 12, 24, and 46 microg/dL in control, low-, moderate- and high-level GLE groups, respectively, at PNDs 0-10. ERG supernormality and an increased rod photoreceptor and rod bipolar cell neurogenesis occurred with low- and moderate-level GLE. In contrast, high-level GLE produced ERG subnormality, rod cell loss, and decreased retinal Zn levels. GLE produced dose-dependent decreases in dopamine and its utilization.Low- and moderate-level GLE produced persistent scotopic ERG supernormality due to an increased neurogenesis of cells in the rod signaling pathway and/or decreased dopamine utilization, whereas high-level GLE produced rod-selective toxicity characterized by ERG subnormality. The ERG is a differential and noninvasive biomarker of GLE. The inverted U-shaped dose-response curves reveal the sensitivity and vulnerability of the developing retina to GLE.
Abstract 1008: Retinoids and TRAIL target early stage intestinal polyps in <i>Apc</i>Min/+ mice
Authors: Jennifer S. Davis, Shaoyi Huang, Xiaoyang Ren, Xiangwei Wu
Journal: Cancer Research (2012)

Abstract The purpose of this study is to determine the optimal timing of treatment for a novel chemoprevention approach in a mouse model of Familial Adenomatous Polyposis (FAP). FAP is an autosomal dominantly inherited disorder caused by mutations in the tumor suppressor Apc (adenomatous polyposis coli) gene, which results in the formation of hundreds to thousands of polyps, predominantly in the colon and rectum. Left untreated, these polyps will form colorectal adenocarcinomas. Although surgical removal of the colon eliminates the colon cancer risk, these individuals are also at increased risk for other primary cancers, including tumors of the small intestine and stomach. Systemic chemopreventive interventions to specifically remove the pre-cancerous cells in these individuals could greatly improve their outcomes and quality of life. Recently, we have developed a new method based on the ability of combined retinoid and TRAIL (tumor necrosis factor related apoptosis inducing ligand) treatment to induce apoptosis and regression of intestinal polyps in ApcMin/+ mice, a mouse model of FAP. Treatment of these mice with retinoid causes an increase in TRAIL death receptors DR4 and DR5 as well as a concomitant decrease in the decoy receptors. APC deficiency leads to a decreased level of the anti-apoptotic protein FLIP (flice-like inhibitory protein). Thus, the combination of TRAIL and retinoid specifically targets APC deficient cells for apoptosis. Following up on these findings, we have tested the hypothesis that early stage adenomas of the intestine will respond more readily to TRAIL and retinoid treatment than those at a later stage. We used ApcMin/+ mice at either two months of age or five-six months of age. Each group of mice was given three treatments of retinyl acetate and TRAIL within one week. Following the last treatment, the intestine was harvested from each mouse and the polyps were counted. The number of polyps in each group of mice was compared with the polyp number in age matched non-treated mice. Results: When treated at two months of age, ApcMin/+ exhibit a nearly 50% decrease in polyp number following only one week of therapy. Conversely, ApcMin/+ treated at five-six months of age did not show any significant difference in polyp number compared to non-treated mice. Conclusion: Earlier stage adenomas respond more readily to the combined treatment of retinoid and TRAIL. This is likely due to additional mutations acquired by the later stage polyps. The cause of this resistance is a current area of study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1008. doi:1538-7445.AM2012-1008
Abstract 4046: Androgen-mediated phenotypic change in prostate carcinoma cells and the microRNA-ome
Authors: Corrinne Segal, Chris J. Powell, Nigel J. Gooderham
Journal: Cancer Research (2010)

Abstract Activation of the androgen receptor (AR) results in phenotypic change in androgen-responsive cells; for example, in the human prostate carcinoma cell line (LNCaP) androgens mediate cell proliferation. Factors controlling the range of phenotypic responses mediated by androgens are only partially understood, but include both transcriptional and post-transcriptional mechanisms. One such mechanism that appears to offer wide ranging, yet highly selective control, is the expression of the miRNA-ome. In the present study, we assessed the influence of endocrine-active compounds that act via the AR pathway on the microRNA (miRNA) profile. As negative regulators of gene expression, miRNA are short non-coding RNA that are able to suppress translation or induce degradation of their target mRNA transcripts (post-transcriptional) leading to decreased protein expression. The effect of exposure of LNCaP cells to the AR agonists mibolerone and dihydrotestosterone, and the antagonist bicalutamide, was determined at various time points up to 120 hours. Phenotypic response to exposure was assessed as an alteration of proliferative ability, expression of prostate-specific antigen (PSA) and alteration of the miRNA-ome. As expected, each of the agonists significantly induced proliferation, compared to vehicle control, and the antagonist decreased proliferation. Concurrent with changes in proliferation, were an up-regulation of PSA secretion for mibolerone and DHT. The temporal effects of exposure to androgenic compounds on the expression profile of 850 miRNAs was assessed using Agilent's miRNA microarray version 3. The ability of androgens to alter the miRNA-ome was confirmed and found to be temporally-dependent. Bioinformatic analysis of the phenotypic changes induced by the androgens is reflected in the changes in the miRNA-ome. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4046.
Improving Indoor Environmental Quality for Public Health: Impediments and Policy Recommendations
Authors: Felicia Wu, David Jacobs, Clifford Mitchell, David Miller, Meryl H. Karol
Journal: Environmental Health Perspectives (2007)

People in modern societies spend more than 90% of their time indoors. Hence, indoor environmental quality (IEQ) has a significant impact on public health. In this article we describe health risks associated with indoor environments, illuminate barriers to overcoming these risks, and provide policy recommendations to achieve healthier indoor environments.The weight of evidence suggests that indoor environmental contaminants pose significant public health risks, particularly among children and the poor, and the societal costs of illnesses related to indoor environments are considerable. Despite the evidence of harm to human health, poor indoor environments are generally difficult to regulate and not of sufficient concern to the general public. We discuss several reasons for this lack of concern about IEQ, focusing specifically on home environments.Economics plays a large role both in political inaction and individual-level indifference. Because little effort has been made to quantify the value of the societal and individual costs of poor housing quality, as well as the benefits achievable by simple interventions, policymakers lack motivation to act on IEQ. Similarly, individual homeowners lack the incentive to remediate homes, as other problems may be more pressing than home environmental quality.Although the problem of IEQ involves multiple stakeholders and multiple levels of governance, it is possible to establish economic incentives that would set the wheels in motion for action at all levels to achieve healthy home environments. Also important are education and information dissemination on the public health risks associated with indoor environments. These recommendations are intended for all decision makers who have an influence in developing policy to improve indoor environmental quality.
The fatal sleep
Authors: T. Dalrymple
Journal: BMJ (2008)

Generally we think of euthanasia in terms of individual cases, but Philip Toynbee, the novelist, poet, and literary critic, who died in 1981, believed in mass euthanasia. In his book The Fearful Choice , published in 1957, when nuclear winter rather than global warning was the apocalypse in vogue, he wrote of the results of a nuclear war: “Have we decided how we are to kill the other members of our household in the event of our being less injured than they are? Over most of the country there will probably be …
Triclonal gammopathy in an extranodal non‐Hodgkin lymphoma patient
Authors: Angelo Tirelli, Salvatore Guastafierro, Benedetto Cava, Giacomo Lucivero
Journal: American Journal of Hematology (2003)

Abstract The case of a patient with an extranodal non‐Hodgkin lymphoma and three M‐components (IgGκ + IgGλ + IgMλ) in the serum is described. Three separate populations of M‐component producing cells have been identified. Since a κ→λ chain switch is not demonstrated, the synthesis of IgGκ and IgGλ by two distinct clones is obvious. IgMλ and IgGλ M‐components are synthesized by two different plasma cell populations that could represent two unrelated cell clones or, alternatively, two subclones originated by a common precursor. After chemotherapy the IgGλ M‐component is replaced by heavy γ chains without evidence of λ light chains. Am. J. Hematol. 73:273–275, 2003. © 2003 Wiley‐Liss, Inc.
396 FASTING REDUCES LIVER FIBROSIS IN A MOUSE MODEL OF CHRONIC CHOLANGIOPATHY
Authors: A. Sokolovic, C.P.A.A. van Roomen, R. Ottenhoff, J. Aten, J.K. Hiralall, P.J. Bosma, R.P.J. Oude Elferink, A.K. Groen, M. Sokolovic
Journal: Journal of Hepatology (2012)
THE OXYGEN CONSUMPTION OE THE GEEMINAL EPITHELIUM IN NORMAL AND PSORIATIC SKIN
Authors: HANS HAMMAR, CLAES HELLERSTROM
Journal: British Journal of Dermatology (1970)

Journal Article THE OXYGEN CONSUMPTION OE THE GEEMINAL EPITHELIUM IN NORMAL AND PSORIATIC SKIN Get access HANS HAMMAR, HANS HAMMAR Departments of Dermatology and Histology, University of Uppsala, Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar CLAES HELLERSTRÖM CLAES HELLERSTRÖM Departments of Dermatology and Histology, University of Uppsala, Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 83, Issue 3, 1 September 1970, Pages 371–375, https://doi.org/10.1111/j.1365-2133.1970.tb15719.x Published: 01 September 1970 Article history Accepted: 24 April 1970 Published: 01 September 1970
NHS pays too much for some supplies
Authors: C. Court
Journal: BMJ (1996)

Britain's public spending watchdog,the National Audit Office, has found wide variations in the prices paid by different divisions of the NHS for goods. It concludes that the NHS Supplies Authority could make substantial savings on the £2bn ($3bn) of goods and services bought annually by the health service.

The report notes that “there were wide variations in the prices NHS Supplies charged to their customers for …
Labour pledges to cut NHS bureaucracy
Authors: J. Warden
Journal: BMJ (1996)

The Labour party pledged this week to cut £100m ($150m) from bureaucracy by ending the system of extracontractual referrals and reducing management costs in all health authorities and NHS trusts to at least the current average. The immediate result would be 100 000 patients taken off waiting lists, says the Road to the Manifesto, a briefing document which is due to be endorsed by the party in the autumn.

Shadow health secretary Harriet Harman, who prepared …
Endomyocardial fibrosis: a case for the tropical doctor
Authors: C. C. Kartha
Journal: Cardiovascular Research (1995)

Journal Article Endomyocardial fibrosis: a case for the tropical doctor Get access Chandrasekharan C. Kartha Chandrasekharan C. Kartha Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695 011, Kerala, India Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 5, November 1995, Pages 636–643, https://doi.org/10.1016/S0008-6363(96)88509-9 Published: 01 November 1995 Article history Received: 21 December 1994 Accepted: 02 June 1995 Published: 01 November 1995
Prenatal Exposure to Nut Allergens and Risk of Childhood Nut Sensitization
Authors: J.T. Hsu, S.A. Missmer, M.C. Young, K.F. Berry, F.J. Twarog, I. Borras, M.D. Hornstein, L.C. Schneider
Journal: Journal of Allergy and Clinical Immunology (2012)
Do women with acute myocardial infarction receive the same treatment as men?
Authors: K W Clarke, D Gray, N A Keating, J R Hampton
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To determine whether women with acute myocardial infarction in the Nottingham health district receive the same therapeutic interventions as their male counterparts. <b>Design</b> : Retrospective study. <b>Setting</b> : University and City Hospitals,20Nottingham. <b>Patients</b> : All patients admitted with a suspected myocardial infarction during 1989 and 1990. <b>Main outcome measures</b> : Route and timing of admission to hospital, ward of admission, treatment, interventions in hospital, and mortality. Results - Women with myocardial infarction took longer to arrive in hospital than men. They were less likely to be admitted to the coronary care unit and20were therefore also less likely to receive thrombolytic treatment. They seemed to have more severe infarcts, with higher Killip classes, and had a slightly higher mortality during admission. They were less likely than men to receive secondary prophylaxis by being discharged taking ß blockers or aspirin. <b>Conclusion</b> : Survival chances both in hospital and after discharge in women with acute myocardial infarction are reduced because they do not have the same opportunity for therapeutic intervention as men.
Clinical Apnea and Brain-Stem Neural Function in Preterm Infants
Authors: David J. Henderson-Smart, Alan G. Pettigrew, David J. Campbell
Journal: New England Journal of Medicine (1983)

We assessed the relation between clinical apnea and brain-stem neuronal function in 58 preterm babies. The brain-stem conduction time of the auditory evoked response (Wave V-I interval) was longer in babies with apnea than in those without it at a similar postconceptional age (at 32 to 33 weeks: mean, 6.16 vs. 5.35 msec, P less than 0.001; at 34 to 35 weeks: mean, 5.98 vs. 5.33 msec, P less than 0.002). The number of apneas per day decreased over a period that was similar to the period during which brainstem conduction time decreased. In general, apneas ceased when the conduction time decreased to the levels observed in babies of a similar age who did not have apnea. Short brain-stem conduction times were observed in some infants who had prenatal stress, such as intrauterine growth retardation or maternal hypertension. These results suggest that the occurrence of apnea in preterm infants is correlated with neural function in the brain stem.
Role of increased cholinergic activity in reperfusion induced ventricular arrhythmias
Authors: N. FERRARA, D. BONADUCE, P. ABETE, D. LEOSCO, G. LONGOBARDI, V. CANONICO, F. RENGO
Journal: Cardiovascular Research (1987)

The effect of increased cholinergic activity on reperfusion induced ventricular arrhythmias was studied in alpha chloralose anaesthetised dogs by administering neostigmine during a 25 min occlusion of the anterior left descending coronary artery. The dogs were divided into five groups, each of 10 animals: the control group received only saline solution; group 1 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion (that is, 5 min before reperfusion); group 2 atropine 0.4 mg.kg-1 iv at 10 min of coronary occlusion and neostigmine 0.03 mg.kg-1 iv at 20 min; and group 3 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion and at the same time underwent atrial pacing at the same rate as that of the sinus node just before neostigmine administration. In group 4 heart rate was slowed (junctional rhythm) by destroying the sinus node at 20 min of coronary occlusion. The results obtained showed that ventricular tachycardia and fibrillation, which occur at the beginning of reperfusion, were significantly less frequent in group 1 (p less than 0.001) and in group 4 (p less than 0.001). The protective action of neostigmine was abolished by previous administration of atropine (group 2) and modified by preventing the decrease in the heart rate by atrial pacing (group 3). In group 3 ventricular tachycardia was more frequent but the incidence of ventricular fibrillation was reduced significantly compared with the control and atropine groups. Thus cholinergic activity has a protective role in reperfusion arrhythmias by decreasing the heart rate before release of the coronary occlusion and therefore reduces the incidence of ventricular fibrillation.
A Patient With Peripheral Arterial Stenosis Diagnosed With Lower Extremity Perfusion Scintigraphy
Authors: Hursit Soyer, Ilhami Uslu
Journal: Clinical Nuclear Medicine (2007)

A 42-year-old man attending cardiology outpatient clinic for single-vessel coronary artery disease was on medical treatment. An exercise myocardial perfusion-SPECT was performed to monitor his response. The exercise test was terminated when claudication occurred in his right leg during the second stage. Planar scintigraphic images of both crural regions were obtained following Tc-99m sestamibi injection. Images were obtained 15 minutes after a single injection of 10 mCi. A remarkable decrease in perfusion was observed in the right crural region, when compared with the left. Doppler examination of the right lower extremity revealed normal arterial circulation. Peripheral arterial angiography was ordered, and revealed multiple stenoses of the right common iliac and right external iliac arteries. In cases where arterial examination may be misleading due to well-developed collateral circulation, or where Doppler examination of intraabdominal vasculature poses anatomic difficulties, perfusion scintigraphy of lower extremities may be helpful before considering more invasive procedures, such as angiography.1–10
Acute Falciparum Malaria
Authors: ROBERT E. BLOUNT
Journal: Annals of Internal Medicine (1969)

The cases described strongly support the effectiveness of quinine and pyrimethamine therapy when falciparum malaria is diagnosed early and treated promptly. Two thousand and three acute falciparum malaria patients were given quinine sulfate, 650 mg every 8 hr for 14 days, and pyrimethamine, 25 mg base every 12 hr for a total of 6 doses. (A slightly higher pyrimethamine dose was given to the earlier patients in the series.) Response to therapy was seen in all patients, and no deaths occurred. Despite the use of such potent drugs dangerous side-effects were encountered infrequently. Adverse reactions were seen primarily in the hematologic system through hemolysis, or bone marrow depression, or both. Complications in the series included cerebral malaria in 24 patients; anemia requiring transfusion, 18; severe pancytopenia, 11; and malarial hemoglobinuria, 8. Clinical management of malaria and its complications are discussed. Chemoprophylaxis used by units from which these patients were derived included chloroquine, 300 mg base; and primaquine, 45 mg base, weekly; and diophenyldiaminosulfone, 25 mg daily. These drugs along with field mosquito discipline and the existing efficient medical evacuation system contributed to the absence of fatalities in the present series.
An evening of unproved treatment
Authors: D. Carnall
Journal: BMJ (1996)

Two documentaries, both broadcast on the same evening, explored two very different approaches to conceptualising and coping with disease. Horizon followed two teams of scientists competing to be the first successfully to reinstall a normal gene in place of the faulty gene of cystic fibrosis, while Cutting Edge brought us Cari Loder, who attributed her remission from her disabling multiple sclerosis to a cocktail of antidepressants, amino acid supplements, and B12 injections.

Shored up in her belief in her treatment by the four occasions on which, having omitted the morning dose of one of the ingredients, she had been unable to climb the stairs, Ms Loder published her findings in Laboratory News. Her phone has not stopped ringing since. Those who rang were initially entered in a trial of the treatment, the success of which …
Serendipitous Detection of Lung Cancer on Hepatic Imaging
Authors: GLORIA M. RAPOPORT, LAWRENCE C. SWAYNE
Journal: Clinical Nuclear Medicine (1987)

A case of a primary lung carcinoma involving the left pulmonary hilum serendipitously detected utilizing hepatic imaging is presented. Malignant stimulation of the reticuloendothelial system resulted in diffuse pulmonary uptake of Tc-99m sulfur colloid, however, only the right lung was visualized. Subsequently, a chest radiograph and computed tomography of the chest demonstrated massive malignant involvement of the left pulmonary hila, adjacent mediastinum, and left atrium. Transbronchial biopsy revealed anaplastic small cell carcinoma.
KIT mutations in primary mediastinal B-cell lymphoma
Authors: P D Nagel, A Stenzinger, F M Feld, M D Herrmann, S Brüderlein, T F E Barth, R Marienfeld, V Endris, W Weichert, K-M Debatin, M-A Westhoff, D Lessel, P Möller, J K Lennerz
Journal: Blood Cancer Journal (2014)

Primary mediastinal B-cell lymphoma (PMBL) is a specific subtype of diffuse large B-cell lymphoma with a distinctive clinical course and a specific genetic profile.1,2 Several prior studies have provided key molecular–genetic aberrations;1,3 however, a targeted next-generation sequencing-based study of relevant oncogenes in all currently available PMBL cell lines has not been performed. Here we report previously unrecognized mutations in known hot-spot regions of the KIT oncogene in ~12.5% of PMBL tumors. Interestingly, activating mutations in the proto-oncogene KIT have already been described in a variety of malignancies, including mast cell leukemia, acute myelogenous leukemia, gastrointestinal stromal tumors, as well as several other solid tumors,4 where they carry, in part, therapeutic relevance due to clinically effective inhibitors.5,6