tbuckley/cabot-search huggingface dataset:
Surface antigens of malaria merozoites. A high molecular weight precursor is processed to an 83,000 mol wt form expressed on the surface of Plasmodium falciparum merozoites.
Authors: R R Freeman, A A Holder
Journal: The Journal of Experimental Medicine (1983)

A technique was developed for obtaining high yields of naturally released Plasmodium falciparum merozoites from synchronous cultures of parasitized erythrocytes. The cultured erythrocytes were treated with trypsin to prevent reinvasion (6), and the released merozoites that accumulated extracellularly were harvested by differential centrifugation. The total biosynthetically labeled proteins of schizonts and merozoites, and those immunoprecipitated by human immune serum were analyzed and compared. The surface antigens of free merozoites, labeled by lactoperoxidase-catalyzed iodination, were also described. A monoclonal antibody, specific for a 195,000 mol wt schizont protein, and processing fragments derived from it (3) were used in immunoprecipitation and Western transfer analyses to determine which of the processing fragments are associated with merozoites and which of them are located on the merozoite surface. It was found that processing of the 195,000 mol wt precursor down to an 83,000 mol wt fragment is complete in free merozoites, and that this fragment is expressed as one of the major surface antigens of P. falciparum merozoites.
Importance of antibodies to the fusion glycoprotein of paramyxoviruses in the prevention of spread of infection.
Authors: D C Merz, A Scheid, P W Choppin
Journal: The Journal of Experimental Medicine (1980)

The effects of monospecific antibodies to the viral glycoprotein with hemagglutinating and neuraminidase activity (HN) and the viral glycoprotein with membrane-fusing activity (F) of the paramyxovirus simian virus 5 (SV5) on the spread of infection in two cell types have been investigated. In CV-1 cells, infection can spread by either released progeny virus adsorbing to and infecting other cells, or by fusion of an infected cell with an adjacent cell as a result of the cell-fusing activity of the F glycoprotein. In these cells, antibodies specific for the HN glycoprotein prevented the dissemination of infection by released infectious virus, but spread by cell fusion was not inhibited. Antibodies to the F glycoprotein completely prevented the spread of infection in these cells. In Madin-Darby bovine kidney cells, which are relatively resistant to SV5-induced fusion, antibodies to either the HN or F glycoproteins were capable of preventing the dissemination of infection. These results indicate that effective immunological prevention of the spread of paramyxovirus infection requires the presence of antibodies that inactivate the F glycoprotein. This requirement for anti-F antibodies has obvious implications for the design of effective paramyxovirus vaccines and provides an explanation for previous failures of formalin-inactivated paramyxovirus vaccines as well as additional insight into the possible immunopathological mechanisms involved in the atypical and severe infections that have occurred in individuals who received inactivated paramyxovirus vaccines and were subsequently infected by the virus.
At the frontier of biomedical publication: Chicago 2005
Authors: Kristina Fister
Journal: BMJ (2005)

macrovascular events, it is surprising that it had no effect on all cause mortality, especially given that over 350 deaths were observed in the trial. Further reviewThe results of the trial will be published in the Lancet.Publication should enable a more informed and detailed debate on the safety and efficacy of pioglitazone in poorly controlled type 2 diabetes, and, hopefully, a shift from sound bite to science.Contributors and sources: NF has worked as the study statistician on several drug and device trials in diabetes and other clinical areas.He has undertaken methodological work in the interpretation of clinical trials and the use of composite outcome measures.He was in the audience for the presentation of the Proactive study, and the article arose from this and subsequent discussions.Competing interests: NF has received funding for research and consultancy from a number of pharmaceutical and device companies that manufacture products for diabetes, including Takeda Pharmaceuticals, which co-sponsored Proactive.He has
Rosiglitazone in Combination With Glimepiride Plus Metformin in Type 2 Diabetic Patients
Authors: John A. Kiayias, Eugenia D. Vlachou, Eleni Theodosopoulou, Elli Lakka-Papadodima
Journal: Diabetes Care (2002)

Type 2 diabetic patients are often treated with a combination of antidiabetic agents. The need to use drugs with different and complementary mechanisms of action frequently arises in daily clinical practice. There are several reasons to do this; namely, the disease itself is progressive, with deterioration of glycemic control over time, and monotherapeutic attempts to achieve and maintain glycemic control often fail in the long run (1,2).

Some patients do not accept insulin treatment because of the fear of needles and injections, the fear that the complications of diabetes are caused by insulin, and other false beliefs, and are willing to take as many antidiabetic pills the doctor is prepared to prescribe.

The combination of a sulfonylurea with metformin is commonly used in clinical practice. But when this potent combination is no longer able to provide acceptable glycemic control, the addition of an antidiabetic drug with a …
Anaphylaxis to dyes during the perioperative period: Reports of 14 clinical cases
Authors: Paul Michel Mertes, Jean Marc Malinovsky, Claudie Mouton-Faivre, Marie Caroline Bonnet-Boyer, Abdelhaouad Benhaijoub, François Lavaud, Jocelyne Valfrey, James O'Brien, Philippe Pirat, Laurent Lalourcey, Pascal Demoly
Journal: Journal of Allergy and Clinical Immunology (2008)
Prolonged Aβ treatment leads to impairment in the ability of primary cortical neurons to maintain K+ and Ca2+ homeostasis
Authors: Lana Shabala, Claire Howells, Adrian K West, Roger S Chung
Journal: Molecular Neurodegeneration (2010)

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterised by the formation of insoluble amyloidogenic plaques and neurofibrillary tangles. Beta amyloid (Aβ) peptide is one of the main constituents in Aβ plaques, and is thought to be a primary causative agent in AD. Neurons are likely to be exposed to chronic, sublethal doses of Aβ over an extended time during the pathogenesis of AD, however most studies published to date using in vitro models have focussed on acute studies. To experimentally model the progressive pathogenesis of AD, we exposed primary cortical neurons daily to 1 μM of Aβ1-40 over 7 days and compared their survival with age-similar untreated cells. We also investigated whether chronic Aβ exposure affects neuronal susceptibility to the subsequent acute excitotoxicity induced by 10 μM glutamate and assessed how Ca2+ and K+ homeostasis were affected by either treatment. We show that continuous exposure to 1 μM Aβ1-40 for seven days decreased survival of cultured cortical neurons by 20%. This decrease in survival correlated with increased K+ efflux from the cells. One day treatment with 1 μM Aβ followed by glutamate led to a substantially higher K+ efflux than in the age-similar untreated control. This difference further increased with the duration of the treatment. K+ efflux also remained higher in Aβ treated cells 20 min after glutamate application leading to 2.8-fold higher total K+ effluxed from the cells compared to controls. Ca2+ uptake was significantly higher only after prolonged Aβ treatment with 2.5-fold increase in total Ca2+ uptake over 20 min post glutamate application after six days of Aβ treatment or longer (P < 0.05). Our data suggest that long term exposure to Aβ is detrimental because it reduces the ability of cortical neurons to maintain K+ and Ca2+ homeostasis in response to glutamate challenge, a response that might underlie the early symptoms of AD. The observed inability to maintain K+ homeostasis might furthermore be useful in future studies as an early indicator of pathological changes in response to Aβ.
Psychiatry and the Legal Rights of Patients
Authors: LAURENCE TANCREDI, DIANA CLARK
Journal: American Journal of Psychiatry (1972)

This study of psychiatric personnel involved with admissions procedures at a leading New England mental health center demonstrates on a small scale that the psychiatric community is generally unaware of patients' legal rights at the time of their admission and during subsequent hospitalization. The hospital staff's awareness of these rights can mean the difference between incarceration and freedom for the patient. The authors conclude that there is a need for educational programs on law for psychiatric personnel; they suggest possible approaches.
Action on the Social Determinants of Health and Health Inequities Goes Global
Authors: Sharon Friel, Michael G. Marmot
Journal: Annual Review of Public Health (2011)

Marked health inequities exist between regions, between countries, and within countries. Reducing these inequities in health requires attention to the unfair distribution of power, money, and resources and the conditions of everyday life. These are the social determinants of health. The World Health Organization (WHO) Commission on Social Determinants of Health (CSDH) brought together a global evidence base of what could be done to reduce these health inequities, demonstrating that economic and social policy, if done well, can improve health and health equity. A global movement for health equity was reignited by the WHO Commission on Social Determinants of Health when it made a call to action upon delivering its final report.
Present and future costs of COPD in Iceland and Norway: results from the BOLD study
Authors: R. Nielsen, A. Johannessen, B. Benediktsdottir, T. Gislason, A. S. Buist, A. Gulsvik, S. D. Sullivan, T. A. Lee
Journal: European Respiratory Journal (2009)

The Burden of Obstructive Lung Disease (BOLD) initiative provides standardised estimates of the burden of chronic obstructive pulmonary disease (COPD) worldwide. We estimate the current and future economic burden of COPD in Reykjavik, Iceland and Bergen, Norway using data from the BOLD initiative. Data on utilisation of healthcare resources were gathered from the BOLD survey, existing literature and unit costs from national sources. Economic data were applied to a Markov model using transition probabilities derived from Framingham data. Sensitivity analyses were conducted varying unit costs, utilisation and prevalence of disease. The cost of COPD was \#8364;478 per patient per yr in Iceland and \#8364;284 per patient per yr in Norway. The estimated cumulative costs of COPD for the population aged ≥40 yrs, were \#8364;130 million and \#8364;1,539 million for the following 10 yrs in Iceland and Norway, respectively. Costs of COPD accounted for 1.2 and 0.7% of healthcare budgets in Iceland and Norway, respectively. Sensitivity analyses showed estimates were most sensitive to changes in exacerbation frequency. COPD has a significant economic burden in both Iceland and Norway and will grow in the future. Interventions aimed at avoiding exacerbations will have the most impact on costs of COPD over the next 20 yrs.
Some histological changes in chronic bronchitis and asthma
Authors: G. Salvato
Journal: Thorax (1968)

The differences in two groups of patients (24 with chronic bronchitis and 24 with bronchial asthma) were compared by bronchoscopy and bronchial biopsies. The same investigations were carried out on 24 healthy control subjects. The only bronchoscopic difference between the two groups was hypertonicity of the bronchial wall, which was frequent in the asthmatics and absent in the chronic bronchitics. Mucus was scanty and viscous in the asthmatics and more abundant and watery in the chronic bronchitics. Hypersecretion of mucus occurred in both groups. In asthma the mucous hyperplasia affected chiefly the goblet cells. In chronic bronchitis the deeper bronchial glands were affected as well as the goblet cells. In asthma the mucus stained predominantly with the periodic-acid Schiff technique, and was thus presumed to contain much neutral mucopolysaccharide. In chronic bronchitis the mucus was strongly alcian blue positive and was thought to consist largely of acid mucopolysaccharide. Thickening of the basement membrane was almost constant in bronchial asthma and rare in chronic bronchitis. Tissue eosinophilia was very frequent and intense in asthma but infrequent and sparse in chronic bronchitis. Mast cells were degranulated and decreased in number in asthma but increased in number and packed with granules in chronic bronchitis. It is presumed that there is a relation between tissue eosinophilia and degranulation of mast cells. The study confirms that bronchial asthma and chronic bronchitis are two distinct diseases, both with a separate pathology.
Smoking, hypertension, and colonic anastomotic healing; a combined clinical and histopathological study.
Authors: A Fawcett, M Shembekar, J S Church, R Vashisht, R G Springall, D M Nott
Journal: Gut (1996)

BACKGROUND--Large bowel anastomotic breakdown occurs as a result of perianastomotic ischaemia. Preservation of the macroscopic arterial supply to the perianastomotic tissues is vital, but little is known about the influence of microvascular disease on anastomotic healing. AIMS--To study the associations between risk factors for macrovascular disease, the presence of colonic microvascular disease, and the incidence of anastomotic dehiscence. PATIENTS--147 consecutive colonic surgery patients. METHODS--The prevalence of smoking, hypertension, diabetes, and ischaemic heart disease were established retrospectively from patient notes. These risk factors were correlated with histopathological assessment of resection margin vasculature and clinical follow up. RESULTS--Smoking and hypertension were significantly associated with an increased incidence of anastomotic dehiscence and microvascular disease. Microvascular disease was positively correlated with an increased incidence of anastomotic dehiscence. CONCLUSIONS--Microvascular disease predisposes to anastomotic breakdown. This effect may in part be due to vasospasm in the diseased vessels, which are hypersensitive to serotonin, a vasoactive amine known to be present in increased quantities in the serum of smokers, hypertensives, and after surgery. Treatment with serotonin antagonists in the perioperative period may be beneficial to anastomotic healing, helping to maintain microvascular flow.
A Prospective, Observational Trial to Further Assess Safety and Efficacy of Regorafenib in Patients with Metastatic Colorectal Cancer (Mcrc) in Routine Clinical Practice (Correlate)
Authors: M.P. Ducreux, A. Falcone, C.J.A. Punt, J. Thaler, C.H. Poehlein, A. Cervantes
Journal: Annals of Oncology (2014)
A Randomized, Double-Blind, Placebo-Controlled Trial of Quetiapine in the Treatment of Bipolar I or II Depression
Authors: Joseph R Calabrese, Paul E Keck, Wayne Macfadden, Margaret Minkwitz, Terence A Ketter, Richard H Weisler, Andrew J Cutler, Robin McCoy, Ellis Wilson, Jamie Mullen
Journal: American Journal of Psychiatry (2005)

There is a major unmet need for effective options in the treatment of bipolar depression.Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire.Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively).Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.
Effects of Montelukast and Budesonide on Airway Responses and Airway Inflammation in Asthma
Authors: Richard Leigh, Dilini Vethanayagam, Makoto Yoshida, Richard M. Watson, Tracy Rerecich, Mark D. Inman, Paul M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Inhaled corticosteroids are effective antiinflammatory therapy for asthma; however, they do not completely abolish allergen-induced airway inflammation. Leukotriene modifiers attenuate both early and late allergen responses and have antiinflammatory properties. We reasoned that treatment with budesonide and montelukast in combination might provide greater antiinflammatory effects than either drug alone, and the purpose of this study was to compare the effects of treatment with budesonide and montelukast, alone or in combination, on outcome variables after allergen inhalation. Ten subjects with asthma with dual responses after allergen inhalation were included in this randomized, double-blind, crossover study. Outcomes included early and late asthmatic responses, and changes in airway responsiveness and sputum eosinophilia, measured before and after challenge. Treatment with montelukast attenuated the maximal early asthmatic response compared with placebo (p < 0.001) and budesonide (p = 0.002). Both budesonide and montelukast, alone and in combination, attenuated the maximal late asthmatic response compared with placebo (p < 0.01). Budesonide and montelukast, alone and in combination, afforded protection against allergen-induced airway hyperresponsiveness (p < 0.05), although the treatment effect of budesonide was greater than that of montelukast (p < 0.05). Treatment with budesonide and montelukast, alone and in combination, also attenuated allergen-induced sputum eosinophilia. Thus, montelukast and budesonide attenuated allergen-induced asthmatic responses, airway hyperresponsiveness, and sputum eosinophilia, although combination treatment did not provide greater antiinflammatory effects than either drug alone.
Targeting TR4 nuclear receptor suppresses prostate cancer invasion via reduction of infiltrating macrophages with alteration of the TIMP-1/MMP2/MMP9 signals
Authors: Xianfan Ding, Dong-Rong Yang, Liqun Xia, Bide Chen, Shicheng Yu, Yuanjie Niu, Mingchao Wang, Gonghui Li, Chawnshang Chang
Journal: Molecular Cancer (2015)

TR4 nuclear receptor 4 (TR4) plays an important role in macrophages-associated foam cell formation of cardiovascular diseases and infiltrating macrophages are critical for prostate cancer (PCa) progression. However, the linkage of macrophages and TR4 and their impacts on PCa metastasis remains unclear. Knocking-down TR4 in human PCa cells (C4-2, CWR22Rv1), but not in human macrophages cells (THP-1), led to suppress the macrophages infiltration to PCa cells. The consequences of such suppression of the recruitment of macrophages toward PCa then resulted in suppressing the PCa cell invasion. Mechanism dissection found that knocking-down TR4 in PCa cells suppressed metastasis-related genes including MMP2, with induction of TIMP-1. Interruption assays using TIMP-1 neutralizing antibody could then reverse TR4-macrophage-mediated PCa invasion. IHC staining showed higher TR4 level, more macrophage infiltration, lower TIMP-1 and stronger MMP2/MMP9 in tumor tissues of the Gleason score 5 + 4 patients compared with the Gleason score 3 + 3 patients. Targeting TR4 in prostate tumor microenvironment might represent a potential new therapeutic approach to better battle PCa metastasis.
Intercellular Adhesion Molecule-1 Deficiency Is Protective against Nephropathy in Type 2 Diabetic db/db Mice
Authors: Fiona Y. Chow, David J. Nikolic-Paterson, Elyce Ozols, Robert C. Atkins, Gregory H. Tesch
Journal: Journal of the American Society of Nephrology (2005)

Diabetic nephropathy is a leading cause of end-stage renal failure and is a growing concern given the increasing incidence of type 2 diabetes. Diabetic nephropathy is associated with progressive kidney macrophage accumulation and experimental studies suggest that intercellular adhesion molecule (ICAM)-1 facilitates kidney macrophage recruitment during type 1 diabetes. To ascertain the importance of ICAM-1 in promoting type 2 diabetic nephropathy, the development of renal injury in ICAM-1 intact and deficient db/db mice with equivalent hyperglycemia and obesity between ages 2 and 8 mo was examined and compared with results with normal db/+ mice. Increases in albuminuria (11-fold), glomerular leukocytes (10-fold), and interstitial leukocytes (three-fold) consisting of predominantly CD68+ macrophages were identified at 8 mo in diabetic db/db mice compared with nondiabetic db/+ mice. In comparison to db/db mice, ICAM-1-deficient db/db mice had marked reductions in albuminuria at 6 mo (77% downward arrow) and 8 mo (85% downward arrow). There was also a significant decrease in glomerular (63% downward arrow) and interstitial (83% downward arrow) leukocytes in ICAM-1-deficient db/db mice, which were associated with reduced glomerular hypertrophy and hypercellularity and tubular damage. The development of renal fibrosis (expression of TGF-beta1, collagen IV, and interstitial alpha-smooth muscle actin) was also strikingly attenuated in the ICAM-1-deficient db/db mice. Additional in vitro studies showed that macrophage activation by high glucose or advanced glycation end products could promote ICAM-1 expression on tubular cells and macrophage production of active TGF-beta1. Thus, ICAM-1 appears to be a critical promoter of nephropathy in mouse type 2 diabetes by facilitating kidney macrophage recruitment.
Dr. T. Khosla, MSc, PhD
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1985)

DISCUSSIONHeight is highly correlated with various linear body dimen- sions and body weight with various breadths, girths and with skinfold measurements.Age, height and weight are good determinants of a number of aspects of physique (Khosla and McBroom, 1985).Women short distance run- ners are younger, taller and heavier for their height than medium and long distance runners.This trend was similar to that observed in men (Khosla, 1978).