tbuckley/cabot-search huggingface dataset:
Peptic Ulcer and Pulmonary Disease in Coal Miners
Authors: Edward M. Schneider, Robert E. Hyatt
Journal: JAMA (1963)

Opinions differ as to whether there is an interrelationship between peptic ulceration and pulmonary disease. In 168 miners occupationally exposed to soft-coal dust, a prevalence of peptic ulcer of 18.5% was found. Key features of the investigation were fluoroscopic and film evaluation of the upper gastrointestinal tract, roentgenogram of the chest, and studies of pulmonary function. No greater prevalence was noted among those with abnormal physical or functional pulmonary findings than among normal subjects. No relationship was indicated between a history of cigarette smoking or alcohol consumption and ulcer. It is probable that the "high" occurrence of ulcer was related to the fact that these men were actively examined for upper gastrointestinal disease, but some other factor, such as occupational stress, may have contributed to these findings.
Fluorimetric analysis of paeonol in Chinese herbal medicine Cynanchi Paniculati Radix by aluminum ion-sensitized fluorescence
Authors: Fei Yang, Cuige Liu, Yongju Wei
Journal: Acta Pharmaceutica Sinica B (2012)

A novel fluorimetric method for determination of paeonol, an active component of Chinese herbal medicine, is proposed. The method is based on the reaction of paeonol with aluminum ion in pH 4.4 HAc-NaAc buffer to form a fluorescent Al(III)-paeonol complex. The maximum excitation wavelength and emission wavelength of the complex were 296 nm and 455 nm, respectively. The fluorescence quantum yield of the complex was determined to be 0.053 at an excitation wavelength of 296 nm. A linear calibration curve covered the concentration range 0.017–1.2 μg/mL. The method has been applied to the analysis of paeonol in medicinal crop Cynanchi Paniculati Radix (Xuchangqing), and the results demonstrated that this method can be used for quality evaluation of crude drug Xuchangqing.
Receptor-independent low density lipoprotein transport in the rat in vivo. Quantitation, characterization, and metabolic consequences.
Authors: D K Spady, S D Turley, J M Dietschy
Journal: Journal of Clinical Investigation (1985)

Receptor-independent low density lipoprotein (LDL) transport plays a critical role in the regulation of plasma cholesterol levels; hence, these studies were done to characterize this process in the tissues of the rat. High rates of receptor-independent clearance were found in the spleen, but other organs, like liver, gastrointestinal tract, and endocrine glands manifested lower clearance rates that varied from 3 to 9 microliter/h per g, while the rates in nervous tissue, muscle, and adipose tissue were less than 1 microliter/h per g. Receptor-dependent uptake was much higher in liver (85 microliter/h per g) and adrenal gland (219 microliter/h per g), but was also low in most other tissues. At normal plasma LDL concentrations, 67% of the receptor-dependent transport in the whole animal was accounted for by LDL uptake in the liver. In contrast, the receptor-independent uptake found in the whole animal took place in many organs, including skeletal muscle (20%), liver (16%), small bowel (15%), skin (10%), and spleen (7%). Furthermore, in liver, the rate of cholesterol synthesis could be varied 11-fold, yet the rate of receptor-independent LDL clearance remained constant at approximately 8 microliter/h per g. When the circulating levels of LDL were systematically increased, receptor-independent LDL clearance also remained constant, so that hepatic LDL-cholesterol uptake by this mechanism increased linearly, from 1 to 20 micrograms/h per g, as the plasma LDL-cholesterol level was increased from 10 to 250 mg/dl. Finally, when equal amounts of LDL-cholesterol were delivered into the liver by either the receptor-dependent or receptor-independent mechanism, there was significant suppression of cholesterol synthesis and an increase in cholesteryl esters. Thus, in any situation in which receptor-dependent LDL degradation is lost, cholesterol balance in the whole animal and across individual organs is maintained by receptor-independent mechanisms, although when the new steady state is achieved, circulating levels of LDL must necessarily be very much increased.
Effects of School Closure on Incidence of Pandemic Influenza in Alberta, Canada
Authors: David J.D. Earn
Journal: Annals of Internal Medicine (2012)

Background: Control of pandemic influenza by social-distancing measures, such as school closures, is a controversial aspect of pandemic planning. However, investigations of the extent to which these measures actually affect the progression of a pandemic have been limited. Objective: To examine correlations between the incidence of pandemic H1N1 (pH1N1) influenza in Alberta, Canada, in 2009 and school closures or weather changes, and to estimate the effects of school closures and weather changes on pH1N1 transmission. Design: Mathematical transmission models were fit to data that compared the pattern of confirmed pH1N1 cases with the school calendar and weather patterns. Setting: Alberta, Canada, from 19 April 2009 to 2 January 2010. Data Sources: 2009 virologic test results, 2006 census data, 2009 daily temperature and humidity data, and 2009 school calendars. Measurements: Age-specific daily counts of positive results for pH1N1 from the complete database of 35 510 specimens submitted to the Alberta Provincial Laboratory for Public Health for virologic testing from 19 April 2009 to 2 January 2010. Results: The ending and restarting of school terms had a major effect in attenuating the first wave and starting the second wave of pandemic influenza cases. Mathematical models suggested that school closure reduced transmission among school-age children by more than 50% and that this was a key factor in interrupting transmission. The models also indicated that seasonal changes in weather had a significant effect on the temporal pattern of the epidemic. Limitations: Data probably represent a small sample of all viral infections. The mathematical models make simplifying assumptions in order to make simulations and analysis feasible. Conclusion: Analysis of data from unrestricted virologic testing during an influenza pandemic provides compelling evidence that closing schools can have dramatic effects on transmission of pandemic influenza. School closure seems to be an effective strategy for slowing the spread of pandemic influenza in countries with social contact networks similar to those in Canada. Primary Funding Source: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Public Health Agency of Canada.
Low frequency of bcl-2 rearrangement in HCV-associated non-Hodgkin's lymphoma tissue
Authors: Massimo Libra, Valli De Re, Salvatore De Vita, Daniela Gasparotto, Annunziata Gloghini, Maurizio Rupolo, Massimo Degan, Alessandra Marzotto, Franca Stivala, Antonino Carbone, Mauro Boiocchi
Journal: Leukemia (2003)
Reduction of advanced liver fibrosis by short-term targeted delivery of an angiotensin receptor blocker to hepatic stellate cells in rats
Authors: Montserrat Moreno, Teresa Gonzalo, Robbert J. Kok, Pau Sancho-Bru, Marike van Beuge, Josine Swart, Jai Prakash, Kai Temming, Constantino Fondevila, Leonie Beljaars, Marie Lacombe, Paul van der Hoeven, Vicente Arroyo, Klaas Poelstra, David A. Brenner, Pere Ginès, Ramón Bataller
Journal: Hepatology (2009)

There is no effective therapy for advanced liver fibrosis. Angiotensin type 1 (AT1) receptor blockers attenuate liver fibrogenesis, yet their efficacy in reversing advanced fibrosis is unknown. We investigated whether the specific delivery of an AT1 receptor blocker to activated hepatic stellate cells (HSCs) reduces established liver fibrosis. We used a platinum-based linker to develop a conjugate of the AT1 receptor blocker losartan and the HSC-selective drug carrier mannose-6-phosphate modified human serum albumin (losartan-M6PHSA). An average of seven losartan molecules were successfully coupled to M6PHSA. Rats with advanced liver fibrosis due to prolonged bile duct ligation or carbon tetrachloride administration were treated with daily doses of saline, losartan-M6PHSA, M6PHSA or oral losartan during 3 days. Computer-based morphometric quantification of inflammatory cells (CD43), myofibroblasts (smooth muscle α-actin [α-SMA]) and collagen deposition (Sirius red and hydroxyproline content) were measured. Hepatic expression of procollagen α2(I) and genes involved in fibrogenesis was assessed by quantitative polymerase chain reaction. Losartan-M6PHSA accumulated in the fibrotic livers and colocalized with HSCs, as assessed by immunostaining of anti-HSA and anti–α-SMA. Losartan-M6PHSA, but not oral losartan, reduced collagen deposition, accumulation of myofibroblasts, inflammation and procollagen α2(I) gene expression. Losartan-M6PHSA did not affect metalloproteinase type 2 and 9 activity and did not cause apoptosis of activated HSCs. Conclusion: Short-term treatment with HSC-targeted losartan markedly reduces advanced liver fibrosis. This approach may provide a novel means to treat chronic liver diseases. (Hepatology 2010.)
Is hepatitis B infection an indication for orthotopic liver transplantation? The answer, my friend, is Blowin' in the wind Samuel D, Muller R, Alexander G, Fassati L, Ducot B, Benhamou J-P, Bismuth H and the Investigators of the European Concerted Action on Viral Hepatitis. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993;329:1842–1847
Authors: F Villamil
Journal: Hepatology (1994)
Leukotriene B4, an activation product of mast cells, is a chemoattractant for their progenitors
Authors: Charlotte L. Weller, Sarah J. Collington, Jeremy K. Brown, Hugh R.P. Miller, Adam Al-Kashi, Peter Clark, Peter J. Jose, Adele Hartnell, Timothy J. Williams
Journal: The Journal of Experimental Medicine (2005)

Mast cells are tissue-resident cells with important functions in allergy and inflammation. Pluripotential hematopoietic stem cells in the bone marrow give rise to committed mast cell progenitors that transit via the blood to tissues throughout the body, where they mature. Knowledge is limited about the factors that release mast cell progenitors from the bone marrow or recruit them to remote tissues. Mouse femoral bone marrow cells were cultured with IL-3 for 2 wk and a range of chemotactic agents were tested on the c-kit+ population. Cells were remarkably refractory and no chemotaxis was induced by any chemokines tested. However, supernatants from activated mature mast cells induced pronounced chemotaxis, with the active principle identified as leukotriene (LT) B4. Other activation products were inactive. LTB4 was highly chemotactic for 2-wk-old cells, but not mature cells, correlating with a loss of mRNA for the LTB4 receptor, BLT1. Immature cells also accumulated in vivo in response to intradermally injected LTB4. Furthermore, LTB4 was highly potent in attracting mast cell progenitors from freshly isolated bone marrow cell suspensions. Finally, LTB4 was a potent chemoattractant for human cord blood–derived immature, but not mature, mast cells. These results suggest an autocrine role for LTB4 in regulating tissue mast cell numbers.
Abstract 2828: Characterization of protein substrates of PSA: effect of PSA stimulating peptides
Authors: Johanna Mattsson, Can Hekim, Ale Närvänen, Magnus Jonsson, Johan Malm, Ulf-Håkan Stenman, Hannu Koistinen
Journal: Cancer Research (2012)

Abstract Increased proteolytic activity is associated with cancer, where proteases play a major role in tumor spread and formation of metastases. However, proteases may also inhibit tumor growth. The prostate produces several proteases, the most abundant one being prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3). The role of PSA in the prostate, and in particular in prostate cancer, is not well known. However, several functions have been proposed, most of which are based on the protein substrates, which PSA cleaves in vitro. These include both tumor growth promoting and inhibiting activities, e.g., antiangiogenic activity of PSA. We have previously used phage display technology to develop peptides, the synthetic analogs of which stimulate the activity of PSA. These peptides are useful for studying the significance of PSA-activity and potentially for prostate cancer treatment. We analyzed the cleavage of different protein substrates of PSA and found that physiological substrates, semenogelin-1 and −2, are cleaved much more efficiently than other substrates, such as IGFBP-3, fibronectin and galectin-3. The peptides increased the proteolytic activity of PSA towards these protein substrates, but the extent of stimulation and the relative efficiency of peptides were different than with small peptide substrates. We conclude that the peptides can be used to stimulate the activity of PSA towards natural protein substrates. Thus, they may be potential lead molecules for drug development. As most of the studied protein substrates are cleaved with very low efficiency, their relevance as PSA substrates is questionable, especially as prostate produces several other highly active proteases, including several kallikreins and trypsin. As compared to other substrates, semenogelins are very efficiently cleaved by PSA, highlighting the substrate specificity of PSA. 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 2828. doi:1538-7445.AM2012-2828
Accumulation of Polychlorinated Biphenyls in Ecosystems
Authors: Robert W. Risebrough, Brock De Lappe
Journal: Environmental Health Perspectives (1972)

Chlorinated biphenyl compounds have become ubiquitous components of the global environment.They were first detected in species of Swedish wildlife (1, 2, 3) and were subsequently found in seals from the North Atlantic (4), in a bird of prey in Great Britain (5), in fish and birds from the Netherlands (6), and in both terrestrial and marine species of wildlife in western North Amer- ica (7).In the Arctic they are present in the polar bears (Thalarctos maritimus) of Hudson Bay ( 8) and in fresh-water fish of tundra lakes that receive no pollutants save those that are present in the fallout from the atmosphere (9).In the Southern Hemisphere, they were found in all bird species analyzed that inhabit waters north of the Ant- arctic Convergence but could not be detected in a number of samples of wildlife resident in Antarctica south of the Convergence (10).In this paper some of the available residue data are summarized within the framework of a preliminary formulation of a mass balance equation for the global distribution of polychlorinated bi- phenyls.Commercial manufacture of PCBs was begun in the United States in 1929 (11), and environ- mental input may be assumed to have begun at that time.Current levels of PCBs in major sinks, such as the oceans, are evidently a function of many parameters, including the proportion of the total amount of PCBs produced over the past forty years that has so far entered the environment, pathways of dissemination, rates of degra- dation -to other compounds, partition coefficients between water and lipid fractions of organisms
Drug-induced liver injury: Summary of a single topic clinical research conference
Authors: Paul B. Watkins, Leonard B. Seeff
Journal: Hepatology (2006)

Idiosyncratic drug induced liver injury (DILI) remains poorly understood. It is assumed that the affected individuals possess a rare combination of genetic and non genetic factors that, if identified, would greatly improve understanding of the underlying mechanisms. This single topic conference brought together basic scientists, translational investigators, and clinicians with an interest in DILI. The goal was to define high priority areas of investigation that will soon be made possible by The Drug-Induced Liver Injury Network (DILIN). Since 2004 DILIN has been collecting clinical data, genomic DNA and some tissues from patients who have experienced bone fide DILI. The presentations spanned many different areas of DILI, and included novel data concerning mechanisms of hepatotoxicity, new "omics" approaches, and the challenges of improving causation assessment.
A 10-Year Experience with Universal Health Insurance in Taiwan: Measuring Changes in Health and Health Disparity
Authors: Chi Pang Wen, Shan Pou Tsai, Wen-Shen Isabella Chung
Journal: Annals of Internal Medicine (2008)

Universal national health insurance, financed jointly by payroll taxes, subsidies, and individual premiums, commenced in Taiwan in 1995. Coverage expanded from 57% of the population (before the introduction of national health insurance) to 98%.To assess the role of national health insurance in improving life expectancy and reducing health disparities in Taiwan.A before-and-after comparison of the decade before the introduction of national health insurance (1982-1984 to 1992-1994) with the decade after (1992-1994 to 2002-2004).Taiwan.All townships (n = 358) in Taiwan were ranked according to overall mortality rates before the introduction of national health insurance and then ranked into 10 health class groups in descending order of health (groups 1 [healthiest] to 10 [least healthy]).Health improvement (change in life expectancy after the introduction of national health insurance) and health disparity (reduction in the difference in life expectancy between the highest- and lowest-ranked health class groups).After the introduction of national health insurance, life expectancy increased more in health class groups that had higher mortality rates before the introduction of national health insurance and health disparity narrowed, reversing an earlier trend toward widening disparity. The major contributors to the reduction in disparity were relatively larger reductions in death from cardiovascular diseases, ill-defined conditions, infectious diseases, and accidents in the lower-ranked health class groups. However, death from cancer increased more in the lower-ranked health class groups. Utilization of medical services increased, whereas cost remained at 5% to 6% of the gross domestic product. The per capita average annual number of visits to the physician's office was 14.The interpretation of comparisons before and after the introduction of national health insurance assumes that the changes were entirely due to the effect of national health insurance rather than secular trends.Life expectancy after the introduction of national health insurance improved more for lower-ranked health classes, resulting in narrowed health disparity. The magnitude of the reduced disparity was small compared with the size of the remaining gaps. Relying on universal insurance alone to eliminate health disparity does not seem realistic. To further reduce health disparity, universal insurance programs should incorporate primary prevention, focusing on lifestyle risk reductions.
The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO
Authors: Fu-Sheng Chou, Andrea Griesinger, Mark Wunderlich, Shan Lin, Kevin A. Link, Mahesh Shrestha, Susumu Goyama, Benjamin Mizukawa, Shuhong Shen, Guido Marcucci, James C. Mulloy
Journal: Blood (2012)
B lymphocytes from X-linked agammaglobulinemia. Delayed expression of light chain and demonstration of Lyonization in carriers.
Authors: J Schwaber, J Payne, R Chen
Journal: Journal of Clinical Investigation (1988)

We report an unusual phenotype of B cells in a patient with X-linked agammaglobulinemia (XLA), and cellular evidence for Lyonization of B cells from his mother and sister. The patient has a failure of B cell maturation at the stage of early B lymphocytes, associated with production of D(mu delta) H chain. The phenotype of his B cells includes: (a) limitation to expression of the mu and delta H chain isotypes, (b) production of mu and delta H chains of reduced size and (c) delayed expression of L chain. Peripheral blood and B cell lines from the patient's mother and sister include 50% cells that express H chain without L chain. B cell lines from the mother and sister produce full-length mu and gamma H chains and truncated mu and delta chains corresponding to the H chains produced by the patient's B cells. Clones with normal and XLA phenotype have been isolated from B cell lines derived from the patient's mother. We conclude that the dimorphism of mother's and sister's B cells results from Lyonization, implying that the gene defect in XLA is intrinsic to B lymphocytes.
Metal toxicity in the central nervous system.
Authors: T W Clarkson
Journal: Environmental Health Perspectives (1987)

The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.