tbuckley/cabot-search huggingface dataset:
Comparative Effects of Thyroxin Analogues as Hypocholesteremic Agents
Authors: MAURICE M. BEST, CHARLES H. DUNCAN
Journal: Circulation (1961)

L-thyroxin and four thyroxin analogues were administered to a group of hypercholesteremic euthyroid patients, the majority with arteriosclerotic heart disease, and the effects on serum total cholesterol compared. L-thyroxin and each of the analogues studied, tetraiodothyroformic acid, dimethyldiiodothyroformic acid, D-thyroxin and D-triiodothyronine, were given to four to nine patients for periods up to 10 months. At the doses employed each of the analogues resulted in a reduction in the mean level of serum cholesterol without obvious evidence of hypermetabolism or aggravation of angina pectoris or congestive heart failure. The reduced level of serum cholesterol was sustained throughout the period of hormone administration, and upon the substitution of a placebo returned to the pretreatment range. L-thyroxin, at the dose employed, also effected a modest sustained reduction in serum cholesterol but both patients with angina included in this group experienced an increase in severity of symptoms. Except for four patients who developed acneiform dermatitis, salivary gland swelling, or gastrointestinal symptoms during the administration of the formic acid analogues, no toxic or undesirable effects were observed from any of the analogues. To evaluate better the general metabolic effects of the analogues each was administered to three or more of a group of seven myxedematous patients for periods of 6 to 12 months. Given in sufficient amount all were observed to increase basal metabolic rate and to maintain a clinically euthyroid state. From these observations, it is concluded that the D-isomers of thyroxin and triiodothyronine, while not without general metabolic effects, are tolerated by the majority of euthyroid patients with coronary atherosclerosis in amounts sufficient to maintain a reduced serum cholesterol level.
The effect of patient technique and training on the accuracy of self-recorded peak expiratory flow
Authors: P.F.G. Gannon, J Belcher, C.F.a Pantin, P.S. Burge
Journal: European Respiratory Journal (1999)

The aim of the study was to investigate the difference between encouraged self-recorded peak expiratory flow (PEF) with unobserved readings and to investigate any long-term changes in PEF self-recording. Patients were trained in the PEF technique and asked to keep 2-hourly PEF records until the next clinic visit. The patients PEF were then rechecked at the second clinic visit by a series of two unobserved, an observed and an encouraged PEF measurement. A subgroup of patients were reassessed at a third clinic visit. Forty-one patients produced serial PEF readings. Significant differences between unobserved and encouraged PEF readings were detected; there was a mean decrement of 21 L x min(-1) and limits of agreements suggested that the decrement could be as high as 60 L x min(-1). Visual and statistical analysis of the serial PEF provided showed a consistent deterioration in PEF over the record in 54% and 39% of cases, respectively. No significant differences were found in the subgroup who attended a third clinic visit. The results suggest that significant inaccuracies in unobserved peak expiratory flow readings can occur between clinic visits and this can be reflected as a consistent deterioration in some. This should be kept in mind when interpreting self-recorded peak expiratory flow measurements. Re-evaluation at the third visit following the retraining effect of the second visit on peak expiratory flow technique appears to reduce inaccuracies. It is believed that peak expiratory flow technique should be reevaluated at each clinic visit.
US Supreme Court says smokers can sue over "light" cigarettes
Authors: J. Hopkins Tanne
Journal: BMJ (2008)

The US Supreme Court ruled on 15 December that smokers can sue tobacco companies under state laws against deceptive advertising practices that suggested that “light” cigarettes were safer than ordinary ones.

The ruling opens the way for a new round of class action lawsuits against tobacco companies in state courts. About 40 cases are pending in 22 states.

The three smokers in the state of Maine who began the lawsuit did not argue that cigarettes were harmful. They claimed that Altria Group, the parent company of the cigarette maker Philip Morris, deceptively labelled its best selling …
Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
Authors: Michelle Goritzka, Spyridon Makris, Fahima Kausar, Lydia R. Durant, Catherine Pereira, Yutaro Kumagai, Fiona J. Culley, Matthias Mack, Shizuo Akira, Cecilia Johansson
Journal: The Journal of Experimental Medicine (2015)

Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)-coupled retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN-dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN-mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation.
Underdiagnosis of allergic rhinitis in underserved children
Authors: Tammy S. Jacobs, Erick Forno, John M. Brehm, Edna Acosta-Pérez, Yueh-Ying Han, Joshua Blatter, Angel Colón-Semidey, María Alvarez, Glorisa Canino, Juan C. Celedón
Journal: Journal of Allergy and Clinical Immunology (2014)
Robot-assisted Partial Nephrectomy in Patients with Baseline Chronic Kidney Disease: A Multi-institutional Propensity Score–Matched Analysis
Authors: Ramesh K Kumar, Jesse D Sammon, Bartosz F Kaczmarek, Ali Khalifeh, Michael A Gorin, Ganesh Sivarajan, Youssef S Tanagho, Sam B Bhayani, Michael D Stifelman, Mohamad E Allaf, Jihad H Kaouk, Craig G Rogers
Journal: European Urology (2013)
A Case of Chronic Hyperplastic Endometritis
Authors: G. E. Herman
Journal: BMJ (1880)

These are much below the real number; and I may here mention that, when attending, some months ago, a married woman who died from tertiary syphilis, her friends were very importunate for me to suppress the real cause of death, on the grounds that it might lead to forfeiture of the burial-club money.I certified the death as due to tertiary syphilis; but now that this word is so familiar to the public, or even its abbreviation (syp.), it would be well if practitioners could, by some modification of our death-registration system, be spared the in- vidious choice of stating the cruel truth, or of suppressing it at the risk of giving an incorrect certificate.My own experience is, that the cases of constitutional syphilis which come under my care in the hospital are just as severe as those I re- member to have seen when I attended the hospital twenty years ago as a stu(lent.Among the patients at the Seamen's Dispensary, very severe forms of primary and secondary syphilis corme before us, being much aggravated by the dirty habits of merchant seamen, want of facilities for cleanliness on board ship, and neglect.In private prac- tice, indurated sores and very severe constitutional symptoms are seen by me daily, and I have observed that, besides merchant-seamen, laboiurers of all kinds, carters, cabmen, and others, suffer very severely from syphilis.It is also very prevalent among mere lads of all classes, some of whom suffer most severely in the attempts to conceal the matter from their parents.It appears to me only what we might expect, that syphilis should prevail to a great extent in our large seaports.That it did do so in Plymouth and Devonport, Portsmouth, Cork, and Queenstown, years ago, is clear; and it is equally clear that, in those ports, it has been considerably reduced among the common prostitutes, the sailors, soldiers, and civil population.It still prevails largely in London, Liverpool, Dublin, Belfast, Kingstown, Leith, Hull, and other ports, and there is no proof of any reduction.As throwing some light upon the reason of its prevalence and severity in Liverpool, I hope in another paper to give some information respecting the number and condition of prosti- tutes in this town.
Environmental Cadmium and Lead Exposures and Hearing Loss in U.S. Adults: The National Health and Nutrition Examination Survey, 1999 to 2004
Authors: Yoon-Hyeong Choi, Howard Hu, Bhramar Mukherjee, Josef Miller, Sung Kyun Park
Journal: Environmental Health Perspectives (2012)

Although cadmium and lead are known risk factors for hearing loss in animal models, few epidemiologic studies have been conducted on their associations with hearing ability in the general population.We investigated the associations between blood cadmium and lead exposure and hearing loss in the U.S. general population while controlling for noise and other major risk factors contributing to hearing loss.We analyzed data from 3,698 U.S. adults 20-69 years of age who had been randomly assigned to the National Health and Nutrition Examination Survey (NHANES) 1999-2004 Audiometry Examination Component. Pure-tone averages (PTA) of hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz were computed, and hearing loss was defined as a PTA > 25 dB in either ear.The weighted geometric means of blood cadmium and lead were 0.40 [95% confidence interval (CI): 0.39. 0.42] µg/L and 1.54 (95% CI: 1.49, 1.60) µg/dL, respectively. After adjusting for sociodemographic and clinical risk factors and exposure to occupational and nonoccupational noise, the highest (vs. lowest) quintiles of cadmium and lead were associated with 13.8% (95% CI: 4.6%, 23.8%) and 18.6% (95% CI: 7.4%, 31.1%) increases in PTA, respectively (p-trends < 0.05).Our results suggest that low-level exposure to cadmium and lead found in the general U.S. population may be important risk factors for hearing loss. The findings support efforts to reduce environmental cadmium and lead exposures.
Brain tumors in children with neurofibromatosis: Additional neuropsychological morbidity?
Authors: Anne E. De Winter, Bartlett D. Moore, John M. Slopis, Joann L. Ater, Donna R. Copeland
Journal: Neuro-Oncology (1999)

Neurofibromatosis type 1 is a common autosomal dominant genetic disorder associated with numerous physical anomalies and an increased incidence of neuropsychological impairment. Tumors of the CNS occur in approximately 15% of children with neurofibromatosis, presenting additional risk for cognitive impairment. This study examines the impact of an additional diagnosis of brain tumor on the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological tests was administered to 149 children with neurofibromatosis. Thirty-six of these children had a codiagnosis of brain tumor. A subset of 36 children with neurofibromatosis alone was matched with the group of children diagnosed with neurofibromatosis and brain tumor. Although mean scores of the neurofibromatosis plus brain tumor group were, in general, lower than those of the neurofibromatosis alone group, these differences were not statistically significant. Children in the neurofibromatosis plus brain tumor group who received cranial irradiation (n = 9) demonstrated weaker academic abilities than did children with brain tumor who had not received that treatment. These results suggest that neurofibromatosis is associated with impairments in cognitive functioning, but the severity of the problems is not significantly exacerbated by the codiagnosis of a brain tumor unless treatment includes cranial irradiation.
Is Pathologic Complete Response a Valid Surrogate Parameter of Treatment Efficacy in HER2 Positive Breast Cancer Patients Undergoing Primary Chemotherapy Plus Trastuzamab?
Authors: Alfredo Berruti, Daniele Generali, Maria Pia Brizzi, Mara Ardine, Luigi Dogliotti, Alberto Bottini
Journal: Journal of Clinical Oncology (2005)
MHC-Resident Variation Affects Risks After Unrelated Donor Hematopoietic Cell Transplantation
Authors: Effie W. Petersdorf, Mari Malkki, Theodore A. Gooley, Stephen R. Spellman, Michael D. Haagenson, Mary M. Horowitz, Tao Wang
Journal: Science Translational Medicine (2012)

The success of HLA-matched unrelated donor hematopoietic cell transplantation depends on non-HLA MHC region genetic variation.
Novel <b> <i>KCNJ2</i> </b> Mutation in Familial Periodic Paralysis With Ventricular Dysrhythmia
Authors: Tomohiko Ai, Yuichiro Fujiwara, Keiko Tsuji, Hideo Otani, Shozo Nakano, Yoshihiro Kubo, Minoru Horie
Journal: Circulation (2002)

Background — Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K + channels (Kir2.1), produce Andersen’s syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results — In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2 , Thr192Ala (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions — T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.
HYDRALAZINE-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS: INFLUENCE OF HLA-DR AND SEX ON SUSCEPTIBILITY
Authors: J.R Batchelor, K.I Welsh, R Mansilla Tinoco, C.T Dollery, G.R.V Hughes, R Bernstein, P Ryan, P.F Naish, G.M Aber, R.F Bing, G.I Russell
Journal: The Lancet (1980)
Cigarette smoke–induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents
Authors: Eunice Andrè, Barbara Campi, Serena Materazzi, Marcello Trevisani, Silvia Amadesi, Daniela Massi, Christophe Creminon, Natalya Vaksman, Romina Nassini, Maurizio Civelli, Pier Giovanni Baraldi, Daniel P. Poole, Nigel W. Bunnett, Pierangelo Geppetti, Riccardo Patacchini
Journal: Journal of Clinical Investigation (2008)

Cigarette smoke (CS) inhalation causes an early inflammatory response in rodent airways by stimulating capsaicin-sensitive sensory neurons that express transient receptor potential cation channel, subfamily V, member 1 (TRPV1) through an unknown mechanism that does not involve TRPV1. We hypothesized that 2 alpha,beta-unsaturated aldehydes present in CS, crotonaldehyde and acrolein, induce neurogenic inflammation by stimulating TRPA1, an excitatory ion channel coexpressed with TRPV1 on capsaicin-sensitive nociceptors. We found that CS aqueous extract (CSE), crotonaldehyde, and acrolein mobilized Ca2+ in cultured guinea pig jugular ganglia neurons and promoted contraction of isolated guinea pig bronchi. These responses were abolished by a TRPA1-selective antagonist and by the aldehyde scavenger glutathione but not by the TRPV1 antagonist capsazepine or by ROS scavengers. Treatment with CSE or aldehydes increased Ca2+ influx in TRPA1-transfected cells, but not in control HEK293 cells, and promoted neuropeptide release from isolated guinea pig airway tissue. Furthermore, the effect of CSE and aldehydes on Ca2+ influx in dorsal root ganglion neurons was abolished in TRPA1-deficient mice. These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases.
MEDIATION OF IMMUNOLOGIC DISCHARGE OF LYSOSOMAL ENZYMES FROM HUMAN NEUTROPHILS BY GUANOSINE 3',5'-MONOPHOSPHATE
Authors: L. J. Ignarro, W. J. George
Journal: The Journal of Experimental Medicine (1974)

The purpose of this investigation was to elucidate the relationship of cyclic GMP and calcium to the immunologic discharge of lysosomal enzymes from purified human neutrophils. Contact of neutrophils with a variety of immunologic stimuli, including zymosan particles treated with either normal or rheumatoid arthritic (RA) serum, heat-aggregated (agg) IgG, particulate and immobilized agg IgG each treated with RA serum, and zymosan-treated serum, provoked the discharge of beta-glucuronidase, but not cytoplasmic lactate dehydrogenase, and stimulated the accumulation of cyclic GMP. Both enzyme release and elevation of cyclic GMP levels required the presence of extracellular calcium as neither cellular event proceeded in its absence. Cholinergic enhancement of the immunologic secretion of beta-glucuronidase from neutrophils by acetylcholine was associated with a concomitant accumulation of cyclic GMP. These actions of acetylcholine on neutrophils did not proceed in the absence of extracellular calcium. Whereas the concentrations of cyclic GMP in neutrophils were elevated by both immune reactants and a combination of the latter and acetylcholine, cyclic AMP levels remained unaltered. Thus, cyclic GMP, but not cyclic AMP, was associated with the immunologic and pharmacologic discharge of lysosomal enzymes from neutrophils. Contrariwise, cyclic AMP, but not cyclic GMP, was associated with inhibition of lysosomal enzyme release. For example, dibutyryl cyclic AMP and epinephrine inhibited the release of beta-glucuronidase from neutrophils that was elicited by each of the immune reactants tested. Moreover, cyclic AMP levels in the cells were elevated markedly in every instance that enzyme discharge was inhibited by epinephrine. Epinephrine did not alter the neutrophil concentrations of cyclic GMP at times when those of cyclic AMP were elevated. The data in this report constitute partial evidence that the immunologic discharge of lysosomal enzymes from human neutrophils is mediated or signaled by intracellular cyclic GMP and that calcium is linked to this stimulation of enzyme secretion.
High proportion of mutant K-ras gene in pancreatic juice of patients with pancreatic cystic lesions
Authors: K Tateishi, M Tada, M Yamagata, H Isayama, Y Komatsu, T Kawabe, Y Shiratori, M Omata
Journal: Gut (1999)

It was recently reported that the quantitative analysis of mutant K-ras gene in pancreatic juice could be useful for the diagnosis of pancreatic cancer. This methodology was applied to patients with pancreatic cystic lesions.DNA was extracted from pancreatic juice collected at the time of endoscopy with injection of secretin. The ratio of the K-ras mutant allele to the wild-type allele was measured by two methods to detect and semiquantify mutant K-ras gene: polymerase chain reaction/preferential homoduplex formation assay and enriched polymerase chain reaction/enzyme linked mini-sequence assay.A high frequency of K-ras mutation was detected (more than 2% of all K-ras genes) in six of 14 patients (43%) with pancreatic cysts. This frequency was similar to those detected in patients with pancreatic adenocarcinoma and in intraductal papillary neoplasms of the pancreas. In contrast, the frequency of mutation was low (less than 2%) in patients without either pancreatic cysts or pancreatic neoplasms.K-ras gene mutation may be derived from duct cells in the pancreas with a high potential for tumorigenesis. Therefore careful follow up of patients with a pancreatic cyst is recommended if they are found to have a high level of the mutant gene in the pancreatic juice.
Targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced by rapamycin in vitro and further improved by hyaluronan in vivo
Authors: Mingzhe Weng, Wei Gong, Mingzhe Ma, Bingfeng Chu, Yiyu Qin, Mingdi Zhang, Xueqing Lun, Grant McFadden, Peter Forsyth, Yong Yang, Zhiwei Quan
Journal: Molecular Cancer (2014)

Gallbladder carcinoma (GBC) is highly lethal, and effective treatment will require synergistic anti-tumor management. The study is aimed at investigating the oncolytic value of myxoma virus (MYXV) infection against GBC and optimizing MYXV oncolytic efficiency. We examined the permissiveness of GBC cell lines to MYXV infection and compared the effects of MYXV on cell viability among GBC and control permissive glioma cells in vitro and in vivo after MYXV + rapamycin (Rap) treatment, which is known to enhance cell permissiveness to MYXV by upregulating p-Akt levels. We also assessed MYXV + hyaluronan (HA) therapy efficiency by examinating Akt activation status, MMP-9 expression, cell viability, and collagen distribution. We further compared hydraulic conductivity, tumor area, and survival of tumor-bearing mice between the MYXV + Rap and MYXV + HA therapeutic regimens. MYXV + Rap treatment could considerably increase the oncolytic ability of MYXV against GBC cell lines in vitro but not against GBC xenografts in vivo. We found higher levels of collagen IV in GBC tumors than in glioma tumors. Diffusion analysis demonstrated that collagen IV could physically hinder MYXV intratumoral distribution. HA–CD44 interplay was found to activate the Akt signaling pathway, which increases oncolytic rates. HA was also found to enhance the MMP-9 secretion, which contributes to collagen IV degradation. Unlike MYXV + Rap, MYXV + HA therapy significantly enhanced the anti-tumor effects of MYXV in vivo and prolonged survival of GBC tumor-bearing mice. HA may optimize the oncolytic effects of MYXV on GBC via the HA–CD44 interaction which can promote viral infection and diffusion.
The role of mannose-binding lectin in pneumococcal infection
Authors: M. Isabel García-Laorden, Felipe Rodríguez de Castro, Jordi Solé-Violán, Antoni Payeras, M. Luisa Briones, Luis Borderías, Javier Aspa, José Blanquer, Olga Rajas, J. Alberto Marcos-Ramos, Estefanía Herrera-Ramos, Miguel A. García-Bello, Judith Noda, José M. Ferrer, Jordi Rello, Carlos Rodríguez-Gallego
Journal: European Respiratory Journal (2012)

The role of mannose-binding lectin (MBL) deficiency ( MBL2 ; XA/O and O/O genotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located near MBL2 , are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes. We studied 348 patients with pneumococcal community-acquired pneumonia (P-CAP) and 2,110 controls. A meta-analysis of MBL2 genotypes in susceptibility to P-CAP and to invasive pneumococcal disease (IPD) was also performed. The extent of LD of MBL2 with SFTPA1 , SFTPA2 and SFTPD was analysed. MBL2 genotypes did not associate with either P-CAP or bacteraemic P-CAP in the case–control study. The MBL-deficient O/O genotype was significantly associated with higher risk of IPD in a meta-analysis, whereas the other MBL-deficient genotype ( XA/O ) showed a trend towards a protective role. We showed the existence of LD between MBL2 and SP genes. The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD among MBL2 and SP genes must be considered in studies on the role of MBL in infectious diseases.