tbuckley/cabot-search huggingface dataset:
Quantitation and identification of organic N-chloramines formed in stomach fluid on ingestion of aqueous hypochlorite.
Authors: F E Scully, K Mazina, D Sonenshine, F Kopfler
Journal: Environmental Health Perspectives (1986)

The chemical reactions that hypochlorite undergoes in the body when chlorinated water is ingested have received very little attention. Because amino nitrogen compounds are important components of the average diet, the reactions of hypochlorite with amino compounds in the stomach were investigated. Stomach fluid was recovered from Sprague-Dawley rats that had been fasted for 48 hr and administered 4 mL deionized water. The chlorine demand of the stomach fluid was determined. An average volume-independent demand of 2.7 mg chlorine was measured. At doses below 40 mg/L chlorine reducing reactions appeared to account for reduction of all oxidizing species within 15 min as measured by the FAS-DPD titrimetric method. At least part of the chlorine demand is associated with amino acids present in the stomach fluid. Amino acids were identified and quantified in the stomach fluid by precolumn derivatization with o-phthalaldehyde and high-pressure liquid chromatography (HPLC). When stomach fluid is chlorinated to concentrations of chlorine between 200 and 1000 mg/L, organic N-chloramines are formed. After derivatization of chlorinated stomach fluid with dansyl sulfinic acid, fluorescent derivatives of chloramines were separated by HPLC. Three chloramino acid derivatives, N-chloroalanine, N-chloroglycine, and N-chlorophenylalanine, were identified by cochromatography with known standards using two chromatographic methods. The yield of a chloramine that would form in stomach fluid on administration of hypochlorite to animals was determined using tritiated piperidine and doses of 200 and 1000 mg/L chlorine. Yields of tritiated N-chloropiperidine in recovered stomach fluid were 70% and 42%, respectively, of the theoretical amount expected.
Scandals have eroded US public's confidence in drug industry
Authors: Jeanne Lenzer
Journal: BMJ (2004)

Only 13% of Americans believe that pharmaceutical companies are “generally honest and trustworthy,” putting the industry on a par with tobacco, oil, and managed care companies, a recent Harris Poll survey has found. Public confidence in drug companies has plunged harder and faster than for any other industry, the survey indicates (17 July, p 128).

The distrust appears to be spreading to respected US medical bodies and academic journals in the wake of a spate of public controversies concerning the influence of drug companies.

Guidelines for lowering cholesterol concentrations, issued on 12 July by the National Heart, Lung, and Blood Institute and the American Heart Association, sparked a furore when it was shown that all but one of the nine authors had financial ties to the manufacturers of …
Potential Role for Interleukin-28B Genotype in Treatment Decision-Making in Recent Hepatitis C Virus Infection
Authors: Jason Grebely, Kathy Petoumenos, Margaret Hellard, Gail V. Matthews, Vijayaprakash Suppiah, Tanya Applegate, Barbara Yeung, Phillipa Marks, William Rawlinson, Andrew R. Lloyd, David Booth, John M. Kaldor, Jacob George, Gregory J. Dore
Journal: Hepatology (2010)

Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B , were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B ), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (Hepatology 2010;)
Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction
Authors: Anabel Brandoni, Silvina R. Villar, Juan C. Picena, Naohiko Anzai, Hitoshi Endou, Adriana M. Torres
Journal: Hepatology (2006)

Renal function in the course of obstructive jaundice has been the subject of great interest; however, little is known about the expression of renal organic anion transporters. The objective of this work was to study, in rats with acute extrahepatic cholestasis, the cortical renal expression of the organic anion transporter 1 (OAT1) and the organic anion transporter 3 (OAT3), in association with the pharmacokinetics and renal excretion of furosemide (FS). Male Wistar rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. All studies were carried out 21 hours after surgery. Rats were anesthetized and the pharmacokinetic parameters of FS and the renal elimination of FS were determined. Afterwards, the kidneys were excised and processed for immunoblot (basolateral membrane and renal homogenates) or immunocytochemical (light microscopic and confocal immunofluorescence microscopic analysis) techniques. The systemic and renal clearance of FS as well as the excreted and secreted load of FS increased in BDL rats. In kidneys from BDL rats, immunoblotting showed a significant increase in the abundance of both OAT1 and OAT3 in homogenates from renal cortex. In basolateral membranes from kidney cortex of BDL rats, OAT1 abundance was also increased and OAT3 abundance was not modified. Immunocytochemical techniques confirmed these results. In conclusion , acute obstructive jaundice is associated with an upregulation of OAT1 and OAT3, which might explain, at least in part, the increased systemic and renal elimination of FS. (Hepatology 2006;43:1092–1100.)
Effect of nitroprusside on hydraulic vascular loads on the right and left ventricle of patients with heart failure.
Authors: F C Yin, P A Guzman, K P Brin, W L Maughan, J A Brinker, T A Traill, J L Weiss, M L Weisfeldt
Journal: Circulation (1983)

We studied the effect of nitroprusside on the hydraulic vascular load of the right and left ventricle in seven patients with severe left ventricular failure. At doses of 0.25-0.75 micrograms/kg/min, stroke volume increased progressively from 40.1 to 48.6 ml and left ventricular end-diastolic pressure decreased from 24.5 to 11.2 mm Hg. Accompanying this improvement in left ventricular performance were dose-related decreases in mean ventricular pressures, pulmonic and systemic resistances and the lower-frequency components of input impedance moduli. Characteristic impedance and both total and oscillatory external power were decreased in the pulmonic, but not the aortic, vasculature. In this class of patients, right ventricular unloading is a striking and direct effect of nitroprusside and may account, in part, for improved left ventricular performance through ventricular interdependence.
Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?
Authors: C Alderman
Journal: Cardiovascular Research (2002)

The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators of this activation. Although LDL are known to be oxidised in vivo, and taken up by macrophages during atherogenesis; their effect on DC has not been explored previously.Human DCs were prepared from peripheral blood monocytes using GM-CSF and IL-4. Plasma LDLs were isolated by sequential gradient centrifugation, oxidised in CuSO(4), and oxidation arrested to yield mild, moderate and highly oxidised LDL forms. DCs exposed to these LDLs were investigated using combined phenotypic, functional (autologous T cell activation), morphological and viability assays.Highly-oxidised LDL increased DC HLA-DR, CD40 and CD86 expression, corroborated by increased DC-induced T cell proliferation. Both native and oxidised LDL induced prominent DC clustering. However, high concentrations of highly-oxidised LDL inhibited DC function, due to increased DC apoptosis.This study supports the hypothesis that oxidised LDL are capable of triggering the transition from sentinel to messenger DC. Furthermore, the DC clustering-activation-apoptosis sequence in the presence of different LDL forms is consistent with a regulatory DC role in immunopathogenesis of atheroma. A sequence of initial accumulation of DC, increasing LDL oxidation, and DC-induced T cell activation, may explain why local breach of tolerance can occur. Above a threshold level, however, supervening DC apoptosis limits this, contributing instead to the central plaque core.
ENDAMEBA HISTOLYTICA IN SEMINAL FLUID IN A CASE OF AMEBIC DYSENTERY
Authors: LAURENCE E. HINES
Journal: JAMA (1923)

The first and only recorded instance of localization of<i>Endameba histolytica</i>in the genital organs of man was made by Warthin,<sup>1</sup>who found amebas after death in the testis and epididymis of a man with chronic amebic dysentery. In the case reported here,<i>Endameba histolytica</i>was found, during life, in the seminal fluid of a man suffering with chronic amebic dysentery. <h3>REPORT OF CASE</h3> Since 1915, a chauffeur, aged 28, has had three or four attacks of diarrhea yearly. In the attacks, which last from one to three weeks, he usually has five or six copious, sour, gas-riddled, mushy stools daily; marked flatulence; slight tenderness over the descending colon; marked nervousness; weakness, and malaise. Fermentative colitis, gas bacillus colitis and nervous diarrhea had been diagnosed, but he did not improve with the usual diets. Ten years ago, he had an attack of gonorrhea that appeared to be cured in
THE CONSERVATIVE MANAGEMENT OF LACHRYMAL OBSTRUCTION.
Authors: S. D. RISLEY
Journal: JAMA (1904)

It is by the request of the chairman that I venture for the third time to present my personal views as to the value of conservative methods in the treatment of lachrymal obstruction. Added experience has served to confirm the conviction that, in many cases, the practically incurable affections of the tear duct so frequently observed, have been produced through faulty technic or by the violent surgical measures adopted at the outset of treatment. In my early experience I approached the treatment of lachrymal retention with a doubtful prognosis; but of late years I entertain this feeling of doubt as to results only in cases which have already been subjected to some form of radical surgical treatment having in view the creation of a patulous nasal duct. It is probable that a normal duct is never patulous, but that the tears escape into the nose from the lachrymal sac by
Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion
Authors: Patricia Boya, Karine Andreau, Delphine Poncet, Naoufal Zamzami, Jean-Luc Perfettini, Didier Metivier, David M. Ojcius, Marja Jäättelä, Guido Kroemer
Journal: The Journal of Experimental Medicine (2003)

A number of diseases are due to lysosomal destabilization, which results in damaging cell loss. To investigate the mechanisms of lysosomal cell death, we characterized the cytotoxic action of two widely used quinolone antibiotics: ciprofloxacin (CPX) or norfloxacin (NFX). CPX or NFX plus UV light (NFX*) induce lysosomal membrane permeabilization (LMP), as detected by the release of cathepsins from lysosomes. Inhibition of the lysosomal accumulation of CPX or NFX suppresses their capacity to induce LMP and to kill cells. CPX- or NFX-triggered LMP results in caspase-independent cell death, with hallmarks of apoptosis such as chromatin condensation and phosphatidylserine exposure on the plasma membrane. LMP triggers mitochondrial membrane permeabilization (MMP), as detected by the release of cytochrome c. Both CPX and NFX* cause Bax and Bak to adopt their apoptotic conformation and to insert into mitochondrial membranes. Bax−/− Bak−/− double knockout cells fail to undergo MMP and cell death in response to CPX- or NFX-induced LMP. The single knockout of Bax or Bak (but not Bid) or the transfection-enforced expression of mitochondrion-targeted (but not endoplasmic reticulum–targeted) Bcl-2 conferred protection against CPX (but not NFX*)-induced MMP and death. Altogether, our data indicate that mitochondria are indispensable for cell death initiated by lysosomal destabilization.
Do asthmatic patients correctly record home spirometry measurements?
Authors: P J Chowienczyk, D H Parkin, C P Lawson, G M Cochrane
Journal: BMJ (1994)

Asthma diary cards for entering measurements of peak expiratory flow and subjective symptom scores are widely used in clinical trials' and have been recom- mended for guiding management.2We compared the record keeping of peak expiratory flow and spirometry measurements of two groups of patients with asthma, with only one group knowing that all data, including time and date, were being electronically recorded and stored by the spirometers.
Dramatic Improvement of Subcutaneous Insulin Resistance with Nafamostat Ointment Treatment
Authors: Satoshi Kawashima, Hideaki Kaneto, Ken'ya Sakamoto, Ikuko Honsho, Tetsuyuki Yasuda, Akio Kuroda, Toshihiko Shiraiwa, Ryuichi Kasami, Taka-aki Matsuoka, Yoshimitsu Yamasaki, Munehide Matsuhisa
Journal: Diabetes Care (2008)

Subcutaneous insulin resistance is characterized by a lack of biological efficacy of subcutaneously injected insulin, with retained sensitivity to intravenously injected insulin. The existence of increased insulin-degrading activity has been suggested as a possible underlying mechanism (1). It has been reported that protease inhibitors exert beneficial effects on the absorption of subcutaneously injected insulin (1). Although the effect of an ointment containing a protease inhibitor has been shown in normal volunteers (2), there has been no report on the ointment's effect in patients with subcutaneous insulin resistance. This is …
Tobacco industry deliberately targets young people in Taiwan
Authors: Roger Dobson
Journal: BMJ (2005)

Foreign tobacco companies have deliberately targeted young people in Taiwan, new research concludes. In the first five years after the market was opened to Western companies, the prevalence of smoking in young adults aged 18 to 24 increased from 36% to 42%, a study in Tobacco Control has found (2005;14:38-44).

“Foreign tobacco companies increased their advertising expenditure, skirted the law via brand stretching, and engaged in aggressive promotional activities at point of sale retail outlets,” say the researchers from the National Health Research Institutes in Taiwan.

“Nearly half of …
The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(γ-benzyl l-glutamate)-b-hyaluronan polymersomes
Authors: Kamal K. Upadhyay, Anant N. Bhatt, Anil K. Mishra, Bilikere S. Dwarakanath, Sanyog Jain, Christophe Schatz, Jean-François Le Meins, Abdullah Farooque, Godugu Chandraiah, Amit K. Jain, Ambikanandan Misra, Sébastien Lecommandoux
Journal: Biomaterials (2010)
Abstract 4721: Polymorphisms in cancer-related genes and survival in early stage non-small cell lung cancer
Authors: Shin Yup Lee, Yi Young Choi, Hyo-Sung Jeon, Jin Eun Choi, Hyo-Gyoung Kang, Seung Soo Yoo, Eung Bae Lee, Won Kee Lee, Jaehee Lee, Seung Ick Cha, Chang H. Kim, Ji Woong Son, Jae Yong Park
Journal: Cancer Research (2014)

Abstract Background: This study was conducted to identify genetic polymorphisms associated with the prognosis of patients with early stage non-small cell lung cancer (NSCLC). Materials and Methods: We genotyped 1,969 potentially functional single nucleotide polymorphisms (SNPs) of 1,151 genes using the Affymetrix custom-made GeneChip, which were related to the development and progression of cancer, in 166 NSCLC patients who underwent curative surgical resection. A replication study was performed on an independent cohort of 626 patients. Results: Fifty six SNPs which were associated with both overall survival (OS) and disease-free survival (DFS) with log-rank P values lower than 0.05 in a discovery set were selected for validation. Among the 56 SNPs, five SNPs (guanine nucleotide binding protein, beta polypeptide 2-like 1 [GNB2L1] rs1279736C&amp;gt;A and rs3756585T&amp;gt;G, complement component 3 [C3] rs2287845T&amp;gt;C, p300/CBP-associated factor [PCAF] rs17006625A&amp;gt;G, and pericentriolar material 1 [PCM1] rs17691523C&amp;gt;G) were found to be significantly associated with survival outcomes in the same direction as the discovery set. In combined analysis, the rs1279736C&amp;gt;A and s3756585T&amp;gt;G were most significantly associated with OS and DFS in multivariate analysis (P for OS = 4x10-5 and 7x10-5, respectively; and P for DFS = 0.003, both; under a codominant model). Conclusions: We identified five SNPs as markers for prognosis of patients with surgically resected NSCLC. Citation Format: Shin Yup Lee, Yi Young Choi, Hyo-Sung Jeon, Jin Eun Choi, Hyo-Gyoung Kang, Seung Soo Yoo, Eung Bae Lee, Won Kee Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Ji Woong Son, Jae Yong Park. Polymorphisms in cancer-related genes and survival in early stage non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4721. doi:10.1158/1538-7445.AM2014-4721
The IL-7 Receptor Controls the Accessibility of the TCRγ Locus by Stat5 and Histone Acetylation
Authors: Sang-Kyu Ye, Yasutoshi Agata, Hai-Chon Lee, Hisanori Kurooka, Toshio Kitamura, Akira Shimizu, Tasuku Honjo, Koichi Ikuta
Journal: Immunity (2001)
Prognosis of Surgically Treated Intracranial Arterial Aneurysm Patients
Authors: Ottis M. Ballenger
Journal: JAMA (1977)

From 1969 to 1973, we undertook a direct surgical therapeutic approach with 62 patients who had intracranial aneurysms. The surgical mortality for patients in the first three clinical grades was 5%. Sixty-eight percent of the entire group of patients had improved conditions at follow-up. When these results are compared to the expected outcome of the natural course of the disease under conservative management, the superiority of the direct approach is seen. With the aid of modern instrumentation, anesthesia, steroid therapy, and magnification, neurosurgical centers handling a reasonable volume of these cases should achieve comparable results.
Interrater reproducibility of clinical tests for rotator cuff lesions
Authors: A J K Ostor, C A Richards, A T Prevost, B L Hazleman, C A Speed
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Rotator cuff lesions are common in the community but reproducibility of tests for shoulder assessment has not been adequately appraised and there is no uniform approach to their use. <b>Objective:</b> To study interrater reproducibility of standard tests for shoulder evaluation among a rheumatology specialist, rheumatology trainee, and research nurse. <b>Methods:</b> 136 patients were reviewed over 12 months at a major teaching hospital. The three assessors examined each patient in random order and were unaware of each other's evaluation. Each shoulder was examined in a standard manner by recognised tests for specific lesions and a diagnostic algorithm was used. Between-observer agreement was determined by calculating Cohen's κ coefficients (measuring agreement beyond that expected by chance). <b>Results:</b> Fair to substantial agreement was obtained for the observations of tenderness, painful arc, and external rotation. Tests for supraspinatus and subscapularis also showed at least fair agreement between observers. 40/55 (73%) κ coefficient assessments were rated at &gt;0.2, indicating at least fair concordance between observers; 21/55 (38%) were rated at &gt;0.4, indicating at least moderate concordance between observers. <b>Conclusion:</b> The reproducibility of certain tests, employed by observers of varying experience, in the assessment of the rotator cuff and general shoulder disease was determined. This has implications for delegation of shoulder assessment to nurse specialists, the development of a simplified evaluation schedule for general practitioners, and uniformity in epidemiological research studies.
Phylogenetic Analysis of the Neuraminidase Gene Reveals that the H5N1 Strains Prevalent in Chickens During 2006 Bird Flu Outbreaks in Two Regions of Maharashtra, India are Genetically Different
Authors: Mohd Danishuddin, Asad U. Khan
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract In February 2006, two outbreaks of highly pathogenic avian influenza A virus subtype H5N1 occurred in chickens in two neighboring districts (first in Nandurbar and second in Jalgaon) of Maharashtra, India, in a span of 12 days. In the present study, the neuraminidase (NA) gene of the two Indian H5N1 isolates was taken into consideration to find if the two strains are genetically similar. Phylogenetic analysis of the NA gene showed that the H5N1 strains isolated from the two outbreaks were not originated from the same source. The first Indian isolate (Nandubar/7972/06) was clustered closest to an isolate from chicken in Vietnam in 2004, whereas the second Indian isolate (Jalgaon/8824/06) showed resemblance to strains isolated from swan in Italy and Iran in 2006. Moreover, amino acid sequence analysis showed varying hot spots for substitutions between these two Indian isolates, and three substitutions were found at functional domain sites. Secondary structure changes due to these substitutions were also reported. This study reveals that the H5N1 strains isolated from chickens during 2006 bird flu outbreaks in two neighboring districts of Maharashtra, India are genetically different.