tbuckley/cabot-search huggingface dataset:
489 Hepatocyte oxidative stress and liver fatty acid binding protein
Authors: G WANG, Y GONG, D SUN, G MINUK, F BURCZYNSKI
Journal: Hepatology (2003)

One of the novel and promising plasma markers for detection of tissue injury is the family of 15 kDa cytoplasmic fatty acid-binding proteins of which various tissue-specific types occur.The present status of heart-type fatty acid-binding protein (H-FABP) as a diagnostic and prognostic marker for acute and chronic cardiac injury, as well as the preliminary diagnostic use of other types of FABP for detecting injury in other organs, is reviewed.This review is based on an overview of the literature on clinical diagnostics of various forms of organ injury, and uses additional literature on physiological aspects relevant for the interpretation of plasma marker concentrations.H-FABP not only proves to be an excellent early marker for cardiac injury in acute coronary syndromes, but also allows detection of minor myocardial injury in heart failure and unstable angina. Preliminary results indicate that sensitivity, rule-out power and prognostic value of H-FABP in cardiac injury surpass the performance of the standard early marker myoglobin. The liver only contains liver-type FABP (L-FABP), but co-expression of H-FABP and L-FABP occurs in the kidney. Similarly, intestinal-type FABP (I-FABP) and L-FABP are found in intestines, and brain-type FABP (B-FABP) and H-FABP occur in the brain. Preliminary but promising applications of these proteins have been demonstrated for liver rejection, viability selection of kidneys from non-heart-beating donors (NHBD), inflammatory and ischemic bowel disease, traumatic brain injury and in the prevention of muscle injury in trained athletes.Further study of the diagnostic and prognostic use of various FABP types is warranted, but their clinical application will require further commercialization of automated and rapid assays.
Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats.
Authors: C Nilsson, M Niklasson, E Eriksson, P Björntorp, A Holmäng
Journal: Journal of Clinical Investigation (1998)

In women, a relative hyperandrogenicity is statistically associated with insulin resistance and centralization of body fat, which are predictors for the development of non-insulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of androgenization of newborn female rats on insulin sensitivity at adult age. To mimic the neonatal androgen peak normally observed in male rats, female pups were administered one high dose of testosterone (T) subcutaneously within 3 h after birth. They were then given back to their mothers and followed to adult age. At the end of the week 9, tail samples were taken, showing no differences in fasting plasma concentrations of glucose, lactate, insulin, or free fatty acids between T-treated rats and controls. Plasma concentrations of T and progesterone were significantly lower in the T-treated rats, whereas no differences were found in the levels of corticosterone, estradiol, insulin-like growth factor I, or ACTH. After 10 wk, insulin sensitivity was studied with hyperglycemic and euglycemic hyperinsulinemic (5 mU insulin/kg/min) clamp techniques. The T-treated rats showed insulin resistance with both techniques, which was overcome with time and increasing insulin concentrations during the clamp measurements. The T-treated rats were also heavier and had increased relative weights of skeletal muscles and the spleen. Parametrial, retroperitoneal, and inguinal adipose tissues decreased in weight while mesenteric adipose tissue tended to increase, resulting in an approximately 30-50% larger mesenteric than other adipose tissues. It is concluded that neonatal T imprinting of female rats is followed by insulin resistance, changes in adipose tissue distribution, and an enlarged lean mass, without elevation of circulating T. Similar changes are seen in adult female rats or women receiving T.
Unraveling the basic biology and clinical significance of the chlamydial plasmid
Authors: Daniel D. Rockey
Journal: The Journal of Experimental Medicine (2011)

Chlamydial plasmids are small, highly conserved, nonconjugative, and nonintegrative DNA molecules that are nearly ubiquitous in many chlamydial species, including Chlamydia trachomatis. There has been significant recent progress in understanding chlamydial plasmid participation in host–microbe interactions, disease, and immune responses. Work in mouse model systems and, very recently, in nonhuman primates demonstrates that plasmid-deficient chlamydial strains function as live attenuated vaccines against genital and ocular infections. Collectively, these studies open new avenues of research into developing vaccines against trachoma and sexually transmitted chlamydial infections.
GONORRHEAL CONJUNCTIVITIS AND IRITIS.
Authors: FRANK S. MILBURY
Journal: JAMA (1898)

Gonorrheal conjunctivitis, or gonorrheal ophthalmia is one of the most serious inflammations met with in the eye. It in produced, usually, by the direct transmission of pus from a gonorrhea into the conjunctival sac. It finds its way to the eye from a urethral or vaginal gonorrhea, or from a similar inflammation in some other eyes, so that the inoculation may either be from the individual himself, as is most commonly the case, or by some one else whose towel has been soiled by the discharge and used subsequently by the patient. Such pus is known to acquire its virulence from the presence of characteristic micro-organisms to which the name of gonococci is given. The first symptoms may begin within from two or three hours to three days after inoculation. The appearance during the first day may be such as to suggest merely an acute attack of simple conjunctivitis. More
Driver Domains in Persistent Atrial Fibrillation
Authors: Michel Haissaguerre, Meleze Hocini, Arnaud Denis, Ashok J. Shah, Yuki Komatsu, Seigo Yamashita, Matthew Daly, Sana Amraoui, Stephan Zellerhoff, Marie-Quitterie Picat, Adam Quotb, Laurence Jesel, Han Lim, Sylvain Ploux, Pierre Bordachar, Guillaume Attuel, Valentin Meillet, Philippe Ritter, Nicolas Derval, Frederic Sacher, Olivier Bernus, Hubert Cochet, Pierre Jais, Remi Dubois
Journal: Circulation (2014)

Background— Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). Methods and Results— In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group ( P &lt;0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P =not significant. Conclusions— Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries.
Modulation of gene expression in subjects at risk for colorectal cancer by the chemopreventive dithiolethione oltipraz.
Authors: P J O'Dwyer, C E Szarka, K S Yao, T C Halbherr, G R Pfeiffer, F Green, J M Gallo, J Brennan, H Frucht, E B Goosenberg, T C Hamilton, S Litwin, A M Balshem, P F Engstrom, M L Clapper
Journal: Journal of Clinical Investigation (1996)

Prolonged exposure to mutagenic substances is strongly associated with an individual's risk of developing colorectal cancer. Clinical investigation of oltipraz as a chemopreventive agent is supported by its induction of the expression of detoxication enzymes in various tissues, and its protective activity against the formation of chemically induced colorectal tumors in animals. The goals of the present study were: to determine if oltipraz could induce detoxicating gene expression in human tissues; to identify effective non-toxic doses for more extensive clinical testing; and to establish a relationship between effects in the colon mucosa and those in a more readily available tissue, the peripheral mononuclear cell. 24 evaluable patients at high risk for colorectal cancer were treated in a dose-finding study with oltipraz 125, 250, 500, or 1,000 mg/m2 as a single oral dose. Biochemical analysis of sequential blood samples and colon mucosal biopsies revealed increases in glutathione transferase activity at the lower dose levels. These effects were not observed at the higher doses. More pronounced changes were observed in detoxicating enzyme gene expression in both tissues at all doses. Peripheral mononuclear cell and colon mRNA content for gamma-glutamylcysteine synthetase (gamma-GCS) and DT-diaphorase increased after dosing to reach a peak on day 2-4 after treatment, and declined to baseline in the subsequent 7-10 d. The extent of induction of gene expression in colon mucosa reached a peak of 5.75-fold for gamma-GCS, and a peak of 4.14-fold for DT-diaphorase at 250 mg/m2 ; higher doses were not more effective. Levels of gamma-GCS and DT-diaphorase correlated closely (P < or = 0.001) between peripheral mononuclear cells and colon mucosa both at baseline and at peak. These findings demonstrate that the administration of minimally toxic agents at low doses may modulate the expression of detoxicating genes in the tissues of individuals at high risk for cancer. Furthermore, peripheral mononuclear cells may be used as a noninvasive surrogate endpoint biomarker for the transcriptional response of normal colon mucosa to drug administration.
A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma
Authors: Giuliana Salvatore, Tito Claudio Nappi, Paolo Salerno, Yuan Jiang, Corrado Garbi, Clara Ugolini, Paolo Miccoli, Fulvio Basolo, Maria Domenica Castellone, Anna Maria Cirafici, Rosa Marina Melillo, Alfredo Fusco, Michael L. Bittner, Massimo Santoro
Journal: Cancer Research (2007)

Here, we show that the anaplastic thyroid carcinoma (ATC) features the up-regulation of a set of genes involved in the control of cell cycle progression and chromosome segregation. This phenotype differentiates ATC from normal tissue and from well-differentiated papillary thyroid carcinoma. Transcriptional promoters of the ATC up-regulated genes are characterized by a modular organization featuring binding sites for E2F and NF-Y transcription factors and cell cycle-dependent element (CDE)/cell cycle gene homology region (CHR) cis-regulatory elements. Two protein kinases involved in cell cycle regulation, namely, Polo-like kinase 1 (PLK1) and T cell tyrosine kinase (TTK), are part of the gene set that is up-regulated in ATC. Adoptive overexpression of p53, p21 (CIP1/WAF1), and E2F4 down-regulated transcription from the PLK1 and TTK promoters in ATC cells, suggesting that these genes might be under the negative control of tumor suppressors of the p53 and pRB families. ATC, but not normal thyroid, cells depended on PLK1 for survival. RNAi-mediated PLK1 knockdown caused cell cycle arrest associated with 4N DNA content and massive mitotic cell death. Thus, thyroid cell anaplastic transformation is accompanied by the overexpression of a cell proliferation/genetic instability-related gene cluster that includes PLK1 kinase, which is a potential molecular target for ATC treatment.
Respiratory Effects of Environmental Tobacco Exposure Are Enhanced by Bronchial Hyperreactivity
Authors: Margaret W. Gerbase, Christian Schindler, Jean-Pierre Zellweger, Nino Künzli, Sara H. Downs, Otto Brändli, Joel Schwartz, Martin Frey, Luc Burdet, Thierry Rochat, Ursula Ackermann-Liebrich, Philippe Leuenberger
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Exposure to environmental tobacco smoke (ETS) is associated with increased reports of respiratory symptoms and reduced lung function, but the long-term effects of ETS are unclear, notably in healthy individuals with bronchial hyperresponsiveness (BHR).To assess the longitudinal effects of ETS exposure on the development of respiratory symptoms and spirometry in subjects with BHR.The study population included 1,661 never-smokers from the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cohort, assessed in 1991 (baseline) and 11 yr later, who were symptom-free at baseline. Incident reports of respiratory symptoms and results of spirometry were assessed at the follow-up survey.Exposure to ETS reported in the two surveys was strongly associated with the development of cough (odds ratio, 2.1; 95% confidence interval, 1.2-3.7; p = 0.01). In subjects with BHR exposed to ETS at both surveys, a trend for strong associations were observed for wheeze, cough, dyspnea, and chronic bronchitis; however, the association reached statistical significance only for the symptom of dyspnea (p < 0.01). Lower FEV1/FVC (mean +/- SD, 72.9 +/- 7.7 vs. 76.8 +/- 6.1%; p < 0.01) and FEF(25-75) (forced expiratory flow, midexpiratory phase)/FVC (mean +/- SD, 56.1 +/- 22.5 vs. 68.1 +/- 21.6%; p < 0.01) were observed in subjects with BHR exposed to ETS compared with nonexposed subjects without BHR. Lower values were found in subjects continuing exposure by the follow-up survey.Exposure to ETS was strongly associated with the development of respiratory symptoms in previously asymptomatic subjects with BHR within 11 yr. Furthermore, subjects with underlying BHR had reduced lung function at follow-up, thus suggesting a higher risk for the development of chronic respiratory disease in this subset of the population.
The treatment of vulval lichen sclerosus with a very potent topical steroid (clobetasol Propionate 0.05%) cream
Authors: K.L. DALZIEL, P.R. MILLARD, F. WOJNAROWSKA
Journal: British Journal of Dermatology (1991)

The clinical and histological response to 12 weeks of treatment with a very potent topical fluorinated steroid was studied in 15 patients with vulval lichen sclerosus (LS) who were treated with twice eaily applications of clobetasol propionate 0.05% cream (Dermovate, Glaxo U.K.), Thirteen patients completed the study and all showed a marked clinical improvement. Histological measurements of skin biopsies taken before and after treatment showed a significant reduction in the characteristic features of LS. One patient developed contact sensitivity to clobetasol propionate. There was no evidence of infection or skin atrophy during the study. Patients completing the study have been followed up for up to 22 months and have been maintained in remission with moderately potent topical steroids which had previously been ineffective.
Sample size calculations II
Authors: P. Sedgwick
Journal: BMJ (2010)

A randomised controlled trial investigated whether a computerised feedback device modified eating behaviour and resulted in weight loss in obese adolescents.1 The primary outcome was change in body mass index (BMI) from recruitment to 12 months. BMI was calculated as weight (kg)/[height (m)]2, adjusted for age and sex. The control intervention was standard lifestyle modification therapy.

The optimal sample size to compare the computerised device with standard care was calculated for the primary outcome. Using data from a previous study, the researchers predicted that the mean change in BMI at 12 months with standard therapy would be a reduction of 0.17 (SD=0.267) kg/m2. For the computerised device to be considered effective, it should double this mean reduction and achieve a decrease in BMI of 0.34 kg/m2 (the smallest effect of clinical interest). A total sample size of 80 children …
OBSERVATIONS CONCERNING THE BLOOD IN CHOREA AND RHEUMATISM
Authors: C. J. Macalister
Journal: BMJ (1909)

murmur in favour of the a-a rhythm.I was much interested in seeing this opinion, and turned to the paper in question, feeling quite sure that if the observa- tion established anything definitely, it would be the early V-8 rhythm.I now beg to ask those readers of the JOUTJNAL interested in the matter to look at the paper in Pfliiger'8 Archiv and say what they do tend to prove.I give the essential points here.Weiss and Joachim have devised a most ingenious instrament called the phonoscope, by which they can record in a wonderful and unmistakable way the normal sounds of the heart and any murmurs louder than the very softest blowing type.They publish several traciDgs, of which two are appended, showing the murmars of mitral stenosis.The points they make are:1.The distance from the beginning of ventricular systole to the rise of the carotid pulse in a normal heart is 0.08 to 0.09 second.2. In mitral regurgitation this is increased to from 0.125 to 0.15 second, according to the degree of muscle failure present.This fact appeared to the writers to be strange, but they explain it by suggesting that blood escapes back through the incompetent valve at the beginning of v-s, and delays the development of sufficient i-v pressure to open the semilunar valves.This is exactly what I say happens in the development of a crescendo murmur, causing delay of the first sound (see Fig. 2).
Recurrent spontaneous abortion and polycystic ovarian disease: comparison of two regimens to induce ovulation.
Authors: P Johnson, J M Pearce
Journal: BMJ (1990)

To determine whether pituitary suppression before induction of ovulation reduces the rate of spontaneous abortion in women with polycystic ovarian disease and primary recurrent spontaneous abortions.Closed, randomised, sequential trial. Pairs of women were allocated to each treatment by the toss of a coin.Supraregional clinic for women who had had recurrent spontaneous abortions.Forty two women with polycystic ovarian disease and primary recurrent spontaneous abortions.Ovulation was induced by clomiphene or pituitary suppression with buserelin followed by pure follicle stimulating hormone.Preference for a particular treatment was noted. A preference occurred when one woman in a pair had a successful pregnancy (defined as one of over 12 weeks' gestation) and one had a spontaneous abortion; the preference was for the treatment resulting in the successful pregnancy.Spontaneous abortions occurred in 11 of 20 women given clomiphene compared with two of 20 who had pituitary suppression. Eleven preferences were found for buserelin and two for clomiphene. In seven pairs both women had successful pregnancies. One pair was discarded because one of the women did not become pregnant. The ratio of luteinising hormone concentration to follicular diameter was found to be a possible diagnostic indicator of spontaneous abortion.Pituitary suppression before induction of ovulation significantly reduces the risk of spontaneous abortion in women with polycystic ovarian disease and primary recurrent spontaneous abortions.
Ian Duncan Willatt
Authors: P. Willatt
Journal: BMJ (2009)

Ian Duncan Willatt (“Duncan”) was born in Stoke on Trent on 12 February 1917 and died on 23 March 2009, aged 92. A scholarship at Newcastle under Lyme School was followed by an offer of a place to read medicine at the age of 17 at Edinburgh University. He graduated in 1939 and undertook the role of house physician at the Royal Infirmary, Edinburgh. He later married Ruth Evershed (obituary, BMJ 2009;338:b2512), a former fellow Edinburgh medical student, on 18 February 1941 at Thakeham, Sussex.

In 1941 he joined the Royal Army Medical Corps and rose to the rank of major. He would proudly relate that during his military service he had met Lord Mountbatten and …
Effect of Route of Breathing on Response to Exposure in a Swine Confinement Building
Authors: YVON CORMIER, MICHEL LAVIOLETTE, GAETANE BEDARD, JAMES DOSMAN, EVELYNE ISRAEL-ASSAYAG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Exposure of naive subjects to swine buildings results in acute nasal, lung, and peripheral blood inflammatory responses with an increase in nonallergic airway responsiveness. Because nasal passages filter large particles and soluble gases and because swine building exposure results in an acute inflammatory response at this level, we questioned what effect breathing through or avoiding this route would have on local and systemic inflammation. Nine normal young men 23 to 37 yr of age were exposed for 5 h to a swine building, once breathing normally and once with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4) (Protocol 2); three subjects participated in both protocols. For each protocol each subject underwent a methacholine challenge for PC20 measurement, a nasal lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and once after each swine building exposure. Bronchial responsiveness as measured by PC20 decreased in most subjects after swine building exposure and was not influenced by the route of breathing. Nasal lavage neutrophils increased tenfold after each swine exposure, except when the nose was occluded where no alteration was observed. Total BAL cells significantly increased after each exposure to the swine building, this increase was not modified by the route of breathing. In Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x 10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L during nasal breathing exclusively. For Protocol 2, these respective values were: 5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes, and serum were increased by swine building exposure, except in the nasal wash when the nose was occluded. In conclusion, the lung and blood responses to exposure in a swine confinement building are not modified by the route of breathing, suggesting that nasal inflammation and filtration are not important in the process and that small respirable particles and/or gases may be responsible for these responses.