tbuckley/cabot-search huggingface dataset:
Eye Care for the Diabetic Patient
Authors: R. Keith Campbell
Journal: JAMA (1981)

DIABETIC retinopathy is the most common cause of blindness in men and women aged 30 to 64 years.<sup>1</sup>It is now the second leading cause of new blindness in the United States and the leading cause in adults younger than 65 years.<sup>2</sup>Diabetic retinopathy occurs in 90% of all persons who have had diabetes for 20 years or longer<sup>3</sup>and in 60% to 70% of patients with diabetes of 15 years' duration.<sup>4</sup>Thus, the longer a patient has been a diabetic, the greater the incidence of diabetic retinopathy. Diabetic retinopathy presents a hemodynamic and structural abnormality brought about by various vaguely understood biochemical or hormonal insults to the retinal vascular tree.<sup>5</sup>The development of diabetic retinopathy appears to be related to not only the duration of the disease but also to the lack of diabetic control that results in elevated blood glucose levels. It can
CD152 (CTLA-4) Determines the Unequal Resistance of Th1 and Th2 Cells against Activation-induced Cell Death by a Mechanism Requiring PI3 Kinase Function
Authors: Pushpa Pandiyan, Dagmar Gärtner, Osman Soezeri, Andreas Radbruch, Klaus Schulze-Osthoff, Monika C. Brunner-Weinzierl
Journal: The Journal of Experimental Medicine (2004)

Survival of antigen-experienced T cells is essential for the generation of adaptive immune responses. Here, we show that the genetic and antibody-mediated inactivation of CD152 (cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of nonapoptotic cells in a completely Fas/Fas ligand (FasL)–dependent manner. CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression. Apoptosis protection conferred by CD152 correlated with the up-regulation of Bcl-2 and was mediated by phosphatidylinositol 3 kinase, which prevented FasL expression through the inhibitory phosphorylation of Forkhead transcription factor FKHRL1. We show that signals induced by CD152 act directly on activated T lymphocytes and, due to its differential surface expression on activated Th1 and Th2 cells, induce resistance to AICD mainly in Th2 cells.
Stabilization of multiple metastatic epithelioid sarcoma under treatment with sunitinib malate
Authors: P. Penot, J.-D. Bouaziz, M. Battistella, D. Kerob, C. Pagès, C. Vilmer, N. Basset-Seguin, N. Madjessli, C. Comte, C. Farges, M. Bagot, C. le Maignan, C. Lebbé
Journal: British Journal of Dermatology (2012)
Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
Authors: Gianluca Fossati, Anne Cooke, Ruby Quartey Papafio, Kathryn Haskins, Brigitta Stockinger
Journal: The Journal of Experimental Medicine (1999)

In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2.5 × A18 mice developed diabetes spontaneously beyond 3–4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy.
Role of atrial fibrillation and atrioventricular conduction (including Wolff-Parkinson-White syndrome) in sudden death
Authors: Frits L. Meijler, Ingeborg van der Twell, Johan N. Herbschleb, Richard N.W. Hauer, Etienne O. Robles de Medina
Journal: Journal of the American College of Cardiology (1985)
Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells
Authors: Atsushi Nishida, Kiyotaka Nagahama, Hirotsugu Imaeda, Atsuhiro Ogawa, Cindy W. Lau, Taku Kobayashi, Tadakazu Hisamatsu, Frederic I. Preffer, Emiko Mizoguchi, Hiroki Ikeuchi, Toshifumi Hibi, Minoru Fukuda, Akira Andoh, Richard S. Blumberg, Atsushi Mizoguchi
Journal: The Journal of Experimental Medicine (2012)

Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1–expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell–mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.
THE EFFECT OF DILUTION OF PLASMA MEDIUM ON THE GROWTH AND FAT ACCUMULATION OF CELLS IN TISSUE CULTURES
Authors: Robert A. Lambert
Journal: The Journal of Experimental Medicine (1914)

1. Dilution of plasma with isotonic solutions causes a more extensive migration in cultures of cells of the actively migratory type, such as those of spleen and bone marrow. Dilution with a limited quantity of distilled water produces the same effect. Less actively motile cells are influenced little or not at all by dilution. The effect on cells of the first type is probably due to the reduction in the quantity of fibrin in the clot producing lessened resistance to cell locomotion. 2. Dilution of plasma with either isotonic solutions or distilled water is without effect on cell multiplication, as is shown by records of the number of mitoses in living culture preparations. 3. Dilution of plasma with suitable quantities of Ringer's solution causes a marked diminution in the quantity of fat accumulated by the cells. This reduction is to be attributed to the decrease in the quantity of fat in the medium. The accumulation of fat by cells in cultures is therefore not to be regarded as the result of a cell degeneration, but as an accumulation, the source of the fat being the medium in which the cells are growing.
Lidocaine Block of LQT-3 Mutant Human Na <sup>+</sup> Channels
Authors: R.-H. An, R. Bangalore, S.Z. Rosero, R.S. Kass
Journal: Circulation Research (1996)

In transiently transfected mammalian cells we have identified pharmacological consequences of a naturally occurring deletion mutation, ΔKPQ, of the human heart Na + channel α subunit that previously has been linked to one form of the long QT syndrome, an inherited heart disease. Our results show that the Class I B antiarrhythmic agent lidocaine blocks maintained inward current through and slows recovery from inactivation of ΔKPQ-encoded Na + channels. Block is greater for maintained than for peak current. Because incomplete inactivation of mutant Na + channels is now thought to underlie the prolonged ventricular action potential, which is the phenotype of this disease, and we find that the ΔKPQ mutation speeds the recovery from inactivation of drug-free mutant channels, our results provide evidence, for the first time, that clinically relevant dysfunctional properties of an ion channel can be selectively targeted on the basis of the molecular properties conferred on the channel by an inherited genetic disorder.
Spatial Heterogeneity of Calcium Transient Alternans During the Early Phase of Myocardial Ischemia in the Blood-Perfused Rabbit Heart
Authors: You-Wen Qian, William T Clusin, Shien-Fong Lin, Jennifer Han, Ruey J Sung
Journal: Circulation (2001)

Background Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca 2+ ] i indicators. We propose that beat-to-beat [Ca 2+ ] i transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents. Methods and Results To test this hypothesis, isolated rabbit hearts were loaded with the fluorescent [Ca 2+ ] i indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca 2+ ] i transients were recorded in each of 8 hearts.[Ca 2+ ] i transient alternans was never present in control records but occurred in each of the hearts during ischemia, with onset after 2 to 4 minutes. Alternans was confined to circumscribed regions of the heart surface 5 to 15 mm across. Multiple regions of alternans were found in most hearts, and regions that were out of phase with one another were found in 6 hearts. Quantitative maps of alternans were constructed by calculating an alternans ratio. This ratio behaved as a continuous variable that reached a maximum value in the center of the regions with alternans. Conclusions These results demonstrate marked spatial heterogeneity of the [Ca 2+ ] i transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts.
Mathematical Modeling of Evolution of Horizontally Transferred Genes
Authors: A. S. Novozhilov
Journal: Molecular Biology and Evolution (2005)

We describe a stochastic birth-and-death model of evolution of horizontally transferred genes in microbial populations. The model is a generalization of the stochastic model described by Berg and Kurland and includes five parameters: the rate of mutational inactivation, selection coefficient, invasion rate (i.e., rate of arrival of a novel sequence from outside of the recipient population), within-population horizontal transmission ("infection") rate, and population size. The model of Berg and Kurland included four parameters, namely, mutational inactivation, selection coefficient, population size, and "infection." However, the effect of "infection" was disregarded in the interpretation of the results, and the overall conclusion was that horizontally acquired sequences can be fixed in a population only when they confer a substantial selective advantage onto the recipient and therefore are subject to strong positive selection. Analysis of the present model in different domains of parameter values shows that, as long as the rate of within-population horizontal transmission is comparable to the mutational inactivation rate and there is even a low rate of invasion, horizontally acquired sequences can be fixed in the population or at least persist for a long time in a substantial fraction of individuals in the population even when they are neutral or slightly deleterious. The available biological data strongly suggest that intense within-population and even between-populations gene flows are realistic for at least some prokaryotic species and environments. Therefore, our modeling results are compatible with the notion of a pivotal role of horizontal gene transfer in the evolution of prokaryotes.
The Epidemiology of Major Depressive Disorder
Authors: Ronald C. Kessler, Patricia Berglund, Olga Demler, Robert Jin, Doreen Koretz, Kathleen R. Merikangas, A. John Rush, Ellen E. Walters, Philip S. Wang
Journal: JAMA (2003)

ContextUncertainties exist about prevalence and correlates of major depressive disorder (MDD).ObjectiveTo present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R).DesignFace-to-face household survey conducted from February 2001 to December 2002.SettingThe 48 contiguous United States.ParticipantsHousehold residents ages 18 years or older (N = 9090) who responded to the NCS-R survey.Main Outcome MeasuresPrevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV.ResultsThe prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence.ConclusionsMajor depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.
High prevalence of smoking among patients with suspected tuberculosis in South Africa
Authors: L. Brunet, M. Pai, V. Davids, D. Ling, G. Paradis, L. Lenders, R. Meldau, R. van Zyl Smit, G. Calligaro, B. Allwood, R. Dawson, K. Dheda
Journal: European Respiratory Journal (2010)

There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). There are no data validating the accuracy of self-reported smoking in TB patients and limited data about the prevalence of smoking in TB patients from high-burden settings. We performed a cross-sectional analysis of 500 patients with suspected TB in Cape Town, South Africa. All underwent comprehensive diagnostic testing. The accuracy of their self-reported smoking status was determined against serum cotinine levels. Of the 424 patients included in the study, 56 and 60% of those with active and latent TB infection (LTBI), respectively, were current smokers. Using plasma cotinine as a reference standard, the sensitivity of self-reported smoking was 89%. No statistically significant association could be found between smoking and active TB or LTBI. In Cape Town, the prevalence of smoking among patients with suspected and confirmed TB was much higher than in the general South African population. Self-reporting is an accurate measure of smoking status. These results suggest the need to actively incorporate tobacco cessation programmes into TB services in South Africa.
Pathophysiology of Tricuspid Regurgitation
Authors: Yan Topilsky, Christophe Tribouilloy, Hector I. Michelena, Sorin Pislaru, Douglas W. Mahoney, Maurice Enriquez-Sarano
Journal: Circulation (2010)

Background— Respiratory dependence of tricuspid regurgitation (TR), a long-held concept suggested by murmur variation, remains unproven and of unclear mechanisms. Methods and Results— In 41 patients with mild or greater TR (median age, 67 years), we performed triple Doppler echocardiographic quantification (TR severity, right ventricular, and right atrial quantification) with simultaneous respirometer recording of respiratory phases. Expiration to inspiration changes (median) affected TR peak velocity (−40 cm/s; 25th to 75th percentile, −60 to −30 cm/s), duration (−12 milliseconds; 25th to 75th percentile, −45 to 2 milliseconds), and time-velocity integral (−17 cm; 25th to 75th percentile, −23.4 to −10 cm; all P &lt;0.001), consistent with decreased TR driving force. Nevertheless, inspiratory TR augmentation was demonstrated by increased effective regurgitant orifice (0.21 cm 2 ; 25th to 75th percentile, 0.09 to 0.34 cm 2 ) and volume (18 mL per beat; 25th to 75th percentile, 10 to 25 mL per beat; all P &lt;0.001) infrequently detected clinically (2 of 41, 5). As a result of reduced TR driving force, regurgitant volume increased less than effective regurgitant orifice (120 [25th to 75th percentile, 78.6 to 169] versus 169 [ 25th to 75th percentile, 12.9 to 226.1]; P &lt;0.001). During inspiration, right ventricular area increased (diastolic, 27.8 [25th to 75th percentile, 22.6 to 36.3] versus 26.5 [21.1 to 31.9]; P &lt;0.0001) with widening of right ventricular shape (length-to-width ratio, 1.6 [ 25th to 75th percentile, 1.37 to 1.95] versus 1.7 [1.46 to 2.1]; P &lt;0.0001), increased systolic annular diameter ( P =0.003), valve tenting height ( P &lt;0.0001) and area ( P &lt;0.0001), and reduced valvular-to-annular ratio ( P =0.006). Effective regurgitant orifice during inspiration was independently determined by inspiratory valvular-to-annular ratio ( P =0.026) and inspiratory change in right ventricular length-to-width ratio ( P =0.008) and valve tenting area ( P =0.015). Conclusions— TR is dynamic with almost universal respiratory changes of large magnitude and complex pathophysiology. During inspiration, a large increase in effective regurgitant orifice causes, despite a decline in regurgitant gradient, a notable increase in regurgitant volume. Effective regurgitant orifice changes are independently linked to inspiratory annular enlargement (decreased valvular coverage) and to inspiratory right ventricular shape widening with increased valvular tenting. These novel physiological insights into TR respiratory dependence underscore right-side heart plasticity and are important for clinical TR severity evaluation.
Interspecific hybridization in Daphnia: distinction and origin of hybrid matrilines.
Authors: K Schwenk
Journal: Molecular Biology and Evolution (1993)

Three coexisting Daphnia species belonging to the D. longispina group (D. galeata, D. hyalina, and D. cucullata) form species-hybrid complexes by producing interspecific hybrids in several lakes in Germany and The Netherlands. To evaluate the genetic consequences of interspecific hybridization, I studied the patterns of mitochondrial DNA (mtDNA) sequence variation. The directionality of interspecific hybridization and divergence of hybrids from parental species was tested, using the DNA sequences of a segment of mtDNA. Via the polymerase chain reaction, it was possible to investigate single animals and even single resting eggs. A species-specific marker was established, using restriction patterns of amplified cytochrome b segments. mtDNA genotypes of hybrids revealed unidirectional mitochondrial gene flow for two hybrids, which were investigated by using multiple clones. No evidence for introgression of mtDNA was found. On the basis of a phylogenetic analysis, the species exhibit considerable distinctness, whereas differences between clones within species and between hybrids and maternal species tend to be very low. These results indicate a recent origin of hybrids and suggest that the radiation of the D. longispina group occurred > 5 Mya.
Patient-Tailored Antiemetic Treatment With 5-Hydroxytryptamine Type 3 Receptor Antagonists According to Cytochrome P-450 2D6 Genotypes
Authors: Rolf Kaiser, Orhan Sezer, Anja Papies, Steffen Bauer, Claudia Schelenz, Pierre-Benoit Tremblay, Kurt Possinger, Ivar Roots, Jürgen Brockmöller
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has substantially reduced, but not eliminated, nausea and vomiting in cancer chemotherapy. This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated. PATIENTS AND METHODS: Included in the study were 270 cancer patients receiving their first day of chemotherapy. Nausea and vomiting were documented using standardized interviews. The intensity of nausea was measured with visual analog scales before and twice during the chemotherapy. The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism analysis. RESULTS: Genetically defined poor metabolizers had higher serum concentrations of tropisetron than all other patients (P &lt; .03). Approximately 30% of all patients receiving chemotherapy experienced nausea and vomiting. Genetically defined ultrarapid meta-bolizers of CYP2D6 substrates had higher frequency of vomiting within the first 4 hours (P &lt; .001) and within the period 5 to 24 hours (P &lt; .03) after treatment than all the other patients; the tendency for nausea was similar. This difference was more pronounced in patients treated with tropisetron than in those treated with ondansetron. CONCLUSION: Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis.
Impact of endocrine disruptor chemicals in gynaecology
Authors: D. Caserta, L. Maranghi, A. Mantovani, R. Marci, F. Maranghi, M. Moscarini
Journal: Human Reproduction Update (2007)

The potential hazardous effects that estrogen- and androgen-like chemicals may have both on wildlife and human health have attracted much attention from the scientific community. Endocrine disruptors (EDCs) are chemicals that have the capacity to interfere with normal signalling systems. EDCs may mimic, block or modulate the synthesis, release, transport, metabolism and binding or elimination of natural hormones. Even though potential EDCs may be present in the environment at only very low levels, they may still cause harmful effects, especially when several different compounds act on one target. EDCs include persistent pollutants, agrochemicals and widespread industrial compounds. Not all EDCs are man-made compounds; many plants produce substances (phytoestrogens) that can have different endocrine effects either adverse or beneficial in certain circumstances. Natural substances such as sex hormones from urban or farm wastes can become concentrated in industrial, agricultural and urban areas; thus, such wastes may be considered potential 'EDCs' for humans and/or wildlife. Much attention has focussed on changing trends in male reproductive parameters in relation to EDC exposure; however, studies on the female reproductive system have been less comprehensive. We have focussed this article on four major aspects of female reproductive health: fertility and fecundability, endometriosis, precocious puberty and breast and endometrial cancer.