tbuckley/cabot-search huggingface dataset:
The Safety and Efficacy of Chorionic Villus Sampling for Early Prenatal Diagnosis of Cytogenetic Abnormalities
Authors: George G. Rhoads, Laird G. Jackson, Sarah E. Schlesselman, Felix F. de la Cruz, Robert J. Desnick, Mitchell S. Golbus, David H. Ledbetter, Herbert A. Lubs, Maurice J. Mahoney, Eugene Pergament, Joe Leigh Simpson, Robert J. Carpenter, Sherman Elias, Norman A. Ginsberg, James D. Goldberg, John C. Hobbins, Lauren Lynch, Patricia H. Shiono, Ronald J. Wapner, Julia M. Zachary
Journal: New England Journal of Medicine (1989)

Chorionic villus sampling is a method of prenatal diagnosis in the first trimester of pregnancy in which tissue for genetic study is aspirated from the developing placenta by means of a catheter inserted transcervically under the guidance of ultrasonography. In this seven-center study, we compared the safety and efficacy of chorionic villus sampling in 2278 women with those of amniocentesis at 16 weeks' gestation in 671 women. Both groups were made up primarily of well-educated private patients; they were recruited in the first trimester of pregnancy and had viable pregnancies verified by ultrasound examination. Cytogenetic diagnoses resulted from 97.8 percent of the chorionic villus sampling procedures and 99.4 percent of the amniocenteses (P<0.05); aneuploidy was found in 1.8 and 1.4 percent, respectively, of the cases in which diagnoses were made. Of the women who underwent chorionic villus sampling, 17 (0.8 percent) subsequently had an amniocentesis because the diagnosis was ambiguous. Two of the diagnoses of aneuploidy (one tetraploidy, one trisomy 22) were later proved to be incorrect. On the basis of pediatric examination of the infants subsequently born to the women in the sample, there were no errors in the determination of sex or the identification of the major trisomies (21, 18, and 13). The rate of combined losses due to spontaneous and missed abortions, termination of abnormal pregnancies, stillbirths, and neonatal deaths was 7.2 percent in the group that underwent chorionic villus sampling and 5.7 percent in the group that had amniocentesis. After adjustment for slight differences in gestational and maternal age, the total loss rate for the women in the chorionic villus sampling group exceeded that for the amniocentesis group by only 0.8 percentage points (80 percent confidence interval, -0.6 to 2.2). The rate of loss of chromosomally normal fetuses after chorionic villus sampling was 10.8 percent among women in whom three or four attempts were made to place the transcervical catheter, as compared with 2.9 percent in those in whom only one attempt was necessary (P<0.01). There were no serious maternal infections among the women in this study or among an additional 1990 women who underwent chorionic villus sampling (upper 95 percent confidence limit, 0.08 percent). We conclude that chorionic villus sampling is a safe and effective technique for the early prenatal diagnosis of cytogenetic abnormalities, but that it probably entails a slightly higher risk of procedure failure and of fetal loss than does amniocentesis. (N Engl J Med 1989; 320: 609–17.)
THE ENTRY OF GRANULE-ASSOCIATED PEROXIDASE INTO THE PHAGOCYTIC VACUOLES OF EOSINOPHILS
Authors: Ramzi S. Cotran, Mortimer Litt
Journal: The Journal of Experimental Medicine (1969)

The ultrastructural localization of peroxidase was studied in guinea pig eosinophils which had phagocytized zymosan or Escherichia coli. After phagocytosis, the membrane of the granule was joined to the membrane of the phagocytic vacuole, and the enzyme, which is ordinarily restricted to the matrix of the granule, was seen in the vacuole surrounding the ingested particle.
Recent Statistics of Carbon Monoxide Poisoning
Authors: A. B. Hill
Journal: BMJ (1956)

MEDICAL JOURN-kL prescribed-3 drops of cells in 12 drops of saline.On account of this result with A3, the directions were accordingly revised, so that only two drops of cells are required if the blood sample has been centrifuged.Clinically, the two errors with A3 blood are insignificant; no complications have been reported-so far as I am awarethrough A3 recipients getting 0 blood; nor have any com-
De Novo Mutation in the <b> <i>SCN5A</i> </b> Gene Associated With Early Onset of Sudden Infant Death
Authors: Horst Wedekind, Jeroen P.P. Smits, Eric Schulze-Bahr, Raoul Arnold, Marieke W. Veldkamp, Thomas Bajanowski, Martin Borggrefe, Bernd Brinkmann, Irene Warnecke, Harald Funke, Zahurul A. Bhuiyan, Arthur A.M. Wilde, Günter Breithardt, Wilhelm Haverkamp
Journal: Circulation (2001)

Background — Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. Methods and Results — In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms 1/2 ) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A , which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. Conclusions — In this study, we report a de novo mutation in the sodium channel gene SCN5A , which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.
Activin-like kinase receptor 1 (ALK1) in atherosclerotic lesions and vascular mesenchymal cells
Authors: Y YAO, A ZEBBOUDJ, A TORRES, E SHAO, K BOSTROM
Journal: Cardiovascular Research (2006)

Activin-like kinase receptor 1 (ALK1) is a transforming growth factor (TGF)-beta type I receptor expressed in vascular mesenchyme, yet its function in vascular mesenchymal cells (VMC) is unclear. We examined ALK1 expression in human coronary atherosclerotic lesions and bovine and human VMC undergoing cellular condensation in vitro. We also examined the effect of activated ALK1 on cell proliferation and smooth muscle cell (SMC) differentiation.Our results showed that ALK1 was expressed in human coronary atherosclerotic lesions as determined by immunohistochemistry. ALK1 was also expressed in cellular condensations of bovine and human VMC as determined by real-time PCR and immunocytochemistry. Bone morphogenetic protein (BMP)-2, which is known to increase condensation size, increased ALK1 expression when induced from a BMP-2 adenoviral vector. In turn, activated ALK1 induced expression of matrix GLA protein (MGP), a BMP-2 inhibitor known to limit condensation size. Activated ALK1 enhanced proliferation of VMC as determined by 3H-thymidine incorporation, whereas MGP decreased proliferation. Activated ALK1 also enhanced expression of SMC lineage markers and ALK5, another TGF-beta type I receptor, as determined by immunoblotting, real-time PCR and immunocytochemistry. Anti-TGF-beta antibodies abolished expression of SMC markers in the presence of constitutively active ALK1, suggesting that ALK1 activation alone is not sufficient to promote SMC differentiation.We conclude that there is a balance between the actions of BMP-2 and MGP in the initiation of vascular mesenchymal cell condensation and SMC differentiation, and that targeting ALK1, BMP2 and/or MGP may lead to novel concepts of atherosclerosis treatment.
Comparison of fat oxidation during exercise in lean and obese pubertal boys: clinical implications
Authors: G Zunquin, D Theunynck, B Sesboüé, P Arhan, D Bouglé
Journal: British Journal of Sports Medicine (2008)

To examine fat oxidation rates during exercise in lean and obese pubescent children.A graded leg cycle ergometry test was performed by two groups of pubescent boys (13 lean: mean (SD) age 12.0 (0.5) years, body mass index (BMI) 18.56 (1.12) kg/m(2); 17 obese: mean (SD) age 12.1 (0.1) years, BMI 26.68 (3.37) kg/m(2); p<0.001). The first step of the test was fixed at 30 W and power was gradually increased by 20 W every 3.5 min. The mean ventilatory gas measurement was obtained during the last 30 s of each step for calculation of fat oxidation rate vs exercise intensity.At low intensity (0-30% of peak oxygen consumption) when fat-free mass is considered, the fat oxidation rate was identical for the two groups. At higher intensities (40%, 50% and 60% of peak oxygen consumption) the fat oxidation rate was significantly higher in lean boys than in obese boys.These results confirm that obese pubertal boys have fat-free mass decreased capacities to use fat during moderate exercise. The findings suggest that obese boys need to practise physical activity at a lower intensity than healthy boys to enhance lipolysis and diminish adipose tissue and the consequences of obesity.
Prostaglandin E2 potentiates the immunologically stimulated histamine release from human peripheral blood-derived mast cells through EP1/EP3 receptors
Authors: X. S. Wang, H. Y. A. Lau
Journal: Allergy (2006)

Background: Mast cells cultured from human peripheral blood have been widely used to study human mast cell function. Prostanoids are the important regulators of mast cell activity, however, there were no reports about the class of prostanoid receptors expressed on such cultured cells. Aims: The present study was to characterize pharmacologically the prostanoid receptors by investigating the effects of prostanoid receptor agonists on the immunoglobulin E (IgE)‐mediated histamine release from the cultured mast cells. Methods: Mast cells cultured from human progenitor cells in peripheral blood were sensitized with human myeloma IgE, and then challenged with anti‐human IgE following pretreatment with diverse prostanoid receptor agonists. The histamine content in supernatants and cell pellets were measured by histamine auto‐analyzer. Results: Of the prostanoid receptor agonists tested, the prostaglandin E 2 (PGE 2 ) receptor (EP receptor) agonist PGE 2 (10 −7 to 10 −11 M) produced concentration‐related potentiation of IgE‐mediated histamine release from the cultured mast cells. Sulprostone, an EP 1 /EP 3 agonist, SC‐46275, a selective EP 3 agonist, and 11‐deoxy‐PGE 1 , a selective EP 2 /EP 3 /EP 4 agonist also caused a significant increase in histamine release induced by anti‐IgE. BW245C, fluprostone, cicaprost and U46619 for the prostaglandin D 2 , F 2 α , I 2 , and thromboxane A 2 receptors respectively, and the EP 2 /EP 4 receptor agonist butaprost had little effect on anti‐IgE stimulated histamine release from mast cells. Conclusions: The present results suggest that PGE 2 potentiates the IgE‐mediated histamine release from the cultured mast cell via EP 3 and/or EP 1 receptors.
Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial
Authors: Zahi A Fayad, Venkatesh Mani, Mark Woodward, David Kallend, Markus Abt, Tracy Burgess, Valentin Fuster, Christie M Ballantyne, Evan A Stein, Jean-Claude Tardif, James H F Rudd, Michael E Farkouh, Ahmed Tawakol
Journal: The Lancet (2011)
Intratumoral Localization of Aromatase and Interaction between Stromal and Parenchymal Cells in the Non–Small Cell Lung Carcinoma Microenvironment
Authors: Yasuhiro Miki, Takashi Suzuki, Keiko Abe, Satoshi Suzuki, Hiromichi Niikawa, Shinya Iida, Shuko Hata, Jun-ichi Akahira, Kazushige Mori, Dean B. Evans, Takashi Kondo, Hisafumi Yamada-Okabe, Hironobu Sasano
Journal: Cancer Research (2010)

Abstract Estrogens produced as a result of intratumoral aromatization has been recently shown to play important roles in proliferation of human non–small cell lung carcinomas (NSCLC), but the details have remained largely unknown. Therefore, in this study, we evaluated the possible roles of intratumoral aromatase in NSCLCs as follows: (a) evaluation of intratumoral localization of aromatase mRNA/protein in six lung adenocarcinoma cases using laser capture microdissection combined with quantitative reverse transcriptase-PCR and immunohistochemistry; (b) examination of the possible effects of isolated stromal cells from lung carcinoma tissues on aromatase mRNA transcript expression in lung carcinoma cell lines (A549 and LK87) through a coculture system; and (c) screening of cytokines derived from stromal LK001S and LK002S cells using cytokine antibody arrays and subsequent evaluation of effects of these cytokines on aromatase expression in A549 and LK87. Both aromatase mRNA and protein were mainly detected in intratumoral carcinoma cells but not in stromal cells. Aromatase expression of A549 and LK87 was upregulated in the presence of LK001S or LK002S cells. Several cytokines such as interleukin-6 (IL-6), oncostatin M, and tumor necrosis factor-α, all known as inducible factors of aromatase gene, were detected in conditioned media of LK001S and LK002S cells. Treatment of both oncostatin M and IL-6 induced aromatase gene expression in A549 an LK87, respectively. These results all indicated that intratumoral microenvironments, especially carcinoma-stromal cell interactions, play a pivotal role in the regulation of intratumoral estrogen synthesis through aromatase expression in human lung adenocarcinomas. Cancer Res; 70(16); 6659–69. ©2010 AACR.
High Cytotoxicity of Cisplatin Nanocapsules in Ovarian Carcinoma Cells Depends on Uptake by Caveolae-Mediated Endocytosis
Authors: Irene H.L. Hamelers, Rutger W.H.M. Staffhorst, Jarno Voortman, Ben de Kruijff, Jan Reedijk, Paul M.P. van Bergen en Henegouwen, Anton I.P.M. de Kroon
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Cisplatin nanocapsules, nanoprecipitates of cisplatin encapsulated in phospholipid bilayers, exhibit increased in vitro toxicity compared with the free drug toward a panel of human ovarian carcinoma cell lines. To elucidate the mechanism of cell killing by nanocapsules and to understand the cell line dependence of nanocapsule efficacy, the route of uptake and the intracellular fate of the nanocapsules were investigated. Experimental Design: Intracellular platinum accumulation and cisplatin-DNA-adduct formation were measured in cell lines that differ in sensitivity to cisplatin nanocapsules. Confocal fluorescence microscopy in combination with down-regulation with small interfering RNA was used to map the route of cellular uptake of nanocapsules containing fluorescein-labeled cisplatin. Results: In sensitive cell lines, cisplatin from nanocapsules is taken up much more efficiently than the free compound. In IGROV-1 cells, the increased platinum accumulation results in augmented cisplatin-DNA-adduct formation. Confocal fluorescence microscopy revealed that the uptake of nanocapsules is energy dependent. Colocalization with markers of early and late endosomes indicated uptake via endocytosis. Down-regulation of caveolin-1 with small interfering RNA inhibited the uptake and cytotoxic effect of nanocapsules in IGROV-1 cells. Ovarian carcinoma cells, in which the nanocapsules are less effective than in IGROV-1 cells, do not internalize the nanocapsules (OVCAR-3) or accumulate them in an endocytic compartment after clathrin-mediated endocytosis (A2780). Conclusions: The high cytotoxicity of cisplatin nanocapsules requires caveolin-1-dependent endocytosis that is followed by release of the drug from a late endosomal/lysosomal compartment and cisplatin-DNA-adduct formation. The findings may be applied in predicting the efficacy of nanoparticulate anticancer drug delivery systems in treating different tumor types.
Amygdala Hypoactivity to Fearful Faces in Boys With Conduct Problems and Callous-Unemotional Traits
Authors: Alice P. Jones, Kristin R. Laurens, Catherine M. Herba, Gareth J. Barker, Essi Viding
Journal: American Journal of Psychiatry (2008)

Objective: Although early-onset conduct problems predict both psychiatric and health problems in adult life, little research has been done to index neural correlates of conduct problems. Emerging research suggests that a subgroup of children with conduct problems and elevated levels of callous-unemotional traits may be genetically vulnerable to manifesting disturbances in neural reactivity to emotional stimuli indexing distress. Using functional MRI, the authors evaluated differences in neural response to emotional stimuli between boys with conduct problems and elevated levels of callous-unemotional traits and comparison boys. Method: Seventeen boys with conduct problems and elevated levels of callous-unemotional traits and 13 comparison boys of equivalent age (mean=11 years) and IQ (mean=100) viewed blocked presentations of fearful and neutral faces. For each face, participants distinguished the sex of the face via manual response. Results: Relative to the comparison group, boys with conduct problems and elevated levels of callous-unemotional traits manifested lesser right amygdala activity to fearful faces. Conclusions: This finding is in line with data from studies of adults with antisocial behavior and callous-unemotional traits (i.e., psychopaths), as well as from a recent study of adolescents with callous-unemotional traits, and suggests that the neural substrates of emotional impairment associated with callous-unemotional antisocial behavior are already present in childhood.
Epididymitis and Testis Tumor
Authors: H. Alan Bigley
Journal: JAMA (1977)

EPIDIDYMITIS is a disorder commonly seen in young, sexually active men. In the preantibiotic era, epididymitis was a frequent sequel to gonococcal urethritis. Now it is seen most often as a nonspecific infection, yielding sterile urine cultures.<sup>1-3</sup>Malignant tumor of the testis, although an uncommon neoplasm, is the second most frequent malignant growth in young adult men next to leukemia.<sup>4</sup> The differential diagnosis between epididymitis and testis tumor can be difficult, as illustrated in the following case report. <h3>Report of a Case</h3> A 36-year-old man was admitted to the Portsmouth Naval Hospital because of tender swelling of the right scrotal contents for approximately one week. He had no fever, chills, or dysuria. On initial examination there was inflammation of the epididymis and vas on the right side. The patient was treated with bed rest, scrotal elevation, oral tetracycline and oxyphenbutazone. He responded well to treatment and was discharged
Geographical Distribution of Selected and Putatively Neutral SNPs in Southeast Asian Malaria Parasites
Authors: Tim J. C. Anderson, Shalini Nair, Dan Sudimack, Jeff T. Williams, Mayfong Mayxay, Paul N. Newton, Jean-Paul Guthmann, Frank M. Smithuis, Tran Tinh Hien, Ingrid V.F. van den Broek, Nicholas J. White, François Nosten
Journal: Molecular Biology and Evolution (2005)

Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (FST = 0.18–0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (FST = 0–0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher FST (P < 8 × 10−5) than simulated neutral expectations based on observed FST values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach.
Minimally invasive surgery. Implications for hospitals, health workers, and patients.
Authors: H D Banta
Journal: BMJ (1993)

Minimally invasive surgery is one of the great innovations of health care in the 20th century. It promises to revolutionise surgery by allowing many more operations to be performed with minimal hospitalisation. Pressure from patients has caused many techniques to spread rapidly before they have been adequately assessed. This must be resisted, and policy makers must pay more attention to minimally invasive surgery to ensure that good assessments are made. The widespread use of minimally invasive techniques has important implications for hospitals and health workers. As more patients are treated on an outpatient basis, fewer hospital beds will be needed, and traditional operating rooms will have to adapt to a greater turnover of patients. Surgeons will have to acquire new operating skills, possibly requiring formal training and accreditation, and, as different specialties fight for control of new technologies, surgery may eventually be merged with internal medicine so that specialists will deal with organ systems. Postoperative care will have to be carried out in the community rather than in hospitals, and policy makers will need to reorganise their health systems to cope with these developments.