tbuckley/cabot-search huggingface dataset:
Targeted Deletions of Cyclooxygenase-2 and Atherogenesis in Mice
Authors: Yiqun Hui, Emanuela Ricciotti, Irene Crichton, Zhou Yu, Dairong Wang, Jane Stubbe, Miao Wang, Ellen Puré, Garret A. FitzGerald
Journal: Circulation (2010)

Although the dominant product of vascular Cyclooxygenase-2 (COX-2), prostacyclin (PGI(2)), restrains atherogenesis, inhibition and deletion of COX-2 have yielded conflicting results in mouse models of atherosclerosis. Floxed mice were used to parse distinct cellular contributions of COX-2 in macrophages and T cells (TCs) to atherogenesis.Deletion of macrophage-COX-2 (Mac-COX-2KOs) was attained with LysMCre mice and completely suppressed lipopolysaccharide-stimulated macrophage prostaglandin (PG) formation and lipopolysaccharide-evoked systemic PG biosynthesis by approximately 30%. Lipopolysaccharide-stimulated COX-2 expression was suppressed in polymorphonuclear leukocytes isolated from MacKOs, but PG formation was not even detected in polymorphonuclear leukocyte supernatants from control mice. Atherogenesis was attenuated when MacKOs were crossed into hyperlipidemic low-density lipoprotein receptor knockouts. Deletion of Mac-COX-2 appeared to remove a restraint on COX-2 expression in lesional nonleukocyte (CD45- and CD11b-negative) vascular cells that express vascular cell adhesion molecule and variably alpha-smooth muscle actin and vimentin, portending a shift in PG profile and consequent atheroprotection. Basal expression of COX-2 was minimal in TCs, but use of CD4Cre to generate TC knockouts depressed its modest upregulation by anti-CD3epsilon. However, biosynthesis of PGs, TC composition in lymphatic organs, and atherogenesis in low-density lipoprotein receptor knockouts were unaltered in TC knockouts.Macrophage-COX-2, primarily a source of thromboxane A(2) and prostaglandin (PG)E(2), promotes atherogenesis and exerts a restraint on enzyme expression by lesional cells suggestive of vascular smooth muscle cells, a prominent source of atheroprotective prostacyclin. TC COX-2 does not detectably influence TC development or function or atherogenesis in mice.
Splenic infarction, splenic sequestration, and functional hyposplenism in hemoglobin S‐C disease
Authors: David A. Sears, Mark M. Udden
Journal: American Journal of Hematology (1985)

Abstract Splenic atrophy or evidence of hyposplenism occurs in as many as one third of all patients with S‐C hemoglobinopathy. Yet there are few reports in the literature of clinically apparent splenic infarction in this disease. We describe four instances of acute splenic infarction in three patients with hemoglobin S‐C disease which illustrate a wide spectrum of clinical manifestations and severity. Of particular interest were the observations of coincident occurrences of splenic sequestration and functional hyposplenism with splenic infarction, suggesting a close pathophysiological relationship among these syndromes.
Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients
Authors: R Rahmé, X Thomas, C Recher, N Vey, J Delaunay, E Deconinck, P Hirsch, D Bordessoule, J-B Micol, A Stamatoullas, C Mariette, C Pautas, P Bories, J-P Marolleau, M Hunault-Berger, N Fegueux, E Raffoux, H Dombret, L Degos, P Fenaux, L Adès
Journal: Leukemia (2014)
Letter from...Denmark. Planning of scientific-ethical committees.
Authors: P Riis
Journal: BMJ (1977)

TABLE-Details of cases of Distalgesic overdosage from the Birmingham District Coroner's Court Age and sex Blood alcohol Estimated overdosage Source of tablets Time to fatal onset Verdict or other drugs (tablets) (hours) 26 (F) 280 mg/ 100 ml.15 50 tablets prescribed 1 Killed herself No other drugs 16 days before death 33 (M) Nil 40 Prescribed for mother Considerably less Killed himself than 10 29 (M) Nil 30 100 tablets (three four-hourly) <2 Killed himself prescribed by GP for sinusitis 20 (M) 145 mgi 100 ml.20-30 Prescribed for friend 5 Open verdict.No other drugs Intention uncertain 25 (M) Nil 40-45 Not known Uncertain Killed himself 47 (F) Alcohol nil.10-20 60 prescribed for self <6 Killed herself Quinalbarbitone 3 days before.400 mg the dosage prescribed was up to 18 tablets to be taken a day-more than twice the manufacturers' recommended maximum dose.Both doctors and patients, therefore, may be lulled into a false sense of
77 EMBOLIZATION OF LARGE SPONTANEOUS PORTOSYSTEMIC SHUNTS FOR REFRACTORY HEPATIC ENCEPHALOPATHY: A EUROPEAN MULTI-CENTER SURVEY ON SAFETY &amp; EFFICACY
Authors: W. Laleman, M. Simon-Talero, G. Maleux, M. Perez, K. Ameloot, G. Soriano, J. Villalba, J.-C. Garcia-Pagan, M. Barrufet, R. Jalan, J. Brookes, E. Thalassinos, A. Burroughs, J. Cordoba, F. Nevens
Journal: Journal of Hepatology (2013)
Insect‐venom allergy in Greek adults
Authors: Ch. Grigoreas, I. D. Galatas, Ch. Kiamouris, D. Papaioannou
Journal: Allergy (1997)

Relatively few studies have investigated the prevalence of insect‐sting allergy and the results of diagnostic procedures in unselected populations. The prevalence of insect‐sting reactions and of venom sensitization in Greece is unknown. We report the results from a stratified random sample of 480 subjects (404 men, 76 women), aged 20–60 years. They all belonged to the ground personnel of the Hellenic Air Force. A detailed history particularly focused on the reactions to Hymenoptera stings was taken in all subjects. Intradermal skin tests (concentration: 1 μg/ml) with three venoms (honeybee, paper wasp, common wasp) were performed. The prevalence of venom sensitization (one or more positive skin tests) was 32.7%. Sensitization appears to be more common (2.69 times) in those living in rural areas than in those living in the capital (Athens). The prevalence of systemic reactions was 3.1% (86.7% of them had positive skin tests). Large local reactions were reported by 4.6% of the subjects (77.3% of them had positive skin tests). Asymptomatic sensitization (positive skin tests to venoms) was observed in 28.7% of subjects with no history of an allergic sting reaction. We concluded that the prevalence of Hymenoptera allergy and venom sensitization in Greece is rather high compared to that of other countries.
THE IMPACT OF EARLY COMPARED TO LATE MORNING HOURS ON BRACHIAL ENDOTHELIAL FUNCTION AND LONG-TERM CARDIOVASCULAR EVENTS IN HEALTHY SUBJECTS WITH NO APPARENT CORONARY HEART DISEASE
Authors: Michael Shechter, Liran Hirsh, Nira Koren-Morag, Micha S. Feinberg
Journal: Journal of the American College of Cardiology (2010)
Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest
Authors: E Boni
Journal: Thorax (2002)

<b>Background:</b> A study was undertaken to investigate whether bronchodilators are associated with less breathlessness at rest and during light exercise in patients with moderate to severe chronic obstructive pulmonary disease (COPD) with resting tidal expiratory flow limitation (EFL; flow limited (FL)) compared with those without EFL (non-flow limited (NFL)). <b>Methods:</b> Twenty subjects (13 men) of mean (SD) age 65 (8) years (range 43–77) suffering from COPD with forced expiratory volume in 1 second (FEV<sub>1</sub>) 47 (18)% predicted were studied before and after inhalation of salbutamol (400 μg). Routine pulmonary function tests were performed in the seated position at rest. EFL was assessed by the negative expiratory pressure (NEP) method and changes in end expiratory lung volume (EELV) were inferred from variations in inspiratory capacity (IC). Dyspnoea was measured using the Borg scale at rest and at the end of a 6 minute steady state exercise test at 33% of the maximal predicted workload. <b>Results:</b> EFL occurred in 11 patients. Following salbutamol IC did not change in NFL patients but increased by 24% (95% CI 15 to 33) in FL patients (p&lt;0.001). Maximal inspiratory pressure (Pimax) improved at EELV from 45 (95% CI 26 to 63) to 55 (95% CI 31 to 79) cm H<sub>2</sub>O (p&lt;0.05) in FL patients after salbutamol but remained unchanged in NFL patients. The workload performed during exercise amounted to 34 (95% CI 27 to 41) and 31 (95% CI 21 to 40) watts (NS) for patients without and with EFL, respectively. After salbutamol, dyspnoea did not change either at rest or during exercise in the NFL patients, but decreased from 0.3 (95% CI –0.1 to 0.8) to 0.1 (95% CI –0.1 to 0.4) at rest (NS) and from 3.7 (95% CI 1.7 to 5.7) to 2.6 (95% CI 1.1 to 4.0) at the end of exercise (p&lt;0.01) in FL patients. <b>Conclusions:</b> Patients with COPD with EFL may experience less breathlessness after a bronchodilator, at least during light exercise, than those without EFL. This beneficial effect, which is closely related to an increase in IC at rest, occurs even in the absence of a significant improvement in FEV<sub>1</sub> and is associated with a greater Pimax.
HLA system and side effects of gold salts and D-penicillamine treatment of rheumatoid arthritis.
Authors: T Bardin, A Dryll, N Debeyre, A Ryckewaert, L Legrand, A Marcelli, J Dausset
Journal: Annals of the Rheumatic Diseases (1982)

Among 67 patients with rheumatoid arthritis treated with gold salts (aurothiopropanol sulphonate) a significant correlation (p less than 10(-2)) was noted between gold toxic reactions, whatever their type, and the HLA antigens A1, B8, Cw7, and DR3. Forty-two patients were genotyped, and a correlation was observed between gold side effects and the haplotype A1 Cw7 B8 DR3 (p less than 10(-2), RR = 8.0). In addition 3 out of 4 cases of renal intolerance to D-penicillamine were observed in patients possessing the Cw7 B8 DR3 haplotype.
Systematic Review: Elective Induction of Labor Versus Expectant Management of Pregnancy
Authors: Aaron B. Caughey
Journal: Annals of Internal Medicine (2009)

Background: The rates of induction of labor and elective induction of labor are increasing. Whether elective induction of labor improves outcomes or simply leads to greater complications and health care costs is commonly debated in the literature. Purpose: To compare the benefits and harms of elective induction of labor and expectant management of pregnancy. Data Sources: MEDLINE (through February 2009), Web of Science, CINAHL, Cochrane Central Register of Controlled Trials (through March 2009), bibliographies of included studies, and previous systematic reviews. Study Selection: Experimental and observational studies of elective induction of labor reported in English. Data Extraction: Two authors abstracted study design; patient characteristics; quality criteria; and outcomes, including cesarean delivery and maternal and neonatal morbidity. Data Synthesis: Of 6117 potentially relevant articles, 36 met inclusion criteria: 11 randomized, controlled trials (RCTs) and 25 observational studies. Overall, expectant management of pregnancy was associated with a higher odds ratio (OR) of cesarean delivery than was elective induction of labor (OR, 1.22 [95% CI, 1.07 to 1.39]; absolute risk difference, 1.9 percentage points [CI, 0.2 to 3.7 percentage points]) in 9 RCTs. Women at or beyond 41 completed weeks of gestation who were managed expectantly had a higher risk for cesarean delivery (OR, 1.21 [CI, 1.01 to 1.46]), but this difference was not statistically significant in women at less than 41 completed weeks of gestation (OR, 1.73 [CI, 0.67 to 4.5]). Women who were expectantly managed were more likely to have meconium-stained amniotic fluid than those who were electively induced (OR, 2.04 [CI, 1.34 to 3.09]). Limitations: There were no recent RCTs of elective induction of labor at less than 41 weeks of gestation. The 2 studies conducted at less than 41 weeks of gestation were of poor quality and were not generalizable to current practice. Conclusion: RCTs suggest that elective induction of labor at 41 weeks of gestation and beyond is associated with a decreased risk for cesarean delivery and meconium-stained amniotic fluid. There are concerns about the translation of these findings into actual practice; thus, future studies should examine elective induction of labor in settings where most obstetric care is provided.
Bedside measurement of factor VIII:C activity in individuals with hemophilia A
Authors: C.M. Kessler, Z. Bernstein, S. Ghesani, Z. Shamsipour, C. Frances, M.L. Zucker, F.M. LaDuca
Journal: American Journal of Hematology (1996)

Factor VIII replacement therapy for patients with hemophilia A is conventionally monitored using a plasma-based factor VIII:C assay (a modified activated partial thromboplastin time [APTT] test). The plasma factor VIII assay requires the preparation of plasma from citrated whole blood and measurement of the clotting times of mixtures of patient plasma, factor VIII-deficient substrate, and APTT reagent. Results are not routinely available in less than 1.5 hr, reducing the clinical value of the laboratory data regarding the ability to immediately adjust patient therapy. Results from the whole blood factor VIII assay, performed on a portable coagulation analyzer and using test tubes prefilled with the necessary APTT and factor VIII-deficient reagents, are available within 5–7 min. This immediate determination of the factor VIII:C level from citrated whole blood provides the opportunity to greatly reduce turnaround time and improve the efficacy of factor VIII replacement therapy. Based on clotting time, factor VIII:C activity is read from a standard curve. A clinical evaluation of this whole blood test was performed in two hemophilia centers. A high degree of correlation was seen (r = 0.813, n = 220) between the whole blood values obtained and conventional laboratory results. This level of correlation was superior to that obtained when comparing two different plasma-based systems (r = 0.753, n = 23). Factor VIII:C activity levels measured using the whole blood assay system were similar, irrespective of the test operator (laboratory technologist, nurse clinician, or patient). This study indicates that the whole blood factor VIII assay provides results comparable to those of conventional plasma-based assays, but in a more rapid and efficient manner. It provides an opportunity to reduce unnecessary patient consumption of replacement preparations, hence reducing the cost of hemophilia A maintenance and prophylaxis regimens, and to reduce overall patient exposure to human blood products. © 1996 Wiley-Liss, Inc.
Connective Tissue, Glycosaminoglycans, and Diseases the Thyroid*
Authors: TERRY J. SMITH, REBECCA S. BAHN, COLUM A. GORMAN
Journal: Endocrine Reviews (1989)

CONNECTIVE tissue imparts cohesion, strength, and form to the organs that it invests. It is comprised of several discrete cellular and noncellular components. The fibroblast and its more specialized derivatives (such as chondrocytes and osteocytes) elaborate and release several important molecules such as fibrous proteins (collagen), attachment proteins (fibronectin), glycoproteins, and ground substance. In this article we review the now abundant evidence that fibroblasts and their products are important mediators of some peripheral expressions of thyroid disease, including myxedema, pretibial dermopathy, thyroid acropachy, and ophthalmopathy of Graves' disease. Our review concentrates predominantly on the glycosaminoglycans that comprise ground substance. The fibrous proteins are given less attention. The early prejudice that the ground substance and connective tissue in general were rather unimportant becomes apparent in a quote attributed to Von Haller (1), who in 1757 wrote that "it is evident that a considerable part of the human body consists of matter which for so many centuries has been regarded as rubbish." Yet it is widely appreciated in contemporary biology that ground substance and the connective tissues play a crucial role in defining the microenvironment for specialized cells to function. They are important in cell attachment and cell-to-cell communication, and they influence the manner in which cells negotiate the extracellular milieu. A brief review of the physicochemical properties of the glycosaminoglycans that compose ground substance precedes the more detailed analysis of the impact that thyroid dysfunction can have on its synthesis and disposal.
Intestinal Bypass Operation as a Treatment for Obesity
Authors: GEORGE A BRAY
Journal: Annals of Internal Medicine (1976)

The intestinal bypass operation has come into wide use as a method for treating the grossly obese patient. Because it carries risks of morbidity and mortality, it is only suitable for those who meet certain minimal criteria. During the first year after surgery, weight loss varies from 9.1 to 68.0 kg [20 to 150 lb]. These patients have shown improved self-esteem and a reduction in the amount of depression. Mortality for this operation is approximately 4%; many serious complications (liver failure, pulmonary embolus, improper wound healing, severe loss of minerals, and vitamin deficiencies) occur. Hyperoxaluria may result from increased intestinal absorption. A dilated colon (pseudocolonic obstruction) may develop from bacterial overgrowth in the distal segment of the bypassed intestine. Since these serious complications affect 40% of the patients, the operation should be done by trained and skilled physicians who will also be able to manage the long-term postoperative period.
Significant Deviations in the Configurations of Homologous Tandem Repeats in Prokaryotic Genomes
Authors: Shintaro Hirayama, Satoshi Mizuta
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract We explored the possibilities of whole-genome duplication (WGD) in prokaryotic species, where we performed statistical analyses of the configurations of the central angles between homologous tandem repeats (TRs) on the circular chromosomes. At first, we detected TRs on their chromosomes and identified equivalent tandem repeat pairs (ETRPs); here, an ETRP is defined as a pair of tandem repeats sequentially similar to each other. Then we carried out statistical analyses of the central angle distributions of the detected ETRPs on each circular chromosome by way of comparisons between the detected distributions and those generated by null models. In the analyses, we estimated a P value by a simulation using the Kullback–Leibler divergence as a distance measure between two distributions. As a result, the central angle distributions for 8 out of the 203 prokaryotic species showed statistically significant deviations (P&amp;lt;0.05). In particular, we found out the characteristic feature of one round of WGD in Photorhabdus luminescens genome and that of two rounds of WGD in Escherichia coli K12.
STRUCTURE OF TYPE 5 ADENOVIRUS
Authors: Wesley C. Wilcox, Harold S. Ginsberg
Journal: The Journal of Experimental Medicine (1963)

Type 5 adenovirus was purified by fluorocarbon (freon 113) treatment followed by banding in a CsCl equilibrium density gradient. This method permitted separation of virus from normal host cell materials and virus-specific soluble antigens. Virus banded in CsCl with a mean bouyant density of 1.3349 gm/cm(3). The three virus-specific soluble antigens (group- and type-specific antigens and toxin) banded together with a mean bouyant density of 1.2832 gm/cm(3). The group-specific antigen was the predominant antigen of the purified virus particle, whereas the group- and type-specific antigens were present in equal titers in the antigen band. Infectious virus particles were inactivated by prolonged dialysis at pH 10.5. Centrifugation of inactivated virus preparations in a CsCl equilibrium density gradient resulted in separation of virus DNA from specific antigen: the antigens banded with a mean bouyant density of 1.2832 gm/cm(3) and the DNA sedimented to the bottom of the tube. The predominant antigen derived from purified virus particles was the group-specific antigen and it was in the same relative proportion to the type-specific antigen as measured in intact particles. The antigens derived from disrupted virus were immunologically identical with the soluble virus antigens present in infected cells.
Abstract 1045: Differentiated tumor cells secrete stem cell factor (SCF) to promote maintenance of cancer stem cells and induce EMT in colorectal tumors
Authors: Szabolcs Fatrai, Susanne J. van Schelven, Inne H.M. Borel Rinkes, Onno Kranenburg
Journal: Cancer Research (2014)

Abstract Colorectal tumors are hierarchically organized in which cancer stem cells (CSCs) are at the top of the hierarchy and give rise to non-tumorigenic differentiated tumor cells (DTC). The maintenance of normal intestinal stem cells requires ‘niche’ signals that are provided, at least in the small intestine, by neighboring differentiated Paneth cells. CSC maintenance may also depend on niche signals although little is known about the nature of such signals and their potential source. For the present study we tested the hypothesis that DTCs could provide CSC-maintaining signals. We used CSC-enriched colonosphere cultures that were established from human colorectal tumors and CSC-derived stably differentiated offspring that was derived from them. We found that DTCs established from multiple colorectal tumors greatly increased the clone-forming capacity of CSCs. This effect was reproduced by DTC-conditioned medium, suggesting the involvement of a secreted factor. By using a cytokine array we identified stem cell factor (SCF) as a major DTC-secreted factor. While SCF was mainly produced by DTCs, its receptor, c-Kit, was mainly expressed by CSCs. Indeed, recombinant SCF enhanced clone-forming capacity to a similar extent as DTC-conditioned medium. Furthermore, basal and DTC-stimulated clone-forming capacity was strongly reduced in the presence of an SCF-neutralizing antibody or in the presence of the cKit inhibitors Imatinib or ISCK03. qPCR and western blot analysis showed that inhibition of cKit caused a strong reduction in the expression of stem cell genes, including LGR5, CD133, OLMF4 and SOX2. Furthermore, DTCs induce the E-to N-cadherin switch in CSCs and to a strong increase in the expression of EMT markers such as vimentin, ZEB1, ZEB2, SNAIL1 and fibronectin. cKIT inhibitors prevented EMT. Our results identify a critical role for non-tumorigenic DTCs in the support of colorectal CSCs. DTCs induce EMT and EMT-associated stem cell characteristics at least in part via paracrine SCF-cKit signaling. We conclude that cKit inhibitors that are widely used in the clinic to treat gastrointestinal stromal tumors (GIST) and acute myeloid leukemia (AML), may have therapeutic value in the treatment of (a subgroup of) colorectal tumors. Citation Format: Szabolcs Fatrai, Susanne J. van Schelven, Inne H.M. Borel Rinkes, Onno Kranenburg. Differentiated tumor cells secrete stem cell factor (SCF) to promote maintenance of cancer stem cells and induce EMT in colorectal tumors. [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 1045. doi:10.1158/1538-7445.AM2014-1045
Phenotypic Male With Mosaic Sex Chromosomes
Authors: Wayne H. Finley, Sara C. Finley, Constance S. Pittman
Journal: JAMA (1964)

SEVERAL DIFFERENT KARYOTYPES, some with mosaicism, have now been demonstrated in cells from patients with the disorder of male sex differentiation known as Klinefelter's syndrome. The XXY sex chromosome pattern was the first aberration described in Klinefelter's syndrome<sup>1</sup>and has been the most frequent finding in cases subsequently studied. It has been suggested that those patients with Klinefelter's syndrome, but with karyotypes other than XXY, be considered as variants.<sup>2</sup>The sex chromosome pattern in the variants thus far recognized include XXXY, XXXXY, XXYY, XXXYY, and the mosaic karyotypes of XX/XXY, XY/XXY, XY/XXXY, XXXY/XXXXY, XX/XXY/ XXYYY. Although patients having these different karyotypes cannot be distinguished unequivocally on clinical grounds alone, it appears that the severity of mental retardation and disturbances of sex differentiation increase as the number of extra X chromosomes increases. This case of Klinefelter's syndrome is reported to provide clinical and cytological findings of a patient with