tbuckley/cabot-search huggingface dataset:
Molecular Determinants and Evolutionary Dynamics of Wobble Splicing
Authors: J. Lv, Y. Yang, H. Yin, F. Chu, H. Wang, W. Zhang, Y. Zhang, Y. Jin
Journal: Molecular Biology and Evolution (2009)

Alternative splicing at tandem splice sites (wobble splicing) is widespread in many species, but the mechanisms specifying the tandem sites remain poorly understood. Here, we used synaptotagmin I as a model to analyze the phylogeny of wobble splicing spanning more than 300 My of insect evolution. Phylogenetic analysis indicated that the occurrence of species-specific wobble splicing was related to synonymous variation at tandem splice sites. Further mutagenesis experiments demonstrated that wobble splicing could be lost by artificially induced synonymous point mutations due to destruction of splice acceptor sites. In contrast, wobble splicing could not be correctly restored through mimicking an ancestral tandem acceptor by artificial synonymous mutation in in vivo splicing assays, which suggests that artificial tandem splice sites might be incompatible with normal wobble splicing. Moreover, combining comparative genomics with hybrid minigene analysis revealed that alternative splicing has evolved from the 3′ tandem donor to the 5′ tandem acceptor in Culex pipiens, as a result of an evolutionary shift of cis element sequences from 3′ to 5′ splice sites. These data collectively suggest that the selection of tandem splice sites might not simply be an accident of history but rather in large part the result of coevolution between splice site and cis element sequences as a basis for wobble splicing. An evolutionary model of wobble splicing is proposed.
High Titers of Anti-Human Herpesvirus 8 Antibodies in Elderly Males in an Endemic Population
Authors: Sabine Plancoulaine, Laurent Abel, Monique van Beveren, Antoine Gessain
Journal: JNCI Journal of the National Cancer Institute (2002)

Human herpesvirus 8 (HHV8) is the etiologic agent of Kaposi's sarcoma (KS), a tumor occurring mainly among elderly men in its endemic and classical forms. The male-to-female ratio of KS in different endemic populations ranges from 3 : 1 to 15 : 1. We investigated the influence of age and gender on anti-HHV8 antibody titers among HHV8-seropositive subjects of an endemic population (1819 villagers with 874 men and 945 women) of African origin living in French Guiana. By using a specific immunofluorescence assay, we found that the overall HHV8 seroprevalence of antibodies against lytic antigens was 11.8%. There was no difference between seroprevalence in males (11.7%) and females (11.8%). Among the 214 HHV8-seropositive subjects, anti-HHV8 antibody titers were found to increase with age (P<.001) and were higher in males than in females (P =.003). The geometric mean of HHV8 antibody titers was 1 : 105 (95% confidence interval [CI] = 1 : 77 to 1 : 144) for males versus 1 : 62 (95% CI = 1 : 47 to 1 : 81) for females. The titers increased from 1 : 59 (95% CI = 1 : 43 to 1 : 80) in males younger than 40 years to 1 : 452 (95% CI = 1 : 244 to 1 : 839) in the oldest male group (aged 50 years and older). Such high antibody titers directed against lytic antigens in males aged 40 years and older parallel the increase of endemic KS incidence in older African men. Our results suggest that the role of gender should also be considered in evaluating the association between anti-HHV8 antibody titers in people aged 40 years and older and the risk of developing KS.
Experimental Verification of Wilson's Derivation of the Principle of the Ventricular Gradient
Authors: MANUEL GARDBERG, IRVING L. ROSEN
Journal: Circulation Research (1961)

The concept of the ventricular gradient is based upon the theoretical representation of the electrogram of a myocardial fiber as the sum of two monophasic action potential (M.A.P.) curves, each of which represents the electrical activity of one-half of the fiber. Wilson showed that from this premise certain mathematical deductions are possible: (1) that the area of the electrogram is equal to the sum of the areas of the two MAP. curves; (2) that this area is independent of the rela tion of the two M.A.P. curves with respect to time and, therefore, that it is independent of the path of excitation; and (3) that as a corol lary of the latter, the measurement of the area of the electrogram may be used as a measure of the net electrical effect of local differences in repolarization. The present paper reports the results of experiments in which the electrical effects of a segment of a strip of turtle heart muscle were recorded as biphasic complexes and as two M.A.P. curves. Accurate measurement of the areas by means of an electronic integrator supports Wilson's premise. These observations furnish experimental confirmation of the theo retical basis of the concept of the ventricular gradient.
Inhibition of IgE-mediated allergic reactions by pharmacologically targeting the circadian clock
Authors: Yuki Nakamura, Nobuhiro Nakano, Kayoko Ishimaru, Noriko Ando, Ryohei Katoh, Katsue Suzuki-Inoue, Satoru Koyanagki, Hideoki Ogawa, Ko Okumura, Shigenobu Shibata, Atsuhito Nakao
Journal: Journal of Allergy and Clinical Immunology (2015)
Quantifying the Benefits and Harms of Screening Mammography
Authors: H. Gilbert Welch, Honor J. Passow
Journal: JAMA Internal Medicine (2013)

Like all early detection strategies, screening mammography involves trade-offs. If women are to truly participate in the decision of whether or not to be screened, they need some quantification of its benefits and harms. Providing such information is a challenging task, however, given the uncertainty--and underlying professional disagreement--about the data. In this article, we attempt to bound this uncertainty by providing a range of estimates-optimistic and pessimistic--on the absolute frequency of 3 outcomes important to the mammography decision: breast cancer deaths avoided, false alarms, and overdiagnosis. Among 1000 US women aged 50 years who are screened annually for a decade, 0.3 to 3.2 will avoid a breast cancer death, 490 to 670 will have at least 1 false alarm, and 3 to 14 will be overdiagnosed and treated needlessly. We hope that these ranges help women to make a decision: either to feel comfortable about their decision to pursue screening or to feel equally comfortable about their decision not to pursue screening. For the remainder, we hope it helps start a conversation about where additional precision is most needed.
2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages II. Dissociation of the inhibitory effects of 2-deoxyglucose on phagocytosis and ATP generation.
Authors: J Michl, D J Ohlbaum, S C Silverstein
Journal: The Journal of Experimental Medicine (1976)

Macrophages incubated in 2-deoxy-D-glucose (2-dG)-containing medium showed a marked decrease in cellular ATP content, and were unable to ingest IgG- and complement-coated erythrocytes via the corresponding membrane receptors for these ligands. However, the inhibitory effects of 2-dG on Fc- and C3 receptor-mediated phagocytosis were not a consequence of lowered macrophage ATP levels since addition of glucose or mannose to the culture medium restored the capacity of the macrophages to ingest IgG- and C3-coated particles without increasing ATP levels. These results indicate that Fc- and C3 receptor-mediated phagocytosis (opsonin dependent) differs qualitatively from the ingestion of latex and zymosan particles (opsonin independent); they suggest that the same regulatory molecules govern the responses of phagocytic cells to signals initiated by both the Fc and C3 receptors. The possibility that these molecules are regulated by glycosylation is discussed.
Transgenic Mice and Oncogenesis
Authors: S Cory, J M Adams
Journal: Annual Review of Immunology (1988)

The creation of transgenic mice carrying specific cancer-promoting genes has opened an exciting new era in oncology. The biological effects of an individual oncogene on diverse cell types can now be assessed directly within the living animal. While transgenic animals bear the introduced oncogene in every tissue, expression of that gene may either be widespread or directed to a particular cell lineage, depending upon the regulatory sequences chosen. The transgene should behave identically in every animal of an established lineage and, indeed, perhaps in every cell of a given type. Thus, a well-characterized transgenic line becomes a permanent resource. Perhaps the most significant opportunity provided by these transgenic animals is the possibility of exploring the pre-neoplastic state. One can attempt to assess whether an oncogene has perturbed differentiation within particular lineages. The perturbations may help to delineate early matu­ ration stages and to clarify how differentiation is controlled. Thus, new insights may emerge regarding the normal biological functions of proto­ oncogenes. The rules for oncogene cooperativity can also be evaluated within diverse cell types. For example, one can isolate the relevant cells from a pre-neoplastic animal bearing an oncogene and attempt to trans­ form them fully in vitro with retroviruses carrying other oncogenes. Alter­ natively, the second oncogene could be introduced simply by breeding mice of two independent transgenic lines. While the study of transgenic oncogenes is still in its infancy, major new insights have already been gained. This chapter briefly summarizes how transgenic animals are produced, and then considers our current state of
HLA-DP-unrestricted TNF- release in beryllium-stimulated peripheral blood mononuclear cells
Authors: M. Amicosante, F. Berretta, A. Franchi, P. Rogliani, C. Dotti, M. Losi, R. Dweik, C. Saltini
Journal: European Respiratory Journal (2002)

Berylliosis is a granulomatous disorder of the lung caused by inhalation of beryllium (Be) and dominated by the accumulation of CD4+ T-helper (Th)1 memory T-cells proliferating in response to Be in the lower respiratory tract. Two gene markers have been associated with susceptibility to berylliosis: 1) the human leucocyte antigen (HLA)-DP gene whose allelic variants, carrying glutamate in position 69 of the β-chain (HLA-DPGlu69), can bind Be directly and present it to interferon (IFN)-γ releasing Th1 T-cell clones from patients with berylliosis; and 2) the cytokine gene tumour necrosis factor (TNF)-α which has been shown to increase berylliosis risk independent of HLA-DPGlu69. In order to determine whether TNF-α release was triggered by Th1 T-cell activation by Be stimulation in the context of HLA-DPGlu69 molecules, the proliferation of BeSO<sub>4</sub>-stimulated blood mononuclear cells and the release of IFN-γ, TNF-α, RANTES (regulated on activation normal T-cell expressed and secreted), granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4, IL-6, IL-8, IL-10 and IL-12 by BeSO<sub>4</sub>-stimulated blood mononuclear cells was quantified in 11 individuals with berylliosis using an anti-HLA-DP antibody as a probe for HLA-DP restricted T-cell activation. While proliferation and IFN-γ release were completely abrogated by HLA-DP inhibition (inhibition with anti-HLA-DP monoclonal antibody (mAb): 88±16 and 77±16%, respectively; anti-HLA-DR: 29±38 and 14±10%, respectively), the release of TNF-α was not (inhibition with anti-HLA-DP mAb: 8.9±7.8%). No other cytokine was detected at significant levels. Moreover, Be was able to induce TNF-α production in healthy control subjects not exposed to Be in the absence of T-cell proliferation and IFN-γ production. In conclusion, these data suggest that the tumour necrosis factor-α response of mononuclear cells is independent of the activation of beryllium-specific human leucocyte anitgen-DP restricted T-cells, which is consistent with the finding that the tumour necrosis factorA2 and the human leucocyte anitgen-DPGlu69 genetic markers are independently interacting in increasing berylliosis risk.
Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens.
Authors: R L Evans, T J Faldetta, R E Humphreys, D M Pratt, E J Yunis, S F Schlossman
Journal: The Journal of Experimental Medicine (1978)

We have studied the modulation of Ia-like antigens on the surface membrane of human T cells responding in a one-way mixed leukocyte culture. A heterologous antiserum, (anti-p23,30), which is specific to HLA-D-related antigens and which is unreactive with normal peripheral T cells or thymocytes, was found to bind significantly to all T cells transformed in mixed leukocyte culture (MLC) as determined by indirect immunofluorescence on a fluorescence-activated cell sorter 1. Furthermore, cytotoxic T cells responsible for cell-mediated lympholysis were shown to react with anti-p23,30, whereas their unactivated progenitors did not. Immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis of a radioactive 29,000 and 34,000 dalton complex from MLC-primed T cells labeled with [35S]methionine indicated that allosensitized T cells synthesized these HLA-D-related antigens.
Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial
Authors: Sophie Liem, Ewoud Schuit, Maud Hegeman, Joke Bais, Karin de Boer, Kitty Bloemenkamp, Jozien Brons, Hans Duvekot, Bas Nij Bijvank, Maureen Franssen, Ingrid Gaugler, Irene de Graaf, Martijn Oudijk, Dimitri Papatsonis, Paula Pernet, Martina Porath, Liesbeth Scheepers, Marko Sikkema, Jan Sporken, Harry Visser, Wim van Wijngaarden, Mallory Woiski, Mariëlle van Pampus, Ben Willem Mol, Dick Bekedam
Journal: The Lancet (2013)
Compound heterozygosity for hemoglobins <scp>S</scp> and <scp>D</scp>
Authors: Kirstin Lund, Subarna Chakravorty, Sarmad Toma, Barbara J. Bain
Journal: American Journal of Hematology (2015)

A 15-year-old refugee from Iraq was referred to our hospital shortly after arriving in the UK. He had a long history of fatigue and bone pain. His blood count showed: WBC 6 × 109/l, hemoglobin concentration 92 g/l, MCV 99.6 fl, MCH 35.1 pg, and platelets 226 × 109/l. Reticulocyte count was 80 × 109/l. His blood film (top image) showed moderate numbers of sickle cells, some macrocytes, and features of hyposplenism (Howell–Jolly bodies, Pappenheimer bodies, and large platelets). The patient was unaware that he suffered from sickle cell disease but reported a prior history of regular transfusion. Before leaving Iraq he had been commenced on treatment with hydroxycarbamide with a resultant improvement in his transfusion requirement. He had also been taking deferasirox and his serum ferritin was 706 μg/l. High performance liquid chromatography (lower image), cellulose acetate electrophoresis at alkaline pH and acid agarose electrophoresis showed hemoglobins S and D. Hemoglobin S was 35.1%, hemoglobin D 42.3%, hemoglobin F 14.3% and hemoglobin A2 4.1%. Beta globin gene analysis by Sanger sequencing confirmed compound heterozygous mutations of HBB, c.20 A>T, p.Glu7Val (historically described as Beta codon 6 GAG>GTG Glu>Val) encoding hemoglobin S and c.364G>C, p.Glu122Gln (historically described as Beta codon 121 GAA>CAA Glu>Gln) encoding hemoglobin D Punjab/D Los Angeles. It is important to remember that “sickle cell disease” is not synonymous with sickle cell anemia but encompasses also a number of symptomatic compound heterozygous states. S/D disease was first recognized in 1951 in a “white American” family from Los Angeles with the newly identified variant hemoglobin being named “d” 1. Hemoglobin D Punjab is unusual in Middle Eastern populations where hemoglobin D Iran is more often found. It is most prevalent (∼2%) in the Sikh population of North West India but also occurs in Gujarati (∼1%), Pakistani, Thai, African American, Afro-Caribbean, northern European Caucasian, Yugoslavian, Turkish, and Chinese populations. Because of its possible interaction with hemoglobin S, hemoglobin D Punjab should be identified in antenatal screening programs.
Letter: Thyopac-5 test.
Authors: J G Hardy, G M Newble
Journal: BMJ (1974)

may be argued that the lymphocytes with complement receptors represent only a part of the total population of B-lymphocytes.'4However, the effect of A.T.G. was identical when either human complement or guinea- pig complement was used for EAC-rosette formation.With human complement the proportion of lymphocytes forning imu ne rosettes is significantly lower than with guinea-pig complement, suggesting that lymphocyte receptor for the two comple- ments may not always be shared.
Left Ventricular Echinococcosis With Peripheral Embolization
Authors: Christoph W. Kopp, Thomas Binder, Michael Grimm, Oliver Merl, Florian Thalhammer, Robert Ullrich, Gottfried Heinz, Gerald Mundigler, Thomas Stefenelli, Gerald Maurer, Helmut Baumgartner, Manfred Zehetgruber
Journal: Circulation (2002)
A PNIPAAm-based thermosensitive hydrogel containing SWCNTs for stem cell transplantation in myocardial repair
Authors: Xia Li, Jin Zhou, Zhiqiang Liu, Jun Chen, Shuanghong Lü, Hongyu Sun, Junjie Li, Qiuxia Lin, Boguang Yang, Cuimi Duan, Malcolm (Mengqiu) Xing, Changyong Wang
Journal: Biomaterials (2014)
Pathophysiological-Based Approaches to Treatment of Sickle Cell Disease
Authors: Martin H. Steinberg, Carlo Brugnara
Journal: Annual Review of Medicine (2003)

Sickle hemoglobin (HbS), as a result of its polymer-related and oxidant effects, damages the sickle erythrocyte, provokes inflammation, and causes endothelial injury. All these elements cause the phenotype of sickle cell disease. Novel treatments inhibit HbS polymerization by inducing fetal hemoglobin expression, prevent or repair erythrocyte dehydration by slowing cellular potassium and water loss, and replace HbS-producing erythroid progenitors by stem cell transplantation. Future treatment prospects include gene therapy, interruption of the interaction of sickle cells with the endothelium, inhibition of oxidative damage, and protection of an injured endothelium.
Effect of commercial airline travel on oxygen saturation in athletes
Authors: C Geertsema, A B Williams, P Dzendrowskyj, C Hanna
Journal: British Journal of Sports Medicine (2007)

Aircraft cabins are pressurised to maximum effective altitudes of 2440 metres, resulting in significant decline in oxygen saturation in crew and passengers. This effect has not been studied in athletes.To investigate the degree of decline in oxygen saturation in athletes during long-haul flights.A prospective cross-sectional study. National-level athletes were recruited. Oxygen saturation and heart rate were measured with a pulse oximeter at sea level before departure, at 3 and 7 hours into the flight, and again after arrival at sea level. Aircraft cabin pressure and altitude, cabin fraction of inspired oxygen and true altitude were also recorded.45 athletes and 18 healthy staff aged between 17 and 70 years were studied on 10 long-haul flights. Oxygen saturation levels declined significantly after 3 hours and 7 hours (3-4%), compared with sea level values. There was an associated drop in cabin pressure and fraction of inspired oxygen, and an increase in cabin altitude.Oxygen saturation declines significantly in athletes during long-haul commercial flights, in response to reduced cabin pressure. This may be relevant for altitude acclimatization planning by athletes, as the time spent on the plane should be considered time already spent at altitude, with associated physiological changes. For flights of 10-13 hours in duration, it will be difficult to arrive on the day of competition to avoid the influence of these changes, as is often suggested by coaches.
Energy metabolism in heart failure and remodelling
Authors: J. S. Ingwall
Journal: Cardiovascular Research (2008)

Myocytes of the failing heart undergo impressive metabolic remodelling. The time line for changes in the pathways for ATP synthesis in compensated hypertrophy is: flux through the creatine kinase (CK) reaction falls as both creatine concentration ([Cr]) and CK activity fall; increases in [ADP] and [AMP] lead to increases in glucose uptake and utilization; fatty acid oxidation either remains the same or decreases. In uncompensated hypertrophy and in other forms of heart failure, CK flux and fatty acid oxidation are both lower; any increases in glucose uptake and utilization are not sufficient to compensate for overall decreases in the capacity for ATP supply and [ATP] falls. Metabolic remodelling is under transcriptional and post-transcriptional control. The lower metabolic reserve of the failing heart contributes to impaired contractile reserve.
Prevalence of infection with TT virus (TTV), a novel DNA virus, in healthy japanese subjects, newborn infants, cord blood and breast milk
Authors: Hidenori Toyoda, Masayuki Naruse, Shoichi Yokozaki, Kiyoshi Morita, Isao Nakano, Atsuo Itakura, Makoto Okamura, Yoshihide Fukuda, Tetsuo Hayakawa
Journal: Journal of Infection (1999)
Immunological and Inflammatory Functions of the Interleukin-1 Family
Authors: Charles A. Dinarello
Journal: Annual Review of Immunology (2009)

More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.
Authors’ response: Long-term lung function in postinfectious bronchiolitis obliterans
Authors: Alejandro Colom, Alberto Maffey, Facundo Garcia Bournissen, Alejandro Teper
Journal: Thorax (2015)

Dear editors

We thank Drs Rosewich, Eckrich and Zielen for their interest and comments1 on our recent Thorax publication.2

We entirely agree that lung growth is clearly related to somatic growth. The main focus of the paper was based on the data obtained from 200 spirometries and not in lung volumes because they were not available in all patients. …
Characteristics of Aortic Diastolic Pressure Decay with Application to the Continuous Monitoring of Changes in Peripheral Vascular Resistance
Authors: MAURICE J. BOURGEOIS, BARRY K. GILBERT, DAVID E. DONALD, EARL H. WOOD
Journal: Circulation Research (1974)

Large changes in stroke volume and peripheral vascular resistance were induced by varying the heart rate and by intra-aortically infusing acetylcholine or angiotensin II in six dogs with heart block and electromagnetic flowmeters chronically implanted around their ascending aortas. Changes in stroke volume, aortic and atrial pressures, and systemic resistance were monitored continuously for 3-6 hours under morphine-pentobarbital anesthesia. The characteristics of diastolic pressure decay at heart rates ranging from 60 beats/min to 200 beats/min and during transient periods of asystole were studied, especially with reference to the distortions caused by reflected pressure waves. The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale. Under the conditions of these experiments, changes in the slope of that line and of its reciprocal, the time constant, correlated well with concomitant variations in peripheral vascular resistance. This relationship appears to be of practical value for continuous monitoring of systemic resistance directly from the diastolic segments of pressure pulses recorded from the lower thoracic aorta.