tbuckley/cabot-search huggingface dataset:
The role of the endometrium and embryo in human implantation
Authors: K. Diedrich, B.C.J.M. Fauser, P. Devroey, G. Griesinger
Journal: Human Reproduction Update (2007)

Despite many advances in assisted reproductive technologies (ART), implantation rates are still low. The process of implantation requires a reciprocal interaction between blastocyst and endometrium, culminating in a small window of opportunity during which implantation can occur. This interaction involves the embryo, with its inherent molecular programme of cell growth and differentiation, and the temporal differentiation of endometrial cells to attain uterine receptivity. Implantation itself is governed by an array of endocrine, paracrine and autocrine modulators, of embryonic and maternal origin. Implantation failure is thought to occur as a consequence of impairment of embryo developmental potential and/or impairment of uterine receptivity and the embryo-uterine dialogue. Therefore a better comprehension of implantation, and the relative importance of the factors involved, is warranted. New techniques for monitoring changes in the endometrium and/or the embryo at the level of gene regulation and protein expression may lead to the identification of better markers for implantation. Moreover, the use of predictive sets of markers may prove to be more reliable than a single marker. Continuing refinements to ART protocols, such as optimizing ovarian stimulation regimens, the timing of human chorionic gonadotrophin injection, or the timing of embryo transfer, should help to increase implantation rates further.
Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia
Authors: Fabio Ghiotto, Franco Fais, Angelo Valetto, Emilia Albesiano, Shiori Hashimoto, Mariella Dono, Hideyuki Ikematsu, Steven L. Allen, Jonathan Kolitz, Kanti R. Rai, Marco Nardini, Anna Tramontano, Manlio Ferrarini, Nicholas Chiorazzi
Journal: Journal of Clinical Investigation (2004)

Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged VHDJH and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb's reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG+ B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both.
Iron sensing and signalling
Authors: Rayko Evstatiev, Christoph Gasche
Journal: Gut (2011)

Iron deficiency is a common condition increasingly diagnosed and treated by gastroenterologists. The most common presentation of iron deficiency is anaemia; however, it is a systemic disorder affecting multiple aspects of health in various organs. Iron is an essential element, with iron-containing proteins exerting a variety of vital functions, including oxygen transport, cellular respiration, intermediary metabolism, regulation of transcription and DNA repair. Major pathways of iron utilisation and production of iron-containing proteins include iron sulphur cluster biosynthesis, haem synthesis and storage within ferritin. The main site of iron absorption is the small intestine, but most iron is recycled by the monocyte–macrophage system via phagocytosis of senescent erythrocytes. Hepcidin, the key iron-regulating peptide binds to the iron exporter ferroportin and leads to its degradation, thereby inhibiting intestinal iron absorption and cellular export. Hepcidin levels are regulated on a transcriptional level by various stimuli, including transferrin saturation, erythropoietic activity, hypoxia and inflammation. Iron deficiency evokes adaptive responses resulting in alteration of cellular metabolism, changes in gene expression, activation of signalling pathways, cell cycle regulation, differentiation and cell death. Such responses are mediated by a number of iron-sensitive signalling pathways, including the IRE/IRP system, HIF and haem signalling. This review provides a molecular perspective for the clinician and highlights important biological aspects of iron deficiency.
Role of Ca2+/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure
Authors: T ZHANG
Journal: Cardiovascular Research (2004)

Journal Article Role of Ca2+/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure Get access Tong Zhang, Tong Zhang Department of Pharmacology 0636, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan Heller Brown Joan Heller Brown * Department of Pharmacology 0636, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA *Corresponding author. Tel.: +1-858-534-2595; fax: +1-858-534-4337. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 63, Issue 3, August 2004, Pages 476–486, https://doi.org/10.1016/j.cardiores.2004.04.026 Published: 15 August 2004 Article history Received: 12 February 2004 Revision received: 05 April 2004 Accepted: 22 April 2004 Published: 15 August 2004
Severe inflammatory upper airway stenosis in ulcerative colitis
Authors: H Rickli, C Fretz, M Hoffman, A Walser, A Knoblauch
Journal: European Respiratory Journal (1994)

Severe upper airway stenosis was diagnosed in a 23 year old woman who presented with hoarseness, cough and dyspnoea 8 yrs after initial diagnosis of ulcerative colitis. The respiratory symptoms worsened over the next few months, the patient eventually developing dysphagia and ultimately severe upper airway obstruction. The narrowest site was the glottis, which was severely stenosed by inflammatory swellings. Systemic corticosteroids led to rapid clinical improvement and restoration of normal airway patency within a few months. Ulcerative colitis is frequently associated with extraintestinal inflammatory manifestations. In the respiratory tract these usually take the form of chronic bronchitis, which occasionally develops into bronchiectasis. This case confirms that the inflammation can also involve the larynx and large airways.
Irbesartan in Patients with Atrial Fibrillation
Authors: Salim Yusuf, Jeff S Healey, Janice Pogue, Susan Chrolavicius, Marcus Flather, Robert G Hart, Stefan H Hohnloser, Campbell D Joyner, Marc A Pfeffer, Stuart J Connolly
Journal: New England Journal of Medicine (2011)

The risk of cardiovascular events among patients with atrial fibrillation is high. We evaluated whether irbesartan, an angiotensin-receptor blocker, would reduce this risk.We randomly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo. These patients were already enrolled in one of two trials (of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants). The first coprimary outcome was stroke, myocardial infarction, or death from vascular causes; the second was this composite outcome plus hospitalization for heart failure.A total of 9016 patients were enrolled and followed for a mean of 4.1 years. The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group, and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater. The first coprimary outcome occurred at a rate of 5.4% per 100 person-years in both groups (hazard ratio with irbesartan, 0.99; 95% confidence interval [CI], 0.91 to 1.08; P=0.85). The second coprimary outcome occurred at a rate of 7.3% per 100 person-years among patients receiving irbesartan and 7.7% per 100 person-years among patients receiving placebo (hazard ratio, 0.94; 95% CI, 0.87 to 1.02; P=0.12). The rates of first hospitalization for heart failure (a prespecified secondary outcome) were 2.7% per 100 person-years among patients receiving irbesartan and 3.2% per 100 person-years among patients receiving placebo (hazard ratio, 0.86; 95% CI, 0.76 to 0.98). Among patients who were in sinus rhythm at baseline, there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography, nor was there a benefit in a subgroup that underwent transtelephonic monitoring. More patients in the irbesartan group than in the placebo group had symptomatic hypotension (127 vs. 64) and renal dysfunction (43 vs. 24).Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation. (Funded by Bristol-Myers Squibb and Sanofi-Aventis; ClinicalTrials.gov number, NCT00249795.).
Early Cystic Fibrosis Lung Disease Detected by Bronchoalveolar Lavage and Lung Clearance Index
Authors: Yvonne Belessis, Barbara Dixon, Glenn Hawkins, John Pereira, Jenny Peat, Rebecca MacDonald, Penny Field, Andrew Numa, John Morton, Kei Lui, Adam Jaffe
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Unrecognized airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease; therefore early detection and treatment is highly desirable.To determine whether the lung clearance index (LCI) is a sensitive and repeatable noninvasive measure of airway infection and inflammation in newborn-screened children with CF.Forty-seven well children with CF (mean age, 1.55 yr) and 25 healthy children (mean age, 1.26 yr) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage performed.The mean (SD) LCI in healthy children was 6.45 (0.49). The LCI was higher in children with CF (7.21 [0.81]; P < 0.001). The upper limit of normal for the LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF, including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. The LCI was higher in children with Pseudomonas (7.92 [1.16]) than in children without Pseudomonas (7.02 [0.56]) (P = 0.038). The LCI correlated with bronchoalveolar lavage IL-8 (R(2) = 0.20, P = 0.004) and neutrophil count (R(2) = 0.21, P = 0.001). An LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas.The LCI is elevated early in CF, especially in the presence of Pseudomonas and airway inflammation. The LCI is a feasible, repeatable, and sensitive noninvasive marker of lung disease in young children with CF.
STUDIES ON TUBERCULIN FEVER
Authors: John M. Moses, Elisha Atkins
Journal: The Journal of Experimental Medicine (1961)

Certain characteristics of tolerance which develops to the pyrogenic effects of old tuberculin (OT) in BCG-vaccinated rabbits have been described. Rabbits made tolerant by several injections of OT lost their ability to produce detectable amounts of endogenous pyrogen (EP) in response to the specific agent (OT) but mobilized normal amounts of EP when given a small unrelated stimulus. On the other hand, when this stimulus followed shortly after an initial tuberculin fever of sufficient magnitude, release of additional EP was suppressed, presumably due to an inhibitory effect of the EP previously mobilized by tuberculin. Similarly, a single large dose of endotoxin almost completely suppressed the response of sensitized rabbits to OT given several hours later. Since several spaced injections of the same dosage were ineffective, this phenomenon does not appear to be attributable to the known mechanisms by which endotoxins promote non-specific resistance to toxicity and infection. Tolerance to tuberculin could not be definitely shown following an injection of Newcastle disease virus which also produces a circulating EP, and it has been inferred that endotoxin blocks the pyrogenic action of antigen on host tissues directly rather than through mobilizing EP. On the basis of these observations, the relationship of specific to non-specific tolerance to tuberculin fever has been compared in terms of the ability of such tolerant animals to mobilize EP to heterologous stimuli and it is concluded that the two forms of tolerance are different. Furthermore, the fact that a number of unrelated agents produce tolerance non-specifically supports the concept that there may be a common source of EP released by a number of stimuli, including endotoxins and myxoviruses, as well as antigen in specifically sensitized hosts.
Spotty Calcification Typifies the Culprit Plaque in Patients With Acute Myocardial Infarction
Authors: Shoichi Ehara, Yoshiki Kobayashi, Minoru Yoshiyama, Kenei Shimada, Yoshihisa Shimada, Daiju Fukuda, Yasuhiro Nakamura, Hajime Yamashita, Hiroyuki Yamagishi, Kazuhide Takeuchi, Takahiko Naruko, Kazuo Haze, Anton E. Becker, Junichi Yoshikawa, Makiko Ueda
Journal: Circulation (2004)

Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented.Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification.Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.
Codon bias and plasticity in immunoglobulins
Authors: T. B. Kepler
Journal: Molecular Biology and Evolution (1997)

Immunoglobulin genes experience Darwinian evolution twice. In addition to the germline evolution all genes experience, immunoglobulins are subjected, upon exposure to antigen, to somatic hypermutation. This is accompanied by selection for high affinity to the eliciting antigen and frequently results in a significant increase in the specificity of the responding population. The hypermutation mechanism displays a strong sequence specificity. Thus arises the opportunity to manipulate codon bias in a site-specific manner so as to direct hypermutation to those parts of the gene that encode the antigen-binding portions of the molecule and away from those that encode the structurally conserved regions. This segregation of mutability would clearly be advantageous; it would enhance the generation of potentially useful variants while keeping mutational loss to acceptably low levels. But it is not clear that the advantage gained would be large enough to produce a measurable effect within the background stochasticity of the evolutionary process. I have performed a pair of statistical tests to determine whether site-specific codon bias in human immunoglobulin genes is correlated with the sequence specificity of the somatic mutation mechanism. The sequence specificity of the mutator was determined by analysis of a database of published immunoglobulin intron sequences that had experienced somatic mutation but not selection. The site-specific codon bias was determined by analysis of published sequences of human germline immunoglobulin V genes. Both tests strongly suggest that evolution has acted to enhance the plasticity of immunoglobulin genes under somatic hypermutation.
Divergence in the Face of Gene Flow: The Case of Two Newts (Amphibia: Salamandridae)
Authors: Krystyna Nadachowska, Wiesław Babik
Journal: Molecular Biology and Evolution (2009)

Understanding the process of divergence requires the quantitative characterization of patterns of gene flow between diverging taxa. New and powerful coalescent-based methods give insight into these processes in unprecedented details by enabling the reconstruction of the temporal distribution of past gene flow. Here, we use sequence variation at eight nuclear markers and mitochondrial DNA (mtDNA) in multiple populations to study diversity, divergence, and gene flow between two subspecies of a salamander, the smooth newt (Lissotriton vulgaris kosswigi and Lissotriton vulgaris vulgaris) in Turkey. The ranges of both subspecies encompass mainly the areas of this important glacial refugial area. Populations in refugia where species have been present for a long time and differentiated in situ should better preserve the record of past gene flow than young populations in postglacial expansion areas. Sequence diversity in both subspecies was substantial (nuclear πsil = 0.69% and 1.31%). We detected long-term demographic stability in these refugial populations with large effective population sizes (Ne) of the order of 1.5–3 × 105 individuals. Gene trees and the isolation with migration (IM) analysis complemented by tests of nested IM models showed that despite deep, pre-Pleistocene divergence of the studied newts, asymmetric introgression from vulgaris to kosswigi has occurred, with signatures of recent gene flow in mtDNA and an anonymous nuclear marker, and evidence for more ancient introgression in nuclear introns. The distribution of migration times raises the intriguing possibility that even the initial divergence may have occurred in the face of gene flow.
Male sex predominance in Chlamydia trachomatis sexually acquired reactive arthritis: are women more protected by anti-chlamydia antibodies?
Authors: S Bas
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To determine whether the humoral anti-chlamydia antibody response might be related to the ineffective bacterial elimination seen in patients with<i>Chlamydia trachomatis</i> reactive arthritis, particularly in men, who have a higher prevalence of the disease than women. <h3>METHODS</h3> The number and specificity of the antibody responses to 27 different<i>C trachomatis</i> antigens were determined by western blots in serum samples from patients with <i>C trachomatis</i> urogenital infection, with and without reactive arthritis, with a special regard to the sex of the patients. <h3>RESULTS</h3> Patients with reactive arthritis had antibodies to significantly fewer chlamydia antigens than those with urethritis only. Antibodies from men recognised significantly fewer antigens than antibodies from women. The IgA class antibodies were slightly more relevant than those of the IgG class for differentiation of patients with reactive arthritis from those with uncomplicated genitourinary infection. <h3>CONCLUSIONS</h3> In patients with acute <i>C trachomatis</i> infection the development of reactive arthritis may be related, particularly in men, to a deficient humoral response, to antigens which perhaps play a part in the clearance of the bacteria. Men who cannot generate antibodies to a large number of antigens may be less able to contain the local infection, allowing a wide systemic dissemination of the organisms to the joints.
Usefulness of Serum Tryptase in the Diagnosis of Anaphylaxis by Food Allergy in Childhood
Authors: M. Narita, I. Nomura, A. Aota, A. Saitoh, M. Akashi, M. Futamura, H. Watanabe, T. Suda, Y. Ohya, M. Ebisawa, A. Akasawa
Journal: Journal of Allergy and Clinical Immunology (2006)
The Evolution of RuBisCO Stability at the Thermal Limit of Photoautotrophy
Authors: Scott R. Miller, Michele A. McGuirl, Darla Carvey
Journal: Molecular Biology and Evolution (2013)

A long-standing question in evolutionary biology is how organisms adapt to novel environments. In North American hot springs, diversification of a clade of the cyanobacterium Synechococcus into hotter environments has resulted in the unique innovation of a light-driven ecosystem at temperatures up to 74°C, and temperature adaptation of photosynthetic carbon fixation with the Calvin cycle contributed to this process. Here, we investigated the evolution of thermostability of the Calvin cycle enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO) during Synechococcus divergence. Circular dichroism thermal scans revealed that the RuBisCO of the most thermotolerant Synechococcus lineage is more stable than those of other lineages or of resurrected ancestral enzymes. Using site-directed mutagenesis, we next identified four amino acid substitutions that together increased stability and activity of this enzyme at higher temperatures. These are clustered near critical subunit interfaces distant from the active site. Each of the four amino acids is also observed in a less thermostable Synechococcus RuBisCO, and the impact on stability of three of these appears to be epistatic. Recombination analyses that allow for recurrent mutation as well as patterns of synonymous variation surrounding these sites suggest that the evolution of a more thermostable RuBisCO may have involved homologous recombination. Our results provide insights on the molecular evolutionary processes that shape niche differentiation and ecosystem function.