tbuckley/cabot-search huggingface dataset:
Comparative Genomics and Evolution of the Alpha-Defensin Multigene Family in Primates
Authors: S. Das, N. Nikolaidis, H. Goto, C. McCallister, J. Li, M. Hirano, M. D. Cooper
Journal: Molecular Biology and Evolution (2010)

Defensin genes encode small cationic antimicrobial peptides that form an important part of the innate immune system.They are divided into three families, alpha (a), beta (b), and theta (h), according to arrangement of the disulfide bonding pattern between cysteine residues.Considering the functional importance of defensins, investigators have studied the evolution and the genomic organization of defensin genes.However, these studies have been restricted mainly to b-defensins.To understand the evolutionary dynamics of a-defensin genes among primates, we identified the a-defensin repertoires in human, chimpanzee, orangutan, macaque, and marmoset.The a-defensin genes in primates can be classified into three phylogenetic classes (class I, II, and III).The presence of all three classes in the marmoset indicates that their divergence occurred before the separation of New World and Old World monkeys.Comparative analysis of the a-defensin genomic clusters suggests that the makeup of the a-defensin gene repertoires between primates is quite different, as their genes have undergone dramatic birthand-death evolution.Analysis of the encoded peptides of the a-defensin genes indicates that despite the overall high level of sequence divergence, certain amino acid residues or motifs are conserved within and between the three phylogenetic classes.The evolution of a-defensins in primates, therefore, appears to be governed by two opposing evolutionary forces.One force stabilizes specific amino acid residues and motifs to preserve the functional and structural integrity of the molecules and the other diversifies the sequences generating molecules with a wide range of activities against a large number of pathogens.
Treatment of variant angina with drugs: a survey of 11 cardiology institutes in Japan.
Authors: E Kimura, H Kishida
Journal: Circulation (1981)

Data from 11 cardiology institutes in Japan were examined to determine the effectiveness of drug therapy, especially with calcium antagonists, on variant angina. The subjects were 243 males and 43 females, most of whom were 40-59 years old. Coronary artery lesions were found in 92 of 162 patients (56.7%) in whom cinecoronary arteriograms were done. The efficacy rates of nifedipine, diltiazem and verapamil were 94.0%, 90.8% and 85.7%, respectively. Regardless of the presence or absence of organic coronary artery lesions, the drugs were effective in 92.3% of the patients with normal or nearly normal coronary arteries and in 82.6% of those with stenosis of more than 50% of the luminal diameter. These findings suggest that the drugs are effective through their antispasmodic actions.
Emergent Complexity in Myosin V-Based Organelle Inheritance
Authors: F. D. Mast, R. A. Rachubinski, J. B. Dacks
Journal: Molecular Biology and Evolution (2011)

How is adaptability generated in a system composed of interacting cellular machineries, each with a separate and functionally critical job to perform? The machinery for organelle inheritance is precisely one such system, requiring coordination between robust and ancient cellular modules, including the cell cycle, cytoskeleton, and organelle biogenesis/identity. Budding yeasts have emerged as powerful models to study these processes, which are critical for cellular survival, propagation, and differentiation, as organelles must compete for access to myosin V motors that travel along polarized actin cables to vectorially deliver bound cargo to the bud. Under the direction of the cell cycle, myosin V motors are recruited to organelles by specific interactions between their carboxyl-terminal globular tail domains and organelle-specific receptors. We used comparative genomics, phylogenetics, and secondary structure modeling to characterize the evolutionary history of these organelle-specific receptors. We find that while some receptors are retained widely across the animals and fungi, others are limited primarily to the Saccharomycetaceae family of budding yeast, with the emergent pattern of a conserved biogenic and inheritance factor often paired with an evolutionarily novel inheritance adaptor. We propose an evolutionary model whereby the emergence of myosin V–based organelle inheritance has utilized mechanisms of paralogy, mutation, and the appearance of pliable evolutionarily novel adaptor proteins. Our findings suggest an overarching evolutionary mechanism for how diverse cargoes compete for a single myosin V motor in organelle transport and detail one system's solution to obtaining evolutionary adaptability amongst constrained cellular modules.
High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer
Authors: K Shibuya
Journal: Thorax (2003)

We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer.Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400-430 nm, B2: 420-470 nm, and G: 560-590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources.The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically (p=0.002).High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.
STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE
Authors: N. A. Mitchison
Journal: The Journal of Experimental Medicine (1955)

The transfer of transplantation immunity by lymph node cells has been the subject of investigation. Transplantable tumors have been used to provoke and to measure transplantation immunity. Cells from the lymph nodes draining a tumor homograft were transferred as mince or in suspension into the peritoneum of a secondary host to confer immunity. These cells could confer immunity while the immunizing graft was undergoing breakdown during the primary, and also during the more rapid secondary, response. Cells from other nodes and from the spleen, and also whole blood or serum failed in these experiments to transfer immunity. In one combination of tumor and host, serum from immunized donors enhanced tumor growth. Evidence has been presented favoring the hypothesis that the lymph node cells were immunologically activated before transfer, and that they conferred immunity by continuing to function in their host. Immunization by tumor cells transferred along with the cells of the nodes could not account for the failure of lymph node transferred into susceptible animals to give rise to tumors; nor for the failure of tumor cells to give rise to immunity as rapidly as transferred lymph node cells. Freezing and thawing of the transferred cells prevented transfer of immunity. Cells from donors immunized against an isoantigen failed to confer immunity on hosts which carried that isoantigen, offering evidence of absorption of antibody. The duration of immunity transferred within an inbred strain was shorter than actively induced immunity, but longer than could have been expected of passively transferred immunity. After transfer of cells into foreign hosts, immunity declined more rapidly, as if the transferred cells were destroyed by the homograft reaction of the host. The possibility that cells of the host were activated has also been discussed. A brief review showed that similar problems are raised in other systems of transfer of immunity by cells.
Relation Between Mild Renal Dysfunction and Outcomes After Coronary Artery Bypass Grafting
Authors: Rosita Zakeri, Nick Freemantle, Vivian Barnett, Graham W. Lipkin, Robert S. Bonser, Timothy R. Graham, Stephen J. Rooney, Ian C. Wilson, Robert Cramb, Bruce E. Keogh, Domenico Pagano
Journal: Circulation (2005)

Risk stratification algorithms for coronary artery bypass grafting (CABG) do not include a weighting for preoperative mild renal impairment defined as a serum creatinine 130 to 199 micromol/L (1.47 to 2.25 mg/dL), which may impact mortality and morbidity after CABG.We reviewed prospectively collected data between 1997 and 2004 on 4403 consecutive patients undergoing first-time isolated CABG with a preoperative serum creatinine <200 micromol/L (2.26 mg/dL)] in a single institution. The in-hospital mortality was 2.5% (112 of 4403), the need for new dialysis/hemofiltration was 1.3% (57 of 4403), and the stroke rate was 2.5% (108 of 4403). There were 458 patients with a serum creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL (mild renal dysfunction group) and 3945 patients with a serum creatinine <130 micromol/L (<1.47 mg/dL). Operative mortality was higher in the mild renal dysfunction group (2.1% versus 6.1%; P<0.001) and increased with increasing preoperative serum creatinine level. New dialysis/hemofiltration (0.8%versus 5.2%; P<0.001) and postoperative stroke (2.2% versus 5.0%; P<0.01) were also more common in the patients with mild renal impairment. Multivariate analysis adjusting for known risk factors confirmed preoperative mild renal impairment (creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL; odd ratio, 1.91; 95% CI, 1.18 to 3.03; P=0.007) or glomerular filtration rate estimates <60 mL/min per 1.73 m2, derived using the Cockroft-Gault formula, (odds ratio, 1.98; 95% CI, 1.16 to 3.48; P=0.015) as independent predictors of in-hospital mortality. Preoperative mild renal dysfunction adversely affected the 3-year survival probability after CABG (93% versus 81%; P<0.001).Mild renal dysfunction is an important predictor of outcome in terms of in-hospital mortality, morbidity, and midterm survival in patients undergoing CABG.
Peripheral Vasoconstriction Associated with Hyperpotassemia
Authors: Frederick N. Sudak, George P. Fulton
Journal: Circulation Research (1962)

Hyperpotassemia was induced in hamsters by intravenous infusions of potassium salts. The caliber of blood vessels (10 to 100µ in diameter) in the cheek pouch was measured and comparisons were made when serum potassium concentration was maintained at 9.0 (σ= ± 1.64 mEq./L.) for 10 to 14 minutes and again at 12.3 (σ= ± 1.14 mEq./L.) for 10 to 14 minutes. In unoperated controls, a significant degree of vasoconstriction occurred in all arterial vessels at both levels of hyperpotassemia. Venular constriction was found at the higher potassium concentrations. Sympathetic denervation of the blood vessels had no effect on the vasoconstrictor response. Adrenalectomy prevented vasoconstriction at a potassium level of 9.0 mEq./L., but vasoconstriction was still evident in small arterioles at higher potassium levels. Sympathetic denervation of blood vessels in adrenalectomized animals, or treatment of intact animals with Dibenzylene, prevented vasoconstriction produced by hyperpotassemia. These data indicate that peripheral vasocontriction associated with hyperpotassemia is an indirect effect of the potassium ion.
Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review
Authors: Tom Jefferson, Chris Del Mar, Liz Dooley, Eliana Ferroni, Lubna A Al-Ansary, Ghada A Bawazeer, Mieke L van Driel, Ruth Foxlee, Alessandro Rivetti
Journal: BMJ (2009)

To systematically review evidence for the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.Search strategy of the Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without language restriction, for any intervention to prevent transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). Study designs were randomised trials, cohort studies, case-control studies, and controlled before and after studies.Of 2300 titles scanned 138 full papers were retrieved, including 49 papers of 51 studies. Study quality was poor for the three randomised controlled trials and most of the cluster randomised controlled trials; the observational studies were of mixed quality. Heterogeneity precluded meta-analysis of most data except that from six case-control studies. The highest quality cluster randomised trials suggest that the spread of respiratory viruses into the community can be prevented by intervening with hygienic measures aimed at younger children. Meta-analysis of six case-control studies suggests that physical measures are highly effective in preventing the spread of SARS: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52); wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03); wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06); wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41); wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12); and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease the spread of respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions being drawn.Routine long term implementation of some physical measures to interrupt or reduce the spread of respiratory viruses might be difficult but many simple and low cost interventions could be useful in reducing the spread.
Evidences that Leptin Up-regulates E-Cadherin Expression in Breast Cancer: Effects on Tumor Growth and Progression
Authors: Loredana Mauro, Stefania Catalano, Gianluca Bossi, Michele Pellegrino, Ines Barone, Sara Morales, Cinzia Giordano, Viviana Bartella, Ivan Casaburi, Sebastiano Andò
Journal: Cancer Research (2007)

Abstract Leptin, a cytokine mainly produced by adipocytes, seems to play a crucial role in mammary carcinogenesis. In the present study, we explored the mechanism of leptin-mediated promotion of breast tumor growth using xenograft MCF-7 in 45-day-old female nude mice, and an in vitro model represented by MCF-7 three-dimensional cultures. Xenograft tumors, obtained only in animals with estradiol (E2) pellet implants, doubled control value after 13 weeks of leptin exposure. In three-dimensional cultures, leptin and/or E2 enhanced cell-cell adhesion. This increased aggregation seems to be dependent on E-cadherin because it was completely abrogated in the presence of function-blocking E-cadherin antibody or EGTA, a calcium-chelating agent. In three-dimensional cultures, leptin and/or E2 treatment significantly increased cell growth, which was abrogated when E-cadherin function was blocked. These findings well correlated with an increase of mRNA and protein content of E-cadherin in three-dimensional cultures and in xenografts. In MCF-7 cells both hormones were able to activate E-cadherin promoter. Mutagenesis studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assays revealed that cyclic AMP–responsive element binding protein and Sp1 motifs, present on E-cadherin promoter, were important for the up-regulatory effects induced by both hormones on E-cadherin expression in breast cancer MCF-7 cells. In conclusion, the present study shows how leptin is able to promote tumor cell proliferation and homotypic tumor cell adhesion via an increase of E-cadherin expression. This combined effect may give reasonable emphasis to the important role of this cytokine in stimulating primary breast tumor cell growth and progression, particularly in obese women. [Cancer Res 2007;67(7):3412–21]
Prevalence of the bifid T waves in genotyped LQTS children
Authors: L. Zhang, K.W. Timothy, J. Fox, M.H. Lehmann, K.J. Meyer, A.J. Moss, J.L. Robinson, P.J. Schwartz, M.T. Keating, J.A. Towbin, G.M. Vincent
Journal: Journal of the American College of Cardiology (1998)
Barrett's oesophagus and oesophageal adenocarcinoma: how does acid interfere with cell proliferation and differentiation?
Authors: R C Fitzgerald
Journal: Gut (2005)

Acid, a principal component of gastro-oesophageal refluxate, may contribute to the development and malignant progression of Barrett's oesophagus. Oesophageal pH monitoring studies have demonstrated that patients with Barrett's oesophagus have severe and chronic acid reflux. However, there is overlap between the amount of acid exposure in patients with oesophagitis compared with patients with Barrett's oesophagus. This suggests that factors other than acid may be important in the aberrant oesophageal cell differentiation process that leads to the development of the metaplastic Barrett's mucosa. The other factors important in the aetiology of Barrett's oesophagus are poorly understood but probably include both genetic and environmental factors.
The unfavorable effects of concomitant asthma and sleeplessness due to the atopic eczema/dermatitis syndrome (AEDS) on quality of life in subjects allergic to house‐dust mites
Authors: I. Terreehorst, H. J. Duivenvoorden, Z. Tempels‐Pavlica, A. J. Oosting, J. G. R. De Monchy, C.A. F. M. Bruijnzeel‐Koomen, M. W. M. Post, R. Gerth van Wijk
Journal: Allergy (2002)

Background: Allergic rhinitis, asthma or the atopic eczema/dermatitis syndrome (AEDS) may independently impair quality of life in patients. However, although many allergic patients may suffer from more than one disorder, the effect of concomitant disease — in particular, the impact of AEDS — is largely unknown. As part of a large multicenter clinical trial on the efficacy of mattress casings in house‐dust mite (HDM) allergy, generic quality of life in a mixed population of 224 subjects with rhinitis ( n = 198) and/or asthma ( n = 111) and/or AEDS ( n = 64) was studied. The study aimed to estimate quality of life impairment in these atopic patients and to address the questionissue of whether one atopic disorder goes beyond other existing allergic diseases, thereby causing further impairment to quality of life. Methods: Generic quality of life was assessed by SF‐36. Quality of life in the atopic group was compared with a Dutch norm population. Multiple linear regression was used to determine the effects of disease (i.e. the presence of allergic rhinitis, asthma or AEDS) or disease severity, as assessed by visual analog scores (VAS) for asthma, rhinitis, VAS sleeplessness and VAS itching being considered as major symptoms in AEDS on SF‐36 domains. Results: Compared to the norm group, atopic patients were impaired in: physical functioning; role physical functioning; general health; vitality; and social functioning. The diagnosis of asthma was negatively associated with the SF‐36 subscales for physical functioning ( P = 0.02), and general health ( P &lt; 0.01). In line with these findings, asthma severity (VAS asthma) was negatively associated with physical functioning ( P &lt; 0.01), role physical functioning ( P &lt; 0.01), general health ( P &lt; 0.0.1), social functioning ( P = 0.01), emotional functioning ( P = 0.01), and vitality ( P = 0.01). VAS sleeplessness had significant negative effect on role physical functioning ( P &lt; 0.01), bodily pain ( P &lt; 0.01), General health ( P = 0.01), mental health ( P &lt; 0.01), social functioning ( P &lt; 0.01), and vitality ( P &lt; 0.01). In contrast, neither the diagnosis of allergic rhinitis or AEDS, nor VAS itching as an outcome parameter of AEDS, exerted additional effects on the SF‐36 domains. Conclusions: Patients with atopic disease based on HDM allergy may have impaired quality of life. The majority of these patients have allergic rhinitis. The (co)existence of asthma, expressed in terms of diagnostic criteria or symptom severity, or the presence of sleep disorders as a consequence of AEDS, may further impair quality of life.
The Binding Site of Human Adenosine Deaminase for Cd26/Dipeptidyl Peptidase IV
Authors: Eva Richard, Francisco X. Arredondo-Vega, Ines Santisteban, Susan J. Kelly, Dhavalkumar D. Patel, Michael S. Hershfield
Journal: The Journal of Experimental Medicine (2000)

Human, but not murine, adenosine deaminase (ADA) forms a complex with the cell membrane protein CD26/dipeptidyl peptidase IV. CD26-bound ADA has been postulated to regulate extracellular adenosine levels and to modulate the costimulatory function of CD26 on T lymphocytes. Absence of ADA–CD26 binding has been implicated in causing severe combined immunodeficiency due to ADA deficiency. Using human–mouse ADA hybrids and ADA point mutants, we have localized the amino acids critical for CD26 binding to the helical segment 126–143. Arg142 in human ADA and Gln142 in mouse ADA largely determine the capacity to bind CD26. Recombinant human ADA bearing the R142Q mutation had normal catalytic activity per molecule, but markedly impaired binding to a CD26+ ADA-deficient human T cell line. Reduced CD26 binding was also found with ADA from red cells and T cells of a healthy individual whose only expressed ADA has the R142Q mutation. Conversely, ADA with the E217K active site mutation, the only ADA expressed by a severely immunodeficient patient, showed normal CD26 binding. These findings argue that ADA binding to CD26 is not essential for immune function in humans.