tbuckley/cabot-search huggingface dataset:
Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties
Authors: Jennifer Debarry, Holger Garn, Anna Hanuszkiewicz, Nina Dickgreber, Nicole Blümer, Erika von Mutius, Albrecht Bufe, Sören Gatermann, Harald Renz, Otto Holst, Holger Heine
Journal: Journal of Allergy and Clinical Immunology (2007)
Emerging Technologies for Assembly of Microscale Hydrogels
Authors: Umut Atakan Gurkan, Savas Tasoglu, Doga Kavaz, Melik C. Demirel, Utkan Demirci
Journal: Advanced Healthcare Materials (2012)

Abstract Assembly of cell encapsulating building blocks ( i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell‐based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems ( e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro‐ and nano‐scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high‐throughput and scalable methods to assemble microscale units with a complex 3D micro‐architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications.
Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells.
Authors: N Killeen, A Moriarty, H S Teh, D R Littman
Journal: The Journal of Experimental Medicine (1992)

The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes.
Degenerative Changes in the Cardiovascular System of the Spawning Pacific Salmon ( <i>Oncorhynchus tshawytscha</i> )
Authors: O. H. ROBERTSON, BERNARD C. WEXLER, BENJAMIN F. MILLER
Journal: Circulation Research (1961)

In a stndy of the cardiovascular system of spawning Pacific salmon, degenerative changes were found in the heart muscle, coronary and visceral arteries, and capillaries of the kidney glomeruli. The heart muscle showed vacuolization of the muscle fibers with loss of fibrils, deposition of collagen, and cartilaginous meta plasia. Changes in the coronary and visceral arteries consisted of intimal hyperplasia with deposition of mucopolysaccharides, disruption of the internal elastic membrane, and destruction of adjacent muscle fibers in the media. The glomerular capillaries showed marked sclerosis. The resemblance of the arterial changes in the salmon to the beginning mani festations of arteriosclerosis in man, mammals, and birds is pointed out, and the relationship of the salmon's state of hyperadrenoeorticism to the occurrence of the vascular lesions is discussed.
Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation.
Authors: H Tsutsui, F G Spinale, M Nagatsu, P G Schmid, K Ishihara, G DeFreyte, G Cooper, B A Carabello
Journal: Journal of Clinical Investigation (1994)

The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements.
Effects of tamoxifen on uterus
Authors: S.M Ismail, T.H Bourne, W.P Collins, S Campbell, T.J Powles, Patrick Neven, Xavier De Muylder, Yves Van Belle, Rudi Campo, Guido Vanderick, Zenon Rayter, Jean-Claude Gazet, John Shephed, Peter Trott, William Svensson, Roger A'Hern
Journal: The Lancet (1994)
Involvement of GTA protein NC2β in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation
Authors: Cinzia Di Pietro, Marco Ragusa, Davide Barbagallo, Laura R Duro, Maria R Guglielmino, Alessandra Majorana, Veronica Giunta, Antonella Rapisarda, Elisa Tricarichi, Marco Miceli, Rosario Angelica, Agata Grillo, Barbara Banelli, Isabella Defferari, Stefano Forte, Alessandro Laganà, Camillo Bosco, Rosalba Giugno, Alfredo Pulvirenti, Alfredo Ferro, Karl H Grzeschik, Andrea Di Cataldo, Gian P Tonini, Massimo Romani, Michele Purrello
Journal: Molecular Cancer (2008)

Abstract Background The General Transcription Apparatus (GTA) comprises more than one hundred proteins, including RNA Polymerases, GTFs, TAFs, Mediator, and cofactors such as heterodimeric NC2. This complexity contrasts with the simple mechanical role that these proteins are believed to perform and suggests a still uncharacterized participation to important biological functions, such as the control of cell proliferation. Results To verify our hypothesis, we analyzed the involvement in Neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2β (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2α (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2β mRNA had also genomic deletions at the corresponding locus. Conclusion Our data show that NC2β is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2β, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.
ERCC1 and ERCC2 Expression in Malignant Tissues From Ovarian Cancer Patients
Authors: M. Dabholkar, F. Bostick-Bruton, C. Weber, V. A. Bohr, C. Egwuagu, E. Reed
Journal: JNCI Journal of the National Cancer Institute (1992)

ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents.Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance.Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene.Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders.We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.
Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells
Authors: Clare A. Notley, Julia J. Inglis, Saba Alzabin, Fiona E. McCann, Kay E. McNamee, Richard O. Williams
Journal: The Journal of Experimental Medicine (2008)

IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55−/− but not p75−/− mice. The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55−/− mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. Treatment of macrophages with rTNF also inhibited p40 production in vitro. These findings indicate that at least one of the ways in which TNF regulates Th1/Th17 responses in arthritis is by down-regulating the expression of p40. Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells.
F<scp>AT</scp> M<scp>ETABOLISM IN</scp> I<scp>NSECTS</scp>
Authors: Lilián E Canavoso, Zeina E Jouni, K Joy Karnas, James E Pennington, Michael A Wells
Journal: Annual Review of Nutrition (2001)

▪ Abstract The study of fat metabolism in insects has received considerable attention over the years. Although by no means complete, there is a growing body of information about dietary lipid requirements, and the absolute requirement for sterol is of particular note. In this review we (a) summarize the state of understanding of the dietary requirements for the major lipids and (b) describe in detail the insect lipid transport system. Insects digest and absorb lipids similarly to vertebrates, but with some important differences. The hallmark of fat metabolism in insects centers on the lipid transport system. The major lipid transported is diacylglycerol, and it is carried by a high-density lipoprotein called lipophorin. Lipophorin is a reusable shuttle that picks up lipid from the gut and delivers it to tissues for storage or utilization without using the endocytic processes common to vertebrate cells. The mechanisms by which this occurs are not completely understood and offer fruitful areas for future research.
A Prospective Study of Plasma Prolactin Concentrations and Risk of Premenopausal and Postmenopausal Breast Cancer
Authors: Shelley S. Tworoger, A. Heather Eliassen, Patrick Sluss, Susan E. Hankinson
Journal: Journal of Clinical Oncology (2007)

Epidemiologic studies suggest that prolactin is associated with breast cancer risk in older women. Because of limited prospective data, particularly in younger women, we examined whether prolactin concentrations were associated with breast cancer risk among women 42 to 55 years (68% premenopausal) from the Nurses' Health Study (NHS), and then conducted a pooled analysis of three studies.The analysis included 377 cases of breast cancer diagnosed after blood draw and before June 2000; two controls were matched per case on age, menopausal status at blood draw and diagnosis, fasting status, and time of day and month of blood collection. These data were pooled with two previously published data sets from the NHS and NHSII cohorts (n = 1,539 cases, 2,681 controls; ages 32 to 70 years).Prolactin was modestly associated with an increased breast cancer risk (relative risk [RR], top v bottom quartile = 1.3; 95% CI, 0.9 to 1.9; P for trend = .12). Risk estimates did not vary by menopausal status, tumor invasiveness, or estrogen receptor (ER) status. In the pooled analysis, the overall RR was 1.3 (95% CI, 1.1 to 1.6; P for trend = .002), and did not vary by menopausal status (P for interaction = .95). The risk was strongest for women with ER+ tumors (RR = 1.6; 95% CI, 1.2 to 2.0; P for trend < .001). Correcting for within-person variability, the RR comparing the median of the top versus the bottom prolactin quartile increased from 1.3 to 1.7 for all women and from 1.5 to 2.1 for ER+ cases.These data, in conjunction with experimental studies, indicate that prolactin likely is important in breast cancer etiology, particularly ER+ tumors, over a wide range of ages.
S104 Exposure to Welding Fume and Adhesion of Streptococcus Pneumoniae to A549 Alveolar Cells
Authors: R Suri, K Palmer, JAS Ross, D Coggon, J Grigg
Journal: Thorax (2012)

<h3>Background and Objectives</h3> Epidemiological studies suggest that that occupational exposure to welding fumes (WF), increases susceptibility to invasive pneumococcal disease.<sup>1</sup> The alveoli are a site for invasive disease caused by <i>Streptococcus pneumoniae</i> (Sp). To date the mechanism whereby welding fumes increases susceptibility to pneumococcal pneumonia is unknown. Platelet activating factor receptor (PAFR) is a host entry receptor for Sp in airway cells exposed to particulate matter air pollution.<sup>2</sup> We assessed the hypothesis that welding fumes increase adhesion of Sp to airway cells via PAFR. <h3>Methods</h3> Fume from a mild steel hyperbaric welding operation (WF) were collected from filtres and resuspended in PBS. Monolayers of the alveolar epithelial cell line, A549, were exposed to either WF alone or WF + a PAFR blocker (CV3988) for 3 h. Cells were then exposed to Sp for 2 h. Adherent and internalised bacteria were assessed by quantitative culture. Data were expressed as a mean±SEM of &gt;4 replicates and were compared by t test. <h3>Results</h3> WF increased pneumococcal adhesion to A549 cells (Fig 1A) in a dose-dependent manner (**p&lt;0.01 vs. control). Blocking PAFR with CV3988 attenuated WF-stimulated adhesion (** p&lt;0.005, Fig 1B). <h3>Conclusion</h3> Increased PAFR-medicated pneumococcaladhesion to lower airway cells is a putative mechanism for the association between exposure to WF and vulnerability to pneumococcal pneumonia. Palmer, KT; Poole, J; Ayres, J G; Mann, J; Burge, P S; Coggon, D. Exposure to Metal Fume and Infectious Pneumonia. <i>American Journal of Epidemiology</i> 157, 227–233 (2003). Mushtaq, N <i>et al.</i> Adhesion ofStreptococcus pneumoniae to human airway epithelial cells exposed to urbanparticulate matter. <i>The Journal of allergy and clinical immunology</i><b>127</b>,1236–42 (2011).
Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women
Authors: Herbert Marini, Letteria Minutoli, Francesca Polito, Alessandra Bitto, Domenica Altavilla, Marco Atteritano, Agostino Gaudio, Susanna Mazzaferro, Alessia Frisina, Nicola Frisina, Carla Lubrano, Michele Bonaiuto, Rosario D'Anna, Maria Letizia Cannata, Francesco Corrado, Elena Bianca Adamo, Steven Wilson, Francesco Squadrito
Journal: Annals of Internal Medicine (2007)

Background: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. Objective: To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Design: Randomized, double-blind, placebo-controlled trial. Setting: 3 university medical centers in Italy. Patients: 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. Intervention: After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. Measurements: The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. Results: At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. −0.053 g/cm2 [CI, −0.058 to −0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. −0.037 g/cm2 [CI, −0.044 to −0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. Limitations: The study did not measure fractures and had limited power to evaluate adverse effects. Conclusion: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.
The Role of Oxidized Low-Density Lipoproteins in the Pathogenesis of Atherosclerosis
Authors: S Parthasarathy, D Steinberg, J L Witztum
Journal: Annual Review of Medicine (1992)

Advances in human genome editing, in particular the development of the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 method, have led to increasing concerns about the ethics of editing the human genome. In response, the US National ...Read More
KIT Pathway Alterations in Mucosal Melanomas of the Vulva and Other Sites
Authors: Katarina Omholt, Eva Grafström, Lena Kanter-Lewensohn, Johan Hansson, Boel K. Ragnarsson-Olding
Journal: Clinical Cancer Research (2011)

Abstract Purpose: A significant proportion of mucosal melanomas contain alterations in KIT. The aim of this study was to characterize the pattern of KIT, NRAS, and BRAF mutations in mucosal melanomas at specific sites and to assess activation of the KIT downstream RAF/MEK/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in mucosal melanoma specimens. Experimental Design: Seventy-one primary mucosal melanomas from various sites were studied. Mutation analysis was done by DNA sequencing. Expression of KIT, phosphorylated (p)-ERK, and p-AKT was evaluated by immunohistochemistry. Results: KIT mutations were detected in 35% (8 of 23) of vulvar, 9% (2 of 22) of anorectal, 7% (1 of 14) of nasal cavity, and 20% (1 of 5) of penile melanomas. No KIT mutations were found in 7 vaginal melanomas. The difference in KIT mutation frequency between vulvar and nonvulvar cases was statistically significant (P = 0.014). The overall frequencies of NRAS and BRAF mutations were 10% and 6%, respectively. Notably, vaginal melanomas showed a NRAS mutation rate of 43%. KIT gene amplification (≥4 copies), as assessed by quantitative real-time PCR, was observed in 19% of cases. KIT expression was associated with KIT mutation status (P &amp;lt; 0.001) and was more common in vulvar than nonvulvar tumors (P = 0.016). Expression of p-ERK and p-AKT was observed in 42% and 59% of tumors, respectively, and occurred irrespective of KIT/NRAS/BRAF mutation status. NRAS mutation was associated with worse overall survival in univariate analysis. Conclusions: Results show that KIT mutations are more common in vulvar melanomas than other types of mucosal melanomas and that both the RAF/MEK/ERK and PI3K/AKT pathways are activated in mucosal melanoma specimens. Clin Cancer Res; 17(12); 3933–42. ©2011 AACR.
A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer
Authors: Javier E. Girardini, Marco Napoli, Silvano Piazza, Alessandra Rustighi, Carolina Marotta, Enrico Radaelli, Valeria Capaci, Lee Jordan, Phil Quinlan, Alastair Thompson, Miguel Mano, Antonio Rosato, Tim Crook, Eugenio Scanziani, Anthony R. Means, Guillermina Lozano, Claudio Schneider, Giannino Del Sal
Journal: Cancer Cell (2011)
Anti-tumor necrosis factor-alpha prevents decreased ventricular contractility in endotoxemic pigs.
Authors: M J Herbertson, H A Werner, C M Goddard, J A Russell, A Wheeler, R Coxon, K R Walley
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

It is not known how the decrease in left ventricular contractility following endotoxin exposure is mediated, or whether this decrease is preventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated with either endotoxin or saline. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (Emax) of the end-systolic pressure-volume relationship. Four hours after the start of endotoxin infusion in the nonspecific IgG pretreated group, Emax had decreased by 44 +/- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly decreasing after an initial increase (p < 0.05). Anti-TNF alpha significantly reduced the decrease in Emax (11 +/- 9%, p < 0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to decreased left ventricular contractility.