tbuckley/cabot-search huggingface dataset:
One-Year Recovery and Relapse Rates of Children With a Prepubertal and Early Adolescent Bipolar Disorder Phenotype
Authors: Barbara Geller, James L. Craney, Kristine Bolhofner, Melissa P. DelBello, Marlene Williams, Betsy Zimerman
Journal: American Journal of Psychiatry (2001)

The study examined 1-year recovery and relapse rates for mania in subjects who met criteria for a prepubertal and early adolescent bipolar disorder phenotype.Outpatients identified by consecutive new-case ascertainment were assessed by means of separate child and parent interviews, consensus conferences, and blind best estimates. The definition of the prepubertal and early adolescent bipolar disorder phenotype was DSM-IV mania with elation and/or grandiosity as one criterion.Of 93 subjects seen at baseline, 89 were seen at 1 year (95.7% retention). The rate of recovery from mania was 37.1%, and the rate of relapse after recovery was 38.3%. No covariates were significantly associated with recovery or relapse.The low recovery and high relapse rates supported the study hypothesis of poor outcomes, which was made on the basis of similarity between the characteristics of the prepubertal and early adolescent bipolar disorder phenotype (long episode duration and high prevalence of mixed mania, psychosis, and rapid cycling) and those of severe bipolar disorder in adults.
Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.
Authors: J S Abramson, J C Lewis, D S Lyles, K A Heller, E L Mills, D A Bass
Journal: Journal of Clinical Investigation (1982)

The present study examined the effect of various unopsonized strains of influenza A virus on release of myeloperoxidase (MPO) and acid phosphatase in polymorphonuclear leukocytes (PMNL). These results were correlated with the effect that these same viruses had on bactericidal activity in PMNL. Several strains of virus inhibited the fusion of azurophil granules with phagosomes containing Staphylococcus aureus. These same strains inhibited the extracellular release of MPO from PMNL (39-59%) and caused depressed killing (42-77%). In contrast, one of the influenza viruses (X-47a) did not inhibit PMNL MPO release or killing. The data indicate a close relationship between the ability of influenza virus to ablate normal intracellular lysosome-phagosome fusion with subsequent depression of bactericidal functions of PMNL.
Asthma therapy: how far have we come, why did we fail and where should we go next?
Authors: L. J. Janssen
Journal: European Respiratory Journal (2008)

Reversible airflow obstruction and nonspecific airway hyperresponsiveness are: 1) the two key features of asthma; 2) the primary concern for asthma patients; and 3) both directly caused by the airway smooth muscle (ASM). As such, controlling bronchoconstriction should be of primary importance. Unfortunately, all existing pharmacological asthma therapies that specifically target the ASM are based on decades old strategies. In the present study, the evolution of pharmacological asthma therapy will be briefly discussed, some explanations will be suggested as to why substantial new advances in this area have not occurred in several years and, finally, several new directions for novel asthma therapies will be proposed.
Direct but not indirect co-culture with osteogenically differentiated human bone marrow stromal cells increases RANKL/OPG ratio in human breast cancer cells generating bone metastases
Authors: Chiara Arrigoni, Paola De Luca, Mara Gilardi, Sara Previdi, Massimo Broggini, Matteo Moretti
Journal: Molecular Cancer (2014)

Bone metastases arise in nearly 70% of patients with advanced breast cancer, but the complex metastatic process has not been completely clarified yet. RANKL/RANK/OPG pathway modifications and the crosstalk between metastatic cells and bone have been indicated as potential drivers of the process. Interactions between tumor and bone cells have been studied in vivo and in vitro, but specific effects of the direct contact between human metastatic cells and human bone cells on RANKL/RANK/OPG pathway have not been investigated. We directly co-cultured bone metastatic human breast cancer cells (BOKL) with osteo-differentiated human mesenchymal cells (BMSCs) from 3 different donors. BMSCs and BOKL were then enzymatically separated and FACS sorted. We found a significant increase in the RANKL/OPG ratio as compared to control, which was not observed in BOKL cultured in medium conditioned by BMSCs, neither in BOKL directly cultured with fibroblasts or medium conditioned by fibroblasts. Direct co-culture with osteo-differentiated BMSCs caused BOKL aggregation while proliferation was not affected by co-culture. To more specifically associate RANKL expression to osteogenic differentiation degree of BMSCs, we determined their osteogenic markers expression and matrix calcification relative to osteoblasts and fibroblasts. In conclusion, our co-culture model allowed to demonstrate for the first time that direct contact but not paracrine interactions between human metastatic breast cancer cells and bone cells has a significant effect on RANKL/OPG expression in bone metastatic cells. Furthermore, only direct contact with the bone microenvironment induced BOKL clustering without however significantly influencing their proliferation and migration.
Design and Baseline Characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) Trial fn1fn1This study was supported by the Department of Veterans Affairs Cooperative Studies Program, Palo Alto, California and Washington, D.C. and by a grant from Hoechst Marion Roussel, Inc., Kansas City, Missouri.
Authors: David R. Ferry, Robert A. O’Rourke, Alvin S. Blaustein, Michael H. Crawford, Prakash C. Deedwania, Peter E. Carson, Robert G. Zoble, Carl J. Pepine, Ronald G. Thomas, Bruce K. Chow, Philip W. Lavori, Mark A. Hlatky, Jeffrey A. Leppo, Marika K. Iwane, Robert E. Kleiger, Hugh Dai, William E. Boden
Journal: Journal of the American College of Cardiology (1998)
Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort
Authors: Denis Poddubnyy, Martin Rudwaleit, Hildrun Haibel, Joachim Listing, Elisabeth Märker-Hermann, Henning Zeidler, Jürgen Braun, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2012)

Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.
The Diffusing Characteristics and Pressure-Volume Relationships of the Pulmonary Capillary Bed in Mitral Valve Disease*
Authors: R. M. McCredie
Journal: Journal of Clinical Investigation (1964)

In 1957, Forster, Roughton, and their associates reported a method of estimating pulmonary capillary blood volume (Vc) and diffusing capacity of the alveolar-capillary membrane (DM) by measuring the diffusing capacity of the lung for carbon monoxide (DL) at varying levels of alveolar oxygen tension (1, 2).1 Since then there hlave been a number of reports on the behavior of membrane diffusion and pulmonary capillary blood volume under physiological and pharmacological stresses (3-7) and in certain disease states (8-17). The purpose of this study was to measure the pulmonary capillary blood volume in normal subjects and in patients with mitral valve disease and to relate the findings to intravascular pressure and flows^ data obtained by cardiac catheterization.
Variation of Female and Male Lineages in Sub-Saharan Populations: the Importance of Sociocultural Factors
Authors: Giovanni Destro-Bisol, Francesco Donati, Valentina Coia, Ilaria Boschi, Fabio Verginelli, Alessandra Caglià, Sergio Tofanelli, Gabriella Spedini, Cristian Capelli
Journal: Molecular Biology and Evolution (2004)

In this paper, we present a study of genetic variation in sub-Saharan Africa, which is based on published and unpublished data on fast-evolving (hypervariable region 1 of mitochondrial DNA and six microsatellites of Y chromosome) and slow-evolving (haplogroup frequencies) polymorphisms of mtDNA and Y chromosome. Our study reveals a striking difference in the genetic structure of food-producer (Bantu and Sudanic speakers) and hunter-gatherer populations (Pygmies, Kung, and Hadza). In fact, the ratio of mtDNA to Y-chromosome Nupsilon is substantially higher in food producers than in hunter-gatherers as determined by fast-evolving polymorphisms (1.76 versus 0.11). This finding indicates that the two population groups differ substantially in female and male migration rate and/or effective size. The difference also persists when linguistically homogeneous populations are used and outlier populations are eliminated (1.78 vs 0.19) or when the jacknife procedure is applied to a paired population data set (1.32 to 7.84 versus 0.14 to 0.66). The higher ratio of mtDNA to Y-chromosome Nnu in food producers than in hunter-gatherers is further confirmed by the use of slow-evolving polymorphisms (1.59 to 7.91 versus 0.12 to 0.35). To explain these results, we propose a model that integrates demographic and genetic aspects and incorporates ethnographic knowledge. In such a model, the asymmetric gene flow, polyginy, and patrilocality play an important role in differentiating the genetic structure of sub-Saharan populations. The existence of an asymmetric gene flow is supported by the phylogeographic features of mtDNA and Y-chromosome haplogroups found in the two population groups. The role of polyginy and patrilocality is sustained by the evidence of a differential pressure of genetic drift and gene flow on maternal and paternal lineages of food producers and hunter-gatherers that is revealed through the analysis of mitochondrial and Y-chromosomal intrapopulational variation.
Path finding methods accounting for stoichiometry in metabolic networks
Authors: Jon Pey, Joaquín Prada, John E Beasley, Francisco J Planes
Journal: Genome biology (2011)

Abstract Graph-based methods have been widely used for the analysis of biological networks. Their application to metabolic networks has been much discussed, in particular noting that an important weakness in such methods is that reaction stoichiometry is neglected. In this study, we show that reaction stoichiometry can be incorporated into path-finding approaches via mixed-integer linear programming. This major advance at the modeling level results in improved prediction of topological and functional properties in metabolic networks.
DDB1 Targets Chk1 to the Cul4 E3 Ligase Complex in Normal Cycling Cells and in Cells Experiencing Replication Stress
Authors: Van Leung-Pineda, Jiwon Huh, Helen Piwnica-Worms
Journal: Cancer Research (2009)

Abstract The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. Chk1 is currently being targeted in anticancer regimens. Here, we identify damaged DNA-binding protein 1 (DDB1) as a novel Chk1-interacting protein. DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B. We report that Cul4A/DDB1 negatively regulates Chk1 stability in vivo. Chk1 associates with Cul4A/DDB1 during an unperturbed cell division cycle and both Chk1 phosphorylation and replication stress enhanced these interactions. Cul4A/DDB1 regulates Chk1 ubiquitination in vivo and Chk1 is directly ubiquitinated in vitro in a Cul4A/DDB1–dependent manner. Furthermore, Chk1 is stabilized in cells deficient for Cul4A/DDB1. This study shows that Chk1 abundance is regulated by the Cul4A/DDB1 ubiquitin ligase during an unperturbed cell division cycle, in response to replicative stress and on heat shock protein 90 inhibition, and that deregulation of the Chk1/Cul4A/DDB1 pathway perturbs the ionizing radiation–induced G2 checkpoint. [Cancer Res 2009;69(6):2630–7]
Associations between Kidney Function and Subclinical Cardiac Abnormalities in CKD
Authors: Meyeon Park, Chi-yuan Hsu, Yongmei Li, Rakesh K. Mishra, Martin Keane, Sylvia E. Rosas, Daniel Dries, Dawei Xie, Jing Chen, Jiang He, Amanda Anderson, Alan S. Go, Michael G. Shlipak
Journal: Journal of the American Society of Nephrology (2012)

Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m2, respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m2 had twofold higher odds of LVH (OR=2.20, 95% CI=1.40–3.40; P<0.001) relative to subjects with eGFR≥60 ml/min per 1.73 m2. This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30–44 ml/min per 1.73 m2 also significantly associated with LVH and abnormal LV geometry compared with eGFR≥60 ml/min per 1.73 m2. In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables.
Gustatory Neural Processing in the Hindbrain
Authors: J B Travers, S P Travers, R Norgren
Journal: Annual Review of Neuroscience (1987)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis.
Authors: K Banki, E Colombo, F Sia, D Halladay, D H Mattson, A H Tatum, P T Massa, P E Phillips, A Perl
Journal: The Journal of Experimental Medicine (1994)

Although the etiology of multiple sclerosis (MS) is unknown, there is compelling evidence that its pathogenesis is mediated through the immune system. Molecular mimicry, i.e., crossreactivity between self-antigens and viral proteins, has been implicated in the initiation of autoimmunity and MS. Based on homology to human T cell lymphotropic virus type I (HTLV-I) a novel human retrotransposon was cloned and found to constitute an integral part of the coding sequence of the human transaldolase gene (TAL-H). TAL-H is a key enzyme of the nonoxidative pentose phosphate pathway (PPP) providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. Another fundamental function of the PPP is to maintain glutathione at a reduced state and, consequently, to protect sulfhydryl groups and cellular integrity from oxygen radicals. Immunohistochemical analyses of human brain sections and primary murine brain cell cultures demonstrated that TAL is expressed selectively in oligodendrocytes at high levels, possibly linked to production of large amounts of lipids as a major component of myelin, and to the protection of the vast network of myelin sheaths from oxygen radicals. High-affinity autoantibodies to recombinant TAL-H were detected in serum (25/87) and cerebrospinal fluid (15/20) of patients with MS. By contrast, TAL-H antibodies were absent in 145 normal individuals and patients with other autoimmune and neurological diseases. In addition, recombinant TAL-H stimulated proliferation and caused aggregate formation of peripheral blood lymphocytes from patients with MS. Remarkable amino acid sequence homologies were noted between TAL-H and core proteins of human retroviruses. Presence of crossreactive antigenic epitopes between recombinant TAL-H and HTLV-I/human immunodeficiency virus type 1 (HIV-1) gas proteins was demonstrated by Western blot analysis. The results suggest that molecular mimicry between viral core proteins and TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS.
Spontaneous Development of Psoriasis in a New Animal Model Shows an Essential Role for Resident T Cells and Tumor Necrosis Factor-α
Authors: Onur Boyman, Hans Peter Hefti, Curdin Conrad, Brian J. Nickoloff, Mark Suter, Frank O. Nestle
Journal: The Journal of Experimental Medicine (2004)

Psoriasis is a common T cell-mediated autoimmune disorder where primary onset of skin lesions is followed by chronic relapses. Progress in defining the mechanism for initiation of pathological events has been hampered by the lack of a relevant experimental model in which psoriasis develops spontaneously. We present a new animal model in which skin lesions spontaneously developed when symptomless prepsoriatic human skin was engrafted onto AGR129 mice, deficient in type I and type II interferon receptors and for the recombination activating gene 2. Upon engraftment, resident human T cells in prepsoriatic skin underwent local proliferation. T cell proliferation was crucial for development of a psoriatic phenotype because blocking of T cells led to inhibition of psoriasis development. Tumor necrosis factor-alpha was a key regulator of local T cell proliferation and subsequent disease development. Our observations highlight the importance of resident T cells in the context of lesional tumor necrosis factor-alpha production during development of a psoriatic lesion. These findings underline the importance of resident immune cells in psoriasis and will have implications for new therapeutic strategies for psoriasis and other T cell-mediated diseases.
EXPERIMENTAL HYPOALBUMINEMIA
Authors: Robert Elman, Carl J. Heifetz
Journal: The Journal of Experimental Medicine (1941)

1. Adult dogs maintained for 6 weeks upon a carrot-protein-deficient diet exhibited a progressive fall in the serum protein confined entirely to the albumin fraction. The degree of hypoalbuminemia was pronounced, i.e. a fall from 3.75 to 2.00 gm. per cent. 2. Parallel microscopic changes in the liver were observed which consisted of a gradual loss in the stainable cytoplasm producing extensive vacuolization. This vacuolization was not due to the accumulation of fat or of glycogen as shown by chemical analyses as well as by stained sections of the livers. 3. The histological changes in the livers were assumed to be due to a loss of protein inasmuch as there was a parallel fall in the protein content of the liver pari passu with the fall in the serum albumin of the blood. This assumption is made more probable by the fact that the water content of the liver increased as the protein content decreased. 4. Liver function, as measured by the excretion of iso-iodeikon, fell with the fall of the serum albumin thus indicating the production of hepatic insufficiency by the protein deficient diet. 5. These observations are discussed in relation to the question whether the liver is the site of formation or of storage of serum albumin. Certain other, particularly therapeutic, implications are also discussed, i.e. the importance of a high protein intake in patients with liver disease.
Clinical outcomes of pandemic (H1N1) 2009 influenza (swine flu) in adults with cystic fibrosis
Authors: E. F. Nash, R. Whitmill, B. Barker, R. Rashid, J. L. Whitehouse, D. Honeybourne
Journal: Thorax (2010)

Patients with cystic fibrosis (CF) suffer recurrent bacterial pulmonary infections, but viral infections can also cause acute clinical deterioration.1 Certain patient groups suffer increased morbidity following pandemic (H1N1) 2009 influenza (swine flu),2 but there are few previous reports of outcomes in individuals with CF.3 4 The West Midlands, along with Greater London, has had the highest incidence of H1N1 influenza in the UK.5 We therefore examined the outcomes of patients diagnosed with H1N1 influenza at the West Midlands Adult CF Centre.

From June 2009 to April 2010 all adults with CF at our regional centre with potential H1N1 influenza had nasopharyngeal swabs tested …
The DNA sequence of the structural gene of gonococcal protein III and the flanking region containing a repetitive sequence. Homology of protein III with enterobacterial OmpA proteins.
Authors: E C Gotschlich, M Seiff, M S Blake
Journal: The Journal of Experimental Medicine (1987)

The insert of a lambda gt11 clone expressing gonococcal protein III was sequenced. The deduced amino acid sequence showed a coding frame of 236 amino acids with a typical 22-amino-acid signal peptide, followed by the known NH2-terminal sequence of PIII. The mature protein has a molecular weight of 23,298. It was found that PIII had extensive and very striking homology to the carboxy-terminal portion of enterobacterial OmpA proteins. The homology encompasses the OmpA domain that is believed to be located in the periplasmic space. If the disposition of PIII across the OM is analogous, then the surface-exposed domain consists of less than 40 amino acids. These include a potential 15-amino-acid disulfide loop, a feature not found in OmpA proteins. Hybridization studies with the sequenced insert indicated that it contained a repetitive sequence that occurred at least 20 times in the genome. By additional hybridization studies the area containing the repetitive sequence was narrowed to a region of 43 bp. This region contained an exact copy of the consensus sequence of a 26-bp repetitive sequence recently described. An analogous sequence recurs in an inverted orientation 53 bp downstream.