tbuckley/cabot-search huggingface dataset:
Abstract 2331: C-terminal of Cav1.3 L-type Ca Channel is Truncated From the Full Length Protein and is Localized to the Nucleus in Cardiomyocytes
Authors: Eddy Karnabi, Yongxia Qu, Yuankun Yue, Mohamed Chahine, Mohamed Boutjdir
Journal: Circulation (2009)

Background: L-type Ca channels encoded by Cav1.2 and Cav1.3 play a major role in activating signaling pathways which control gene expression. The C-terminal fragment of Cav1.2 has been recently sho...
Abstract #LB-294: Loss of Pten decreases survival in a mouse model of medulloblastoma
Authors: Robert Castellino, Donald Durden
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma (MB). Our primary objective was to determine if loss of Pten promotes MB tumor formation. We used a mouse model of MB with constitutive activation of Smoothened , SmoA1 . When mice expressing SmoA1 were crossed with mice heterozygous for Pten , Pten +/- mice exhibited decreased survival compared to Pten +/+ mice (p < 0.0001). 32 of 101 (32%) SmoA1 +; Pten +/+ mice versus 21 of 33 (64%) SmoA1 +; Pten +/- mice developed symptoms of MB. SmoA1 +; Pten +/+ mice exhibited a median survival of 37 weeks compared to SmoA1 +; Pten +/- mice, which had a median survival of 12 weeks. SmoA1 +; Pten +/- mice also had an earlier mean time to onset of symptoms. Tumors from SmoA1 +; Pten +/+ mice exhibited classic histology. Tumors from SmoA1 +; Pten +/- mice, in contrast, exhibited predominantly nodular histology. Analysis by gene expression microarray revealed a clear separation of the gene signatures, with a total of 1830 genes upregulated and 2240 genes downregulated in the SmoA1 +; Pten +/- versus the SmoA1 +; Pten +/+ mouse MBs. The gene expression of Pten itself was decreased in the SmoA1 +; Pten +/- tumors. Upregulated genes in the SmoA1 +; Pten +/- tumors included Pik3cb , which codes for the p110\#946; catalytic subunit of PI-3 kinase, Mapk8 , Frap1 , and multiple genes involved in angiogenesis. Downregulated genes included Trp53 and Rb1 . Western blotting revealed that MBs from SmoA1 +; Pten +/- mice exhibited decreased expression of Pten and increased expression of activated Akt. Some Pten +/- tumors also displayed increased activation of p70S6 kinase and decreased p53 protein. Immunohistochemical staining revealed diffuse expression of Pten in tumors from SmoA1 +; Pten +/+ mice, but almost no expression of Pten in tumors from SmoA1 +; Pten +/- mice. Immunohistochemical staining for activated Akt was more intense in tumors from SmoA1 +; Pten +/- mice. SmoA1 +; Pten +/- tumors also exhibited intense staining for the marker of neuronal differentiation, NeuN. Consistent with these findings, we detected strong expression of PCNA throughout the wild-type Pten tumors and focal areas of intense staining for PCNA in tumors from SmoA1 +/-; Pten +/- mice. Conversely, staining for Cleaved Caspase 3 revealed multiple punctuate foci in SmoA1 +; Pten +/+ tumors and almost no staining in SmoA1 +/-; Pten +/- tumors. These results suggest that increased signaling through PI-3 kinase pathways promotes MB tumorigenesis. Our intent is to use these mouse models to examine the efficacy of PI-3 kinase inhibition, using small molecule inhibitors of PI-3 kinase, as a strategy for improving the treatment of children with MB.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-294.
Causality and Psychopathology: Finding the Determinants of Disorders and Their Curesedited by ShroutPatrick E., Ph.D., KeyesKatherine M., Ph.D., M.P.H., and OrnsteinKatherine, M.P.H. New York, Oxford University Press, 2010, 376 pp., $69.50.
Authors: Carlos Blanco
Journal: American Journal of Psychiatry (2011)
Cartridge based nucleic acid amplification technique (CBNATT) for diagnosis of rifampicin resistance from sputum smear in revised national tuberculosis control of India (RNTCP) - Implications of preliminary data
Authors: Jai Kishan Karahyla, Kamlesh Kumari, Aekta Gupta, Pritpal Kaur Atwal
Journal: European Respiratory Journal (2013)

CBNAAT offers very high sensitivity and specificity equivalent to solid culture and DST. It is very easy to perform. In RNTCP new patients of pulmonary tuberculosis are given Category-I regimen consisting of 2 months of Rifampicin (R), Isoniazid (H), Pyrazinamide (Z) and Ehthambutol (E), followed by 4 months of R & H. However, failure, retreatment and defaulted cases on category-I are given Category-II regimen of 2 months of Streptomycin (S),RHZE followed by 1 Month of RHZE and 5 months of RHE. There is a concern that addition of Streptomycin only in category-II tantamount to adding single drug in category-I failure which can lead to amplification of drug resistance and can also lead to spread of drug resistant TB and additional morbidity and mortality. CBNATT was undertaken at our center in 377 patients suspected of MDR-TB like failure, retreatment sputum positive at 4th month, contact of any known MDR-TB case, sputum positive or negative at diagnosis in retreatment case and sputum positive at follow up. Preliminary data revealed Rifampicin sensitivity and resistance in 261 (69.23%) and 64 (16.97%) cases respectively. All 64, R resistance cases were started MDR treatment and 261 (69.23%) R sensitive cases were started category-II treatment. Thus introduction of CB-NATT in category-I failure or cases suspected of MDR-TB lead to early identification of R resistance/sensitivity. It helped in starting appropriate treatment in R resistant/sensitive cases in the form of MDR/ category-II respectively. It brought confidence in treating physicians.
Overexpression of Crry protects mesangial cells from complement-mediated injury.
Authors: M Nangaku, R J Quigg, S J Shankland, N Okada, R J Johnson, W G Couser
Journal: Journal of the American Society of Nephrology (1997)

Crry is a membrane-associated complement regulatory protein expressed on glomerular mesangial, endothelial, and epithelial cells, which reduces C3/C5 convertase activity. This study utilized an overexpression strategy to determine the functional significance of Crry in cultured rat mesangial cells. A Crry expression vector was constructed and was tagged with a c-myc epitope that allowed transfected Crry to be distinguished from the constitutively expressed protein. In stable clones, overexpressed Crry was clearly detected immunocytochemically both by anti-c-myc and anti-Crry antibody in a membrane localization. The overexpression of Crry was also confirmed by Western blotting and immunoprecipitation. To determine if overexpression of Crry by mesangial cells confers a protective effect from complement attack, complement-mediated cell lysis assays were performed. Crry-transfected mesangial cells demonstrated complete resistance to complement-mediated cell lysis, which was reversed by neutralization of Crry with both monoclonal antibody and F(ab')2 fragments of the antibody. This study also investigated the role of Crry in protecting cells from the effects of sublytic complement attack. Overexpressed Crry suppressed antibody/complement induced production of superoxide, one of the inflammatory mediators induced by sublytic complement attack. Immunocytochemical staining confirmed a reduction in C3 and C5b-9 deposition in Crry-transfected cells. These results demonstrate directly that transfected Crry functions as a potent protector of mesangial cells against complement-mediated injury. Crry may play an important role in modulating the glomerular response to immune injury in vivo.
Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by <i>BCR‐ABL1</i> fusion gene
Authors: Mauricio Chandia, José-María Sayagués, María-Laura Gutiérrez, María-Carmen Chillón, José-Alejandro Aristizábal, Alejandro Corrales, Marta Castellanos, Alberto Melón, María-Luz Sánchez, Paloma Bárcena, Sergio Matarraz, María González‐González, Susana Barrena, Antonio López, María-Consuelo del Cañizo, Fermín Sánchez‐Guijo, Alberto Orfao
Journal: American Journal of Hematology (2013)

For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell(HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%615%), basophils (95%612%), eosinophils (90%68%), CD341 precursors cells (90%67%),monocytes (84%630%), nucleated red blood cells (87%624%), and mast cells (77%633%). By contrast, MPC(30%634%), B-cells (15%627%), T-lymphocytes (50%626%), and NK-cells (35%634%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL11 subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD341 cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene inMPC, CD341 precursors, and other different BM hematopoietic myeloid cell lineages from CML patients,including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes.Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL11 subclone.
A disparity in the association of asthma, rhinitis, and eczema with allergen‐specific IgE between Finnish and Russian Karelia
Authors: P. T. Pekkarinen, L. Von Hertzen, T. Laatikainen, M. J. Mäkelä, P. Jousilahti, T. U. Kosunen, V. Pantelejev, E. Vartiainen, T. Haahtela
Journal: Allergy (2007)

A substantial variation in the association of asthma, rhinitis and eczema with elevated serum allergen-specific immunoglobulin E (sIgE) levels between different populations has been reported. Here, we wanted to clarify whether these proportions are different in Finnish and Russian Karelia, and compared the ability of questionnaires, skin prick tests (SPT) and sIgE measurements to detect atopic conditions in these adjacent areas with different living conditions.Randomly selected schoolchildren, aged 6-16 years, and their mothers from Finland (n = 344 children, 344 mothers) and Russia (427 and 284 respectively) participated. SPTs and sIgE measurements to common inhalant and food allergens were performed. The occurrence of asthma, rhinitis, eczema and related symptoms was assessed with an International Study of Asthma and Allergies in Childhood-based questionnaire. Correlation between SPT and sIgE was estimated using the Spearman correlation coefficient.The rate of positive sIgE results was significantly higher in Finland among both mothers and children. Seventy-seven per cent of Finnish children and 43% of Russian children with asthma were sIgE positive. The respective figures for hay fever were 94% and 67%, and for eczema 68% and 41%. This discrepancy was similar but of lower magnitude among mothers. The overall occurrence of asthma, rhinitis and eczema was very low in Russian Karelia. The correlation between SPT and sIgE results was generally good.Asthma, rhinitis and eczema in Russian Karelia are not only rare but also, to a large extent, have no sIgE component. Therefore, the ability of questionnaires to detect sIgE-mediated atopic conditions in this area of Russia is poor.
The different faces of the asthma−COPD overlap syndrome
Authors: Dirkje S. Postma, Maarten van den Berge
Journal: European Respiratory Journal (2015)

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent, chronic, diseases [1, 2]. Asthma symptoms usually start at a young age, whereas COPD generally becomes symptomatic after the fourth decade of life. It has been recognised in clinical practice and by international asthma and COPD guidelines [1, 2] that many people have clinical features compatible with both diseases; the term suggested to describe this is ACOS (asthma−COPD overlap syndrome). However, the underlying mechanisms of ACOS and its appropriate treatment are unclear, particularly since these patients have been excluded from studies determining the pathophysiology and pathology of asthma and COPD, as well as from efficacy studies of respiratory treatments. A new prospective population-based study in the ERJ makes new strides in understanding the ACOS phenomenon <http://ow.ly/PnuaQ>
Therapeutic options for low-risk prostate cancer: A cost-effectiveness analysis.
Authors: J. H. Hayes, D. A. Ollendorf, M. J. Barry, S. D. Pearson, P. M. McMahon
Journal: Journal of Clinical Oncology (2010)

6012 Background: The optimal therapeutic approach for low-risk clinically localized prostate cancer (CaP) is unknown. Over 50% of screen-detected men are overtreated and treatment is associated with significant side effects (SE). This analysis examines the cost-effectiveness of radical prostatectomy (RP), radiation therapy (IMRT), brachytherapy (BT), proton beam therapy (PBT) and active surveillance (AS) in these men. Methods: A Markov Monte Carlo model was constructed: men received treatment or AS and incurred SE for 1-2 y and costs until death of CaP/other cause. Men on AS could elect therapy or be treated with IMRT at progression. The base case used 65 yo men and included therapy and patient time costs. Transition probabilities and utilities were developed from literature review. Sensitivity analysis on key parameters was performed. Main outcomes were costs (2008 US$) and quality-adjusted life-years (QALYs), both discounted at 3%/y, and incremental cost-effectiveness ratios (ICERs). Results: AS was most effective, providing 8.58 QALYs at a cost of $30,422. Compared to RP, AS provided an additional 9.1 mo of QALE at an added cost of $2,074 (ICER $2,729/QALY). Among initial therapies, BT was most effective and least expensive, providing an additional 3.5 mo of QALE at a cost savings of $2,743 vs. RP. IMRT and PBT were more expensive than BT, RP, or AS. Alternative Analyses. AS followed by BT was more effective and less expensive than initial therapy or AS followed by IMRT. The relative risk of CaP- specific death would have to be 0.6 for therapy vs AS for quality of life to be equal. Sensitivity Analysis (SA). AS was most effective on SA including probability of SE, progressive disease on AS and utilities. If IMRT cost was reduced to <$17000 AS was more effective and less expensive than initial therapy. Conclusions: In this model, AS is associated with better quality of life than initial therapy and carries a minimal additional cost relative to RP or BT. AS is underutilized in these patients. Strategy Cost ($) Incremental cost ($) QALYs Incremental QALYs ICER BT 25,606 - 8.11 - - RP 28,348 2,743 7.82 -0.29 Dominated (D)* AS 30,422 2,074 8.58 0.76 $2,729/QALY IMRT 37,808 7,386 8.09 -0.88 D PBT 53,828 16,020 7.96 -0.13 D * Dominated: more expensive and less effective than BT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aetna Foundation, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Health Plans, UnitedHealth Group
THE SO-CALLED RETICULOHISTIOCYTOMA OF THE SKIN..
Authors: B. T. DAVIES, S. R. WOOD
Journal: British Journal of Dermatology (1955)

Journal Article THE SO‐CALLED RETICULOHISTIOCYTOMA OF THE SKIN.: A Comparison of Two Distinct Types. Get access B. T. DAVIES, M.B., Ch.B., B. T. DAVIES, M.B., Ch.B. Lecturer in Pathology, University of Birmingham Search for other works by this author on: Oxford Academic Google Scholar S. R. WOOD, M.B., M.R.C.P. S. R. WOOD, M.B., M.R.C.P. Senior Dermatological Registrar, United Birmingham Hospitals and Birmingham Regional Hospital Board Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 67, Issue 6, 1 June 1955, Pages 205–211, https://doi.org/10.1111/j.1365-2133.1955.tb12721.x Published: 01 June 1955
Abstract 15599: Klf4 Regulates the Extent of Lung Microvessel Endothelial Cell Regeneration
Authors: Tina Perkins, Kishore Wary
Journal: Circulation (2014)

Rationale: Transcription factor Krüppel like factor (Klf)-4 might regulate endothelial cell (EC) regeneration; however, the underlying mechanisms are poorly understood. Objective: The goal of this study was to delete EC- Klf4 in a timed manner using the lox-P elements, Cdh5 (VE-cadherin) as a promoter to drive the Cre recombinase, and to address the role of Klf4 in adult lung microvessels. Methods and Results: After 12 generations of backcrossing, we transferred Klf4 fl to a C57BL background. Male Klf4 fl/+ were crossed with female Klf4 fl/+ mice to generate Klf4 fl/fl (25%) offspring. In the next breeding scheme, Klf4 fl/fl mice were crossed with male tg- Cdh5 CreERT2 (tamoxifen inducible) mice to produce heterozygous Klf4 fl ::tg- Cdh5 CreERT2 offspring (100%). I then crossed male Klf4 fl ::tg-Cdh5 CreERT2 with female Klf4 fl ::tg- Cdh5 CreERT2 to produce offspring of Klf4 fl/fl ::tg- Cdh5 CreERT2 genotype (25%). Groups of these mice received tamoxifen everyday for 5 days, and on the 10 th day, (now called Klf4 ECKO mice) all mice were sacrificed. To determine the loss-of-EC-Klf4 protein and to examine the phenotypic alterations, lungs were collected, subjected to biochemical and molecular experiments, fixed and stained for microscopic analyses. Tamoxifen treatment decreased EC-Klf4-protein expression significantly in the Klf4 ECKO lung, as compared to Klf4 fl/fl or tg- Cdh5 CreERT2 controls. Klf4 ECKO lung tissue showed increased recruitment of neutrophils and inflammatory cells. Trichrome staining revealed increased collagen deposition in the Klf4 ECKO versus the control mice. Importantly, I observed decreased lung alveoli (p&lt;0.05 vs control, n=5), hemorrhage in Klf4 ECKO mice, compared to the control groups. Anti-CD31 and anti-von Willebrand Factor (vWF) staining showed significant decrease (p&lt;0.5 versus control) in microvessel densities in the lung. Summary: These compelling sets of results predict the ability of endothelial-Klf4 to regulate EC regeneration, and its loss in lung fibrosis.
Cerebrospinal Fluid Asparagine Concentrations After <i>Escherichia</i> <i>coli</i> Asparaginase in Children With Acute Lymphoblastic Leukemia
Authors: Michael H. Woo, Lawrence J. Hak, Michael C. Storm, Amar J. Gajjar, John T. Sandlund, Patricia L. Harrison, Bo Wang, Ching-Hon Pui, Mary V. Relling
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase. PATIENTS AND METHODS: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m 2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing. RESULTS: The percentage of patients with undetectable (&lt; 0.04 μmol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during asparaginase therapy, and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P &lt; .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P &lt; .001). Median CSF asparagine concentrations were 4.42 μmol/L before, less than 0.04 μmol/L during, and less than 0.04 μmol/L at 1 to 5 days, 1.63 μmol/L at 6 to 10 days, 1.70 μmol/L at 11 to 30 days, and 5.70 μmol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003). CONCLUSION: CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.
Cytogenetic Studies in Human T-cell Lymphoma Virus (HTLV)-Positive Leukemia-Lymphoma in the United States
Authors: Whang-Peng J, Bunn Pa, Knutsen T, Kao-Shan Cs, Broder S, Jaffe Es, Gelmann E, Blattner W, Lofters W, Young Rc
Journal: JNCI Journal of the National Cancer Institute (1985)

Cytogenetic studies were conducted on fresh and cultured cells from 11 patients with human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma. Clones with abnormal karyotypes were detected in 9 of the 11 patients. Chromosome numbers were near-diploid in cells from all but 1 patient who also had a tetraploid clone. The chromosome abnormalities in these cells were extensive; numerous complex structural changes were seen in every chromosome pair. Structural abnormalities occurred most frequently in chromosome 6. The 6 patients with chromosome 6 deletions had breakpoints at bands q11, q13, q16q23, q21q23, q22q24, and q23q24. The characteristic clinical features of these 6 patients were aggressive course, short survival, poor response to chemotherapy, high white blood cell counts, hypercalcemia, and bone lesions, whereas cytogenetically abnormal patients without chromosome 6q deletions tended to have a more indolent course. The precise role of the 6q deletion cannot be established with certainty from these data. However, this abnormality appears to occur with a greater than expected frequency in this large cell aggressive lymphoma, in association with hypercalcemia and lytic bone lesions.
Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity
Authors: M. Manise, F. Schleich, N. Gusbin, L. Godinas, M. Henket, N. Antoine, J. L. Corhay, R. Louis
Journal: Allergy (2010)

Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern.The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-gamma, and tumor necrosis factor alpha was measured by immunotrapping after 24 h sputum or blood cell culture.Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count.Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics.