tbuckley/cabot-search huggingface dataset:
Preclinical Evaluation of Radiation and Perifosine in a Genetically and Histologically Accurate Model of Brainstem Glioma
Authors: Oren J. Becher, Dolores Hambardzumyan, Talia R. Walker, Karim Helmy, Javad Nazarian, Steffen Albrecht, Rebecca L. Hiner, Sarah Gall, Jason T. Huse, Nada Jabado, Tobey J. MacDonald, Eric C. Holland
Journal: Cancer Research (2010)

Abstract Brainstem gliomas (BSG) are a rare group of central nervous system tumors that arise mostly in children and usually portend a particularly poor prognosis. We report the development of a genetically engineered mouse model of BSG using the RCAS/tv-a system and its implementation in preclinical trials. Using immunohistochemistry, we found that platelet-derived growth factor (PDGF) receptor α is overexpressed in 67% of pediatric BSGs. Based on this observation, we induced low-grade BSGs by overexpressing PDGF-B in the posterior fossa of neonatal nestin tv-a mice. To generate high-grade BSGs, we overexpressed PDGF-B in combination with Ink4a-ARF loss, given that this locus is commonly lost in high-grade pediatric BSGs. We show that the likely cells of origin for these mouse BSGs exist on the floor of the fourth ventricle and cerebral aqueduct. Irradiation of these high-grade BSGs shows that although single doses of 2, 6, and 10 Gy significantly increased the percent of terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)–positive nuclei, only 6 and 10 Gy significantly induce cell cycle arrest. Perifosine, an inhibitor of AKT signaling, significantly induced TUNEL-positive nuclei in this high-grade BSG model, but in combination with 10 Gy, it did not significantly increase the percent of TUNEL-positive nuclei relative to 10 Gy alone at 6, 24, and 72 hours. Survival analysis showed that a single dose of 10 Gy significantly prolonged survival by 27% (P = 0.0002) but perifosine did not (P = 0.92). Perifosine + 10 Gy did not result in a significantly increased survival relative to 10 Gy alone (P = 0.23). This PDGF-induced BSG model can serve as a preclinical tool for the testing of novel agents. Cancer Res; 70(6); 2548–57
Doctors will feed into review of children's heart services
Authors: A. O'Dowd
Journal: BMJ (2013)

An expert clinical advisory panel is to be formed to ensure that clinicians have their say in an imminent review being planned for the provision of children’s heart surgery across England.

Details of the new review, being led by NHS England at the request of the health secretary, Jeremy Hunt, will be made public at the end of September and a workable solution is expected to be ready for implementation by June of next year.

NHS cardiac surgery for children is currently provided by 10 hospitals in England and specialist paediatric cardiology is provided by a further three centres. Attempts to rationalise these specialist services have been ongoing for the last five years. A review recommended closure of three centres, and local campaigners took two of the decisions to the High Court and …
Prevalence, Demographics, and Psychological Associations of Sleep Disruption in Patients With Cancer: University of Rochester Cancer Center–Community Clinical Oncology Program
Authors: Oxana G. Palesh, Joseph A. Roscoe, Karen M. Mustian, Thomas Roth, Josée Savard, Sonia Ancoli-Israel, Charles Heckler, Jason Q. Purnell, Michelle C. Janelsins, Gary R. Morrow
Journal: Journal of Clinical Oncology (2009)

Purpose Sleep disruption is prevalent in patients with cancer and survivors, but the prevalence of insomnia, a distressing sleep disorder, in these populations has yet to be determined in large-scale studies. Patients and Methods A total of 823 patients with cancer receiving chemotherapy (mean age, 58 years; 597 female patients) reported on sleep difficulties in a prospective study. Results During day 7 of cycle 1 of chemotherapy, 36.6% (n = 301) of the patients with cancer reported insomnia symptoms, and 43% (n = 362) met the diagnostic criteria for insomnia syndrome. Patients with cancer younger than 58 years were significantly more likely to experience either symptoms of insomnia or insomnia syndrome (χ 2 = 13.6; P = .0002). Patients with breast cancer had the highest number of overall insomnia complaints. A significant positive association was found between symptoms of insomnia during cycles 1 and 2 of chemotherapy (ϕ = .62, P &lt; .0001), showing persistence of insomnia during the first two cycles of chemotherapy. Sixty percent of the patient sample reported that their insomnia symptoms remained unchanged from cycle 1 to cycle 2. Those with insomnia complaints had significantly more depression and fatigue than good sleepers (all P &lt; .0001). Conclusion The proportions of patients with cancer in this sample reporting symptoms of insomnia and meeting diagnostic criteria for insomnia syndrome during chemotherapy are approximately three times higher than the proportions reported in the general population. Insomnia complaints persist throughout the second chemotherapy cycle for the majority of patients with cancer in this study. Insomnia is prevalent, underrecognized, undermanaged, and understudied among patients with cancer receiving chemotherapy.
Increased T-regulatory cells within lymphocyte follicles in moderate COPD
Authors: J. Plumb, L. J. C. Smyth, H. R. Adams, J. Vestbo, A. Bentley, S. D. Singh
Journal: European Respiratory Journal (2009)

Lymphoid follicles in the lung parenchyma are a characteristic feature of chronic obstructive pulmonary disease (COPD). There are reports of altered CD4 T-regulatory cell numbers in COPD lungs, but the location of these cells within COPD lung tissue specific follicles has not been investigated. The presence of CD4<sup>+</sup>FOXP3<sup>+</sup> T-regulatory cells was assessed in surgically resected lung tissue from 12 COPD patients, 11 smokers with normal lung function and seven nonsmokers by combined immunofluorescence and immunohistochemistry. Organised lymphoid follicles were observed in all three groups of patients, as well as lymphoid clusters lacking organisation. The percentage of CD4 cells that were T-regulatory cells were significantly increased (p = 0.02) within COPD (16%) follicles compared with smokers (10%) and nonsmokers (8%). In contrast, there was no change (p&gt;0.05) in the percentage of T-regulatory cells in clusters or the subepithelium between groups. Lymphoid follicles in COPD patients have increased T-regulatory cells. Therefore, T-regulatory activity may be altered within COPD lymphoid follicles.
Impaired Gastric Emptying in Diabetic Patients With Cardiac Autonomic Neuropathy
Authors: Martin Buysschaert, Michel Moulart, Jean Luc Urbain, Stany Pauwels, Luc De Roy, Jean Marie Ketelslegers, Andre E Lambert
Journal: Diabetes Care (1987)

The aim of our study was to measure the gastric emptying rate for a solid meal in diabetic patients who had no gastrointestinal complaints with (group 1, n = 12) or without (group 2, n = 10) cardiac autonomic neuropathy and in normal controls comparable in age and sex (group 3, n = 10). Gastric emptying rate was assessed with a sequential scintiscanning method. The percentages of the initial isotope activity remaining in the stomach at different times (20, 40, 60, 80, 100, and 120 min) after the ingestion of a Tc-99m-labeled test meal and the emptying half-time were calculated. Cardiac autonomic neuropathy was determined by the beat-to-beat variations in heart rate during deep breathing. A significant reduction of the gastric emptying rate was observed in group 1. Indeed, at 80, 100, and 120 min the percentage of residual isotope activity was 73 ± 4, 60 ± 6, and 50 ± 6% (mean ± SE), respectively, in group 1 versus 61 ± 3 (P &amp;lt; .05), 45 ± 4 (P &amp;lt; .05), and 32 ± 4% (P &amp;lt; .02) in group 2. In group 3, residual isotope activity was 57 ± 4 (P &amp;lt; .05 vs. group 1), 41 ± 4 (P &amp;lt; .05), and 29 ± 4% (P &amp;lt; .02), respectively. Emptying half-time was also longer in group 1 (121 ± 9 min) than in group 2 (95 ± 6 min, P &amp;lt; .05) or group 3 (90 ± 4 min, P &amp;lt; .02). For a given diabetic patient, there was no correlation between abnormal low gastric emptying and cardiac autonomic neuropathy. In conclusion, this study shows that in a group of diabetic patients with cardiac autonomic neuropathy, mean gastric emptying rate for solid meals is significantly impaired when compared with patients without cardiac autonomic neuropathy or normal controls, even when gastrointestinal symptoms are absent.
Black and Brown Pigment Gallstones Differ in Microstructure and Microcomposition
Authors: Peter F. Malet, Arimichi Takabayashi, Bruce W. Trotman, Roger D. Soloway, Norman E. Weston
Journal: Hepatology (1984)

The two subtypes of pigment gallstones, black and brown stones, differ in chemical composition and pathogenesis. We examined a black bilirubinate stone and a black phosphate stone (which represented opposite ends of the compositional spectrum of black noncarbonate stones), a black carbonate stone, and a brown pigment stone using scanning electron microscopy and microchemical techniques to determine if stone microstructure and microcomposition reflected different patterns of formation. The cross-sectional surfaces of the black bilirubinate and black phosphate stones were smooth and homogenous. Electron probe microanalysis demonstrated high concentrations of sulfur and copper in the center of the black bilirubinate stone; sulfur was in a low valence state consistent with disulfide linkages in proteins. The brown stone was rough-surfaced with lamellated bands on cross-section. The lighter-colored bands in this stone contained virtually all of the detected calcium palmitate, while the darker sections contained much more calcium bilirubinate. Plasma oxygen etching demonstrated a network of protein interdigitating with calcium bilirubinate salts in the black bilirubinate and black phosphate stones but not in the black carbonate or brown stones. Argon ion etching demonstrated that calcium bilirubinate was in a closely packed rod-shaped arrangement in all three black stones but not in the brown stone. We conclude that the marked differences in structure and composition between the black noncarbonate and brown pigment gallstones support the hypothesis that the two major pigment gallstone types form by different mechanisms. In addition, the layered structures of the black carbonate and brown stones suggest that stone growth is affected by cyclic changes in biliary composition.
Randomized Phase II Study Comparing Thalidomide With Medroxyprogesterone Acetate in Patients With Metastatic Renal Cell Carcinoma
Authors: Chooi P. Lee, Poulam M. Patel, Peter J. Selby, Barry W. Hancock, Ian Mak, Lynda Pyle, Maggie G. James, Debbie A. Beirne, Sarah Steeds, Roger A'Hern, Martin E. Gore, Tim Eisen
Journal: Journal of Clinical Oncology (2006)

To investigate escalating doses of thalidomide compared with medroxyprogesterone in patients with metastatic renal cell carcinoma (RCC), who had either progressed after first-line immunotherapy or who were not suitable for immunotherapy.Thalidomide was started at 100 mg/d orally (PO) and escalated by 100 mg/d every 2 weeks to the maximum dose of 400 mg/d. Medroxyprogesterone was given at a fixed dose of 300 mg PO daily.Sixty patients were entered (thalidomide:medroxyprogesterone = 29:31; median age, 59 [thalidomide], 60 [medroxyprogesterone]; No. of patients assessable for response, 22 [thalidomide], 26 [medroxyprogesterone]). In the thalidomide arm, there was no objective response seen. The best response was SD in three patients lasting 5+, 6+, and 12 months, respectively. All patients in the medroxyprogesterone arm progressed. There was no difference in overall survival between the two arms; median survival in the thalidomide arm was 8.2 months compared with 4.8 months in the medroxyprogesterone arm (P = .62). Hazard ratio was 0.88 (95% CI, 0.67 to 1.94). Median duration of treatment was 73 days (range, 14 to 364 days) in the thalidomide arm, and 84 days (range, 7 to 175 days) in the medroxyprogesterone arm. The high incidence of toxicity in the thalidomide arm, mainly somnolence, constipation, fatigue and paraesthesia, meant that only 30.8% of patients were able to tolerate the maximum dose of 400 mg/d of treatment.Thalidomide is not superior to medroxyprogesterone acetate in patients with metastatic RCC. Its risk/benefit ratio does not favor its use in this patient population.
Search for mycoplasma in synovial fluids from patients with rheumatoid arthritis.
Authors: G D Windsor, A Nicholls, R N Maini, D G Edward, R M Lemcke, D C Dumonde
Journal: Annals of the Rheumatic Diseases (1974)

4)The isolation of Mycoplasma fermentans from over 40 per cent. of synovial fluids taken from patients with rheumatoid arthritis has been reported by Williams (1967a, b; 1970).Although other studies have suggested an association between this disease and other species of mycoplasma (Bartholomew, 1965; Jansson and Wager, 1967; Jansson, Makisara, Vainio, Vainio, Snellman, and Tuuri, 1971; Fraser, Shirodaria, Haire, and Middleton, 1971), the possibility that M. fermentans was associated with rheumatoid arthritis was supported by the finding that there was inhibition of peripheral leucocyte migration in the presence ofextracts of M.fermentans, indicating the existence of a specific immunological response (Williams, Brostoff, and Roitt, 1970).In view of the importance of such an association between M. fermentans and rheumatoid arthritis, we have attempted to isolate mycoplasmas from synovial -fluids by techniques including those described by Williams.* Details of media in text.t AER = Aerobic culture; AN = Anaerobic (95 per cent.N2/5 per cent.Co2) culture.
Protein Engineering in the Development of Functional Hydrogels
Authors: Scott Banta, Ian R. Wheeldon, Mark Blenner
Journal: Annual Review of Biomedical Engineering (2010)

Proteins, which are natural heteropolymers, have evolved to exhibit a staggering array of functions and capabilities. As scientists and engineers strive to tackle important challenges in medicine, novel biomaterials continue to be devised, designed, and implemented to help to address critical needs. This review aims to cover the present advances in the use of protein engineering to create new protein and peptide domains that enable the formation of advanced functional hydrogels. Three types of domains are covered in this review: (a) the leucine zipper coiled-coil domains, (b) the EF-hand domains, and (c) the elastin-like polypeptides. In each case, the functionality of these domains is discussed as well as recent advancements in the use of these domains to create novel hydrogel-based biomaterials. As protein engineering is used to both create and improve protein domains, these advances will lead to exciting new biomaterials for use in a variety of applications.
Inhaled corticosteroids and decline of lung function in community residents with asthma
Authors: P Lange
Journal: Thorax (2006)

<b>Background:</b> Inhaled corticosteroids (ICS) constitute the cornerstone of treatment for asthma. Many studies have reported beneficial short term effects of these drugs, but there are few data on the long term effects of ICS on the decline in forced expiratory volume in 1 second (FEV<sub>1</sub>). This study was undertaken to determine whether adults with asthma treated with ICS have a less pronounced decline in FEV<sub>1</sub> than those not treated with ICS. <b>Methods:</b> Two hundred and thirty four asthmatic individuals from a longitudinal epidemiological study of the general population of Copenhagen, Denmark were divided into two groups; 44 were treated with ICS and 190 were not treated with ICS. The annual decline in FEV<sub>1</sub> was measured over a 10 year follow up period. <b>Results:</b> The decline in FEV<sub>1</sub> in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year in the 190 patients not receiving this treatment (p&lt;0.001). The linear regression model with ICS as the variable of interest and sex, smoking, and wheezing as covariates showed that treatment with ICS was associated with a less steep decline in FEV<sub>1</sub> of 18 ml/year (p = 0.01). Adjustment for additional variables including age, socioeconomic status, body mass index, mucus hypersecretion, and use of other asthma medications did not change these results. <b>Conclusions:</b> Treatment with ICS is associated with a significantly reduced decline in ventilatory function.
Curry Compound Fights Cancer in the Clinic
Authors: A. Carter
Journal: JNCI Journal of the National Cancer Institute (2008)

Kavita Chopra recalls the way that her grandmother would dissolve a teaspoon of the Indian curry spice turmeric in water each morning to promote good health. Today, Chopra takes an 8-g pill of curcumin — the molecule that gives turmeric its bright yellow color — to fight
Inhibition of CD11-CD18 Complex Prevents Acute Lung Injury and Reduces Mortality after Peritonitis in Rabbits
Authors: MARCO GARDINALI, EMMA BORRELLI, OSVALDO CHIARA, CLAES LUNDBERG, PIETRO PADALINO, LUISA CONCIATO, CRISTINA CAFARO, STEFANO LAZZI, PIETRO LUZI, PIER PAOLO GIOMARELLI, ANGELO AGOSTONI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Acute lung injury is frequent after severe peritonitis. The aim of this study was to investigate whether inhibition of the adhesion molecule CD11-CD18 on polymorphonuclear leukocytes (PMNs) would have any beneficial effects on pulmonary function and mortality in an animal model reproducing these clinical conditions. Acute peritonitis was induced in 36 rabbits by intraperitoneal injection of zymosan (0.6 g/kg) suspended in mineral oil; 20 were pretreated with a murine-specific IgG2a anti-CD18 monoclonal antibody, 16 (controls) with nonspecific purified murine IgG (1 mg/kg). The animals were followed for 10 d, then killed for histologic examination of the lungs. Blood samples were taken on Days 0, 1, 3, 7, and 10 for red blood cell (RBC), white blood cell (WBC), and platelet counts, pH, PO(2), PCO(2), carbon dioxide content (HCO(3)(-)) measurements, and renal and liver tests. Treatment with the anti-CD18 monoclonal antibody reduced mortality by approximately 40% (p < 0.05). PO(2) was higher in these treated animals than in the control animals throughout the study (p < 0.05 on Day 1, 3, and 10). On Day 1 control animals had significant leukopenia, whereas anti-CD18-treated animals had a moderate increase of the number of circulating WBC compared with baseline values (p < 0.05 between groups). The lungs of the anti-CD18-treated animals showed minor signs of inflammation and PMN infiltration whereas controls had interstitial and intra-alveolar edema and a large number of granulocytes. Quantification of PMNs by morphometry showed that there were constantly less granulocytes in the lungs of the animals treated with the anti-CD18 antibody (p < 0.001). PMN infiltration correlated with the levels of PO(2) (p < 0.001). Lung tissue of anti-CD18-treated rabbits contained less malonyldialdehyde, a by-product of membrane lipid peroxidation by PMN oxygen radicals (950 +/- 120 versus 1,710 +/- 450 pM/mg of protein) and, conversely, more of the antioxidant alpha-tocopherol (136 +/- 22 versus 40 +/- 9 ng/mg of protein), than the control rabbits (p < 0.01). In this particular model of ARDS the monoclonal antibody against the CD11-CD18 complex had a beneficial effect, reducing PMN infiltration and oxygen radical release in the lungs, preventing alveolocapillary membrane damage, improving gas exchange and, finally, significantly reducing mortality.
The Accumulation of Specific Amplifications Characterizes Two Different Genomic Pathways of Evolution of Familial Breast Tumors
Authors: Lorenzo Melchor, Sara Álvarez, Emiliano Honrado, José Palacios, Alicia Barroso, Orland Díez, Ana Osorio, Javier Benítez
Journal: Clinical Cancer Research (2005)

Abstract Purpose and Methods: High-level DNA amplifications are recurrently found in breast cancer, and some of them are associated with poor patient prognosis. To determine their frequency and co-occurrence in familial breast cancer, we have analyzed 80 tumors previously characterized for BRCA1 and BRCA2 germ-line mutations (26 BRCA1, 18 BRCA2, and 36 non-BRCA1/2) using high-resolution comparative genomic hybridization. Results: Twenty-one regions were identified as recurrently amplified, such as 8q21-23 (26.25%), 17q22-25 (13.75%), 13q21-31 (12.50%), and 8q24 (11.25%), many of which were altered in each familial breast cancer group. These amplifications defined an amplifier phenotype that is correlated with a higher genomic instability. Based on these amplifications, two different genomic pathways have been established in association with 8q21-23 and/or 17q22-25 and with 13q21-31 amplification. These pathways are associated with specific genomic regions of amplification, carry specific immunohistochemical characteristics coincident with high and low aggressiveness, and have a trend to be associated with BRCA1 and BRCA2/X, respectively. Conclusion: In summary, our data suggest the existence of two different patterns of evolution, probably common to familial and sporadic breast tumors.
Amino-Terminal Brain Natriuretic Peptide is Related to the Presence of Diabetic Polyneuropathy Independently of Cardiovascular Disease
Authors: Jeroni Jurado, Juan Ybarra, Maria Ferrandiz, Lourdes Comerma, Jose Maria Pou
Journal: Diabetes Care (2007)

Diabetic polineuropathy (DPN) is among the most common long-term complications of diabetes, affecting up to 50% of patients (1,2). Type 2 diabetes is considered by many to be a cardiovascular disease (CVD) (3).

Plasma levels of the NH2-terminal fragment of the brain natriuretic peptide (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction in type 2 diabetes. Excessive secretion of NT-proBNP is independently associated with coronary artery disease and overt nephropathy (4) in addition …
EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice
Authors: Hai Po H. Liang, Edward J. Kerschen, Irene Hernandez, Sreemanti Basu, Mark Zogg, Fady Botros, Shuang Jia, Martin J. Hessner, John H. Griffin, Wolfram Ruf, Hartmut Weiler
Journal: Blood (2015)
Negative Regulation of Estrogen Receptor α Transactivation Functions by LIM Domain Only 4 Protein
Authors: Rajesh R. Singh, Christopher J. Barnes, Amjad H. Talukder, Suzanne A.W. Fuqua, Rakesh Kumar
Journal: Cancer Research (2005)

Abstract LIM domain only 4 (LMO4), a member of the LIM-only family of transcriptional coregulatory proteins, consists of two LIM protein-protein interaction domains that enable it to function as a linker protein in multiprotein complexes. Here, we have identified estrogen receptor α (ERα) and its corepressor, metastasis tumor antigen 1 (MTA1), as two novel binding partners of LMO4. Interestingly, LMO4 exhibited binding with both ERα and MTA1 and existed as a complex with ERα, MTA1, and histone deacetylases (HDAC), implying that LMO4 was a component of the MTA1 corepressor complex. Consistent with this notion, LMO4 overexpression repressed ERα transactivation functions in an HDAC-dependent manner. Accordingly, silencing of endogenous LMO4 expression resulted in a significant increased recruitment of ERα to target gene chromatin, stimulation of ERα transactivation activity, and enhanced expression of ERα-regulated genes. These findings suggested that LMO4 was an integral part of the molecular machinery involved in the negative regulation of ERα transactivation function in breast cells. Because LMO4 is up-regulated in human breast cancers, repression of ERα transactivation functions by LMO4 might contribute to the process of breast cancer progression by allowing the development of ERα-negative phenotypes, leading to increased aggressiveness of breast cancer cells.