tbuckley/cabot-search huggingface dataset:
Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2-Elk-1 signaling to attenuate TRAIL-induced apoptosis
Authors: Nadzeya Goncharenko-Khaider, Isabelle Matte, Denis Lane, Claudine Rancourt, Alain Piché
Journal: Molecular Cancer (2012)

Abstract Background Ascites may affect the progression of ovarian cancer (OC). In particular, soluble factors present in OC ascites can create a protective environment for tumor cells that promote de novo resistance to drug- and death receptor-induced apoptosis. However, the underlying molecular mechanisms responsible for ascites-induced drug resistance are not well characterized. Methods Using human OC cell lines and tissues microarrays of human OC biopsies, we assessed the mechanism by which OC ascites increase Mcl-1 expression using Western blots, chemical inhibitors of ERK and small-inhibitory RNA treatments. Results In the present study, we found that both Mcl-1 mRNA and protein levels were upregulated within 2 h upon treatment of OC cells with ascites obtained from women with advanced OC. In contrast, the expression of other Bcl-2 family antiapoptotic members such as Bcl-2 and Bcl-X L was not affected by ascites. An increase of Mcl-1 expression was consistently observed across different ascites from women with advanced serous OC. The knockdown of Mcl-1 significantly blocked ascites-induced Mcl-1 upregulation and ascites-mediated inhibition of TRAIL-induced apoptosis. Ascites induced a rapid phosphorylation of ERK1/2 and Elk-1 transcription factor. Furthermore, we found that ERK1/2 inhibition or Elk-1 knockdown was sufficient to block ascites-induced Mcl-1 expression. In high grade serous OC, we found a positive correlation between phosphorylated ERK1/2 and Mcl-1 expression. Conclusions These results indicate that ascites-induced ERK1/2/Elk-1 signaling is critical for Mcl-1 expression and for the ascites-mediated attenuation of TRAIL-induced apoptosis. The ERK1/2/Elk-1/Mcl-1 pathway represents a novel mechanism by which ascites induce de novo TRAIL resistance in OC cells.
Influenza Vaccination of Pregnant Women and Protection of Their Infants
Authors: Shabir A. Madhi, Clare L. Cutland, Locadiah Kuwanda, Adriana Weinberg, Andrea Hugo, Stephanie Jones, Peter V. Adrian, Nadia van Niekerk, Florette Treurnicht, Justin R. Ortiz, Marietjie Venter, Avy Violari, Kathleen M. Neuzil, Eric A.F. Simões, Keith P. Klugman, Marta C. Nunes
Journal: New England Journal of Medicine (2014)

There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples. The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.).
[<sup>18</sup>F]Fluorodeoxyglucose Uptake by Positron Emission Tomography Predicts Outcome of Non–Small-Cell Lung Cancer
Authors: Ryohei Sasaki, Ritsuko Komaki, Homer Macapinlac, Jeremy Erasmus, Pamela Allen, Kenneth Forster, Joe B. Putnam, Roy S. Herbst, Cesar A. Moran, Donald A. Podoloff, Jack A. Roth, James D. Cox
Journal: Journal of Clinical Oncology (2005)

To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC).One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses.There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs (</= 5.0) showed significantly better DFS rates than those with high SUVs (> 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs (</= 5.0) indicated a significantly better DFS than those with high SUVs (> 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001).The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.
DEVELOPMENT OF AGGLUTININS AND PROTECTIVE ANTIBODIES IN RABBITS, AFTER INHALATION OF TYPE II PNEUMOCOCCI
Authors: Ernest G. Stillman
Journal: The Journal of Experimental Medicine (1930)

1. Following repeated inhalations of the degenerated non-virulent "R" forms of Type II pneumococcus, no type specific antibodies can be demonstrated in the serum of rabbits. 2. Following repeated inhalations of slightly virulent Type II (SAv) pneumococci, only protective antibodies can be demonstrated in the serum of rabbits. 3. Following repeated inhalations of virulent Type II (Sv) pneumococci, agglutinins and protective antibodies can be demonstrated in the serum of rabbits. 4. Following repeated exposures of rabbits to inhalation of pneumococci, the type specific response, evidenced by type specific protective antibodies and agglutinins, varies in direct proportion to the virulence of the culture used.
Selective preoperative endoscopic retrograde cholangiography with sphincterotomy avoids bile duct exploration during laparoscopic cholecystectomy.
Authors: C R Welbourn, D Mehta, C P Armstrong, M W Gear, I A Eyre-Brook
Journal: Gut (1995)

A policy of preoperative endoscopic retrograde cholangiography (ERC) for suspected bile duct stones was used in 1507 patients considered for laparoscopic cholecystectomy in three district general hospitals. Altogether 306 patients underwent ERC, and bile duct cannulation was achieved in 276 (90%). Bile ducts were cleared by endoscopic sphincterotomy in 128 of 161 patients (79%) with proven duct stones. Laparoscopic cholecystectomy was completed in 1396 patients. Ten laparotomies were necessary for complications of laparoscopic cholecystectomy. The complication rate for endoscopic sphincterotomy/laparoscopic cholecystectomy was 2.7%, with no mortality. Overall, a combined endoscopic/laparoscopic approach succeeded in 1386 patients (92%). Fourteen patients (1%) had retained stones during a median of 14 months (range 1-42) follow up, all of which were removed by ERC/endoscopic sphincterotomy. If a policy of selective ERC before laparoscopic cholecystectomy is used for all patients with symptomatic gall stones, most will avoid an open operation and laparoscopic exploration of the bile duct is not necessary.
Stomach Cancer and Food Storage
Authors: D. Coggon, D. J. P. Barker, R. B. Cole, M. Nelson
Journal: JNCI Journal of the National Cancer Institute (1989)

To examine the influence of food storage habits on the development of stomach cancer, we compared 95 patients and 190 controls selected from the general population. Information about food storage and diet was obtained from the patients and the controls by use of a questionnaire mailed to each subject followed by an interview. Low intake of salad vegetables and fruit and high intake of salt were clearly associated with stomach cancer development. No association was found with recent refrigerator use, but a halving of stomach cancer risk in subjects who had used a refrigerator for ≥29 years persisted after allowance was made for recent diet. Risk was elevated in subjects who, when children, had lived in houses without a larder built specifically for the storage of food. [J Natl Cancer Inst 81:1178–1182, 1989]
THE INFLUENCE OF TEMPERATURE AND FLUID MEDIUM ON THE SURVIVAL OF EMBRYONIC TISSUES IN VITRO
Authors: Robert A. Lambert
Journal: The Journal of Experimental Medicine (1913)

1. Embryonic chick and rat tissues preserved at temperatures ranging from -7 degrees to +20 degrees C. live longest at about +6 degrees C. The duration of life under the most favorable conditions is less than twenty days. 2. The kind of isotonic medium used,-plasma serum, Ringer solution, or normal salt solution,-does not appreciably influence the period of survival. The quantity of medium in proportion to tissue is similarly without marked effect.
Psychotherapy Designed to Detect and Treat Suicidal Potential
Authors: HARVEY M. SHEIN, ALAN A. STONE
Journal: American Journal of Psychiatry (1969)

The authors point out the present failure of many psychiatrists to recognize potentially suicidal patients. They describe a five-stage clinical approach to treatment of such patients, utilizing a continuous assessment of suicidal potential. The approach introduces a system of priority of values, with preservation, of life uppermost.
Association of NAD(P)H Oxidase <i>p</i>22 phox Gene Variation With Advanced Carotid Atherosclerosis in Japanese Type 2 Diabetes
Authors: Rieko Hayaishi-Okano, Yoshimitsu Yamasaki, Yoshitaka Kajimoto, Ken’ya Sakamoto, Kentaro Ohtoshi, Naoto Katakami, Dan Kawamori, Takeshi Miyatsuka, Masahiro Hatazaki, Yoji Hazama, Masatsugu Hori
Journal: Diabetes Care (2003)

To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects.C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients' clinical characteristics and the level of 8-hydroxy-2'deoxyguanosine (8-OHdG) as an index of oxidative DNA damage.The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 +/- 0.31 vs. 1.31 +/- 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 +/- 0.14 vs. 0.94 +/- 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 +/- 15.6 vs. 64.2 +/- 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 +/- 0.66 vs. 2.60 +/- 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group.These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.
Stimulated plasmacytoid dendritic cells impair human T-cell development
Authors: Heike Schmidlin, Wendy Dontje, Fedde Groot, Suzanne J Ligthart, Arnaud D Colantonio, Monique E Oud, Esther J Schilder-Tol, Marcel Spaargaren, Hergen Spits, Christel H Uittenbogaart, Bianca Blom
Journal: Blood (2006)
Failure of High-Dose Ergocalciferol to Correct Vitamin D Deficiency in Adults with Cystic Fibrosis
Authors: Michael P. Boyle, Michelle L. Noschese, Sharon L. Watts, Marsha E. Davis, Shane E. Stenner, Noah Lechtzin
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Treatment guidelines for vitamin D monitoring and supplementation in cystic fibrosis (CF) have recently been developed and published by a consensus committee, but have not been prospectively tested. Objectives: To use these guidelines to determine the percentage of adults with CF requiring vitamin D repletion therapy and to evaluate the effectiveness of the currently recommended high-dose oral ergocalciferol repletion protocol. Methods: Prospective study of clinical outcomes after therapy with the recommended vitamin D repletion algorithm. Results: Of 134 adults with CF, 109 (81.3%) were found to have 25-hydroxyvitamin D (25-OHD) levels below the recommended 30 ng/ml. Sixty-six of these adults completed the recommended course of 400,000 IU of oral ergocalciferol over 2 months, and only five (8%) responded with correction of their serum 25-OHD to the goal of 30 ng/ml or greater (mean change, +0.3 ng/ml; from 18.8 to 19.1 ng/ml). In the 33 adults with CF who also completed the recommended second course of 800,000 IU of ergocalciferol over 2 months, none demonstrated correction of their deficiency (mean change, −1.2 ng/ml). Conclusion: The results of this study demonstrate that a majority of adults with CF have serum 25-OHD levels below 30 ng/ml, and the currently recommended ergocalciferol repletion regimen often does not fully correct vitamin D deficiency and may need to be revised to include even higher dosing of ergocalciferol. Further work is needed to establish the ideal 25-OHD level for maximizing calcium absorption and bone health in CF.
Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3
Authors: Feng Lan, Nan Zhang, Jie Zhang, Olga Krysko, Quanbo Zhang, Junming Xian, Lara Derycke, Yanyu Qi, Kai Li, Shixi Liu, Ping Lin, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2013)
Predetermined challenge eligibility and cessation criteria for oral food challenges in the HealthNuts population-based study of infants
Authors: Jennifer J. Koplin, Mimi L.K. Tang, Pamela E. Martin, Nicholas J. Osborne, Adrian J. Lowe, Anne-Louise Ponsonby, Marnie N. Robinson, Dean Tey, Leone Thiele, David J. Hill, Lyle C. Gurrin, Melissa Wake, Shyamali C. Dharmage, Katrina J. Allen
Journal: Journal of Allergy and Clinical Immunology (2011)
Evaluation of applied potential tomography as a new non-invasive gastric secretion test.
Authors: A J Baxter, Y F Mangnall, E H Loj, B Brown, D C Barber, A G Johnson, N W Read
Journal: Gut (1988)

Applied potential tomography (APT) is a new, non-invasive technique that can yield sequential images of changes in the resistivity of gastric contents. Studies were performed to investigate the application of APT to measure gastric acid secretion. Experiments in 20 normal volunteers showed that changes in gastric resistivity were closely correlated with changes in the volume (r = 0.80), the acidity (r = 0.83) and the total conductivity of gastric contents (r = 0.87). Studies in 13 patients referred for a pentagastrin test showed that changes in gastric resistivity before pentagastrin were closely correlated with basal acid output measured on a separate occasion (r = 0.85, p less than 0.001), while changes in gastric resistivity after pentagastrin were correlated with maximal acid output (r = 0.58, p less than 0.05). Ingestion of alcohol by six normal subjects decreased gastric resistivity markedly, probably due to alcohol induced gastric acid secretion as it was prevented by cimetidine. Applied potential tomography is a safe non-invasive method of measuring gastric acid secretion. The equipment is simple to use, and the test is comfortable and acceptable to patients.
Continuous Control of Tracheal Cuff Pressure and Microaspiration of Gastric Contents in Critically Ill Patients
Authors: Saad Nseir, Farid Zerimech, Clément Fournier, Rémy Lubret, Philippe Ramon, Alain Durocher, Malika Balduyck
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP).To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents.Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61).The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups.Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.
Anatomic Brain Abnormalities in Monozygotic Twins Discordant for Attention Deficit Hyperactivity Disorder
Authors: F. Xavier Castellanos, Wendy S. Sharp, Rebecca F. Gottesman, Deanna K. Greenstein, Jay N. Giedd, Judith L. Rapoport
Journal: American Journal of Psychiatry (2003)

To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD.National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD.The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins.These results provide further support for striatal models of ADHD pathophysiology.
Chronic Chlamydia pneumoniae infection and asthma exacerbations in children
Authors: AF Cunningham, SL Johnston, SA Julious, FC Lampe, ME Ward
Journal: European Respiratory Journal (1998)

This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms. One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a daily diary of respiratory symptoms and peak flow rates. When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained. In total 292 episodes were reported. After the study 65 children provided samples when asymptomatic. The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p&lt; 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p&lt;0.02). M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations. We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms. In contrast Mycoplasma pneumoniae was not found to be important in this study.
Intracardiac Phonocardiogram in Thirty Cases of Atrial Septal Defect
Authors: GEORGE A. FERUGLIO, AKKAYA SREENIVASAN
Journal: Circulation (1959)

Thirty cases of atrial septal defect proved by cardiac catheterization, surgery, or postmortem examination have been investigated with the technic of intracardiac phonocardiography, which provided precise localization of the source of heart sounds and murmurs. The site and mechanism of origin of the many auscultatory signs in uncomplicated atrial septal defect and in cases of Lutembacher's syndrome, tricuspid atresia, and persistent atrioventricular canal were elucidated by direct intracardiac sound recordings and simultaneous external chest phonocardiograms.
Canstatin Acts on Endothelial and Tumor Cells via Mitochondrial Damage Initiated through Interaction with αvβ3 and αvβ5 Integrins
Authors: Claire Magnon, Ariane Galaup, Brian Mullan, Valérie Rouffiac, Jean-Michel Bidart, Frank Griscelli, Paule Opolon, Michel Perricaudet
Journal: Cancer Research (2005)

Abstract Canstatin, the noncollagenous domain of collagen type IV α-chains, belongs to a series of collagen-derived angiogenic inhibitors. We have elucidated the functional receptors and intracellular signaling induced by canstatin that explain its strong antitumor efficacy in vivo. For this purpose, we generated a canstatin-human serum albumin (CanHSA) fusion protein, employing the HSA moiety as an expression tag. We show that CanHSA triggers a crucial mitochondrial apoptotic mechanism through procaspase-9 cleavage in both endothelial and tumor cells, which is mediated through cross-talk between αvβ3- and αvβ5-integrin receptors. As a point of reference, we employed the first three kringle domains of angiostatin (K1-3), fused with HSA, which, in contrast to CanHSA, act only on endothelial cells through αvβ3-integrin receptor–mediated activation of caspase-8 alone, without ensuing mitochondrial damage. Taken together, these results provide insights into how canstatin might exert its strong anticancer effect.