tbuckley/cabot-search huggingface dataset:
Abstract 12639: Ventricular Energetics in Fontan Circulation: A Potential Therapeutic Target for Preserving Myocardial Function
Authors: Hirofumi Saiki, Seiko Kuwata, Clara Kurishima, Yoichi Iwamoto, Hirotaka Ishido, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2014)

Background: Cardiac dysfunction is one of the vital determinants of long-term outcome in patients with Fontan circulation. However, underlying mechanisms for the development of ventricular dysfunction remain unclear. Energy depletion is a key feature of failing ventricles, and heart failure alters ventricular energy consumption for intracellular Ca2+ handling during excitation-contraction (E-C) coupling. We hypothesized that ventricular energetic efficiency for Ca2+ handling as well as for external work production is reduced in Fontan circulation compared with biventricular circulation.

Method: A pressure-volume (PV) relationship was constructed during cardiac catheterization in 14 Fontan patients and 29 controls with biventricular heart. Myocardial oxygen consumption (MVO2) was estimated by PV area (PVA), and ventricular mechanical efficiency (Ve) was calculated as the ratio of stroke work (SW) and PVA. The fraction of the total amount of Ca2+ recycled by the sarcoplasmic reticulum during E-C coupling, termed recirculation fraction (RF), was computed by fitting the decay of contractile index after rapid atrial pacing to a combined sinusoid and logistic function.

Result: MVO2 was significantly higher (3.2 ± 1.0 vs. 2.6 ± 0.5 mLO2/beat/100g, p < .05), whereas SW was significantly lower in Fontan patients than in controls, indicating higher oxygen cost for ventricular work in Fontan patients. This was consistent with a significantly lower Ve in Fontan patients than in controls (p < .01). Furthermore, oxygen cost for Ca2+ handling was significantly higher in Fontan patients than in controls, as indicated by a lower RF in Fontan patients than in controls (0.66 ± 0.04 vs. 0.77 ± 0.02, p < .05). Importantly, RF was significantly correlated with Ve independent of ventricular contractility and afterload (p < .05).

Conclusion: Higher oxygen cost for E-C coupling in the Fontan ventricle appears to affect the mechanical efficiency. Since RF is known to be independent of catecholamine status, these features of Fontan ventricular energetics can lead to myocardial energy depletion throughout a patient’s life. Strategies involving Ca2+ handling may effectively terminate the vicious cycle of developing ventricular dysfunction in Fontan circulation.
Internet-Based Continuing Medical Education—Reply
Authors: Michael Fordis, Jason E. King, Christie M. Ballantyne, Peter H. Jones, Katharine H. Schneider, Stephen J. Spann, Stephen B. Greenberg, Anthony J. Greisinger
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Soft tissue sarcomas: research of prognostic factors and therapeutics scheme.
Authors: A Montagnese, M Sturla, I Bruno, R Bracaglia, M Salgarello, A Seccia, E Farallo
Journal: Journal of experimental & clinical cancer research (2003)

The Soft Tissue Sarcomas shows consisting mortality that grazes 50%. Commonly the histologic type, the largeness of the tumor and the degree of malignity, are considered prognostic factors influencing the survival of patients affected from such tumor. The aim of our study is to characterize the new prognostic factors influencing the local recidives and metastatic dissemination. We have analysed 17 possible clinical and histologic prognostic factors in 80 patients affected of soft tissue sarcomas. The results have dimonstrated that: the compartimentality and the cellular differentiation seem to be more influent to the insurgence of local recidives and metastasis; while the low malignity degree, the wide surgical margins and the histopatological characters of benignity can influense positively the survival.
Abstract 1773: Outcomes of Childbirth Among Women With Congenital Heart Disease in the United States
Authors: Omar K Siddiqi, Benjamin D'Souza, Michael J Landzberg, Gary D Webb, Alexander R Opotowsky
Journal: Circulation (2009)

Introduction: A growing number of patients with congenital heart disease (CHD) are reaching reproductive age, and CHD is now more common than acquired cardiac disease among pregnant women. Methods:...
Individuals and Global Health Improvement—Reply
Authors: Andy Haines, Gill Walt, Kelley Lee
Journal: JAMA (2004)

Pharmacogenomics of lipid-lowering therapy is further complicated in that the appropriate response phenotype is unclear.For example, pharmacogenetic studies investigating apolipoprotein E (APOE) polymorphisms suggest a gene-dose effect, with ⑀2 carriers showing greater reductions in LDL cholesterol in response to statins, while ⑀4 carriers are least responsive. 2,3 In contrast, when adverse cardiovascular outcomes were examined in a substudy of the Scandinavian Simvastatin Survival Study, ⑀4 carriers had the greatest reduction in death rates in response to simvastatin compared with non-⑀4 carriers. 4Therefore, while ⑀2 carriers may have a better response to statins using a surrogate outcome, ⑀4 carriers have a better response using mortality as the outcome.Of note, these differences in risk reduction based on APOE genotype do not appear to be related to variable LDL cholesterol treatment responses.
Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis
Authors: R.N. Cardili, T.G. Alves, J.C.O.C. Freitas, C.P. Soares, C.T. Mendes-Junior, E.G. Soares, E.A. Donadi, C. Silva-Souza
Journal: British Journal of Dermatology (2010)

Background The nonclassical human leucocyte antigen (HLA)‐G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases. Objectives To evaluate the expression of HLA‐G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables. Methods Thirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA‐G expression in formalin‐fixed paraffin‐embedded cutaneous skin biopsies. Results Soluble and membrane‐bound HLA‐G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA‐G expression, the epidermis was primarily targeted. HLA‐G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA‐G expression (P <0·0001). The intensity of HLA‐G expression was not associated with type I/II psoriasis, Psoriasis Area and Severity Index score or clinical forms. Conclusions As the HLA‐G molecule was consistently expressed in affected and, to a lesser extent, in nonaffected areas of untreated patients with psoriasis, irrespective of the severity of the clinical variants, one may hypothesize that the presence of HLA‐G may be responsible, at least in part, for the regulation of autoimmune effector cells.
Gastrin-releasing peptide receptor upregulation in human lung adenocarcinoma
Authors: Edwina Lerner, Jill Siegfried, Xuwan Liu
Journal: Cancer Research (2007)

4405   Gastrin-releasing peptide (GRP) is a mitogen for lung epithelial cells and initiates signaling through a G protein-coupled receptor, gastrin-releasing peptide receptor (GRPR). Previous work from our laboratory has shown that GRP induces Akt activation through a c-Src-mediated transactivation of the epidermal growth factor receptor (EGFR) in non-small cell lung carcinoma (NSCLC) cells. In this study, we investigated the level of GRPR protein expression in human lung tissue microarrays (TMA) consisting of 26 cases of NSCLC (19 adenocarcinomas, 3 squamous cell carcinomas, 4 designated as “other”) as well as matched normal lung tissue from 25 cases and positive and negative lymph nodes from 7 and 9 cases, respectively. Immunostaining was carried out using a GRPR antibody recognizing the 2 nd  extracellular domain of the human form (MBL Intl., Woburn, MA), which in an immunoblot gives a single band migrating at 50kD. GRPR immunostaining was scored by ranking the intensity of staining from 0-3 and the percentage of positive cells from 0-5, with the sum of the two rankings accounting for the total staining score. For all cases combined, the median total GRPR staining score was 3.50 in normal lung compared to 5.38 in tumor tissue (P = 0.0002, Mann-Whitney test). The difference in GRPR staining between adenocarcinoma tissue (median 5.6) and matched normal tissue (median 3.38) was significant (P = 0.0001, Mann-Whitney test), while the difference in GRPR staining score between squamous cell and other tumor types combined was not significantly different from their matched normal lung. Lymph nodes that scored positive for tumor infiltration by H & E staining had a significantly higher median GRPR staining score (5.65) compared to nodes scored negative for tumor infiltration (score 1.25, P = 0.005, Mann-Whitney test). For adenocarcinoma cases alone, the median GRPR score in positive nodes was 5.8, compared to 0 in negative nodes. These results suggest that GRPR protein expression is increased in human lung adenocarcinomas compared to its surrounding normal lung tissue. Furthermore, we have shown that GRP can rescue NSCLC cells exposed to gefitinib through release of amphiregulin and activation of Akt. Amphiregulin release is blocked by expression of a dominant negative Src. Pretreatment of NSCLC cells with 100 nM GRP resulted in a 5-fold increase in the IC 50  of gefitinib. This protective effect was mimicked by pre-treatment of cells with amphiregulin and reversed by inhibition of AKT using the PI-3kinase inhibitor LY294002. These results suggest that GRPR and/or EGFR autocrine pathways may modulate therapeutic responses to EGFR inhibitors, and that GRPR may be a novel target for therapy in NSCLC either alone or in combination with EGFR inhibitors. This work was supported by the National Cancer Institute Lung SPORE grant P50 CA090440 to J.M.S.
The Efficacy of the FLT3 Inhibitor Lestaurtinib in AML Depends on Adequate Plasma Inhibitory Activity (PIA), and Is Unaffected by Rising FLT Ligand Levels: An Update of the NCRI AML15 &amp; 17 Trials
Authors: Steven Knapper, Paul White, Mark J. Levis, Robert K Hills, Nigel H. Russell, Alan Burnett
Journal: Blood (2011)
Intensive chemotherapy, azacitidine, or supportive care in older acute myeloid leukemia patients: An analysis from a regional healthcare network
Authors: Pierre Bories, Sarah Bertoli, Emilie Bérard, Julie Laurent, Eliane Duchayne, Audrey Sarry, Eric Delabesse, Odile Beyne‐Rauzy, Françoise Huguet, Christian Récher
Journal: American Journal of Hematology (2014)

We assessed in a French regional healthcare network the distribution of treatments, prognostic factors, and outcome of 334 newly diagnosed acute myeloid leukemia patients aged 60 years or older over a 4‐year period of time (2007–2010). Patients were selected in daily practice for intensive chemotherapy ( n = 115), azacitidine ( n = 95), or best supportive care ( n = 124). In these three groups, median overall survival was 18.9, 11.3, and 1.8 months, respectively. In the azacitidine group, multivariate analysis showed that overall survival was negatively impacted by higher age ( P = 0.010 for one unit increase), unfavorable cytogenetics ( P = 0.001), lymphocyte count &lt;0.5 G/L ( P = 0.015), and higher lactate dehydrogenase level ( P = 0.005 for one unit increase). We compared the survival of patients treated by azacitidine versus intensive chemotherapy and best supportive care using time‐dependent analysis and propensity score matching. Patients treated by intensive chemotherapy had a better overall survival compared with those treated by azacitidine from 6 months after diagnosis, whereas patients treated by azacitidine had a better overall survival compared with those treated by best supportive care from 1 day after diagnosis. This study of “real life” practice shows that there is a room for low intensive therapies such as azacitidine in selected elderly acute myeloid leukemia patients. Am. J. Hematol. 89:E244–E252, 2014. © 2014 Wiley Periodicals, Inc.
Comparison of AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting With Direct Stenting Alone in Patients With Acute Myocardial Infarction
Authors: Angela Migliorini, Amerigo Stabile, Alfredo E. Rodriguez, Caterina Gandolfo, Alfredo M. Rodriguez Granillo, Renato Valenti, Guido Parodi, Franz-Josef Neumann, Antonio Colombo, David Antoniucci
Journal: Journal of the American College of Cardiology (2010)
Physical training and connective tissues in young mice.
Authors: A. KIISKINEN, E. HEIKKINEN
Journal: British Journal of Dermatology (1976)

The effect of physical training on some connective tissue components of the skin was studied in male mice of NMRI-strain. The mice to be trained and their controls were about 2-weeks-old at the beginning of the training, which took place on a 5 degree inclined treadmill 5 days a week for 3-22 weeks progressively. The final exercise bouts were 50 and 80 min for moderate programmes and 180 min for the intensive programme at a speed of 30 cm/s. At the end of each experiment skin samples from trained and control animals were taken for the analyses. We found increased concentrations of nitrogen, hexosamines and hydroxyproline in the skin of the trained mice compared to the controls. The unchanged DNA concentration suggests that the activation of synthesis occurred in a constant number of cells.
One-Year Survival of Extremely Preterm Infants After Active Perinatal Care in Sweden
Authors: Vineta Fellman, Lena Hellström-Westas, Mikael Norman, Magnus Westgren, Karin Källén, Hugo Lagercrantz, Karel Marsál, Fredrik Serenius, Margareta Wennergren
Journal: JAMA (2009)

Context Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.Objective To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007. Design, Setting, and PatientsPopulation-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007.Main Outcome Measures Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade Ͼ2, retinopathy of prematurity stage Ͼ2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia).Associations between perinatal interventions and survival. ResultsThe incidence of extreme prematurity was 3.3 per 1000 infants.Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths.Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%).The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively.Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52),antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81),surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71),and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75).Among 1-year survivors, 45% had no major neonatal morbidity. ConclusionDuring 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.
Abstract P171: Hemoglobin A1c and Incident Albuminuria Among Individuals Without Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: April P Carson, Paul Muntner, Mercedes R Carnethon, Myron D Gross, Cora E Lewis
Journal: Circulation (2015)

Background: Higher hemoglobin A1c (HbA1c) has been associated with an increased risk of reduced estimated glomerular filtration rate &lt;60 mls/min/1.73m2 among individuals without diabetes. However, it is unclear whether higher HbA1c in the non-diabetic glycemic range also is associated with an increased risk of albuminuria. This study investigated the association of HbA1c with incident albuminuria in a biracial cohort of middle-aged men and women without a history of diabetes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods: The CARDIA Study is a prospective cohort study of 5,115 African-American and white adults, age 18-30 years at baseline (1985-86), from four field centers in the United States: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. Participants with prevalent diabetes (defined as fasting glucose ≥126 mg/dL, 2-hour post-challenge glucose ≥ 200 mg/dL, HbA1c ≥ 6.5%, or used diabetes medications) or albuminuria (defined as a race- and sex-adjusted urine albumin-to-creatinine ratio ≥ 25 mg/g) at the year 20 examination (2005-06; baseline for this analysis) were excluded. This study included 2174 participants who had HbA1c measured at the year 20 examination and had urine albumin and creatinine measured at the year 25 examination (2010-11). Poisson regression with robust error variances was used to obtain risk ratios (RR) and 95% confidence intervals (CI) for the association of HbA1c, both as a continuous variable and dichotomous variable using its prediabetes cut-point, with albuminuria in unadjusted models and models adjusted for socio-demographics and cardiovascular risk factors. Results: During the follow-up period, 103 (4.7%) participants developed incident albuminuria. In unadjusted analyses, each 1% increase in HbA1c was associated with incident albuminuria (RR=2.55, 95% CI=1.48, 4.39). This association was attenuated and not statistically significant after adjustment for age, race, sex, and education (RR=1.68, 95% CI=0.98, 2.88) and further adjustment for cardiovascular risk factors (RR=1.42, 95% CI=0.81, 2.50). Additionally, individuals with HbA1c in the prediabetes range (5.7%-6.4%) had an increased risk of albuminuria (RR=1.59, 95% CI=1.04, 2.43) compared with those with HbA1c in the normal glycemic range (&lt;5.7%) in the unadjusted model. However, this association was attenuated after adjustment for socio-demographics (RR=1.11, 95% CI=0.71, 1.72) and cardiovascular risk factors (RR=0.98, 95% CI=0.61, 1.55). Conclusions: After taking into account socio-demographics and traditional cardiovascular risk factors, HbA1c was not associated with incident albuminuria among individuals without diabetes.
Diadenosine tetraphosphate (Ap4A) produced by lysyl-tRNA synthetase may play a role in inhibiting the function of the HINT1 tumor suppressor in human colon cancer cells
Authors: Amane Harada, Haiyang Li, I. Weinstein
Journal: Cancer Research (2008)

1782   HINT1 is a member of the highly conserved histidine triad nucleotide binding protein family. Previously we demonstrated that HINT1 is a haplo-insufficient tumor suppressor in mice, and overexpression of HINT1 in human cancer cells causes growth inhibition. However, analysis of cellular levels of HINT1 in various human cancer cell lines indicated that many cancer cells continue to express considerable amounts of the HINT1 protein. Therefore, mechanisms other than repressing gene expression of HINT1 may contribute to inactivation of HINT1 in these cells. In this study we examined the effects of changes in cellular Ap 4 A level on the tumor suppressing function of HINT1 in human colon cancer cells. One of the ligands of HINT1, Ap 4 A, is an exotic nucleotide produced by lysyl-tRNA synthetase (LysRS). In mast cells, an increased cellular level of Ap 4 A attenuated the inhibitory effect of HINT1 on MITF transcription activity. To evaluate whether similar effect of Ap 4 A may contribute to inactivation of HINT1 in human colon cancer cells, we first determined the expression levels of LysRS in these cells. We found that there was a positive correlation between the protein levels of HINT1 and LysRS in a series of human colon cancer cells. HCT116 and SW834 cells expressed high levels of both proteins, and SW480 cells expressed low levels of both proteins. The normalized LysRS/HINT1 ratio was similar in the three cancer cell lines. On the other hand, a normal colon cell line, CCD841, had a significantly lower LysRS/HINT1 ratio, compared with the colon cancer cell lines. Since overexpression of LysRS increases the cellular level of Ap 4 A, this result suggested that HINT1 might be inactivated by high level of cellular Ap 4 A in human colon cancer cells. Because of the importance of TCF/β-catenin signaling in the growth of human colon cancer cells, and HINT1 inhibits the activity of β-catenin through interacting with Pontin and Reptin, which form complex with and regulate the activity of β-catenin, we next conducted GST-pull down assay to examine the effect of Ap 4 A on the association of HINT1 and Pontin. Using recombinant GST-tagged HINT1 and non-tagged Pontin, we found that Ap 4 A caused dissociation of these two proteins in a dose-dependent manner, and that 100 μM of Ap 4 A completely abolished the association of HINT1 and Pontin. Co-immunoprecipitation assays indicated that Pontin formed a complex with LysRS, and overexpression of LysRS inhibited the interaction between HINT1 and Pontin, as well as HINT1 and β-catenin. Consistent with the above findings, overexpression of HINT1 inhibited TCF/β-catenin-mediated gene transcription, and co-overexpression of LysRS reversed this inhibitory effect. Taken together, our results suggest that overexpression of LysRS might contribute to functional inactivation of the tumor suppressor HINT1.
Antileukemia multifunctionality of CD4+ T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer
Authors: H Fujiwara, T Ochi, F Ochi, Y Miyazaki, H Asai, M Narita, S Okamoto, J Mineno, K Kuzushima, H Shiku, M Yasukawa
Journal: Leukemia (2015)
Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells
Authors: GJ Elfenbein, DS Brogaonkar, WB Bias, WH Burns, R Saral, LL Sensenbrenner, PJ Tutschka, BS Zaczek, AR Zander, RB Epstein, JD Rowley, GW Santos
Journal: Blood (1978)