tbuckley/cabot-search huggingface dataset:
Impact of Neonatal Screening and Surveillance for the <i>TP53</i> R337H Mutation on Early Detection of Childhood Adrenocortical Tumors
Authors: Gislaine Custódio, Guilherme A. Parise, Nilton Kiesel Filho, Heloisa Komechen, Cesar C. Sabbaga, Roberto Rosati, Leila Grisa, Ivy Z.S. Parise, Mara A.D. Pianovski, Carmem M.C.M. Fiori, Jorge A. Ledesma, José Renato S. Barbosa, Francisco R.O. Figueiredo, Elis R. Sade, Humberto Ibañez, Sohaila B.I. Arram, Sérvio T. Stinghen, Luciano R. Mengarelli, Mirna M.O. Figueiredo, Danilo C. Carvalho, Sylvio G.A. Avilla, Thiago D. Woiski, Lisiane C. Poncio, Geneci F.R. Lima, Roberto Pontarolo, Enzo Lalli, Yinmei Zhou, Gerard P. Zambetti, Raul C. Ribeiro, Bonald C. Figueiredo
Journal: Journal of Clinical Oncology (2013)

Purpose The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. Patients and Methods Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age &lt; 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. Results Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P &lt; .001); six patient cases were identified among 228 carrier relatives age &lt; 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P &lt; .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). Conclusion These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable.
Serial pulmonary function tests in the diagnosis of P. carinii pneumonia
Authors: DM Mitchell, J Fleming, None Harris, RJ Shaw
Journal: European Respiratory Journal (1993)

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)
Origin and Ascendancy of a Chimeric Fusion Gene: The / -Globin Gene of Paenungulate Mammals
Authors: J. C. Opazo, A. M. Sloan, K. L. Campbell, J. F. Storz
Journal: Molecular Biology and Evolution (2009)

The δ-globin gene (HBD) of eutherian mammals exhibits a propensity for recombinational exchange with the closely linked β-globin gene (HBB) and has been independently converted by the HBB gene in multiple lineages. Here we report the presence of a chimeric β/δ fusion gene in the African elephant (Loxodonta africana) that was created by unequal crossing-over between misaligned HBD and HBB paralogs. The recombinant chromosome that harbors the β/δ fusion gene in elephants is structurally similar to the “anti-Lepore” duplication mutant of humans (the reciprocal exchange product of the hemoglobin Lepore deletion mutant). However, the situation in the African elephant is unique in that the chimeric β/δ fusion gene supplanted the parental HBB gene and is therefore solely responsible for synthesizing the β-chain subunits of adult hemoglobin. A phylogenetic survey of β-like globin genes in afrotherian and xenarthran mammals revealed that the origin of the chimeric β/δ fusion gene and the concomitant inactivation of the HBB gene predated the radiation of “Paenungulata,” a clade of afrotherian mammals that includes three orders: Proboscidea (elephants), Sirenia (dugongs and manatees), and Hyracoidea (hyraxes). The reduced fitness of the human Hb Lepore deletion mutant helps to explain why independently derived β/δ fusion genes (which occur on an anti-Lepore chromosome) have been fixed in a number of mammalian lineages, whereas the reciprocal δ/β fusion gene (which occurs on a Lepore chromosome) has yet to be documented in any nonhuman mammal. This illustrates how the evolutionary fates of chimeric fusion genes can be strongly influenced by their recombinational mode of origin.
Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase
Authors: Mohammad Ali Faghihi, Farzaneh Modarresi, Ahmad M Khalil, Douglas E Wood, Barbara G Sahagan, Todd E Morgan, Caleb E Finch, Georges St. Laurent III, Paul J Kenny, Claes Wahlestedt
Journal: Nature Medicine (2008)
Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice
Authors: Xiaohe Liu, Jodi L. Karnell, Bu Yin, Ruan Zhang, Jidong Zhang, Peiying Li, Yongwon Choi, Jonathan S. Maltzman, Warren S. Pear, Craig H. Bassing, Laurence A. Turka
Journal: Journal of Clinical Investigation (2010)

Mutations in the tumor-suppressor gene phosphatase and tensin homolog deleted on chromosome 10 (Pten) are associated with multiple cancers in humans, including T cell malignancies. Targeted deletion of Pten in T cells induces both a disseminated "mature phenotype" lymphoma and a lymphoproliferative autoimmune syndrome in mice. Here, we have shown that these two diseases are separable and mediated by T lineage cells of distinct developmental stages. Loss of PTEN was found to be a powerful driver of lymphomagenesis within the thymus characterized by overexpression of the c-myc oncogene. In an otherwise normal thymic environment, PTEN-deficient T cell lymphomas invariably harbored RAG-dependent reciprocal t(14:15) chromosomal translocations involving the T cell receptor alpha/delta locus and c-myc, and their survival and growth was TCR dependent, but Notch independent. However, lymphomas occurred even if TCR recombination was prevented, although these lymphomas were less mature, arose later in life, and, importantly, were dependent upon Notch pathways to upregulate c-myc expression. In contrast, using the complementary methods of early thymectomy and adoptive transfers, we found that PTEN-deficient mature T cells were unable to undergo malignant transformation but were sufficient for the development of autoimmunity. These data suggest multiple and distinct regulatory roles for PTEN in the molecular pathogenesis of lymphoma and autoimmunity.
Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.
Authors: Y Kohno, J A Berzofsky
Journal: The Journal of Experimental Medicine (1982)

We studied the genetic restrictions on the interaction between T cells, B cells, and antigen-presenting cells (APC) involved in the H-2-linked Ir gene control of the in vitro secondary antibody response to sperm whale myoglobin (Mb) in mice. The B cells in this study were specific for Mb itself, rather than for a hapten unrelated to the Ir gene control, as in many previous studies. Low responder mice immunized in vivo with Mb bound to an immunogenic carrier, fowl gamma globulin (F gamma G), produced B cells competent to secrete anti-Mb antibodies in vitro if they received F gamma G-specific T cell help. However, (high-responder X low responder) F1 T cells from Mb-immune mice did not help these primed low responder (H-2k or H-2b) B cells in vitro, even in the presence of various numbers of F1 APC that were demonstrated to be component to reconstitute the response of spleen cells depleted by APC. Similar results were obtained with B6 leads to B6D2F1 radiation bone marrow chimeras. Genotypic low responder (H-2b) T cells from these mice helped Mb-primed B6D2F1B cells plus APC, but did not help syngeneic chimeric H-2b B cells, even in the presence of F1 APC. In contrast, we could not detect any Ir restriction on APC function during these in vitro secondary responses. Moreover, in the preceding paper, we found that low responder mice neonatally tolerized to higher responder H-2 had competent Mb-specific helper T cells capable of helping high responder but not low responder B cells and APC. Therefore, although function Mb-specific T cells and B cells both exist in low responder mice, the Ir gene defect is a manifestation of the failure of syngeneic collaboration between these two cell types. This genetic restriction on the interaction between T cells and B cells is consistent with the additional new finding that Lyb-5-negative B cells are a major participant in ths vitro secondary response because it is this Lyb-5-negative subpopulation of B cells that have recently been shown to require genetically restricted help. The Ir gene defect behaves operationally as a failure of low responder B cells to receive help from any source of Mb-specific T cells either high responder, low responder, or F1. The possible additional role of T cell-APC interactions, either during primary immunization in vivo or in the secondary culture is discussed.
Calcium in Pregnancy and Lactation
Authors: Ann Prentice
Journal: Annual Review of Nutrition (2000)

Pregnancy and lactation are periods of high calcium requirement. This review highlights recent advances in our understanding of calcium and bone metabolism during human pregnancy and lactation and discusses the findings in relation to the calcium nutrition of the mother. The evidence indicates that pregnancy and lactation are characterized by physiological adaptive processes that are independent of maternal calcium intake and that provide the calcium necessary for fetal growth and breast-milk production without requiring an increase in maternal calcium intake. There are firm data that demonstrate that a low calcium intake during lactation does not lead to impaired lactational performance or to exaggerated bone loss. However, more research is required to define whether a low calcium intake prior to or during pregnancy can have deleterious effects on reproductive and lactational performance, and on the long-term health of the mother and child.
Ultrasmall Manganese Ferrite Nanoparticles as Positive Contrast Agent for Magnetic Resonance Imaging
Authors: Zhen Li, Shu Xia Wang, Qiao Sun, Hong Li Zhao, Hao Lei, Min Bo Lan, Zhen Xiang Cheng, Xiao Lin Wang, Shi Xue Dou, Gao Qing (Max) Lu
Journal: Advanced Healthcare Materials (2013)

Reducing ferromagnetic particle size is an important strategy to improve their positive effect on imaging through the suppression of their negative effect, demonstrated by ultrasmall manganese ferrite nanoparticles prepared from an environmentally-friendly aqueous route. These ultrasmall particles exhibit pronounced paramagnetic characteristics and nontoxicity, making them efficient T1-positive contrast agent and manganese contrast agents for manganese enhanced MRI.
Procoagulant and fibrinolytic activities in bronchoalveolar fluid of HIV-positive and HIV-negative patients
Authors: E De Benedetti, L Nicod, G Reber, C Vifian, P de Moerloose
Journal: European Respiratory Journal (1992)

Imbalance between intra-alveolar procoagulant activity (PCA) and fibrinolytic activity may lead to fibrin deposition, as described in several pneumopathies, and may eventually contribute to fibrotic changes as observed in Pneumocystis carinii pneumonia (PCP). The aim of our study was to compare these activities in bronchoalveolar lavages of human immunodeficiency virus (HIV)-positive and HIV-negative patients. The material comprised: a) controls (n = 7); b) HIV-positive patients subdivided into PCP (n = 11), bacterial pneumonia (n = 8) and other pneumopathies (n = 22); and c) HIV-negative patients with bacterial pneumonia (n = 8). PCA was significantly increased (p less than 0.05) in all patient groups compared to controls. The urokinase-type plasminogen activator (u-PA) antigen levels were highest during bacterial pneumonia. Regardless of the HIV status, in bacterial pneumonia there was a marked elevation of plasminogen activator inhibitor antigens with little residual fibrinolytic activity. In contrast, the fibrinolytic activity was not decreased in PCP. D-dimer were elevated during PCP compared to controls; the highest levels were found in HIV-negative bacterial pneumonia. These data indicate that transient fibrotic changes seen in PCP may be favoured by increased PCA, but not by a depressed fibrinolytic activity. In bacterial pneumonia PCA is increased and fibrinolysis decreased independently of the HIV status.
Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.
Authors: G A Pantely, S A Malone, W S Rhen, C G Anselone, A Arai, J Bristow, J D Bristow
Journal: Circulation Research (1990)

The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine.
Chlorhexidine–Alcohol versus Povidone–Iodine for Surgical-Site Antisepsis
Authors: Rabih O. Darouiche, Matthew J. Wall, Kamal M.F. Itani, Mary F. Otterson, Alexandra L. Webb, Matthew M. Carrick, Harold J. Miller, Samir S. Awad, Cynthia T. Crosby, Michael C. Mosier, Atef AlSharif, David H. Berger
Journal: New England Journal of Medicine (2010)

Since the patient's skin is a major source of pathogens that cause surgical-site infection, optimization of preoperative skin antisepsis may decrease postoperative infections. We hypothesized that preoperative skin cleansing with chlorhexidine-alcohol is more protective against infection than is povidone-iodine.We randomly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint. The primary outcome was any surgical-site infection within 30 days after surgery. Secondary outcomes included individual types of surgical-site infections.A total of 849 subjects (409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group) qualified for the intention-to-treat analysis. The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group (9.5% vs. 16.1%; P=0.004; relative risk, 0.59; 95% confidence interval, 0.41 to 0.85). Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections (4.2% vs. 8.6%, P=0.008) and deep incisional infections (1% vs. 3%, P=0.05) but not against organ-space infections (4.4% vs. 4.5%). Similar results were observed in the per-protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period. Adverse events were similar in the two study groups.Preoperative cleansing of the patient's skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery. (ClinicalTrials.gov number, NCT00290290.)
Expression of p53 Enhances Selenite-Induced Superoxide Production and Apoptosis in Human Prostate Cancer Cells
Authors: Rui Zhao, Nong Xiang, Frederick E. Domann, Weixiong Zhong
Journal: Cancer Research (2006)

Abstract Although the anticancer effects of selenium have been shown in clinical, preclinical, and laboratory studies, the underlying mechanism(s) remains unclear. Our previous study showed that sodium selenite induced LNCaP human prostate cancer cell apoptosis in association with production of reactive oxygen species, alteration of cell redox state, and mitochondrial damage. In the present study, we showed that selenite-induced apoptosis was superoxide mediated and p53 dependent via mitochondrial pathways. In addition, we also showed that superoxide production by selenite was p53 dependent. Our study showed that wild-type p53–expressing LNCaP cells were more sensitive to selenite-induced apoptosis than p53-null PC3 cells. Selenite treatment resulted in high levels of superoxide production in LNCaP cells but only low levels in PC3 cells. LNCaP cells also showed sequential increases in levels of phosphorylated p53 (serine 15), total p53, Bax, and p21Waf1 proteins following selenite treatment. The effects of selenite were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. LNCaP cells treated with selenite also showed p53 translocation to mitochondria, cytochrome c release into the cytosol, and activation of caspase-9. On the other hand, restoration of wild-type p53 expression in PC3 cells increased cellular sensitivity to selenite and resulted in increased superoxide production, caspase-9 activation, and apoptosis following selenite treatment. These results suggest that selenite induces apoptosis by producing superoxide to activate p53 and to induce p53 mitochondrial translocation. Activation of p53 in turn synergistically enhances superoxide production and apoptosis induced by selenite. (Cancer Res 2006; 66(4): 2296-304)
Changes in bone mineral density in patients with Paget's disease treated with risedronate
Authors: S. Patel, D. Pearson, A. Bhallah, W. Maslanka, D. A White, D. J Hosking
Journal: Annals of the Rheumatic Diseases (1997)

To study changes in bone mineral density (BMD) in patients with Paget's disease of bone treated with risedronate.Whole body dual energy x ray absorptiometry (DXA) scans were carried out on 20 patients with Paget's disease treated with oral risedronate. DXA scanning was carried out at baseline and 11 months. Whole body bone mineral content (BMC) was measured. In addition, regions of interest were drawn around the skull, individual lumbar vertebrae, hemipelvis, femora, and tibiae to obtain BMD for these sites. An uncoupling index was also calculated as the area under the curve for serum alkaline phosphatase (ALP) divided by the area under the curve for hydroxyproline excretion (HYPRO) for the period of treatment.Median whole body BMC increased from 3057 g to 3156 g (p < 0.001) resulting from an increase in pagetic and non-pagetic BMD. From the analysis of regions of interest it was found that pagetic trabecular bone showed the largest increase in BMD. The pretreatment HYPRO and the uncoupling index were significantly related to the change in BMD for all pagetic sites for a patient (r = 0.65, p < 0.01 and r = 0.57, p < 0.05 respectively).Bisphosphonate treatment of Paget's disease results in an increase in BMD of pagetic bone without redistribution of mineral from non-pagetic bone. The remodelling space and extent of uncoupling are significantly related to increases in BMD at pagetic sites.
Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: an Italian case-control study
Authors: J. Polesel, R. Talamini, M. Montella, M. Parpinel, L. Dal Maso, A. Crispo, M. Crovatto, M. Spina, C. La Vecchia, S. Franceschi
Journal: Annals of Oncology (2006)
Mental Health Consequences of Disasters
Authors: Emily Goldmann, Sandro Galea
Journal: Annual Review of Public Health (2013)

We present in this review the current state of disaster mental health research. In particular, we provide an overview of research on the presentation, burden, correlates, and treatment of mental disorders following disasters. We also describe challenges to studying the mental health consequences of disasters and discuss the limitations in current methodologies. Finally, we offer directions for future disaster mental health research.
Design of the Heart failure Endpoint evaluation of AII‐Antagonist Losartan (HEAAL) study in patients intolerant to ACE‐inhibitor
Authors: Marvin A. Konstam, Philip A. Poole‐Wilson, Kenneth Dickstein, Helmut Drexler, Steven J. Justice, Michel Komajda, William Malbecq, Felipe A. Martinez, James D. Neaton, Gunter A.J. Riegger, Soneil Guptha
Journal: European Journal of Heart Failure (2008)
The inextricable role of the kidney in hypertension
Authors: Thomas M. Coffman
Journal: Journal of Clinical Investigation (2014)

An essential link between the kidney and blood pressure control has long been known. Here, we review evidence supporting the premise that an impaired capacity of the kidney to excrete sodium in response to elevated blood pressure is a major contributor to hypertension, irrespective of the initiating cause. In this regard, recent work suggests that novel pathways controlling key sodium transporters in kidney epithelia have a critical impact on hypertension pathogenesis, supporting a model in which impaired renal sodium excretion is a final common pathway through which vascular, neural, and inflammatory responses raise blood pressure. We also address recent findings calling into question long-standing notions regarding the relationship between sodium intake and changes in body fluid volume. Expanded understanding of the role of the kidney as both a cause and target of hypertension highlights key aspects of pathophysiology and may lead to identification of new strategies for prevention and treatment.