tbuckley/cabot-search huggingface dataset:
Expression of CAAT enhancer binding protein beta (C/EBP beta) in cervix and endometrium.
Authors: Brenda Arnett, Patrick Soisson, Barbara S Ducatman, Peilin Zhang
Journal: Molecular Cancer (2003)

The CCAAT element binding protein family of transcriptional factors consists of at least six members of the basic leucine zipper DNA binding proteins that bind to the same CCAAT palindromic DNA sequence through homo- or hetero-dimerization with the same family members. C/EBP β has been shown to play an important role in mediating the effects of the LH/hCG in ovarian development. C/EBP β was also found increased in ovarian cancer and correlated to ovarian cancer progression. We assessed the C/EBP β expression pattern in the normal and neoplastic conditions of the female genital tract by immunostaining the normal cervix – 10 cases, squamous intraepithelial lesion (SIL)-10, invasive squamous carcinomas of cervix – 10 cases, normal endometrial tissue – 10 cases, and invasive endometrial adenocarcinomas carcinomas-10 cases. The staining pattern and intensity were graded from 0 to 2+. Results were statistically analyzed utilizing JMP 4.1. C/EPB β expression was detected in the normal proliferative squamous, dysplastic and malignant squamous epithelial cells. There was no statistical correlation between C/EPB β staining in benign squamous, endocervical tissue, SIL, and squamous cancer, as the majority of all stained positively (91%, 79%, 71% and 89%, respectively, p = 0.3448). However, endometrial carcinoma was significantly more likely to stain positively with C/EPB β than benign endometrial glands (92% versus 3% respectively, p < 0.0001, Fisher's exact test). C/EBP β is more likely to be preferentially expressed in endometrial adenocarcinoma as compared to benign endometrial tissue. There is no difference of C/EPB β expression in squamous neoplasia of the cervix.
Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis
Authors: Francesco Ciccia, Giuliana Guggino, Aroldo Rizzo, Laura Saieva, Sergio Peralta, AnnaRita Giardina, Alessandra Cannizzaro, Guido Sireci, Giacomo De Leo, Riccardo Alessandro, Giovanni Triolo
Journal: Annals of the Rheumatic Diseases (2015)

The aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).ILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed.ILC3 characterised as Lyn(-)RORc(-)Tbet(+) NKp44(+) cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R(+) cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1.Gut-derived IL-17(+) and IL-22(+)ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.
Validation of a Breast Cancer Risk Prediction Model Developed for Black Women
Authors: Deborah A. Boggs, Lynn Rosenberg, Michael J. Pencina, Lucile L. Adams-Campbell, Julie R. Palmer
Journal: JNCI Journal of the National Cancer Institute (2013)

A breast cancer risk prediction model for black women, developed from data in the Women's Contraceptive and Reproductive Experiences (CARE) study, has been validated in women aged 50 years or older but not among younger women or for specific breast cancer subtypes.We assessed calibration and discrimination of the CARE model in the Black Women's Health Study (BWHS) with data from 45 942 women aged 30 to 69 years at baseline.During a mean follow-up of 9.5 years, we identified 852 invasive breast cancers. The CARE model predicted 749.6 breast cancers, yielding an expected-to-observed (E/O) ratio of 0.88 (95% confidence interval [CI] = 0.82 to 0.94). The E/O ratio did not appreciably differ between women aged less than 50 years and those aged 50 years or older. The model underpredicted risk to the greatest degree among women aged 25 years or older at birth of first child (E/O = 0.71, 95% CI = 0.63 to 0.81); the model was well calibrated among women aged less than 25 years at birth of first child. The prevalence of later age at birth of first child was higher in the BWHS than in the CARE study, and breast cancer incidence was higher in the BWHS compared with national rates used in the CARE model. With respect to discriminatory accuracy, the concordance statistic was 0.57 (95% CI = 0.55 to 0.59) for breast cancer overall, 0.59 (95% CI = 0.57 to 0.61) for estrogen receptor (ER)-positive breast cancer, and 0.54 (95% CI = 0.50 to 0.57) for ER-negative breast cancer.The CARE model underpredicted breast cancer risk in the BWHS, at least in part because of older age at first birth in this cohort, which led to higher breast cancer incidence rates. Our results suggest that inclusion of age at first birth may improve model performance. Discriminatory accuracy was modest and worse for ER-negative breast cancer.
Sepsis induces early phrenic nerve neuropathy in rats
Authors: A. Nayci, S. Atis, U. Comelekoglu, A. Ozge, O. Ogenler, B. Coskun, S. Zorludemir
Journal: European Respiratory Journal (2005)

The aim of the present study was to investigate the electrophysiology of the phrenic nerve and the diaphragm muscle during sepsis. In total, 26 rats underwent either sham laparotomy or caecal ligation and puncture (CLP). Electrophysiology was evaluated via a phrenic nerve conduction study and needle electromyography of the diaphragm, prior to CLP, 6 and 24 h post-CLP and on day 7. The histopathology of the diaphragm muscle and phrenic nerve was also examined on day 7. In the sepsis group, the phrenic nerve conduction study showed decreased amplitude of compound action potential (CMAP), and prolongation in the duration and the latency of CMAP. The diaphragmatic needle electromyography showed decreased amplitude and frequency of the motor unit action potential (MUP), and prolongation in the duration of MUP, at all time points, compared with the pre-CLP values. The electrophysiological abnormalities were consistent with axonal and demyelinating phrenic nerve neuropathy. Electrophysiological abnormalities were present at 6 h with worsening at 24 h and on day 7. Histopathological examination showed normal muscular fibres and focally slight myelin degenerations of the phrenic nerve fibres. In conclusion, sepsis induced phrenic nerve neuropathy as early as the 6th h in rats.
How deep is your love?
Authors: J. McKnight, N. W. Bond
Journal: Behavioral and Brain Sciences (1999)

The thesis that women will be more intent on staying alive fails to take into account that current strategies are those of the winners in the evolutionary race. Moreover, because like tends to mate with like, risk taking will be averaged out between the sexes. Finally, Campbell's narrow view of parental investment fails to acknowledge the indirect contributions of males.
A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump
Authors: Jacqueline R.M Plass, Olaf Mol, Janette Heegsma, Mariska Geuken, Joost de Bruin, Geeske Elling, Michael Müller, Klaas Nico Faber, Peter L.M Jansen
Journal: Journal of Hepatology (2003)
Dystrophin production induced by myoblast transfer therapy in Duchenne muscular dystrophy
Authors: PeterK. Law, TulioE. Bertorini, TenaG. Goodwin, Ming Chen, Qiuwen Fang, Hua-Ju Li, DanaS. Kirby, J.Ann Florendo, HenryG. Herrod, GeraldS. Golden
Journal: The Lancet (1990)
Association of the <i>PDCD5</i> Locus With Lung Cancer Risk and Prognosis in Smokers
Authors: Monica Spinola, Peter Meyer, Stefan Kammerer, F. Stefania Falvella, Melanie B. Boettger, Carolyn R. Hoyal, Carmen Pignatiello, Reiner Fischer, Richard B. Roth, Ugo Pastorino, Karl Haeussinger, Matthew R. Nelson, Rainer Dierkesmann, Tommaso A. Dragani, Andreas Braun
Journal: Journal of Clinical Oncology (2006)

Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample.A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancer patients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls.Patients with genotypes GG or CG for the rs1862214 single nucleotide polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared with those with the common genotype CC showed an increased risk of lung cancer (odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship (HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability.These results suggest that the rs1862214 polymorphism in PDCD5 is predictive for lung cancer risk and prognosis, and that PDCD5 may represent a novel tumor suppressor gene influencing lung cancer.
Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-City Cohort
Authors: Rosalind J. Wright, Cynthia M. Visness, Agustin Calatroni, Mitchell H. Grayson, Diane R. Gold, Megan T. Sandel, Aviva Lee-Parritz, Robert A. Wood, Meyer Kattan, Gordon R. Bloomberg, Melissa Burger, Alkis Togias, Frank R. Witter, Rhoda S. Sperling, Yoel Sadovsky, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Stress-elicited disruption of immunity begins in utero.Objectives: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).Methods: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).Measurements and Main Results: Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-α to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-γ.Conclusions: Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.
Radiotherapy for Glioblastoma in the Elderly
Authors: Florence Keime-Guibert, Olivier Chinot, Luc Taillandier, Stéphanie Cartalat-Carel, Marc Frenay, Guy Kantor, Jean-Sébastien Guillamo, Eric Jadaud, Philippe Colin, Pierre-Yves Bondiau, Philippe Meneï, Hugues Loiseau, Valérie Bernier, Jérôme Honnorat, Maryline Barrié, Karima Mokhtari, Jean-Jacques Mazeron, Anne Bissery, Jean-Yves Delattre
Journal: New England Journal of Medicine (2007)

There is no community standard for the treatment of glioblastoma in patients 70 years of age or older. We conducted a randomized trial that compared radiotherapy and supportive care with supportive care alone in such patients.Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were randomly assigned to receive supportive care only or supportive care plus radiotherapy (focal radiation in daily fractions of 1.8 Gy given 5 days per week, for a total dose of 50 Gy). The primary end point was overall survival; secondary end points were progression-free survival, tolerance of radiotherapy, health-related quality of life, and cognition.We randomly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone. The trial was discontinued at the first interim analysis, which showed that with a preset boundary of efficacy, radiotherapy and supportive care were superior to supportive care alone. A final analysis was carried out for the 81 patients with glioblastoma (median age, 73 years; range, 70 to 85). At a median follow-up of 21 weeks, the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks, as compared with 16.9 weeks for the 42 patients who received supportive care alone. The hazard ratio for death in the radiotherapy group was 0.47 (95% confidence interval, 0.29 to 0.76; P=0.002). There were no severe adverse events related to radiotherapy. The results of quality-of-life and cognitive evaluations over time did not differ significantly between the treatment groups.Radiotherapy results in a modest improvement in survival, without reducing the quality of life or cognition, in elderly patients with glioblastoma. (ClinicalTrials.gov number, NCT00430911 [ClinicalTrials.gov].).
Validation of a Model to Predict Perioperative Mortality from Lung Cancer Resection in the Elderly
Authors: Max Kates, Xavier Perez, Julie Gribetz, Scott J. Swanson, Thomas McGinn, Juan P. Wisnivesky
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Surgical resection is the mainstay therapy for localized non-small cell lung cancer (NSCLC), yet elderly patients are less likely to be treated due to concerns about morbidity and mortality related to surgery.To validate and refine a clinical model to predict 30-day perioperative mortality (POM) in elderly patients undergoing curative resection for lung cancer.We identified 14,297 patients aged 65 years and older with stage I, II, or IIIA NCSLC from the Surveillance, Epidemiology, and End-Results Registry linked to Medicare claims. We used logistic regression analysis to identify independent risk factors for POM and to validate and refine a previously derived prediction model.Overall, POM was 4.6% (95% confidence interval, 4.2-4.9%). Multiple regression analysis revealed that greater age, male sex, resections of multiple lobes, advanced stage, greater tumor size, and certain comorbidities were associated with increased risk for POM. These risk factors were similar to those observed in the prior model. When patients were stratified according to their predicted risk of POM, the observed mortality increased from 1.2 to more than 10%.Among elderly patients with lung cancer, a prediction rule can identify those patients at higher risk for fatal complications from surgery. Further studies should evaluate whether use of the model can lead to improvements in treatment decision making.
Genetics and Molecular Biology of Ionic Channels in Drosophila
Authors: M A Tanouye, C A Kamb, L E Iverson, L Salkoff
Journal: Annual Review of Neuroscience (1986)

In this review we examine mutations that alter electrical excitability in the
nervous system of the fruitfly, Drosophila melanogaster, and discuss how
these mutations may be used to approach the molecular basis of ionic
channel function.
Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin.
Authors: E Leitersdorf, A Reshef, V Meiner, R Levitzki, S P Schwartz, E J Dann, N Berkman, J J Cali, L Klapholz, V M Berginer
Journal: Journal of Clinical Investigation (1993)

The sterol 27-hydroxylase (EC 1.14.13.15) catalyzes steps in the oxidation of sterol intermediates that form bile acids. Mutations in this gene give rise to the autosomal recessive disease cerebrotendinous xanthomatosis (CTX). CTX is characterized by tendon xanthomas, cataracts, a multitude of neurological manifestations, and premature atherosclerosis. A relatively high prevalence of the disease has been noted in Jews originating from Morocco. The major objectives of the present investigation were to determine the gene structure and characterize the common mutant alleles that cause CTX in Moroccan Jews. The gene contains nine exons and eight introns and encompasses at least 18.6 kb of DNA. The putative promoter region is rich in guanidine and cytosine residues and contains potential binding sites for the transcription factor Sp1 and the liver transcription factor, LF-B1. Blotting analysis revealed that the mutant alleles do not produce any detectable sterol 27-hydroxylase mRNA. No major gene rearrangements were found and single-strand conformational polymorphism followed by sequence analysis identified two underlying mutations: deletion of thymidine in exon 4 and a guanosine to adenosine substitution at the 3' splice acceptor site of intron 4 of the gene. The molecular characterization of CTX in Jews of Moroccan origin provides a definitive diagnosis of this treatable disease.
Molecular Pathways: Extracting Medical Knowledge from High-Throughput Genomic Data
Authors: Theodore C. Goldstein, Evan O. Paull, Matthew J. Ellis, Joshua M. Stuart
Journal: Clinical Cancer Research (2013)

High-throughput genomic data that measures RNA expression, DNA copy number, mutation status, and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. Although the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First-generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care, which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the "activitome," helps connect genomic events to clinical factors to predict the drivers of poor outcome.
Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen.
Authors: S Vorstrup, L Henriksen, O B Paulson
Journal: Journal of Clinical Investigation (1984)

The aim of this study was to evaluate the effect of acetazolamide on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). CBF, arterial and jugular venous partial O2 pressure, partial CO2 pressure, pH, and O2 saturation percentage were measured in six patients before and 3 and 20 minutes after intravenous administration of 1 g of acetazolamide. CBF was measured by the intracarotid 133xenon injection technique. In addition, changes in CBF were estimated from the arteriovenous oxygen content difference. CBF increased in all patients after acetazolamide, by approximately 55 and 70% after 3 and 20 min, respectively. The CBF changes were of the same order whether calculated from the 133Xe clearance or from the arteriovenous oxygen differences (A-V)O2. CMRO2, calculated from (A-V)O2 differences and CBF, remained constant. Except for an increase in the venous oxygen saturation, the blood gases remained constant. Acetazolamide, in a dose sufficient to inhibit the erythrocyte carbonic anhydrase (EC 4.2.1.1), thus induced a rapid and marked increase in CBF, leaving CMRO2 unchanged. This effect of acetazolamide on CBF is probably explained by a decrease in brain pH rather than by brain tissue hypoxia due to inhibition of oxygen unloading in the brain capillaries.
THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS
Authors: David Bodian, Howard A. Howe
Journal: The Journal of Experimental Medicine (1947)

1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of lesion production.