tbuckley/cabot-search huggingface dataset:
Aldosterone Stimulation of Riboflavin Incorporation into Rat Renal Flavin Coenzymes and the Effect of Inhibition by Riboflavin Analogues on Sodium Reabsorption
Authors: Daniel Trachewsky
Journal: Journal of Clinical Investigation (1978)

This study was designed to investigate a possible relationship between the effect of aldosterone upon urinary electrolytes and the incorporation of [14C]riboflavin into renal [14C]flavin mononucleotide (FMN) and [14C]flavin adenine dinucleotide (FAD). Adrenalectomized Sprague-Dawley rats that weighed between 185 and 210 g were pretreated with 15 μg/100 g body wt dexamethasone intraperitoneally. 16 h later they were administered aldosterone (1.5 μg/100 g body wt) and [14C]riboflavin (5.0 μCi/200 g body wt). The urethra of each rat was ligated, and the rats were sacrificed by decapitation 3 h later. The urine was aspirated from the bladders of each rat and analyzed for total Na+ and K+ excretion while the kidneys were removed and the formation of [14C]FMN and [14C]FAD was determined for each kidney. There was a significant increase in the formation of renal [14C]FMN and [14C]FAD (27.3 and 14.4%, respectively) after aldosterone treatment. Aldosterone significantly decreased the excretion of Na+ by 50%, and increased that of K+ by 55%.
Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case reports and review of the literature
Authors: Utkarsh Acharya, Jen-Tzer Gau, William Horvath, Paolo Ventura, Chung-Tsen Hsueh, Wayne Carlsen
Journal: Journal of Hematology & Oncology (2008)

Abstract Concurrent hemolysis in patients with vitamin B12 deficiency is a well-recognized phenomenon and has been attributed to intramedullary destruction of erythrocytes (ineffective erythropoiesis). Recent studies revealed that homocysteine increased the risk of hemolysis in vitamin B12 deficiency in vitro and there is a high frequency (30%) of vitamin B12 deficiency in asymptomatic patients with homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation, a known cause of hyperhomocysteinemia. Here we report three patients with MTHFR mutations and vitamin B12 deficiency presenting with hemolytic anemia and severely elevated homocysteine levels. Patients demonstrated complete resolution of hemolysis with simultaneous normalization of serum homocysteine levels after vitamin B12 treatments. We reviewed pertinent literature, and hypothesized that hemolytic anemia may be more prevalent in patients who have a coexisting MTHFR gene mutation and vitamin B12 deficiency possibly related to severely elevated homocysteine levels. The hemolysis in these cases occurred predominantly in peripheral blood likely due to the combined effects of structurally defective erythrocytes and homocysteine-induced endothelial damage with microangiopathy.
Discussing an uncertain future: end-of-life care conversations in chronic obstructive pulmonary disease. A systematic literature review and narrative synthesis: Figure 1
Authors: Natalie Momen, Peter Hadfield, Isla Kuhn, Elizabeth Smith, Stephen Barclay
Journal: Thorax (2012)

<h3>Background</h3> Guidelines recommend open discussions between patients and healthcare professionals as the end-of-life (EOL) approaches. Much of the knowledge about the EOL is based on the needs of patients with cancer and the applicability of this to other diseases is often queried. A literature review was undertaken concerning EOL care (EOLC) conversations in chronic obstructive pulmonary disease (COPD). <h3>Design</h3> A systematic literature review and narrative synthesis obtained papers reporting on EOLC conversations between patients with COPD and their healthcare professionals with respect to the prevalence of conversations; each party9s preferences for timing and content; and the facilitators and blockers. Inclusion criteria were articles published in peer-reviewed journals, written in English, reporting studies of adult patients with COPD and/or their healthcare professionals concerning discussions of care at the EOL. <h3>Results</h3> 30 papers were identified. Most patients reported that they have not had EOLC discussions with healthcare professionals. While many patients would like these conversations, a potentially large minority would not; the proportions varied among studies. Healthcare professionals find these discussions difficult and many prefer patients to initiate them. <h3>Conclusions</h3> Patients9 preferences for EOLC conversations vary greatly. Healthcare professionals need to respect the wishes of those not wanting to discuss EOLC and provide multiple opportunities for those who do wish to have these discussions. Recommendations on how to approach the conversation are made.
Neoadjuvant Treatment of Unresectable Medullary Thyroid Cancer With Sunitinib
Authors: James M. Cleary, Peter M. Sadow, Gregory W. Randolph, Edwin L. Palmer, Thomas P. Lynch, Yuri E. Nikiforov, Lori J. Wirth
Journal: Journal of Clinical Oncology (2010)

Medullary Thyroid Cancer With SunitinibA 45-year-old man presented with a midline neck mass, cervical adenopathy, and hoarseness.A computed tomography (CT) scan revealed a left level IV conglomerate nodal mass measuring 5.8 ϫ 3.5 ϫ 3.3 cm that surrounded the carotid artery.In addition, there was a mass arising from the left lobe of thyroid with extension into the tracheoesophageal groove.Multiple borderline enlarged lymph nodes were also present.There was no evidence of distant metastasis.Alcohol-fixed fine needle aspiration (FNA) material showed a highgrade carcinoma with large, pleomorphic cells (Fig 1A ,arrow head) and scattered giant cells (Fig 1A, arrow) suggestive of an undifferentiated carcinoma.Based on these clinical, radiographic, and cytologic data, a diagnosis of unresectable anaplastic (undifferentiated) thyroid carcinoma (ATC) was made.Radiotherapy, to a total dose of 70 Gy, with concurrent chemotherapy was initiated.The patient initially received 5 weeks of cisplatin and doxorubicin.However, because of lack of response, for the final 2 weeks of radiation his chemotherapy was switched to carboplatin and paclitaxel.After chemoradiotherapy, CT scans showed no change in tumor size.He received four additional cycles of carboplatin and paclitaxel.Despite this, restaging CT scans showed no change in tumor size and the disease remained unresectable.2][3][4][5] His initial regimen was sunitinib 50 mg daily, 4 weeks on, 2 weeks off.In response to the sunitinib, there was marked decrease in the size and [ 18 F]fluorodeoxyglucose avidity of his neck masses.Figures 2A and2B show his pretreatment positron emission tomography (PET)/CT scans and
P106 Lung Clearance Index is a Repeatable Test of Lung Function and Superior Predictor of CT Scan Abnormalities in Bronchiectasis
Authors: S Rowan, J Bradley, I Bradbury, J Lawson, T Lynch, K O'Neill, M Ennis, JS Elborn
Journal: Thorax (2013)

<h3>Introduction</h3> In cystic fibrosis, lung clearance index (LCI) is a sensitive predictor of CT scan determined lung pathology. In bronchiectasis (BE) there is a need for improved markers of lung function to gauge disease severity and response to interventions in clinical trials. <h3>Aims</h3> To assess if LCI is a repeatable and superior predictor of CT scan abnormalities compared with FEV<sub>1 </sub>in BE. <h3>Methods</h3> 60 patients with stable BE were recruited. LCI (using SF<sub>6 </sub>multiple breath washout), spirometry and CT scores were collected. Health related quality of life (HRQoL) was measured using the St. George’s Respiratory Questionnaire. A separate group of 30 BE patients were recruited and LCI, spirometry and HRQoL were assessed when clinically stable on 2 occasions, 2 weeks apart. <h3>Results</h3> Mean (SD) age was 62 (10) years, FEV<sub>1</sub> 76.5 (18.9)% predicted, LCI 9.1 (2.0) and total CT score 14.1 (10.2)%. FEV<sub>1</sub> negatively correlated with LCI (r = -0.51, p &lt; 0.0001.) Across all CT score subscales, there was clear evidence of a relationship with LCI, with no or very weak evidence of any additional effect of FEV<sub>1</sub>. The strongest correlations of subgroup CT scores with LCI were seen in),% parenchymal score (r = 0.56, p &lt; 0.001),% mucus plugging (r = 0.49, p &lt; 0.001),% total score (r = 0.55, p &lt; 0.001)% bronchiectasis (r = 0.41, p &lt; 0.01. There was no association for either FEV<sub>1 </sub>or LCI with% airway thickening and for % bronchiectasis score and FEV<sub>1</sub>. There were no significant associations between LCI or FEV<sub>1 </sub>and HRQoL. The inter-visit ICC for LCI was 0.94 (95% CI 0.89 to 0.97, p &lt; 0.001). <h3>Conclusions</h3> LCI is a valid and repeatable test of lung function in BE. It is a superior predictor of lung function than FEV<sub>1</sub> in the detection of abnormalities demonstrated on CT scan. LCI is a useful test in patients with early lung disease or those with preserved spirometric scores. LCI also has the potential to be an alternative outcome measure to spirometry in clinical trials.
Fc-rosette inhibition by hypocomplementaemic systemic lupus erythematosus sera
Authors: T. Morito, K. Tanimoto, Y. Hashimoto, Y. Horiuchi, T. Juji
Journal: Annals of the Rheumatic Diseases (1976)

Human red cells sensitized with one of the Rh antisera (Ripley) form rosettes (Fc-rosette) with human B lymphocytes and the rosettes are well inhibited by aggregated human IgG. Since sera of hypocomplementaemic patients with systemic lupus erythematosus (SLE) have frequently been reported to contain immune complexes, they were used for the inhibition of Fc-rosette formation in this study. The results of Fc-rosette inhibition rates of the sera were inversely correlated with the serum CH50 levels. When the sera were separated into top, middle, and bottom fractions by ultracentrifugation, the bottom fractions showed more effective inhititions than the others. Similarly, the strongest inhibition was found in the void volume of the serum separated by Sephadex G200 gel filtration. Reduction and alkylation of IgG resulted in the loss of reactivity with Fc receptor of B lymphocytes, and the rosette inhibiting activities of the SLE sera were markedly reduced after reduction and alkylation. Some of anti-HLA sera were inhibitory for the Fc-rosette formation, while the tested sera did not contain anti-HLA activity assessed by the microcytotoxicity test. These results indicated that circulating immune complexes contained in the sera inhibit the rosette formation, and that the Fc-rosette inhibition test is a simple and relatively sensitive method for the detection of circulating immune complexes. Antinuclear antibody activities of the sera were tested by the indirect immunofluorescent method; however, clear correlations were not obtained between Fc-rosette inhibition rates and staining patterns of antinuclear antibodies. On the other hand, the positive groups of LE-test exhibited slightly greater inhibition rates of the rosette than the negative groups.
Molecular evolution of the CMT1A-REP region: a human- and chimpanzee- specific repeat
Authors: M. P. Keller, B. A. Seifried, P. F. Chance
Journal: Molecular Biology and Evolution (1999)

The CMT1A-REP repeat consists of two copies of a 24-kb sequence on human chromosome 17p11.2-12 that flank a 1.5-Mb region containing a dosage-sensitive gene, peripheral nerve protein-22 (PMP22). Unequal meiotic crossover mediated by misalignment of proximal and distal copies of the CMT1A-REP in humans leads to a 1.5-Mb duplication or deletion associated with two common peripheral nerve diseases, Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). Previous molecular hybridization studies with CMT1A-REP sequences suggested that two copies of the repeat are also found in the chimpanzee, raising the possibility that this unique repeat arose during primate evolution. To further characterize the structure and evolutionary synthesis of the CMT1A-REP repeat, fluorescent in situ hybridization (FISH) analysis and heterologous PCR-based assays were carried out for a series of primates. Genomic DNA was analyzed with primers selected to differentially amplify the centromeric and telomeric ends of the human proximal and distal CMT1A-REP elements and an associated mariner (MLE) sequence. All primate species examined (common chimpanzee, pygmy chimpanzee, gorilla, orangutan, gibbon, baboon, rhesus monkey, green monkey, owl monkey, and galago) tested positive for a copy of the distal element. In addition to humans, only the chimpanzee was found to have a copy of the proximal CMT1A-REP element. All but one primate species (galago) tested positive for the MLE located within the CMT1A-REP sequence. These observations confirm the hypothesis that the distal CMT1A-REP element is the ancestral sequence which was duplicated during primate evolution, provide support for a human-chimpanzee clade, and suggest that insertion of the MLE into the CMT1A-REP sequence occurred in the ancestor of anthropoid primates.
Management of Lung Nodules Detected by Volume CT Scanning
Authors: Rob J. van Klaveren, Matthijs Oudkerk, Mathias Prokop, Ernst T. Scholten, Kristiaan Nackaerts, Rene Vernhout, Carola A. van Iersel, Karien A.M. van den Bergh, Susan van 't Westeinde, Carlijn van der Aalst, Erik Thunnissen, Dong Ming Xu, Ying Wang, Yingru Zhao, Hester A. Gietema, Bart-Jan de Hoop, Harry J.M. Groen, Geertruida H. de Bock, Peter van Ooijen, Carla Weenink, Johny Verschakelen, Jan-Willem J. Lammers, Wim Timens, Dik Willebrand, Aryan Vink, Willem Mali, Harry J. de Koning
Journal: New England Journal of Medicine (2009)

The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT.A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more.In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up.Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.)
The type of sensitizing allergen can affect the evolution of respiratory allergy
Authors: M. Marogna, A. Massolo, D. Berra, P. Zanon, E. Chiodini, G. W. Canonica, G. Passalacqua
Journal: Allergy (2006)

Background: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. Methods: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria ) was identified based on symptom distribution and when needed on nasal challenge. Results: 6750 patients (age range 12–46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years ( P &lt; 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria , with a significant difference among allergens ( P &lt; 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. Conclusion: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.
Mucosal Atrophy in Celiac Disease: Extent of Involvement, Correlation With Clinical Presentation, and Response to Treatment
Authors: Joseph A. Murray, Alberto Rubio–tapia, Carol T. Van Dyke, Deanna L. Brogan, Mary A. Knipschield, Brian Lahr, Ashwin Rumalla, Alan R. Zinsmeister, Christopher J. Gostout
Journal: Clinical Gastroenterology and Hepatology (2007)
TGF-β signaling in vascular fibrosis
Authors: M RUIZORTEGA, J RODRIGUEZVITA, E SANCHEZLOPEZ, G CARVAJAL, J EGIDO
Journal: Cardiovascular Research (2007)

Transforming growth factor-β (TGF-β) participates in the pathogenesis of multiple cardiovascular diseases, including hypertension, restenosis, atherosclerosis, cardiac hypertrophy and heart failure. TGF-β exerts pleiotropic effects on cardiovascular cells, regulating cell growth, fibrosis and inflammation. TGF-β has long been believed to be the most important extracellular matrix regulator. We review the complex mechanisms involved in TGF-β-mediated vascular fibrosis that includes the Smad signaling pathway, activation of protein kinases and crosstalk between these pathways. TGF-β blockade diminishes fibrosis in experimental models, however better antifibrotic targets are needed for an effective therapy in human fibrotic diseases. A good candidate is connective tissue growth factor (CTGF), a downstream mediator of TGF-β-induced fibrosis. Among the different factors involved in vascular fibrosis, Angiotensin II (AngII) has special interest. AngII can activate the Smad pathway independent of TGF-β and shares with TGF-β many intracellular signals implicated in fibrosis. Blockers of AngII have demonstrated beneficial effects on many cardiovascular diseases and are now one of the best options to block TGF-β fibrotic responses. A better knowledge of the intracellular signals of TGF-β can provide novel therapeutic approaches for fibrotic diseases.
Multiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete Remission
Authors: Leonor Puchades-Carrasco, Ramón Lecumberri, Joaquín Martínez-López, Juan-José Lahuerta, María-Victoria Mateos, Felipe Prósper, Jesús F. San-Miguel, Antonio Pineda-Lucena
Journal: Clinical Cancer Research (2013)

Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by (1)H-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma.Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The (1)H-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences.Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations.The results highlight the potential of metabolic profiles obtained by 1H-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment.
HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer
Authors: Giuseppina Raspaglio, Ilaria De Maria, Flavia Filippetti, Enrica Martinelli, Gian Franco Zannoni, Silvia Prislei, Gabriella Ferrandina, Shohreh Shahabi, Giovanni Scambia, Cristiano Ferlini
Journal: Cancer Research (2010)

The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III beta-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3' flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival.
The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke
Authors: Anna Helgadottir, Andrei Manolescu, Gudmar Thorleifsson, Solveig Gretarsdottir, Helga Jonsdottir, Unnur Thorsteinsdottir, Nilesh J Samani, Gudmundur Gudmundsson, Struan F A Grant, Gudmundur Thorgeirsson, Sigurlaug Sveinbjornsdottir, Einar M Valdimarsson, Stefan E Matthiasson, Halldor Johannsson, Olof Gudmundsdottir, Mark E Gurney, Jesus Sainz, Margret Thorhallsdottir, Margret Andresdottir, Michael L Frigge, Eric J Topol, Augustine Kong, Vilmundur Gudnason, Hakon Hakonarson, Jeffrey R Gulcher, Kari Stefansson
Journal: Nature Genetics (2004)