tbuckley/cabot-search huggingface dataset:
Metabolic Control in Diabetic Subjects in Three Swedish Areas With High, Medium, and Low Sales of Antidiabetic Drugs
Authors: Jan Stålhammar, Ulf Bergman, Kurt Boman, Magnus Dahlén
Journal: Diabetes Care (1991)

Objective The relationship between use of antidiabetic drugs and metabolic control was studied in Swedish diabetic populations in areas with high (Gotland), medium (Tierp), and low (Skellefteå) sales of antidiabetic drugs. Research Design and Methods The study population consisted of 405 drug-treated diabetic subjects aged 50–74 yr. In all three areas, glyburide comprised ∼75% of the oral treatment. Results In accordance with sales, Gotland was found to be a heavy-use area, characterized by a high prevalence of insulin treatment (43%), combination therapy with sulfonylureas and biguanide (28%), and high prescribed daily doses (PDDs) of glyburide (15.5 ± 0.8 mg) compared with other areas. In Skellefteå, 38% were on insulin, 4% were on combination therapy, and the PDD of glyburide was 7.1 ± 0.6 mg. In Tierp, 27% were on insulin, 26% were on combination therapy, and the PDD of glyburide was 11.4 ± 0.7 mg. In Gotland, both men and women had significantly lower HbA1c levels, regardless of treatment mode, and a tendency to be more overweight compared with the area with the least pharmacological intensity (Skellefteå). Conclusions In the three diabetic populations, good metabolic control, defined as an HbA1c level of &amp;lt; 7% and acceptable weight control (body mass index &amp;lt; 27 for men and &amp;lt; 25 for women), was achieved among only 16% in Gotland, 17% in Skellefteå, and 12% in Tierp.
Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome
Authors: R.L. Upton, Y. Chen, S. Mumby, J.M.C. Gutteridge, P.B. Anning, A.G. Nicholson, T.W. Evans, G.J. Quinlan
Journal: European Respiratory Journal (2003)

Acute respiratory distress syndrome (ARDS) is associated with altered plasma and lung iron chemistry. Iron can promote microbial virulence and catalyse pro-oxidant reactions, thereby contributing to the oxidative stress that characterises the syndrome. Therefore, the expression of ferritin and transferrin receptors (TfR) were sought in the lungs and hearts of rodents treated with lipopolysaccharide (LPS), and measurements of TfR and ferritin protein expression were taken from lung biopsy specimens from patients with ARDS and appropriate controls. TfR messenger ribonucleic acid (mRNA) was significantly upregulated in the lungs and significantly downregulated in the hearts of rats 4 h after LPS. Ferritin mRNA levels (light and heavy chains) remained unaltered. Protein TfR levels were significantly upregulated in lungs and downregulated in hearts 4 h post-LPS. Ferritin protein levels were significantly downregulated in lungs compared to baseline values but were unaltered in hearts. Nonhaem iron levels were increased in lungs and decreased in hearts, and iron-regulatory-protein activity increased in hearts but not lungs. TfR protein levels were significantly increased in lung biopsies from patients with ARDS compared to controls. Transferrin receptors are upregulated in rodent lungs during inflammation but are downregulated in the heart. Transferrin receptor protein levels were significantly increased in the lungs in clinical acute respiratory distress syndrome. These findings have implications for the pathogenesis of acute respiratory distress syndrome, especially in relation to the role of iron as a mediator of oxidative stress.
Potential fields on the ventricular surface of the exposed dog heart during normal excitation.
Authors: G Arisi, E Macchi, S Baruffi, S Spaggiari, B Taccardi
Journal: Circulation Research (1983)

We studied the normal spread of excitation on the anterior and posterior ventricular surface of open-chest dogs by recording unipolar electrograms from an array of 1124 electrodes spaced 2 mm apart. The array had the shape of the ventricular surface of the heart. The electrograms were processed by a computer and displayed as epicardial equipotential maps at 1-msec intervals. Isochrone maps also were drawn. Several new features of epicardial potential fields were identified: (1) a high number of breakthrough points; (2) the topography, apparent widths, velocities of the wavefronts and the related potential drop; (3) the topography of positive potential peaks in relation to the wavefronts. Fifteen to 24 breakthrough points were located on the anterior, and 10 to 13 on the posterior ventricular surface. Some were in previously described locations and many others in new locations. Specifically, 3 to 5 breakthrough points appeared close to the atrioventricular groove on the anterior right ventricle and 2 to 4 on the posterior heart aspect; these basal breakthrough points appeared when a large portion of ventricular surface was still unexcited. Due to the presence of numerous breakthrough points on the anterior and posterior aspect of the heart which had not previously been described, the spread of excitation on the ventricular surface was "mosaic-like," with activation wavefronts spreading in all directions, rather than radially from the two breakthrough points, as traditionally described. The positive potential peaks which lay ahead of the expanding wavefronts moved along preferential directions which were probably related to the myocardial fiber direction.
Association of Systemic Concentrations of Macrophage Migration Inhibitory Factor With Impaired Glucose Tolerance and Type 2 Diabetes
Authors: Christian Herder, Hubert Kolb, Wolfgang Koenig, Burkhard Haastert, Sylvia Müller-Scholze, Wolfgang Rathmann, Rolf Holle, Barbara Thorand, H.-Erich Wichmann
Journal: Diabetes Care (2006)

OBJECTIVE—Macrophage migration inhibitory factor (MIF) is a central cytokine in innate immunity. MIF expression can be regulated by glucose and insulin, but data on the association with type 2 diabetes are sparse. The aim of this study was to test whether MIF is associated with impaired glucose tolerance (IGT) and type 2 diabetes and whether these associations are independent of metabolic and immunological risk factors and to compare the associations of MIF and IGT/type 2 diabetes with those of C-reactive protein (CRP) and interleukin-6 (IL-6) with IGT/type 2 diabetes. RESEARCH DESIGN AND METHODS—The Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4 (KORA S4) is a population-based survey performed in Southern Germany (1999–2001). Of 1,653 participants aged 55–74 years, 236 patients with type 2 diabetes, 242 subjects with IGT, and 244 normoglycemic control subjects matched for age and sex were included in this cross-sectional study. Serum concentrations of MIF were measured by enzyme-linked immunosorbent assay. RESULTS—Serum MIF concentrations are highly increased in individuals with IGT and type 2 diabetes. The associations of MIF with IGT and type 2 diabetes were independent of classical risk factors and of CRP and IL-6 and were much stronger before and after multivariate adjustment than the associations of CRP and IL-6 with IGT and type 2 diabetes. CONCLUSIONS—Our data suggest that elevations of systemic MIF concentrations precede the onset of type 2 diabetes. This finding may be relevant because MIF has been reported to contribute to the development of type 2 diabetes–related diseases such as atherosclerosis and cancer.
Hepatitis B virus X protein sensitizes cells to starvation-induced autophagy via up-regulation of beclin 1 expression
Authors: Hong Tang, Liang Da, Yi Mao, Ying Li, Dong Li, Zhenhua Xu, Feng Li, Yifei Wang, Pierre Tiollais, Tsaiping Li, Mujun Zhao
Journal: Hepatology (2008)

Human beclin 1 is the first identified mammalian gene to induce autophagy. It is commonly expressed at reduced levels in breast tumors; however, it is overexpressed in hepatitis B virus (HBV)-infected cancerous liver tissues. To expose the possible mechanism and biological significance of this up-regulation of beclin 1, we investigated the regulation of beclin 1 expression by HBV x protein (HBx) in hepatic or hepatoma cell lines. Here, we showed that enforced expression of HBx by transfection technology results in the up-regulation of the endogenous messenger RNA (mRNA) and protein levels of Beclin 1 in the tested cells. Using a luciferase- reporter assay, we demonstrated that HBx transactivates beclin 1 promoter activity in a dose-dependent manner. The promoter region of the beclin 1 gene identified in this study is located at nt −277/+197 and has the maximum transcriptional activity. HBx-mediated up-regulation of beclin 1 expression might be direct, that is, via its promoter. Furthermore, the cells that transiently or stably expressed HBx showed an enhanced accumulation of vacuoles carrying the autophagy marker LC3 as compared with the control cells, which was induced by nutrient starvation, indicating HBx-enhanced autophagy. Moreover, this enhanced autophagy occurred in HepG2.2.15 cells that replicate HBV and in cells transfected with HBV genomic DNA, suggesting that HBV infection also causes increased levels of autophagy under starvation conditions. Treatment of cells with beclin 1 small interfering RNA (siRNA) blocked HBx–enhanced autophagy, demonstrating that the function of HBx in influencing autophagy is Beclin 1 dependent. Conclusion: Our findings suggest a novel function of HBx in increasing autophagy through the up-regulation of beclin1 expression, and this may provide an important mechanism in HBV-infected hepatocytes growing under nutrient-deficient conditions. (HEPATOLOGY 2009;49:60-71)
“Mindscoping” pain and suffering
Authors: Jaak Panksepp, Marcia Smith Pasqualini
Journal: Behavioral and Brain Sciences (2002)

No adequate evidence exists for the evolution of facial pain expression and detection mechanisms, as opposed to social-learning processes. Although brain affective/emotional processes, and resulting whole body action patterns, have surely evolved, we should also aspire to monitor human suffering by direct neural measures rather than by more indirect indices.
An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins.
Authors: J C Skipper, R C Hendrickson, P H Gulden, V Brichard, A Van Pel, Y Chen, J Shabanowitz, T Wolfel, C L Slingluff, T Boon, D F Hunt, V H Engelhard
Journal: The Journal of Experimental Medicine (1996)

T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.
PIK3CA Mutations in <i>In situ</i> and Invasive Breast Carcinomas
Authors: Alexander Miron, Maria Varadi, Daniel Carrasco, Hailun Li, Lauren Luongo, Hee Jung Kim, So Yeon Park, Eun Yoon Cho, Gretchen Lewis, Sarah Kehoe, J. Dirk Iglehart, Deborah Dillon, D. Craig Allred, Laura Macconaill, Rebecca Gelman, Kornelia Polyak
Journal: Cancer Research (2010)

The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of PIK3CA have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant PIK3CA plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in PIK3CA have been invasive breast carcinomas and the frequency of PIK3CA mutations in preinvasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of PIK3CA in pure ductal carcinoma in situ (DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas. In a subset of cases, both in situ and invasive areas were analyzed from the same tumor. We found that the frequency of PIK3CA mutations was essentially the same ( approximately 30%) in all three histologic groups. In some cases, in situ and invasive areas of the same tumor were discordant for PIK3CA status, and in two cases in which multiple invasive and adjacent in situ areas within the same tumor were analyzed independently, we detected intratumor heterogeneity for PIK3CA mutations. Our results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded.
wingless and aristaless2 Define a Developmental Ground Plan for Moth and Butterfly Wing Pattern Evolution
Authors: A. Martin, R. D. Reed
Journal: Molecular Biology and Evolution (2010)

Butterfly wing patterns have long been a favorite system for studying the evolutionary radiation of complex morphologies. One of the key characteristics of the system is that wing patterns are based on a highly conserved ground plan of pattern homologies. In fact, the evolution of lepidopteran wing patterns is proposed to have occurred through the repeated gain, loss, and modification of only a handful of serially repeated elements. In this study, we examine the evolution and development of stripe wing pattern elements. We show that expression of the developmental morphogen wingless (wg) is associated with early determination of the major basal (B), discal (DI and DII), and marginal (EI) stripe patterns in a broad sampling of Lepidoptera, suggesting homology of these pattern elements across moths and butterflies. We describe for the first time a novel Lepidoptera-specific homeobox gene, aristaless2 (al2), which precedes wg expression during the early determination of DII stripe patterns. We show that al2 was derived from a tandem duplication of the aristaless gene, whereupon it underwent a rapid coding and cis-regulatory divergence relative to its more conserved paralog aristaless1 (al1), which retained an ancestral expression pattern. The al2 stripe expression domain evolutionarily preceded the appearance of the DII pattern elements in multiple lineages, leading us to speculate that al2 represented preexisting positional information that may have facilitated DII evolution via a developmental drive mechanism. In contrast to butterfly eyespot patterns, which are often cited as a key example of developmental co-option of preexisting developmental genes, this study provides an example where the origin of a major color pattern element is associated with the evolution of a novel lepidopteran homeobox gene.
Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method
Authors: F.J. Verbaan, S.M. Bal, D.J. van den Berg, J.A. Dijksman, M. van Hecke, H. Verpoorten, A. van den Berg, R. Luttge, J.A. Bouwstra
Journal: Journal of Controlled Release (2008)
Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons
Authors: Eric M. Pietras, Ranjani Lakshminarasimhan, Jose-Marc Techner, Sarah Fong, Johanna Flach, Mikhail Binnewies, Emmanuelle Passegué
Journal: The Journal of Experimental Medicine (2014)

Type I interferons (IFN-1s) are antiviral cytokines that suppress blood production while paradoxically inducing hematopoietic stem cell (HSC) proliferation. Here, we clarify the relationship between the proliferative and suppressive effects of IFN-1s on HSC function during acute and chronic IFN-1 exposure. We show that IFN-1-driven HSC proliferation is a transient event resulting from a brief relaxation of quiescence-enforcing mechanisms in response to acute IFN-1 exposure, which occurs exclusively in vivo. We find that this proliferative burst fails to exhaust the HSC pool, which rapidly returns to quiescence in response to chronic IFN-1 exposure. Moreover, we demonstrate that IFN-1-exposed HSCs with reestablished quiescence are largely protected from the killing effects of IFNs unless forced back into the cell cycle due to culture, transplantation, or myeloablative treatment, at which point they activate a p53-dependent proapoptotic gene program. Collectively, our results demonstrate that quiescence acts as a safeguard mechanism to ensure survival of the HSC pool during chronic IFN-1 exposure. We show that IFN-1s can poise HSCs for apoptosis but induce direct cell killing only upon active proliferation, thereby establishing a mechanism for the suppressive effects of IFN-1s on HSC function.
C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study
Authors: P. Póvoa, L. Coelho, E. Almeida, A. Fernandes, R. Mealha, P. Moreira, H. Sabino
Journal: European Respiratory Journal (2005)

The aim of this study was to evaluate C-reactive protein (CRP) levels, body temperature and white cell count (WCC) after prescription of antibiotics in order to describe the clinical resolution of ventilator-associated pneumonia (VAP). A cohort of 47 VAP patients with microbiological confirmation of disease was assessed. CRP levels, body temperature and WCC were monitored daily. On day 4 of the antibiotic therapy, the CRP level of survivors was 0.62 times the initial value, whereas, in nonsurvivors, it was 0.98. Body temperature and WCC remained almost unchanged. By day 4, a CRP of &gt;0.6 times the initial level was a marker of poor outcome (sensitivity 0.92; specificity 0.59). Patients were divided according to their CRP patterns of response to antibiotics: fast response, slow response, nonresponse, and biphasic response. All patients with fast and slow response patterns survived, whereas those showing nonresponse and a biphasic response pattern exhibited a mortality of 78 and 75%, respectively. The adequacy of the initial antibiotic therapy had a marked influence on the rate of CRP decrease, as well as on mortality. In conclusion, daily C-reactive protein measurements after antibiotic prescription were useful in the identification, as early as day 4, of ventilator-associated pneumonia patients with poor outcome. The identification of the pattern of C-reactive protein response to antibiotics was useful in the recognition of individual clinical course, improving or worsening, as well as of the rate of improvement.
MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children
Authors: T.C. Darton, D.L. Jack, M. Johnson, R. Borrow, M. Guiver, E.B. Kaczmarski, M.W. Turner, N.J. Klein, R.C. Read
Journal: Clinical Microbiology and Infection (2014)

Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.
CLINICAL SIGNIFICANCE OF ANTIBODY TO THE HEPATITIS DELTA VIRUS IN SYMPTOMLESS HBsAg CARRIERS
Authors: Sarino Arico, Mario Rizzetto, Alessandro Zanetti, Silvana Diana, Michele Arnone, Antonio Ascione, Giuseppe Pastore, Marcello Aragona, Francesco Caredda, Giovanni Marinucci, Patrizia Farci, Nicola Caporaso, Pietro Dentico, Giovanni Raimondo, Antonio Craxi
Journal: The Lancet (1985)
Effects of sodium restriction and hydrochlorothiazide on RAAS blockade efficacy in diabetic nephropathy: a randomised clinical trial
Authors: Arjan J Kwakernaak, Jan A Krikken, S Heleen Binnenmars, Folkert W Visser, Marc H Hemmelder, Arend-Jan Woittiez, Henk Groen, Gozewijn D Laverman, Gerjan Navis
Journal: The Lancet Diabetes & Endocrinology (2014)
Pharmacogenetics of Sulfotransferase
Authors: K. Nagata, Y. Yamazoe
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Cytosolic sulfotransferase catalyzes sulfoconjugation of relatively small lipophilic endobiotics and xenobiotics. At least 44 cytosolic sulfotransferases have been identified from mammals, and based on their amino acid sequences, these forms are shown to constitute five different families. In humans, 10 sulfotransferase genes have been identified and shown to localize on at least five different chromosomes. The enzymatic properties characterized in the recombinant forms indicate the association of their substrate specificity with metabolisms of such nonpeptide hormones as estrogen, corticoid, and thyroxine, although most forms are also active on the sulfation of various xenobiotics. Genetic polymorphisms are observed on such human sulfotransferases as ST1A2, ST1A3, and ST2A3.
Contralateral haemorrhagic pulmonary metastases ("choriocarcinoma syndrome") after pneumonectomy for primary pulmonary choriocarcinoma
Authors: I Durieu, N Berger, R Loire, J P Gamondes, P H Guillaud, J F Cordier
Journal: Thorax (1994)

The case history is presented of a patient which illustrates both the diagnostic difficulties of an extremely rare tumour (choriocarcinoma of the lung) and its associated haemorrhagic metastases ("choriocarcinoma syndrome").