tbuckley/cabot-search huggingface dataset:
The Atrial Natriuretic Peptide Genetic Variant rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population
Authors: Valentina Cannone, Angelo Baldassare Cefalu’, Davide Noto, Christopher G. Scott, Kent R. Bailey, Giovanni Cavera, Michele Pagano, Michelangelo Sapienza, Maurizio R. Averna, John C. Burnett
Journal: Diabetes Care (2013)

We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population.We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068.Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: -1.7 kg/m(2) [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels <40 mg/dL are less frequent (P = 0.05) and obesity tends to be less prevalent (P = 0.07). Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0.02). After adjusting for BMI, the above associations were attenuated. Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (-6.0 mmHg [2.5], P = 0.02) and lower prevalence of hypertension (odds ratio 0.41 [95% CI 0.20-0.83], P = 0.01).The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.
Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients.
Authors: J J Curtis, D A Laskow, P A Jones, B A Julian, R S Gaston, R G Luke
Journal: Journal of the American Society of Nephrology (1993)

It was found that two known renal vasodilators had different effects on RBF and GFR in the setting of therapeutic blood levels of cyclosporine in hypertensive renal transplant patients. Captopril lowered blood pressure in these patients but also lowered blood flow and GFR. Nifedipine lowered blood pressure to the same degree but without lowering either RBF or GFR.
THE RELEASE OF CHOLESTEROL ESTERS FROM SERUM LIPOPROTEINS BY EXTRACTS OF CERTAIN GROUP A STREPTOCOCCI
Authors: Robert Rowen
Journal: The Journal of Experimental Medicine (1961)

A chemical explanation has been provided for the production of opalescence in human and animal sera by extracts of certain Group A streptococci. Opalescence results from the selective liberation of specific lipids from alpha(1)-serum lipoprotein. The released lipids have been quantitatively separated through the relatively simple technique of ultracentrifugal flotation, and subsequently analyzed by chemical and chromatographic means. Esterified cholesterol constitutes by far the major low density reaction product, accounting for 85 to 90 per cent of the total lipid released. A small amount of phospholipid (apparently limited to lecithin) was the only other lipid consistently found in low density product fractions. Comparative kinetics of opalescence development and cholesterol release under varying conditions of pH, extract concentration, and temperature reveal that the two effects do not run exactly parallel but are, nevertheless, probably closely related manifestations of a specific enzymic degradation of serum lipoprotein. It has been suggested that enzymic action may occur at a site within the lipoprotein remote from the cholesterol esters themselves. Although the over-all reaction appears to be mediated by an enzyme present in many Group A streptococci, it is uncertain whether this enzyme acts directly on lipoprotein or acts by causing the activation of a serum enzyme which in turn attacks the lipoprotein.
Nicotine yield and roll your own (RYO) cigarette usage in a large municipal hospital smoking cessation center
Authors: Marios Kougias, Christina Goga, Evangelos Balis, Stavroula Boulia, Marousa Kouvela, George Tatsis
Journal: European Respiratory Journal (2012)

Purpose

Men and women differ in their sensitivity to nicotine. In addition many smokers believe that roll-your-own (RYO) cigarettes are not as addictive as manufactured cigarettes. The purpose of our study was to compare the different characteristics of smokers addressing to our smoking cessation center.

Methods

Forty three people (20 male and 23 female), mean age of 48,81 ± 1,62, smoking 41,92 ± 3,46 packyears participated in our survey, at Evaggelismos Hospital during the last year.

Nineteen(19) used RYO cigarettes, while 24 used manufactured cigarettes.Analysis was performed with the aid of the independent sample t- test.

Results**

Men using RYO cigarettes were of mean age 40.43 ± 3,45 and smoked 48,28 ± 8,65 packyears while women using manufactured cigarettes aged 55,46 ± 2,84 and smoked 49,38 ± 6,52 packyears.

On the other hand women using RYO cigarettes were of mean age 45,91 ± 3,45 smoking 26,29 ± 5,06 while women using manufactured cigarettes aged 49,45 ± 2,36 and smoked 46,09 ± 6,25 packyears.

The difference of smoking usage (packyears) is statistical significant at 0,05 (both sided).

Nicotine yield of manufactured cigarettes was different between men and women (0,68 ± 0,067 mg vs 0,48 ± 0,073 mg) at a p =0,052), while there is no record of RYO nicotine composition.

**results expressed as mean ± SE

Conclusions

Smokers using RYO cigarettes are younger than those using manufactured cigarettes. Interestingly women using RYO cigarettes present a significantly smaller (by 46%) amout of packyears than those using manufactured cigarettes. In addition women smoke less than men and they chose cigarettes with less nicotine yield.
Psychological factors associated with hand dermatoses: which subgroup needs additional psychological care?
Authors: V. Niemeier, M. Nippesen, J. Kupfer, W-B. Schill, U. Gieler
Journal: British Journal of Dermatology (2002)

The aetiology of hand dermatoses (HD) is very heterogeneous. Psychological influences on severity and coping in hand eczema have been only rarely investigated.To investigate whether psychological factors correlate with somatic factors, in order to be able to estimate the possible need for psychosocial treatment of these patients.In a cross-sectional study 101 hand dermatosis patients (49F, 52M) with psoriasis (n = 26), vesicular hand eczema (n = 33) or contact dermatitis (n = 42) were examined with regard to dermatological [diagnosis, severity, Erlanger Atopy Score (EAS)], allergic (patch test) and psychological aspects [Coping with Chronic Skin Diseases questionnaire (CSD), Allover Depression Scale (ADS), Social Readjustment Rating Scale (SRRS), questionnaire for measuring Factors of Aggression (FAF)],and Visual Analogue Scales (VAS) concerning itching, scratching and impairment. Subgroups of high stress responders (high-SR) vs. low stress responders (low-SR) were also examined.Of the patients with HD, 47.52% are convinced that 'stress' influences the course of their disease. Analysis of variance shows that the subjective reaction to stress (high-SR) correlates with higher severity scores, more itching, higher depression scores and more life events. High-SRs were younger and the onset of the disease was earlier compared with patients without a subjective reaction to stress (low-SR). In the CSD those with especially high-SR but negative patch-test results stated significantly higher values for itching, helplessness and search for information.Psychological factors should be taken into consideration in the treatment of patients with HD. High-SR patients with a negative patch-test seem to require more adjuvant psychological care.
Randomized Study Comparing a Basal-Bolus With a Basal Plus Correction Insulin Regimen for the Hospital Management of Medical and Surgical Patients With Type 2 Diabetes
Authors: Guillermo E. Umpierrez, Dawn Smiley, Kathie Hermayer, Amna Khan, Darin E. Olson, Christopher Newton, Sol Jacobs, Monica Rizzo, Limin Peng, David Reyes, Ingrid Pinzon, Maria Eugenia Fereira, Vicky Hunt, Ashwini Gore, Marcos T. Toyoshima, Vivian A. Fonseca
Journal: Diabetes Care (2013)

Effective and easily implemented insulin regimens are needed to facilitate hospital glycemic control in general medical and surgical patients with type 2 diabetes (T2D).This multicenter trial randomized 375 patients with T2D treated with diet, oral antidiabetic agents, or low-dose insulin (≤ 0.4 units/kg/day) to receive a basal-bolus regimen with glargine once daily and glulisine before meals, a basal plus regimen with glargine once daily and supplemental doses of glulisine, and sliding scale regular insulin (SSI).Improvement in mean daily blood glucose (BG) after the first day of therapy was similar between basal-bolus and basal plus groups (P = 0.16), and both regimens resulted in a lower mean daily BG than did SSI (P = 0.04). In addition, treatment with basal-bolus and basal plus regimens resulted in less treatment failure (defined as >2 consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL) than did treatment with SSI (0 vs. 2 vs. 19%, respectively; P < 0.001). A BG <70 mg/dL occurred in 16% of patients in the basal-bolus group, 13% in the basal plus group, and 3% in the SSI group (P = 0.02). There was no difference among the groups in the frequency of severe hypoglycemia (<40 mg/dL; P = 0.76).The use of a basal plus regimen with glargine once daily plus corrective doses with glulisine insulin before meals resulted in glycemic control similar to a standard basal-bolus regimen. The basal plus approach is an effective alternative to the use of a basal-bolus regimen in general medical and surgical patients with T2D.
Downstream EWS/FLI1 - upstream Ewing's sarcoma
Authors: Heinrich Kovar
Journal: Genome Medicine (2010)

Ewing's sarcoma family tumors are a good example of how genome research has advanced our understanding of the molecular pathogenesis of an otherwise enigmatic disease. This group of embryonal bone tumors is characterized by the expression of a chimeric ETS-family oncogene, predominantly EWS/FLI1. There is now convincing evidence for a mesenchymal descent from an early pluripotent progenitor. EWS/FLI1 has been shown to drive proliferation of Ewing's sarcoma cells and block most of the differentiation potential except for a partial neural gene expression program. The EWS/FLI1 fusion protein acts mainly as a gene activator, directly interacting with chromatin at two kinds of binding site: distant enhancers enriched in GGAA microsatellites, and proximal promoters containing classical ETS-binding motifs and recognition motifs for other transcription factors. EWS/FLI1 also represses a large number of genes, mainly indirectly, presumably by altering microRNA expression and epigenetic mechanisms, and potentially affecting post-transcriptional gene regulation. Modulation of EWS/FLI1 expression is not only a desirable therapeutic goal, but may also occur under physiological conditions and influence the course of the disease.
<i>S</i> -Nitrosylation from GSNOR Deficiency Impairs DNA Repair and Promotes Hepatocarcinogenesis
Authors: Wei Wei, Bin Li, Martha A. Hanes, Sanjay Kakar, Xin Chen, Limin Liu
Journal: Science Translational Medicine (2010)

A reductase that removes harmful nitrosyl groups from cellular proteins guards against liver cancer, perhaps in part by ensuring the health of a crucial DNA repair enzyme.
Poly(ADP-Ribose) Polymerase Is Hyperactivated in Homologous Recombination–Defective Cells
Authors: Ponnari Gottipati, Barbara Vischioni, Niklas Schultz, Joyce Solomons, Helen E. Bryant, Tatjana Djureinovic, Natalia Issaeva, Kate Sleeth, Ricky A. Sharma, Thomas Helleday
Journal: Cancer Research (2010)

Poly(ADP-ribose) (PAR) polymerase 1 (PARP1) is activated by DNA single-strand breaks (SSB) or at stalled replication forks to facilitate DNA repair. Inhibitors of PARP efficiently kill breast, ovarian, or prostate tumors in patients carrying hereditary mutations in the homologous recombination (HR) genes BRCA1 or BRCA2 through synthetic lethality. Here, we surprisingly show that PARP1 is hyperactivated in replicating BRCA2-defective cells. PARP1 hyperactivation is explained by the defect in HR as shRNA depletion of RAD54, RAD52, BLM, WRN, and XRCC3 proteins, which we here show are all essential for efficient HR and also caused PARP hyperactivation and correlated with an increased sensitivity to PARP inhibitors. BRCA2-defective cells were not found to have increased levels of SSBs, and PAR polymers formed in HR-defective cells do not colocalize to replication protein A or gammaH2AX, excluding the possibility that PARP hyperactivity is due to increased SSB repair or PARP induced at damaged replication forks. Resistance to PARP inhibitors can occur through genetic reversion in the BRCA2 gene. Here, we report that PARP inhibitor-resistant BRCA2-mutant cells revert back to normal levels of PARP activity. We speculate that the reason for the sensitivity of HR-defective cells to PARP inhibitors is related to the hyperactivated PARP1 in these cells. Furthermore, the presence of PAR polymers can be used to identify HR-defective cells that are sensitive to PARP inhibitors, which may be potential biomarkers.
Independent Wheat B and G Genome Origins in Outcrossing Aegilops Progenitor Haplotypes
Authors: B Kilian, H Özkan, O Deusch, S Effgen, A Brandolini, J Kohl, W Martin, F Salamini
Journal: Molecular Biology and Evolution (2006)

The origin of modern wheats involved alloploidization among related genomes. To determine if Aegilops speltoides was the donor of the B and G genomes in AABB and AAGG tetraploids, we used a 3-tiered approach. Using 70 amplified fragment length polymorphism (AFLP) loci, we sampled molecular diversity among 480 wheat lines from their natural habitats encompassing all S genome Aegilops, the putative progenitors of wheat B and G genomes. Fifty-nine Aegilops representatives for S genome diversity were compared at 375 AFLP loci with diploid, tetraploid, and 11 nulli–tetrasomic Triticum aestivum wheat lines. B genome–specific markers allowed pinning the origin of the B genome to S chromosomes of A. speltoides, while excluding other lineages. The outbreeding nature of A. speltoides influences its molecular diversity and bears upon inferences of B and G genome origins. Haplotypes at nuclear and chloroplast loci ACC1, G6PDH, GPT, PGK1, Q, VRN1, and ndhF for ∼70 Aegilops and Triticum lines (0.73 Mb sequenced) reveal both B and G genomes of polyploid wheats as unique samples of A. speltoides haplotype diversity. These have been sequestered by the AABB Triticum dicoccoides and AAGG Triticum araraticum lineages during their independent origins.
Increased Accumulation of Tissue ACE in Human Atherosclerotic Coronary Artery Disease
Authors: Frank Diet, Richard E. Pratt, Gerald J. Berry, Naoko Momose, Gary H. Gibbons, Victor J. Dzau
Journal: Circulation (1996)

Background Angiotensin may play a pathophysiological role in experimental and human cardiovascular disease. Clinical studies have shown that ACE inhibitors reduce mortality, recurrent myocardial infarction, and ischemic events in patients with left ventricular dysfunction. Animal studies suggest that tissue ACE, particularly within blood vessels, may be an important target. Methods and Results To study tissue ACE in human coronary artery disease and to identify potential mechanisms of ACE inhibitor action, we examined ACE expression immunohistochemically in nonatherosclerotic and diseased human coronary arteries. In nonatherosclerotic arteries, ACE immunoreactivity was found in luminal and adventitial vasa vasorum endothelium. In early- and intermediate-stage atherosclerotic lesions, ACE was detected prominently in regions of fat-laden macrophages and in association with T lymphocytes. In advanced lesions, ACE immunoreactivity was also localized to the endothelium of the microvasculature throughout the plaques. Immunoreactive angiotensin II was also detected in these areas. ACE expression in macrophages was further examined by in vitro experiments with a monocytoid cell line. ACE activity was induced threefold after differentiation of the cells into macrophages and was further increased after stimulation with acetylated LDL. Conclusions These observations demonstrate that significant sources of tissue ACE in human atherosclerotic plaques are regions of inflammatory cells, especially areas of clustered macrophages as well as microvessel endothelial cells. These results suggest that ACE accumulation within the plaque may contribute to an increased production of local angiotensin that may participate in the pathobiology of coronary artery disease. Plaque ACE probably is an important target of drug action.
Uncovering Genes and Regulatory Pathways Related to Urinary Albumin Excretion
Authors: Rachael S. Hageman, Magalie S. Leduc, Christina R. Caputo, Shirng-Wern Tsaih, Gary A. Churchill, Ron Korstanje
Journal: Journal of the American Society of Nephrology (2010)

Identifying the genes underlying quantitative trait loci (QTL) for disease is difficult, mainly because of the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals, test candidate genes, and define pathways affected by these QTL. In this study, we mapped three significant QTL and one suggestive QTL for an increased albumin-to-creatinine ratio on chromosomes (Chrs) 1, 4, 15, and 17, respectively, in a cross between the inbred MRL/MpJ and SM/J strains of mice. By combining data from several sources and by utilizing gene expression data, we identified <i>Tlr12</i> as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL, including the glycan degradation, leukocyte migration, and antigen-presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
GAS CHROMATOGRAPHIC ANALYSIS OF THE FATTY ACID COMPOSITION OF THE PLASMA LIPIDS IN NORMAL AND DIABETIC SUBJECTS*
Authors: Bo Hallgren, Stina Stenhagen, Alvar Svanborg, Lars Svennerholm
Journal: Journal of Clinical Investigation (1960)

Epidemiological, clinical-pathological, hormonal and nutritional studies during the last ten years indicate that disturbances of the lipid metabolism are important factors in the pathogenesis of atherosclerosis. Increased serum lipid level, induced by nutritional and pathological conditions, is correlated with an increased frequency of atherosclerosis. In diabetic acidosis, hyperlipemia (1-3) with a pronounced increase of free fatty acids (FFA) (4) is regularly found. After treatment with insulin and diet a normal serum lipid level usually occurs in patients with diabetes of short duration, although isolated increase of FFA often is found (5). Even in well controlled diabetic patients an elevation of the serum lipids is often seen when the diabetes has lasted for some years. Adlersberg and co-workers (6) reported that diabetic patients with vascular complications had significantly higher serum lipid levels than did cases with uncomplicated diabetes or normal controls. Lowy and Barach (7) found that this augmentation of the lipids preceded the symptoms of vascular complications. In the present study a detailed analysis of the fatty acid composition of the different plasma lipid fractions in the postabsorbtive state was performed in seven diabetic patients and in eight healthy individuals used as controls.
Manipulation of ascending aortic pressure and flow wave reflections with the Valsalva maneuver: relationship to input impedance.
Authors: J P Murgo, N Westerhof, J P Giolma, S A Altobelli
Journal: Circulation (1981)

Dramatic changes in the shape of pulsatile ascending aortic pressure and flow wave forms occur during the Valsalva maneuver in man. To study these changes, aortic pressure and flow signals were recorded in eight patients using a multisensor catheter. Aortic input impedance was derived during the control, strain and postrelease phases of the Valsalva maneuver. During control, well-defined minima and maxima occurred in the spectral plots of impedance moduli. This pattern was accentuated during the postrelease phase. In contrast, input impedance during strain was almost equal to the characteristic impedance for all harmonics. These results imply that during the control and postrelease phases, strong reflections return to the ascending aorta, but during the strain phase, reflections are minimal, absent or more diffuse. From wave transmission theory, it also follows that pulsatile pressure and flow wave forms should be similar in shape in the absence of reflections and dissimilar in the presence of reflections. This was observed in all eight patients. By provoking changes in the arterial tree during the Valsalva maneuver, the magnitude and timing of wave reflections were significantly altered, resulting in marked changes in the shape of pulsatile aortic pressure and flow wave forms. This study demonstrates the importance of reflections in determining the shape of the arterial pulse.
A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients☆
Authors: Massimo Puoti, Barbara Zanini, Gian Paolo Quinzan, Laura Ravasio, Giuseppe Paraninfo, Teresa Santantonio, Adriano Rollo, Stefania Artioli, Franco Maggiolo, Serena Zaltron
Journal: Journal of Hepatology (2004)

Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients.
Nucleotide sequence of a marsupial LINE-1 element and the evolution of placental mammals.
Authors: M Dörner, S Pääbo
Journal: Molecular Biology and Evolution (1995)

L1 (LINE-1) elements, previously described in several placental species, were shown to exist in several thousands of copies dispersed in the genome of a marsupial (the North American opossum, Didelphis virginiana). A restriction fragment containing the partial nucleotide sequence of the reverse transcriptase gene (ORF-2) from the marsupial L1 element was cloned and sequenced. The element was shown to evolve in concert within the marsupial when compared to placental mammals. When the marsupial L1 element is used as an outgroup to root a phylogeny of placental mammals, the results support the view that humans more recently shared a common ancestor with ungulates than with rodents.