tbuckley/cabot-search huggingface dataset:
Continuous measurement of canine coronary blood volume change with alterations of heart rate
Authors: K. Hangai, S. Satoh, F. Sato, J. Watanabe, Y. Maruyama, T. Takishima
Journal: Cardiovascular Research (1993)

The aim was to examine the effects of heart rate on total coronary blood volume with pressure-type plethysmography in isolated and vasodilated canine hearts.Nine hearts were excised from anaesthetised mongrel dogs (13.1-15.2 kg) and perfused with arterial blood of other dogs (17.0-29.0 kg). The venous blood returning to the right atrium and both ventricles was drained under constant negative pressure (-10 mm Hg). A thin latex balloon filled with water was inserted into the left ventricle to keep the intraventricular volume constant. The pressure difference between the cylinder into which the heart was placed and a compensation chamber was measured as a change in coronary blood volume while heart rate was altered from 120 beats.min-1 (control heart rate) to a target level (60, 90, 150, or 180 beats.min-1).The mean coronary blood volume change compared with that at control heart rate was 1.65(SEM 0.32) ml x 100 g-1 at 60 beats.min-1 (p < 0.005) and -0.74(0.20) ml x 100 g-1 at 180 beats.min-1 (p < 0.005) under the perfusion pressure of 70 mm Hg. The mean volume decreased with the increase in heart rate. Diastolic-systolic variations in coronary blood volume also decreased with an increase in heart rate, from 0.61(0.06) ml x 100 g-1 (60 beats.min-1) (p < 0.005) to 0.12 ml.100 g-1 (180 beats.min-1). Both mean change and variation were almost linear functions of R-R interval (r = 0.88 and r = 0.83). Lowering the perfusion pressure from 70 to 40 mm Hg diminished the changes in both mean and variation of the coronary blood volume.Tachycardia reduces the mean coronary blood volume and the diastolic-systolic variations in isolated vasodilated canine hearts.
Large Gene Family Expansions and Adaptive Evolution for Odorant and Gustatory Receptors in the Pea Aphid, Acyrthosiphon pisum
Authors: C. Smadja, P. Shi, R. K. Butlin, H. M. Robertson
Journal: Molecular Biology and Evolution (2009)

Gaining insight into the mechanisms of chemoreception in aphids is of primary importance for both integrative studies on the evolution of host plant specialization and applied research in pest control management because aphids rely on their sense of smell and taste to locate and assess their host plants. We made use of the recent genome sequence of the pea aphid, Acyrthosiphon pisum, to address the molecular characterization and evolution of key molecular components of chemoreception: the odorant (Or) and gustatory (Gr) receptor genes. We identified 79 Or and 77 Gr genes in the pea aphid genome and showed that most of them are aphid-specific genes that have undergone recent and rapid expansion in the genome. By addressing selection within sets of paralogous Or and Gr expansions, for the first time in an insect species, we show that the most recently duplicated loci have evolved under positive selection, which might be related to the high degree of ecological specialization of this species. Although more functional studies are still needed for insect chemoreceptors, we provide evidence that Grs and Ors have different sets of positively selected sites, suggesting the possibility that these two gene families might have different binding pockets and bind structurally distinct classes of ligand. The pea aphid is the most basal insect species with a completely sequenced genome to date. The identification of chemoreceptor genes in this species is a key step toward further exploring insect comparative genetics, the genomics of ecological specialization and speciation, and new pest control strategies.
Comparison of the oxidative phosphorylation (OXPHOS) nuclear genes in the genomes of Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae.
Authors: Gaetano Tripoli, Domenica D'Elia, Paolo Barsanti, Corrado Caggese
Journal: Genome biology (2005)

Abstract Background In eukaryotic cells, oxidative phosphorylation (OXPHOS) uses the products of both nuclear and mitochondrial genes to generate cellular ATP. Interspecies comparative analysis of these genes, which appear to be under strong functional constraints, may shed light on the evolutionary mechanisms that act on a set of genes correlated by function and subcellular localization of their products. Results We have identified and annotated the Drosophila melanogaster , D. pseudoobscura and Anopheles gambiae orthologs of 78 nuclear genes encoding mitochondrial proteins involved in oxidative phosphorylation by a comparative analysis of their genomic sequences and organization. We have also identified 47 genes in these three dipteran species each of which shares significant sequence homology with one of the above-mentioned OXPHOS orthologs, and which are likely to have originated by duplication during evolution. Gene structure and intron length are essentially conserved in the three species, although gain or loss of introns is common in A. gambiae . In most tissues of D. melanogaster and A. gambiae the expression level of the duplicate gene is much lower than that of the original gene, and in D. melanogaster at least, its expression is almost always strongly testis-biased, in contrast to the soma-biased expression of the parent gene. Conclusions Quickly achieving an expression pattern different from the parent genes may be required for new OXPHOS gene duplicates to be maintained in the genome. This may be a general evolutionary mechanism for originating phenotypic changes that could lead to species differentiation.
An alternative to prophylactic colectomy for colon cancer prevention in HNPCC syndrome
Authors: S Olschwang
Journal: Gut (2004)

The French Ad-Hoc Committee on Hereditary Non-polyposis Colon Cancer (HNPCC) management meeting on behalf of the French Health Minister has recently released its statement.1 The report on prophylactic colorectal resections for HNPCC related adenocarcinomas ( Gut 2003; 52 :1752–5) is in contrast with ours and we would like to discuss this point.

Use of decision analysis models is a smart approach in dealing with such complex situations. However, life expectancy related to the occurrence of metachronous colorectal carcinoma should be balanced against the negative impact on quality of life in the case of prophylactic extensive colorectal resections. Thus quality adjusted life expectancy, integrating the individual patient’s choice,2 might be a more accurate approach. Comprehensive, fair, and loyal information of what the patient can hope for is mandatory to fulfil the requirements of patient autonomy in such a shared decision. From …
Effects of Orally Active Taxanes on P-Glycoprotein Modulation and Colon and Breast Carcinoma Drug Resistance
Authors: M. R. Vredenburg, I. Ojima, J. Veith, P. Pera, K. Kee, F. Cabral, A. Sharma, P. Kanter, W. R. Greco, R. J. Bernacki
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: The taxane paclitaxel (Taxol) is often of limited efficacy in chemotherapeutic regimens because some cancer cells express high levels of the efflux pump, P-glycoprotein (Pgp), which removes the drug from the cells. The orally active paclitaxel analog IDN-5109 has been reported to overcome Pgp-mediated drug resistance. We tested whether IDN-5109 acts by modulating Pgp activity. Methods: Human MDA435/LCC6mdr1 and MDA435/LCC6 breast carcinoma cells, which express and do not express Pgp, respectively, were incubated with [3H]IDN-5109 and paclitaxel to determine intracellular drug accumulation. Flow cytometry was used to analyze intracellular retention of two Pgp substrates, rhodamine 123 (Rh-123) and doxorubicin, in both breast carcinoma cell lines and in human colon carcinoma cells (SW-620, DLD1, and HCT-15, whose Pgp levels vary) treated with different taxanes. The effects of IDN-5109 and paclitaxel on tumor growth in vivo were studied with the use of tumors established through xenografts of Pgp-expressing SW-620 and DLD1 cells in severe combined immunodeficiency mice. All statistical tests were two-sided. Results: Pgp-expressing cells treated with IDN-5109 or with the taxane-based drug resistance reversal agent tRA96023, which blocks Pgp activity, retained 8.1- and 9.4-fold more Rh-123 (P = .0001), respectively, and 1.7- and 1.9-fold more doxorubicin (P = .001), respectively, than cells treated with paclitaxel. Non-Pgp-expressing cells treated similarly demonstrated no increased retention of either substrate. MDA435/LCC6mdr1 cells retained 5.3-fold more [3H]IDN-5109 than [3H]paclitaxel after 2 hours (P = .01). IDN-5109 showed statistically significantly higher tumor growth inhibition than paclitaxel against the SW-620 xenograft (P = .003). Conclusions: IDN-5109 modulates Pgp activity, resulting in superior tumor growth inhibition against Pgp-expressing tumors as compared with paclitaxel. IDN-5109 may broaden the spectrum of taxane use to include colon tumors.
Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.
Authors: J Conger, J Robinette, A Villar, L Raij, P Shultz
Journal: Journal of Clinical Investigation (1995)

Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a significantly greater decline in RBF to intravenous L-NAME in NE- than sham-ARF rats (-65 +/- 8 vs. -37 +/- 5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham- and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity is in response to ischemia-induced renal vasoconstrictor activity. Attenuated response to endothelium-dependent vasodilators cannot be interpreted only as evidence for decreased NOS activity.
Trends in the Risks and Benefits to Patients With Cancer Participating in Phase 1 Clinical Trials
Authors: Thomas G. Roberts
Journal: JAMA (2004)

In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown.To determine trends in the rates of treatment-related (toxic) death, objective response, and serious toxicity and to identify factors associated with these outcomes.We searched abstracts and journal articles reporting the results of phase 1 cancer treatment trials originally submitted to annual meetings of the American Society of Clinical Oncology (ASCO) from 1991 through 2002.We focused on published single-agent trials that enrolled patients with advanced solid tumors and excluded studies testing agents already approved by the US Food and Drug Administration at the time of the ASCO presentation.Multiple observers independently extracted information on trial design, location, sponsorship, types of tumors treated, drug class, route of administration, and clinical outcomes.The overall toxic death rate for 213 studies (involving 6474 cancer patients) published in peer-reviewed journals was 0.54%, while the overall objective response rate was 3.8%. Toxic death rates decreased over the study period, from 1.1% over the first 4 years of the study (1991-1994) to 0.06% over the most recent 4-year period (1999-2002) (P<.01). Response rates also decreased but by proportionally much less. After adjusting for characteristics of the experimental trials and the investigational agents, the odds of a patient dying from an experimental treatment while participating in a trial submitted during the most recent 4-year period were less than one tenth those of a patient participating in a trial submitted during the first 4-year period (odds ratio, 0.09; 95% confidence interval, 0.01-0.67; P = .009). In comparison, the adjusted odds of a patient experiencing an objective response over the same time periods decreased by approximately half (odds ratio, 0.46; 95% confidence interval, 0.32-0.66; P<.001).The level of risk experienced by cancer patients who participate in phase 1 treatment trials appears to have improved over the 12-year period from 1991 through 2002. Because toxic death rates have decreased more quickly than have objective response rates, the ratio of risk to benefit may have also improved. These changes relate in part to the targeted and less-toxic nature of newer cancer drugs and are coincident with the increased attention that has been paid to the safety of clinical research over the time period we analyzed.
A clinical study of chronic pancreatitis
Authors: O. Fitzgerald, P. Fitzgerald, J. Fennelly, J. P. McMullin, S. J. Boland
Journal: Gut (1963)

A series of 53 cases of chronic pancreatic disease is described and attention drawn to the frequency with which symptoms are persistent rather than intermittent. A plea is made for the use of the term ;progressive' rather than ;relapsing' in describing many of these cases. Alcohol was an unimportant factor in the aetiology. The possibility of achieving an accurate and early diagnosis using the serum secretin/pancreozymin test is emphasized. The frequent relief of symptoms and the prevention of progress of the disease by surgery, especially sphincterotomy, is recorded.
The Status of Health Assessment 1994
Authors: John E. Ware
Journal: Annual Review of Public Health (1995)

General health status and a broader concept of quality of life are discussed and methods of widely used surveys are reviewed. A consensus regarding the inclusion of measures of physical, mental, social, and role functioning and general health perceptions is noted for comprehensive assessments of health. A schematic of relationships among condition-specific and generic measures is presented along with results expected for objective and subjective measures of physical and mental dimensions of health. Suggestions are offered for the labeling of disease-specific and generic measures and ways to avoid confounding of content. Applications of health surveys in general population monitoring, health policy evaluation, clinical trials of alternative treatments, monitoring and improving of health care outcomes, and in everyday clinical practice are exemplified and discussed. A unified measurement strategy is proposed and arguments in favor of standardizing the content of health surveys across applications are offered.
Long-Term Survivor With Pulmonary Veno-Occlusive Disease
Authors: Kensuke Matsushita, Masahiko Kanna, Takuya Yazawa, Satoru Shimizu, Manabu Nitta, Tetsu Takamizawa, Kentaro Arakawa, Hideto Yano, Masanori Nishikawa, Hideo Himeno
Journal: Circulation (2012)
Relationship between osseointegration and superelastic biomechanics in porous NiTi scaffolds
Authors: Xiangmei Liu, Shuilin Wu, Kelvin W.K. Yeung, Y.L. Chan, Tao Hu, Zushun Xu, Xuanyong Liu, Jonathan C.Y. Chung, Kenneth M.C. Cheung, Paul K. Chu
Journal: Biomaterials (2010)
Gene expression profiling in rheumatoid arthritis: current concepts and future directions
Authors: E J M Toonen, P Barrera, T R D J Radstake, P L C M van Riel, H Scheffer, B Franke, M J H Coenen
Journal: Annals of the Rheumatic Diseases (2008)

Over the last years microarray technologies have generated new perspectives for the high-throughput analysis of biological systems. Nowadays, it is possible to monitor thousands of genes in a single experiment. This molecular profiling technology combined with standardised and validated clinical measurements can allow a more precise characterisation of a patient's phenotype, and may lead to the design of therapeutic protocols and procedures better tailored to an individual patient's needs. In this report we provide an overview of expression profiling studies in rheumatoid arthritis (RA). RA is a chronic inflammatory disease in which both genetic and environmental factors are involved. The precise molecular mechanisms underlying RA are not fully understood. A systematic literature search revealed nine array-based expression profiling studies in patients with RA. Findings from these studies were compared with those of linkage and genome-wide association (GWA) studies. Although we observed many differences in study design, analysis and interpretation of results between the different studies, we extracted two sets of genes: (1) those differentially expressed in more than one study, and (2) genes differentially expressed in at least one of the reviewed studies and present in RA linkage or GWA loci. We suggest that both sets of genes include interesting candidate genes for further study in RA.
Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency
Authors: Stefan D. Anker, Josep Comin Colet, Gerasimos Filippatos, Ronnie Willenheimer, Kenneth Dickstein, Helmut Drexler, Thomas F. Lüscher, Boris Bart, Waldemar Banasiak, Joanna Niegowska, Bridget-Anne Kirwan, Claudio Mori, Barbara von Eisenhart Rothe, Stuart J. Pocock, Philip A. Poole-Wilson, Piotr Ponikowski
Journal: New England Journal of Medicine (2009)

Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia.
Phospholipase A <sub>2</sub> Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events After Acute Coronary Syndromes
Authors: Sung Kee Ryu, Ziad Mallat, Joelle Benessiano, Alain Tedgui, Anders G. Olsson, Weihang Bao, Gregory G. Schwartz, Sotirios Tsimikas
Journal: Circulation (2012)

Background— Secretory phospholipase A2 (sPLA 2 ) and lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) are enzyme biomarkers of increased cardiovascular risk and targets of emerging therapeutic agents. Their relationship to cardiovascular events in the setting of high-dose statin therapy compared with placebo in patients with acute coronary syndrome is not known. Methods and Results— sPLA 2 and Lp-PLA 2 mass and activity were measured in 2587 patients in the Myocardial Ischemia Reduction With Acute Cholesterol Lowering (MIRACL) trial at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. Baseline levels of sPLA 2 and Lp-PLA 2 mass and activity were not associated with the primary efficacy measure of the trial of death, myocardial infarction, or unstable angina. However, in the overall cohort, baseline sPLA 2 mass predicted risk of death after multivariable adjustment (hazard ratio for 2-fold increase, 1.30; 95% confidence interval, 1.09–1.56; P =0.004). This association remained significant when examined separately in the placebo group but not in the atorvastatin group. Compared with placebo, atorvastatin reduced median sPLA 2 mass (−32.1% versus −23.1%), sPLA 2 activity (−29.5% versus −19.2%), Lp-PLA 2 mass (−35.8% versus −6.2%), and Lp-PLA 2 activity (−24.3% versus 5.4%; P &lt;0.001 for all). Atorvastatin reduced the hazard of death associated with elevated sPLA 2 mass and activity by ≈50%. Conclusions— sPLA 2 mass independently predicts death during a 16-week period after acute coronary syndrome. High-dose atorvastatin significantly reduces sPLA 2 and Lp-PLA 2 mass and activity after acute coronary syndrome and mitigates the risk of death associated with sPLA 2 mass. Atorvastatin may exert antiinflammatory effects on phospholipases that contribute to its therapeutic benefit after acute coronary syndrome.
Origin and Evolution of the Unique Tetra-Domain Hemoglobin from the Hydrothermal Vent Scale Worm Branchipolynoe
Authors: J. Projecto-Garcia, N. Zorn, D. Jollivet, S.W. Schaeffer, F.H. Lallier, S. Hourdez
Journal: Molecular Biology and Evolution (2009)

Hemoglobin is the most common respiratory pigment in annelids. It can be intra or extracellular, and this latter type can form large multimeric complexes. The hydrothermal vent scale worms Branchipolynoe symmytilida and Branchipolynoe seepensis express an extracellular tetra-domain hemoglobin (Hb) that is unique in annelids. We sequenced the gene for the single-domain and tetra-domain globins in these two species. The single-domain gene codes for a mature protein of 137 amino acids, and the tetra-domain gene codes for a mature protein of 552 amino acids. The single-domain gene has a typical three exon/two intron structure, with introns located at their typical positions (B12.2 and G7.0). This structure is repeated four times in the tetra-domain gene, with no bridge introns or linker sequences between domains. The phylogenetic position of Branchipolynoe globins among known annelid globins revealed that, although extracellular, they cluster within the annelid intracellular globins clade, suggesting that the extracellular state of these Hbs is the result of convergent evolution. The tetra-domain structure likely resulted from two tandem duplications, domain 1 giving rise to domain 2 and after this the two-domain gene duplicated to produce domains 3 and 4. The high O(2) affinity of Branchipolynoe extracellular globins may be explained by the two key residues (B10Y and E7Q) in the heme pocket in each of the domains of the single and tetra-domain globins, which have been shown to be essential in the oxygen-avid Hb from the nematode Ascaris suum. This peculiar globin evolutionary path seems to be very different from other annelid extracellular globins and is most likely the product of evolutionary tinkering associated with the strong selective pressure to adapt to chronic hypoxia that characterizes hydrothermal vents.