tbuckley/cabot-search huggingface dataset:
Review focus on inorganic nitrite and nitrate in cardiovascular health and disease
Authors: C. G. Kevil, D. J. Lefer
Journal: Cardiovascular Research (2010)

This editorial refers to the following review articles in the issue which are part of a Review Focus on Inorganic Nitrite and Nitrate: M. Gilchrist et al .[7][1], pp. 492–498 ; J.W. Calvert[10][2], pp. 499–506; R.P. Patel et al .[12][3], pp. 507–515; Q. Yu et al .[16][4], pp. 516–524; J.O. Lundberg et al .[17][5], pp. 525–532; C.B. Patillo et al .[19][6], pp. 533–541; B.S. Zuckerbraun et al .[23][7], pp. 542–552; A. Cauwels and P. Brouckaert[24][8], pp. 553–559. 

Reviews and original articles in this focused issue of Cardiovascular Research address the topic of inorganic nitrite and nitrate in cardiovascular pathophysiology. It is well accepted that nitric oxide (NO) is a critical regulator of cardiovascular health that is routinely depleted during vascular disease and dysfunction.1,2 Since the original discovery of NO as a mediator of cardiovascular health, thousands of studies have focused on mechanisms of NO generation and function, largely addressing NO synthase (NOS) activity and NO-dependent signalling responses (e.g. soluble guanylate cyclase and nitrosylation reactions).3,4 From the beginning, a physiological role for inorganic nitrite or nitrate in mediating the biological effects of NO was briefly considered; however, early experimental data did not support a compelling role for these molecules in participating in NO physiology. Over the last decade, a handful of investigators have challenged this dogma through studies re-examining the relationship between NO, nitrite, and nitrate and have elucidated the newly described nitrite/nitrate/NO endocrine system. In the current review papers, the authors discuss how nitrite/nitrate serve as an important reservoir for NO and detail how under specific conditions nitrite/nitrate can be reduced back to NO to increase its bioavailability independent of classical NOS activity. The importance and mechanisms of this unique feature of nitrite/nitrate anion are further detailed with respect to cardiovascular health and potential therapeutic uses.

Historical and new, emerging evidence …

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 [5]: #ref-17
 [6]: #ref-19
 [7]: #ref-23
 [8]: #ref-24
Extreme differences in rates of molecular evolution of foraminifera revealed by comparison of ribosomal DNA sequences and the fossil record
Authors: J. Pawlowski, I. Bolivar, J. F. Fahrni, C. de Vargas, M. Gouy, L. Zaninetti
Journal: Molecular Biology and Evolution (1997)

Foraminifera have one of the best known fossil records among the unicellular eukaryotes. However, the origin and phylogenetic relationships of the extant foraminiferal lineages are poorly understood. To test the current paleontological hypotheses on evolution of foraminifera, we sequenced about 1,000 base pairs from the 3' end of the small subunit rRNA gene (SSU rDNA) in 22 species representing all major taxonomic groups. Phylogenies were derived using neighbor-joining, maximum-parsimony, and maximum-likelihood methods. All analyses confirm the monophyletic origin of foraminifera. Evolutionary relationships within foraminifera inferred from rDNA sequences, however, depend on the method of tree building and on the choice of analyzed sites. In particular, the position of planktonic foraminifera shows important variations. We have shown that these changes result from the extremely high rate of rDNA evolution in this group. By comparing the number of substitutions with the divergence times inferred from the fossil record, we have estimated that the rate of rDNA evolution in planktonic foraminifera is 50 to 100 times faster than in some benthic foraminifera. The use of the maximum-likelihood method and limitation of analyzed sites to the most conserved parts of the SSU rRNA molecule render molecular and paleontological data generally congruent.
Functional and morphological characteristics of compensated and decompensated cardiac hypertrophy in dogs with chronic infrarenal aorto-caval fistulas.
Authors: F Legault, J L Rouleau, C Juneau, C Rose, K Rakusan
Journal: Circulation Research (1990)

The relation between cardiac hypertrophy, shunt size, myocardial contractility, capillary density, adrenergic responsiveness, and neurohumoral stimulation was evaluated in dogs with compensated and decompensated cardiac hypertrophy caused by an infrarenal aorto-caval shunt. Shunt size varied from 5 to 35 mm2 due to an inability to create a uniform size. Dogs that developed heart failure within 4 months had 25 +/- 2 mm2 shunts, whereas those that developed it after 4 months had 19 +/- 3 mm2 shunts; those that did not develop heart failure had 10 +/- 1 mm2 shunts. Hypertrophy developed at the same rate in all the dogs that developed heart failure, which occurred at a critical heart weight (hypertrophy) for a given load (shunt size). In the dogs with heart failure there was a decrease in myocardial contractility (tension = 5.7 +/- 0.6 vs. 7.3 +/- 0.3 g/mm2, p less than 0.05), a decrease in adrenergic responsiveness (maximal heart rate with isoproterenol = 203 +/- 7 vs. 249 +/- 5 beats/min, p less than 0.01), an increase in circulating neurohormones, and a decrease in urinary sodium excretion (0.4 +/- 0.1 vs. 5.0 +/- 1.3 meq/3 hr, p less than 0.01). None of these abnormalities occurred in dogs with compensated hypertrophy. There were no differences in cardiac capillary density between the control dogs and the dogs with compensated cardiac hypertrophy or heart failure. Thus, it would appear that if heart failure is to develop after an initial toleration of a sudden volume overload, it will develop at a given combination of cardiac hypertrophy and volume overload, with cardiac hypertrophy developing at the same rate in all cases. In this model, once heart failure develops, myocardial contractility and cardiac adrenergic responsiveness are decreased and there is pronounced neurohumoral activation. All these changes are absent in hearts with compensated hypertrophy.
Continuation of Statin Therapy in Patients with Presumed Infection
Authors: Peter S. Kruger, Christopher J. Joyce, Meg L. Harward, Mark A. Jones, Karam M. Kostner, Michael S. Roberts, Bala Venkatesh
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: In patients on prior statin therapy who are hospitalized for acute infections, current literature is unclear on whether statins should be continued during their hospitalization.Objectives: To test the hypothesis that continuation of therapy with statins influences the inflammatory response to infection and that cessation may cause an inflammatory rebound.Methods: Prospective randomized double-blind placebo-controlled trial of atorvastatin (20 mg) or matched placebo in 150 patients on preexisting statin therapy requiring hospitalization for infection.Measurements and Main Results: The primary end point was progression of sepsis during hospitalization. At baseline, the rate of severe sepsis was 32% in both groups. Compared with baseline, the odds ratio for severe sepsis declined in both groups: 0.43 placebo and 0.5 statins (Day 3) versus 0.14 placebo and 0.12 statins (Day 14). The rate of decline of severe sepsis was similar between the groups (odds ratio 1.17 [0.56–2.47], P = 0.7 Day 3; 0.85 [0....
Mapping of the immune response genes in the major histocompatibility complex of the Rhesus monkey.
Authors: M E Dorf, H Balner, B Benacerraf
Journal: The Journal of Experimental Medicine (1975)

Interest in the Ir genes of rheus monkeys stems from their phylogenetic relationship to man and the extensive data already available on the major histocompatibility complex of the monkey. At least two independent dominant H-linked Ir genes have been identified in the rhesus. These genes control the ability of monkeys to respond to the random linear copolymer of glutamyl alanine (GA), or the dinitrophenyl conjugate of glutamyl lysine (DNP-GL). These synthetic polymers can elicit weak delayed-type skin reactions and strong humoral responses in some monkeys. In a series of unrelated monkeys phenotyped for the serologically defined RhL-A specificities of both segregant series, there were no correlations between any RhL-A specificity and responder status to the GA or DNP-GL polymers. However, segregation analysis of 21 rhesus families sired by 3 fathers indicated the capacity of the offspring to form antibodies was associated with genes coded for in the RhL-A complex. In three monkeys, verified recombination within the RhL-A complex between the genes coding for the serologically defined determinants (SD loci) and the gene(s) controlling the lymphocyte-activating determinants (Lad loci) responsible for mixed lymphocyte reactivity was established. In two of these monkeys the immune response genes controlling the DNP-GL response segregated with the Lad genes, while in the third case the Ir-GL gene segregated with the SD loci, tentatively localizing the Ir-GL gene between the SD and Lad loci. In addition, we have shown that genetically distinct genes control responsiveness to DNP-GL and GA. These genes were separated by recombination, thus one monkey inherited the Lad, Ir-GL, and SD loci from one paternal haplotype and by crossing over inherited the gene controlling GA responsiveness from the other paternal haplotype. The fine structure mapping of the RhL-A gene complex is compared with the H-2 and HL-A gene complexes. Several striking similarities were noted.
Brn-2 Represses Microphthalmia-Associated Transcription Factor Expression and Marks a Distinct Subpopulation of Microphthalmia-Associated Transcription Factor–Negative Melanoma Cells
Authors: Jane Goodall, Suzanne Carreira, Laurence Denat, Dominique Kobi, Irwin Davidson, Paolo Nuciforo, Richard A. Sturm, Lionel Larue, Colin R. Goding
Journal: Cancer Research (2008)

Abstract The origin of tumor heterogeneity is poorly understood, yet it represents a major barrier to effective therapy. In melanoma and in melanocyte development, the microphthalmia-associated transcription factor (Mitf) controls survival, differentiation, proliferation, and migration/metastasis. The Brn-2 (N-Oct-3, POU3F2) transcription factor also regulates melanoma proliferation and is up-regulated by BRAF and β-catenin, two key melanoma-associated signaling molecules. Here, we show that Brn-2 also regulates invasiveness and directly represses Mitf expression. Remarkably, in melanoma biopsies, Mitf and Brn-2 each mark a distinct subpopulation of melanoma cells, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy. [Cancer Res 2008;68(19):7788–94]
Targeting the Platelet-Derived Growth Factor Receptor in Antivascular Therapy for Human Ovarian Carcinoma
Authors: Sachin M. Apte, Dominic Fan, Jerald J. Killion, Isaiah J. Fidler
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We sought to determine whether blockade of platelet-derived growth factor receptor (PDGF-R) activation by oral administration of a PDGF-R tyrosine kinase inhibitor (STI571) alone or in combination with i.p. paclitaxel can inhibit the progression of tumors caused by human ovarian carcinoma cells growing in the peritoneal cavity of female nude mice. Experimental Design: In several different experiments, paclitaxel-sensitive and paclitaxel-resistant metastatic human ovarian carcinoma cells were injected into the peritoneal cavity of nude mice. Seven days later, groups (n = 10) of mice began receiving a control treatment, STI571 alone, paclitaxel alone, or a combination of STI571 and paclitaxel. The mice were necropsied after 45 days of treatment. Results: Treatment with combination therapy significantly reduced tumor weight (relative to control or single-agent therapy) in all three human ovarian cancer cell lines. Immunohistochemical analyses revealed that PDGF-R activation was blocked by STI571 administered alone or in combination with paclitaxel. Tumor-associated endothelial cells expressed both PDGF-R and phosphorylated PDGF-R. In mice receiving combination therapy, tumor-associated endothelial cells underwent apoptosis, leading to decreases in microvessel density and tumor cell proliferation relative to control and single-agent therapy. Conclusions: These results show that administration of a PDGF-R tyrosine kinase inhibitor in combination with paclitaxel impairs the progression of ovarian cancer in the peritoneal cavity of nude mice, in part, by blockade of PDGF, an endothelial cell survival factor, which results in the increased apoptosis of tumor-associated endothelial cells.
Effects of topically-applied antiperspirant on sweat gland function
Authors: S.A. McWILLIAMS, I. MONTGOMERY, D. McEWAN JENKINSON, H.Y. ELDER, S.M. WILSON, ANN M. SUTTON
Journal: British Journal of Dermatology (1987)

In subjects exposed to a hot environment, short‐term topical pretreatment with aluminium zirconium tetrachlorhydrate delayed the onset of visible sweating although it failed to prevent the response. The delay was considered most probably to be due to the occlusivc action, in the duct within the upper epidermis, of aluminium‐containing conglomerates, which disappear after continuous sweating. However, microanalytical evidence indicated that ionic transport within the fundus secretory cells was also modified.
Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1
Authors: B.M. Ryan, G.E. Konecny, S. Kahlert, H.-J. Wang, M. Untch, G. Meng, M.D. Pegram, K.C. Podratz, J. Crown, D.J. Slamon, M.J. Duffy
Journal: Annals of Oncology (2006)
Preferential Accumulation of Antigen-specific Effector CD4 T Cells at an Antigen Injection Site Involves CD62E-dependent Migration but Not Local Proliferation
Authors: R. Lee Reinhardt, Daniel C. Bullard, Casey T. Weaver, Marc K. Jenkins
Journal: The Journal of Experimental Medicine (2003)

The migration of antigen-specific T cells to nonlymphoid tissues is thought to be important for the elimination of foreign antigens from the body. However, recent results showing the migration of activated T cells into many nonlymphoid tissues raised the possibility that antigen-specific T cells do not migrate preferentially to nonlymphoid tissues containing antigen. We addressed this question by tracking antigen-specific CD4 T cells in the whole body after a localized subcutaneous antigen injection. Antigen-specific CD4 T cells proliferated in the skin-draining lymph nodes and the cells that underwent the most cell divisions acquired the ability to bind to CD62P. As time passed, CD62P-binding antigen-specific CD4 T cells with interferon γ production potential accumulated preferentially at the site of antigen injection but only in recipients that expressed CD62E. Surprisingly, these T cells did not proliferate in the injection site despite showing evidence of more cell divisions than the T cells in the draining lymph nodes. The results suggest that the most divided effector CD4 T cells from the lymph nodes enter the site of antigen deposition via recognition of CD62E on blood vessels and are retained there in a nonproliferative state via recognition of peptide–major histocompatibility complex II molecules.
The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells.
Authors: A Muraguchi, T Hirano, B Tang, T Matsuda, Y Horii, K Nakajima, T Kishimoto
Journal: The Journal of Experimental Medicine (1988)

The role of recombinant B cell stimulatory factor 2 (BSF-2/IL-6) in the regulation of growth and differentiation of B cells was investigated. rBSF-2 at 200 pg/ml could induce 50% of the maximum Ig production in B lymphoblastoid cell lines, the specific activity being estimated as 5 X 10(6) U/mg. rBSF-2 augmented PWM-induced IgM, IgG, and IgA production in mononuclear cells (MNC); the effect was exerted by directly acting on PWM-induced B blast cells to induce Ig production. However, rBSF-2 did not induce any growth of activated B cells. In contrast, rBSF-2 showed a potent growth activity on a murine hybridoma clone, MH60.BSF2. The concentration required for half-maximal [3H]TdR uptake was approximately 5 pg/ml, which was 40 times less than that required for Ig induction in a B cell line. Anti-BSF-2 antibody inhibited PWM-induced Ig production in MNC, but not PWM-induced proliferation. The antibody was effective even when added on day 4 of an 8-d culture, indicating that BSF-2 is one of the essential late-acting factors in PWM-induced Ig production.
Clinical Indications of <sup>11</sup>C-Choline PET/CT in Prostate Cancer Patients with Biochemical Relapse
Authors: Maria Picchio, Paolo Castellucci
Journal: Theranostics (2012)

Several studies investigated the potential role of imaging modalities in prostate cancer patients in case of biochemical recurrence. However, the role of molecular imaging has not been well established yet. Considering the results of the literature and of our own experience, we tried to summarize the potential applications of (11)C-choline PET/CT in prostate cancer patients in case of biochemical relapse for the detection of lymph node and distant recurrence.
“Déjà vu all over again”
Authors: PETER B ERNST
Journal: Gut (1997)

See article on page 442 

A quick examination of the history of scientific discovery related to microbial pathogenesis confirms that scientists follow a predictable pattern of investigation. Typically, key virulence factors are identified and vaccines or therapies are designed to neutralise them. The characterisation of cholera toxin serves as an example of the potential benefits of being able to identify a single molecular entity that contributes to so much of humanity’s suffering. The understanding of the biological function of this molecule has yielded important insights into cell signalling, cytokine networks and mucosal immune regulation. Yamaoka and colleagues, in this issue (see page 442) have applied this time honoured approach in their studies of potential virulence factors associated with Helicobacter pylori . They show that isolates of H pylori bearing the cagA gene induce higher levels of cytokines and inflammation in the gastric mucosa than cagA − strains.

Studies to define virulence factors of H pylori included the work of Leunk and colleagues who showed that H pylori produced a soluble factor that induced vacuolisation of epithelial cell lines.1 Shortly thereafter, the cytotoxin associated gene ( cagA ) and the vacuolating cytotoxin gene ( vacA ) were cloned and characterised. The link between virulence factors and disease was supported by Crabtree et al who astutely observed that …
Prospective Association Between Lung Function and the Incidence of Diabetes
Authors: Earl S. Ford, David M. Mannino
Journal: Diabetes Care (2004)

To determine whether impaired pulmonary function is a significant predictor of the incidence of diabetes.Using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study, a cohort study of a representative sample of U.S. adults, we examined the prospective associations between pulmonary function and incidence of diabetes. Our analyses included 4,830 U.S. men and women aged 25-74 years who had a baseline interview and examination (including spirometry) from 1971 through 1975 and were followed through 1992-1993. Incident diabetes (n=443) was based on self- or proxy reports, hospitalization, or death certificates.After multiple adjustment, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), percentage of predicted FEV1, and percentage of predicted FVC were significantly and inversely associated with the incidence of diabetes, but the ratio of FEV1 to FVC was not. Obstructive lung disease (defined by the Global Initiative for Chronic Obstructive Lung Disease classification) was not significantly associated with the incidence of diabetes, but restrictive lung disease was (hazard ratio=1.45, 95% CI 1.04-2.03). The association did not differ significantly by smoking status.Although several prospective studies have found that impaired pulmonary function may increase the risk for developing diabetes, additional research is needed to better understand these relationships and their possible implications.
N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus
Authors: Xue-En Liu, Liesbeth Desmyter, Chun-Fang Gao, Wouter Laroy, Sylviane Dewaele, Valerie Vanhooren, Ling Wang, Hui Zhuang, Nico Callewaert, Claude Libert, Roland Contreras, Cuiying Chen
Journal: Hepatology (2007)

We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by α-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer–based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP. Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further.
Social Networks, Social Support, and Survival After Breast Cancer Diagnosis
Authors: Candyce H. Kroenke, Laura D. Kubzansky, Eva S. Schernhammer, Michelle D. Holmes, Ichiro Kawachi
Journal: Journal of Clinical Oncology (2006)

We prospectively examined social ties and survival after breast cancer diagnosis.Participants included 2,835 women from the Nurses' Health Study who were diagnosed with stages 1 to 4 breast cancer between 1992 and 2002. Of these women, 224 deaths (107 of these related to breast cancer) accrued to the year 2004. Social networks were assessed in 1992, 1996, and 2000 with the Berkman-Syme Social Networks Index. Social support was assessed in 1992 and 2000 as the presence and availability of a confidant. Cox proportional hazards models were used in prospective analyses of social networks and support, both before and following diagnosis, and subsequent survival.In multivariate-adjusted analyses, women who were socially isolated before diagnosis had a subsequent 66% increased risk of all-cause mortality (HR = 1.66; 95% CI, 1.04 to 2.65) and a two-fold increased risk of breast cancer mortality (HR = 2.14; 95% CI, 1.11 to 4.12) compared with women who were socially integrated. Women without close relatives (HR = 2.65; 95% CI, 1.03 to 6.82), friends (HR = 4.06; 95% CI, 1.40 to 11.75), or living children (HR = 5.62; 95% CI, 1.20 to 26.46) had elevated risks of breast cancer mortality and of all-cause mortality compared with those with the most social ties. Neither participation in religious or community activities nor having a confidant was related to outcomes. Effect estimates were similar in analyses of postdiagnosis networks.Socially isolated women had an elevated risk of mortality after a diagnosis of breast cancer, likely because of a lack of access to care, specifically beneficial caregiving from friends, relatives, and adult children.