tbuckley/cabot-search huggingface dataset:
Expression of the Nucleus-Encoded Chloroplast Division Genes and Proteins Regulated by the Algal Cell Cycle
Authors: S.-y. Miyagishima, K. Suzuki, K. Okazaki, Y. Kabeya
Journal: Molecular Biology and Evolution (2012)

Chloroplasts have evolved from a cyanobacterial endosymbiont and their continuity has been maintained by chloroplast division, which is performed by the constriction of a ring-like division complex at the division site. It is believed that the synchronization of the endosymbiotic and host cell division events was a critical step in establishing a permanent endosymbiotic relationship, such as is commonly seen in existing algae. In the majority of algal species, chloroplasts divide once per specific period of the host cell division cycle. In order to understand both the regulation of the timing of chloroplast division in algal cells and how the system evolved, we examined the expression of chloroplast division genes and proteins in the cell cycle of algae containing chloroplasts of cyanobacterial primary endosymbiotic origin (glaucophyte, red, green, and streptophyte algae). The results show that the nucleus-encoded chloroplast division genes and proteins of both cyanobacterial and eukaryotic host origin are expressed specifically during the S phase, except for FtsZ in one graucophyte alga. In this glaucophyte alga, FtsZ is persistently expressed throughout the cell cycle, whereas the expression of the nucleus-encoded MinD and MinE as well as FtsZ ring formation are regulated by the phases of the cell cycle. In contrast to the nucleus-encoded division genes, it has been shown that the expression of chloroplast-encoded division genes is not regulated by the host cell cycle. The endosymbiotic gene transfer of minE and minD from the chloroplast to the nuclear genome occurred independently on multiple occasions in distinct lineages, whereas the expression of nucleus-encoded MIND and MINE is regulated by the cell cycle in all lineages examined in this study. These results suggest that the timing of chloroplast division in algal cell cycle is restricted by the cell cycle-regulated expression of some but not all of the chloroplast division genes. In addition, it is suggested that the regulation of each division-related gene was established shortly after the endosymbiotic gene transfer, and this event occurred multiple times independently in distinct genes and in distinct lineages.
Interrogating 11 Fast-Evolving Genes for Signatures of Recent Positive Selection in Worldwide Human Populations
Authors: A. Moreno-Estrada, K. Tang, M. Sikora, T. Marques-Bonet, F. Casals, A. Navarro, F. Calafell, J. Bertranpetit, M. Stoneking, E. Bosch
Journal: Molecular Biology and Evolution (2009)

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs in chimpanzee, mouse, rat, and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes was then further explored for signatures of recent positive selection using single nucleotide polymorphism (SNP) data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP-CEPH diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintenance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal of recent selection in this region may come from a different, neighboring gene (CD5) rather than from the candidate gene itself (VPS37C). For this set of positively selected genes in the human lineage, we find no indication that these genes maintained their rapid evolutionary pace among human populations. Based on these data, it therefore appears that adaptation for human-specific and for population-specific traits may have involved different genes.
The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine.
Authors: J B Weinberg, D L Granger, D S Pisetsky, M F Seldin, M A Misukonis, S N Mason, A M Pippen, P Ruiz, E R Wood, G S Gilkeson
Journal: The Journal of Experimental Medicine (1994)

MRL-lpr/lpr mice spontaneously develop various manifestations of autoimmunity including an inflammatory arthropathy and immune complex glomerulonephritis. This study examines the role of nitric oxide, a molecule with proinflammatory actions, in the pathogenesis of MRL-lpr/lpr autoimmune disease. MRL-lpr/lpr mice excreted more urinary nitrite/nitrate (an in vivo marker of nitric oxide production) than did mice of normal strains and MRL-(+/+) and B6-lpr/lpr congenic strains. In addition, MRL-lpr/lpr peritoneal macrophages had an enhanced capacity to produce nitric oxide in vitro as well as increased nitric oxide synthase activity, and certain tissues from MRL-lpr/lpr mice had increased expression of inducible nitric oxide synthase (NOS) mRNA and increased amounts of material immunoreactive for inducible NOS. Oral administration of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, prevented the development of glomerulonephritis and reduced the intensity of inflammatory arthritis in MRL-lpr/lpr mice. By using interspecific backcross mice, the gene for inducible NOS (Nosi) was mapped to mouse chromosome 11. This chromosomal localization was different from those loci that we have previously demonstrated to be linked to enhanced susceptibility to renal disease in an MRL-lpr/lpr cross. However, the chromosomal location of the NOS gene was consistent with an insulin-dependent diabetes locus identified in an analysis of nonobese diabetic (NOD) mice. These results suggest that elevated nitric oxide production could be important in the pathogenesis of autoimmunity, and that treatments to block the production of nitric oxide or block its effects might be valuable therapeutically.
An Outbreak of Primary Pneumonic Tularemia on Martha's Vineyard
Authors: Katherine A. Feldman, Russell E. Enscore, Sarah L. Lathrop, Bela T. Matyas, Michael McGuill, Martin E. Schriefer, Donna Stiles-Enos, David T. Dennis, Lyle R. Petersen, Edward B. Hayes
Journal: New England Journal of Medicine (2001)

In the summer of 2000, an outbreak of primary pneumonic tularemia occurred on Martha's Vineyard, Massachusetts. The only previously reported outbreak of pneumonic tularemia in the United States also occurred on the island in 1978.
Cytoplasmic <i>CUL9/PARC</i> Ubiquitin Ligase Is a Tumor Suppressor and Promotes p53-Dependent Apoptosis
Authors: Xin-Hai Pei, Feng Bai, Zhijun Li, Matthew D. Smith, Gabrielle Whitewolf, Ran Jin, Yue Xiong
Journal: Cancer Research (2011)

Abstract A wide range of cell stresses, including DNA damage, signal to p53 through posttranslational modification of p53. The cytoplasmic functions of p53 are emerging as an important constituent of role of p53 in tumor suppression. Here, we report that deletion of the Cul9 (formerly Parc) gene, which encodes an E3 ubiquitin ligase that binds to p53 and localizes in the cytoplasm, resulted in spontaneous tumor development, accelerated Eμ-Myc–induced lymphomagenesis, and rendered mice susceptible to carcinogenesis. Cul9-p53 double-mutant mice exhibited indistinguishable tumor phenotypes as p53 single-mutant mice, indicating that the function of Cul9 in tumor suppression is largely mediated by p53. Deletion of Cul9 had no significant effect on cell-cycle progression, but attenuated DNA damage–induced apoptosis. Ectopic expression of wild-type CUL9, but not a point mutant CUL9 deficient in p53 binding, promotes apoptosis. These results show CUL9 as a potential p53-activating E3 ligase in the cytoplasm. Cancer Res; 71(8); 2969–77. ©2011 AACR.
PRAMEing a Picture of Differentiation Therapy for AML?
Authors: Robert L. Redner
Journal: Clinical Cancer Research (2013)

Abstract Addition of retinoic acid to chemotherapy improves survival of patients with acute myeloid leukemia. This effect is more pronounced in leukemias that express high levels of PRAME. PRAME is an inhibitor of retinoic acid signaling, which may prove to be an important marker for retinoic acid response. Clin Cancer Res; 19(9); 2277–9. ©2013 AACR.
Ischemic Preconditioning Activates Phosphatidylinositol-3-Kinase Upstream of Protein Kinase C
Authors: Haiyan Tong, Weina Chen, Charles Steenbergen, Elizabeth Murphy
Journal: Circulation Research (2000)

Abstract —The present study is designed to test whether phosphatidylinositol 3-kinase (PI3-kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of global ischemia, Langendorff-perfused rat hearts were perfused for 20 minutes (control); preconditioned with 4 cycles of 5-minute ischemia and 5-minute reflow (PC); treated with either wortmannin (WM) or LY 294002 (LY), each of which is a PI3-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2-dioctanoyl- sn -glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated identically to the DOG group except with WM added 10 minutes before and during perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP), measured after 30 minutes of reflow, was improved by PC (72±2% versus 36±4% in control; P &lt;0.001), and this was blocked by WM and LY (41±4% and 43±5%, respectively; P &lt;0.05 compared with PC). DOG addition improved postischemic LVDP (67±6%; P &lt;0.001 compared with control), but in contrast to its effect on PC, WM did not completely eliminate the protective effect of DOG (52±4%; P &gt;0.05 compared with DOG; P &lt;0.05 compared with control). PC induced phosphorylation of protein kinase B and translocation of PKCε, and it increased NO production, and these effects were blocked by WM, which suggests a role for PI3-kinase in PC upstream of PKC and NO.
Group II and IV phospholipase A2 are produced in human pancreatic cancer cells and influence prognosis
Authors: M Kashiwagi, H Friess, W Uhl, P Berberat, M Abou-Shady, M Martignoni, S E Anghelacopoulos, A Zimmermann, M W Buchler
Journal: Gut (1999)

Phospholipase A(2) (PLA(2)) is involved in regulating biosynthesis of arachidonic acid and its metabolites. There are three major structurally different forms of PLA(2): group I, also called pancreatic PLA(2) (PLA(2)-I); group II, referred to as secretory non-pancreatic or synovial or platelet PLA(2) (PLA(2)-II); group IV, referred to as cytosolic PLA(2) (PLA(2)-IV).To examine PLA(2)-I, PLA(2)-II, and PLA(2)-IV in normal and pancreatic cancer tissues. Patients-PLA(2) was studied in 58 pancreatic adenocarcinomas, obtained from 25 women and 33 men undergoing pancreatic resection. Normal organ donor pancreas served as control.The enzymes were analysed by northern blot, in situ hybridisation, and immunohistochemistry. The molecular findings were correlated with clinical variables of the patients.Northern blot analysis of total RNA showed enhanced PLA(2) group II and IV mRNA expression in 52% and 55% of the pancreatic cancer samples respectively compared with the normal controls (p = 0.0013 and p = 0.0025). On immunohistochemical analysis, intense PLA(2)-I immunoreactivity was seen in acinar cells, but not in ductal cells, in the normal pancreas. In pancreatic cancer cells, PLA(2)-I immunostaining was absent. PLA(2)-II immunostaining was visible only in some acinar and ductal cells in the normal pancreas, whereas in pancreatic cancer increased PLA(2)-II immunoreactivity was present in 65% of the cancer samples. On in situ hybridisation, weak PLA(2)-IV mRNA signals were detected in acinar and ductal cells of normal samples; these signals were present to a much greater extent in pancreatic cancer cells. The presence of PLA(2)-II in pancreatic cancer was associated with a higher degree of fibrosis (p<0.01). Furthermore, there was a significant correlation between the enhanced expression of PLA(2)-II and longer survival after surgery (p<0.03), but not of PLA(2)-IV and longer postoperative survival.These data suggest that PLA(2)-II and PLA(2)-IV are upregulated in human pancreatic cancer, and that upregulation of PLA(2)-II in pancreatic cancer covariates negatively with cancer cell growth.
Acute generalized exanthematous pustulosis associated with pseudoephedrine
Authors: M.A. Padial, J. Alvarez-Ferreira, B. Tapia, R. Blanco, C. Manas, M. Blanca, T. Bellon
Journal: British Journal of Dermatology (2004)

Acute generalized exanthematous pustulosis (AGEP) is an uncommon skin disorder most often caused by drugs. Few adverse reactions to sympathomimetic drugs have been reported, despite their extensive use. Although the aetiology of AGEP remains uncertain, recent data have reported involvement of drug‐specific T cells and interleukin (IL)‐8 production. We characterized an adverse reaction to pseudoephedrine both clinically and immunologically. Histological analysis of skin biopsies confirmed the clinical entity as AGEP, while epicutaneous tests confirmed the specificity of the reaction to the drug. Moreover, immunohistochemical studies showed a mononuclear infiltrate consisting of activated memory T cells in addition to polymorphonuclear cells. Reverse transcription‐polymerase chain reaction revealed an increased expression of IL‐8 in AGEP‐affected skin.
Perinatal and Family Risk Factors for Non-Hodgkin Lymphoma in Early Life: A Swedish National Cohort Study
Authors: C. Crump, K. Sundquist, W. Sieh, M. A. Winkleby, J. Sundquist
Journal: JNCI Journal of the National Cancer Institute (2012)

The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood. We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973–2008 who were followed for incidence of NHL through 2009 (ages 0–37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests. There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; Ptrend = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; Ptrend = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL. In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life.
Response-Independent Survival Benefit in Metastatic Colorectal Cancer: A Comparative Analysis of N9741 and AVF2107
Authors: Axel Grothey, Eric E. Hedrick, Robert D. Mass, Somnath Sarkar, Sam Suzuki, Ramesh K. Ramanathan, Herbert I. Hurwitz, Richard M. Goldberg, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2008)

In the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.For these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partial response was achieved with first-line therapy.Compared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.In both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.
Allergic lung inflammation induces pulmonary vascular hyperresponsiveness
Authors: M. Witzenrath
Journal: European Respiratory Journal (2006)

Pulmonary arterial vasoconstriction is an important early component of pulmonary hypertension. Inflammatory mechanisms play a prominent role in the pathogenesis of pulmonary hypertension. The present authors investigated the potential role of acute allergic lung inflammation for alterations in pulmonary haemodynamics. BALB/c mice were intraperitoneally sensitised to ovalbumin and challenged by ovalbumin inhalation. Subsequently, lungs were ventilated and perfused <i>ex vivo</i>, and pulmonary arterial pressure (<i>P</i><sub>pa</sub>) was continuously monitored. Isolated perfused lungs of allergen-sensitised and -challenged mice showed five-fold enhanced P<sub>pa</sub> responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in <i>P</i><sub>pa</sub> was abolished by the serotonin receptor-2A antagonist ketanserin, but not the serotonin receptor-1B antagonist GR127935. Intracellular signalling to serotonin involved phosphatidylcholine-specific phospholipase C and protein kinase C, as well as Rho-kinase, as assessed by employing the specific inhibitors D609, bisindolylmaleimide and Y27632, respectively. In addition to serotonin, impressively enhanced <i>P</i><sub>pa</sub> increases in allergic lungs were also evoked by the thromboxane receptor agonist U46619, angiotensin II and endothelin-1. In conclusion, allergic lung inflammation was accompanied by impressive pulmonary vascular hyperresponsiveness. These results suggest a possible role for allergic inflammation in the development of pulmonary arterial hypertension.
Endoscopic resection of airway benign tumors by argon plasma coagulation
Authors: George Dabar, Samir Challita
Journal: European Respiratory Journal (2012)

Benign airway tumors with central airway obstruction require immediate intervention for symptoms relief. Argon Plasma Coagulation (APC) is a cheap tool readily available in hospitals.  Four patients presented for obstructing tracheal or bronchial tumor (2008 to 2011). Initial investigations included fiberoptic bronchoscopy and CT imaging of the chest. Argon plasma was set to 35 Watt and delivered in non-contact fashion through a large fiber during rigid bronchoscopy. Initially tumor coagulation was done followed by mechanical resection and finally APC was applied to tumor base. Patients were discharged next day and followed clinically by CT imaging and bronchoscopy. All patients were reevaluated one year after ablation to eliminate recurrence.  Case1: 24 years old female presented for uncontrolled asthma. Endoscopic resection with APC revealed tracheal schwannoma.  Case2: 35 years old female, 6 month pregnant, intubated for respiratory failure due to obstructive tracheal tumor. Endoscopic resection yielded low-grade muco-epidermoid carcinoma of the trachea.  Case3: 60 years old male, smoker, with concomitant sarcomatous carcinoma of the kidney presents for dyspnea, persistent cough and obstructive lesion of the right main bronchus. Ablation by rigid bronchoscopy and APC unraveled bronchial hamartoma.  Case4: 57 years old male, smoker, presents for persistent cough. Rigid bronchoscopy and APC resection of right bronchial obstruction uncovered a hamartoma.  APC is an effective and efficient tool to use during resection of benign bronchial tumors, it9s safe to use in pregnant patient and provides immediate airway relief. Shwannoma, hamartoma and low-grade muco-epidermoid tumors can be treated with this modality.
Angiotensin converting enzyme insertion or deletion polymorphism and coronary restenosis: meta-analysis of 16 studies
Authors: F. Bonnici
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the association between genotype at the insertion or deletion polymorphism of the angiotensin converting enzyme gene and risk of coronary restenosis after percutaneous coronary intervention. <b>Design:</b> Meta-analysis of studies before July 2001 that reported on these genotypes and risk of coronary restenosis after a percutaneous coronary intervention, with or without coronary stenting. <b>Results:</b> 16 studies, involving 4631 patients undergoing a percutaneous coronary intervention, yielded 1683 patients with restenosis after a mean weighted follow up of 5.5 months. The combined odds ratio for restenosis in people with the DD genotype was 1.23 (99% confidence interval 1.03 to 1.46). When studies were grouped by size, however, the combined odds ratios for restenosis in people with the DD genotype were 1.94 (1.39 to 2.71) for studies with less than 100 cases, 1.33 (0.92 to 1.93) for studies with 100-200 cases, and 0.92 (0.72 to 1.18) for studies with more than 200 cases (trend P=0.02). Similarly, when studies were grouped by genotyping procedures, significantly larger odds ratios were found in the studies that did not conceal disease status from laboratory staff and in the studies that did not use a second polymerase chain reaction amplification to reduce genetic mistyping. <b>Conclusion:</b> Compared with other studies, larger and more rigorous studies show a weaker association between the angiotensin converting enzyme gene DD genotype and restenosis. Publication bias or detection biases can produce artefactual associations at least as large as those that might be expected for common polymorphisms in complex diseases, suggesting the need for larger and more rigorous genetic epidemiological investigations than are now customary.