tbuckley/cabot-search huggingface dataset:
Cloning of a Novel Prolyl 4-Hydroxylase Subunit Expressed in the Fibrous Cap of Human Atherosclerotic Plaque
Authors: Caroline Van Den Diepstraten, Karen Papay, Zuzana Bolender, Arthur Brown, J. Geoffrey Pickering
Journal: Circulation (2003)

The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase.We report the cloning of a novel prolyl 4-hydroxylase catalytic (alpha) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe2+ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity. Furthermore, when the recombinant protein was expressed in cells, it associated with the beta-subunit of prolyl 4-hydroxylase and could catalyze prolyl 4-hydroxylation of a collagen-like peptide. The tissue distribution was dissimilar from that of the 2 previously cloned alpha-subunits, suggesting a role beyond redundancy. Importantly, the novel gene was expressed in the fibrous cap of human carotid atherosclerotic lesions.The discovery of a novel prolyl 4-hydroxylase alpha-subunit, here termed the alpha(III)-subunit, suggests a new participant in collagen synthesis that, in view of the expression findings, may be relevant to atherosclerotic disease.
Assessing the Impact of Asthma and Exercise-Induced Bronchospasm/Exercise-Induced Asthma in the General Population: Results from the EIB Landmark Survey
Authors: S. Stoloff, G. Colice, M. Hayden, T. Craig, N. Ostrom, N. Eid, J. Parsons
Journal: Journal of Allergy and Clinical Immunology (2011)
Reduced Lecithin
Authors: Stephen Boorjian, Satish K. Tickoo, Nigel P. Mongan, Huayin Yu, Dean Bok, Robert R. Rando, David M. Nanus, Douglas S. Scherr, Lorraine J. Gudas
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Retinoids, which include vitamin A (retinol; ROL) and its derivatives, have been investigated in the treatment of bladder cancer. We have shown that expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL to retinyl esters, is reduced in several human cancers. Here we evaluated expression of LRAT protein and mRNA in normal and malignant bladder tissue specimens from human patients. We also examined the effect of retinoids on LRAT expression in bladder cancer cell lines. Experimental Design: We evaluated 49 bladder cancer specimens for LRAT protein expression using immunohistochemistry with affinity-purified antibodies to human LRAT. LRAT mRNA expression was assessed using reverse transcription-PCR in bladder specimens from an additional 16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA expression in five human bladder cancer cell lines. Results: LRAT protein was detected throughout the nonneoplastic bladder epithelium in all of the specimens. In bladder tumors, LRAT protein expression was reduced compared with the nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial tumors versus 16 of 17 (94.1%) invasive tumors (P &amp;lt; 0.001). All of the non-neoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression, compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P = 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression was induced by retinoid treatment. Conclusions: We report a significant reduction in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse correlation of LRAT mRNA and protein expression with increasing tumor stage. These data suggest that loss of LRAT expression is associated with invasive bladder cancer.
Prognosis after extension of myocardial infarct: the role of Q wave or non-Q wave infarction.
Authors: A S Maisel, S Ahnve, E Gilpin, H Henning, A L Goldberger, D Collins, M LeWinter, J Ross
Journal: Circulation (1985)

We examined whether or not subsets of patients with extension of myocardial infarct were at high risk for early and late mortality. Some data suggest increased risk in patients with non-Q wave infarcts and we hypothesized that infarct extension in this group might be associated with a poorer prognosis than that for patients with extension of Q wave infarcts. A total of 1253 patients with acute myocardial infarction who were included in our data base were followed prospectively. The patients were classified according to electrocardiographic results into the following groups: those with non-Q wave (n = 277) infarcts and those with Q-anterior (n = 462) and Q-inferior (n = 497) infarcts. Extension was diagnosed by two of the following criteria: (1) recurrent chest pain 24 hr or more after admission to the hospital, (2) new persistent electrocardiographic changes, and (3) elevation or reappearance of creatine kinase. By these criteria 85 (6%) patients had extension (8% of non-Q wave infarcts, 6% of Q-anterior infarcts, and 6% of Q-inferior infarcts). Hospital mortality in patients with extension was 15% in those with Q wave infarcts vs 43% in those with non-Q wave infarcts (p less than .01). Nine hundred and fifty-two patients were followed for 1 year. In 24% of those who did not survive 1 year there was extension of infarct; only 6% of survivors had extension (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Randomized Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine With Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer: Interim Analysis of a Phase III Trial of the Southern Italy Cooperative Oncology Group
Authors: Pasquale Comella, Giuseppe Frasci, Nicola Panza, Luigi Manzione, Giuseppe De Cataldis, Riccardo Cioffi, Luigi Maiorino, Enrico Micillo, Vito Lorusso, Gaetano Di Rienzo, Gianfranco Filippelli, Alfredo Lamberti, Michele Natale, Domenico Bilancia, Gianpaolo Nicolella, Angelo Di Nota, Giuseppe Comella
Journal: Journal of Clinical Oncology (2000)

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non–small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of ≤ 70 years, and an Eastern Cooperative Oncology Group performance status ≤ 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m 2 , gemcitabine 1,000 mg/m 2 , and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m 2 on day 1 and gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m 2 on days 1 and 29 and vinorelbine 30 mg/m 2 /wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P &lt; .01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST &gt; 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.
Codon Usage and the Origin of P Elements
Authors: Emmanuelle Lerat, Christian Biémont, Pierre Capy
Journal: Molecular Biology and Evolution (2000)

The authors of a recent comparison of the P transposable element and three genes of Drosophila melanogaster and Drosophila willistoni suggested that the codon usage of the D. melanogaster P element is similar to that of D. willistoni genes (Powell and Gleason 1996).They concluded that this could be further evidence of the recent horizontal transfer of the P element from D. willistoni to D. melanogaster indicated by several previous findings (Clark and Kidwell 1997).More specifically, it was shown that D. willistoni genes tend to be T-ending-codon genes, whereas those of D. melanogaster tend to be C-ending-codon genes.The transposase genes of the P elements from both species was found to be AT-ending-codon genes, and one explanation for this may be that the P element of D. melanogaster originated from D. willistoni.This hypothesis assumes that the codon usage in transposable elements (TEs) and that in the host genome are similar.However, analysis of a large number of genes and TEs in D. melanogaster suggests that the T-ending-codon feature of the P element could be a general characteristic of all TEs in Drosophila species and independent of the host genome (Shields and Sharp 1989).We extracted from the GenBank DNA sequence database the sequences of six genes common to D. melanogaster and D. willistoni: Alcohol dehydrogenase (Adh, M11290 and L08648), Amylase-related gene (amyrel, U69607 and AF039560), superoxide dismutase (SOD, Y00367 and L13281), xanthine dehydrogenase (Xdh, Y00307 and AF058985), glycerol 3 phosphate dehydrogenase (Gpdh, X80204 and L37038), and period (per, M30114 and U51055).The sequences of the last three genes have been only partially determined for D. willistoni.We therefore used only the homologous regions in both species to avoid bias due to differences in gene length (Moryiama and Powell 1998;Duret and Mouchiroud 1999).P elements, which have been reported in distantly related Drosophila species, were also added.These elements were described in Drosophila bifasciata (Hagemann, Miller, and Pinkser 1992), Drosophila subobscura (Paricio et al. 1991), and Scaptomyza pallida (Simonelig and Anxolabe ´he `re 1991).All sequences of RNA (class I) and DNA (class II) elements described in the species previously mentioned were also used to compare P element features with those of other elements.
Endoscopic work-up of early Barrett’s neoplasia
Authors: W. Curvers, A. Bansal, P. Sharma, J. Bergman
Journal: Endoscopy (2008)

In recent years, endoscopic therapy of early Barrett's esophagus neoplasia has become a safe and effective alternative to esophagectomy [1] [2] [3] [4]. Only patients with high-grade intraepithelial neoplasia (HGIN) or mucosal cancer are eligible for curative endoscopic treatment. Lesions that invade the submucosa are associated with a significant risk of lymph node metastases and are therefore preferably to be treated surgically. There are two main types of endoscopic therapy: endoscopic resection and endoscopic ablation. An important difference between these two modalities is that endoscopic resection permits histopathological evaluation of the resection specimen, whereas this safeguard is missing with endoscopic ablation therapy. A practical approach is to resect the areas with endoscopically visible lesions by endoscopic resection followed by ablation of residual Barrett's esophagus [5] [6] [7] [8]. This assumes that if the histopathological evaluation of the most involved areas is favorable, the chances that the residual Barrett's esophagus harbors more advanced neoplasia elsewhere are small and thus additional ablation therapy without histological correlation is justified. It is, therefore, crucial that the most involved area in the Barrett's esophagus is indeed identified and resected rather than overlooked and ablated, since this may lead to undertreatment of submucosal lesions.
Neural Blockade by Local Anesthetics
Authors: Rudolph H. de Jong
Journal: JAMA (1977)

Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base penetrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base—proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ratio is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged. (<i>JAMA</i>238:1383-1385, 1977)
Glucocorticoid receptors are downregulated in hepatic T lymphocytes in rats with experimental cholangitis
Authors: K Tjandra
Journal: Gut (2003)

and aims: Primary sclerosing cholangitis is a Th1 cytokine driven disease with a poor clinical responsiveness to glucocorticoid therapy. We have previously documented elevated circulating glucocorticoid levels in cholestatic rats and in addition have noted increased hepatic expression of the Th1 cytokine interferon gamma (IFN-gamma) in a rat model of cholangitis. Therefore, we examined the relationship between circulating glucocorticoid levels, hepatic IFN-gamma expression, and hepatic T cell glucocorticoid receptor (GR) expression in a rat model of cholangitis to provide insight into the possible mechanism underlying hepatic T cell glucocorticoid resistance in cholangitic diseases.Cholangitis was induced in male Sprague-Dawley rats by oral administration of low dose alpha-naphthylisothiocyanate (ANIT). On day 14, ANIT fed and control rats were sacrificed, serum collected, and hepatic, splenic, and peripheral blood T lymphocytes isolated for GR expression, as determined by reverse transcription-polymerase chain reaction and western blotting.Circulating glucocorticoid levels were markedly elevated in ANIT fed rats. Hepatic T lymphocyte GR mRNA and protein levels were significantly reduced in ANIT treated rats compared with controls. In contrast, GR mRNA and protein expression in splenic and circulating T lymphocytes was similar in both groups. Furthermore, reduced hepatic T cell GR expression in ANIT fed rats was associated with reduced hepatic CD4(+) T cell sensitivity to dexamethasone inhibitory effects (that is, inhibition of interleukin 2 receptor expression).We conclude that hepatic T lymphocyte resistance to elevated endogenous glucocorticoid levels in rats with experimental cholangitis appears, in part, to be mediated by decreased GR expression.
Preclinical Safety of RNAi-Mediated HTT Suppression in the Rhesus Macaque as a Potential Therapy for Huntington's Disease
Authors: Jodi L McBride, Mark R Pitzer, Ryan L Boudreau, Brett Dufour, Theodore Hobbs, Sergio R Ojeda, Beverly L Davidson
Journal: Molecular Therapy (2011)

To date, a therapy for Huntington's disease (HD), a genetic, neurodegenerative disorder, remains elusive. HD is characterized by cell loss in the basal ganglia, with particular damage to the putamen, an area of the brain responsible for initiating and refining motor movements. Consequently, patients exhibit a hyperkinetic movement disorder. RNA interference (RNAi) offers therapeutic potential for this disorder by reducing the expression of HTT, the disease-causing gene. We have previously demonstrated that partial suppression of both wild-type and mutant HTT in the striatum prevents behavioral and neuropathological abnormalities in rodent models of HD. However, given the role of HTT in various cellular processes, it remains unknown whether a partial suppression of both alleles will be safe in mammals whose neurophysiology, basal ganglia anatomy, and behavioral repertoire more closely resembles that of a human. Here, we investigate whether a partial reduction of HTT in the normal non-human primate putamen is safe. We demonstrate that a 45% reduction of rhesus HTT expression in the mid- and caudal putamen does not induce motor deficits, neuronal degeneration, astrogliosis, or an immune response. Together, these data suggest that partial suppression of wild-type HTT expression is well tolerated in the primate putamen and further supports RNAi as a therapy for HD. To date, a therapy for Huntington's disease (HD), a genetic, neurodegenerative disorder, remains elusive. HD is characterized by cell loss in the basal ganglia, with particular damage to the putamen, an area of the brain responsible for initiating and refining motor movements. Consequently, patients exhibit a hyperkinetic movement disorder. RNA interference (RNAi) offers therapeutic potential for this disorder by reducing the expression of HTT, the disease-causing gene. We have previously demonstrated that partial suppression of both wild-type and mutant HTT in the striatum prevents behavioral and neuropathological abnormalities in rodent models of HD. However, given the role of HTT in various cellular processes, it remains unknown whether a partial suppression of both alleles will be safe in mammals whose neurophysiology, basal ganglia anatomy, and behavioral repertoire more closely resembles that of a human. Here, we investigate whether a partial reduction of HTT in the normal non-human primate putamen is safe. We demonstrate that a 45% reduction of rhesus HTT expression in the mid- and caudal putamen does not induce motor deficits, neuronal degeneration, astrogliosis, or an immune response. Together, these data suggest that partial suppression of wild-type HTT expression is well tolerated in the primate putamen and further supports RNAi as a therapy for HD.
The Transition to Self-Compatibility in Arabidopsis thaliana and Evolution within S-Haplotypes over 10 Myr
Authors: Jesper S. Bechsgaard, Vincent Castric, Deborah Charlesworth, Xavier Vekemans, Mikkel H. Schierup
Journal: Molecular Biology and Evolution (2006)

A recent investigation found evidence that the transition of Arabidopsis thaliana from ancestral self-incompatibility (SI) to full self-compatibility occurred very recently and suggested that this occurred through a selective fixation of a nonfunctional allele (ΨSCR1) at the SCR gene, which determines pollen specificity in the incompatibility response. The main evidence is the lack of polymorphism at the SCR locus in A. thaliana. However, the nearby SRK gene, which determines stigma specificity in self-incompatible Brassicaceae species, has extremely high sequence diversity, with 3 very divergent SRK haplotypes, 2 of them present in multiple strains. Such high diversity is extremely unusual in this species, and it suggests the possibility that multiple, different SRK haplotypes may have been preserved from A. thaliana's self-incompatible ancestor. To study the evolution of S-haplotypes in the A. thaliana lineage, we searched the 2 most closely related Arabidopsis species Arabidopsis lyrata and Arabidopsis halleri, in which most populations have retained SI, and found SRK sequences corresponding to all 3 A. thaliana haplogroup sequences. Our molecular evolutionary analyses of these 3 S-haplotypes provide an independent estimate of the timing of the breakdown of SI and again exclude an ancient transition to selfing in A. thaliana. Comparing sequences of each of the 3 haplogroups between species, we find that 2 of the 3 SRK sequences (haplogroups A and B) are similar throughout their length, suggesting that little or no recombination with other SRK alleles has occurred since these species diverged. The diversity difference between the SCR and SRK loci in A. thaliana, however, suggests crossing-over, either within SRK or between the SCR and SRK loci. If the loss of SI involved fixation of the ΨSCR1 sequence, the exchange must have occurred during its fixation. Divergence between the species is much lower at the S-locus, compared with reference loci, and we discuss two contributory possibilities. Introgression may have occurred between A. lyrata and A. halleri and between their ancestral lineage and A. thaliana, at least for some period after their split. In addition, the coalescence times of sequences of individual S-haplogroups are expected to be less than those of alleles at non–S-loci.
Grass Pollen Allergic Patients Treated with Subcutaneous Immunotherapy (SCIT) Have Elevated Src-Homology-2 Domain-Containing Inositol-5'phosphatase-1 (SHIP-1) Protein Levels During the Pollen Season
Authors: Mohammad Nasiri, Becky Vonakis, Johannes M. Schmid, Hans Jurgen Hoffmann
Journal: Journal of Allergy and Clinical Immunology (2013)
Quantitative Comparison of Optical Coherence Tomography after Pegaptanib or Bevacizumab in Neovascular Age-Related Macular Degeneration
Authors: Sandra Joeres, Kevin Kaplowitz, Jacob W Brubaker, Paul G Updike, Allyson T Collins, Alexander C Walsh, Peggy W Romano, Srinivas R Sadda
Journal: Ophthalmology (2007)
Neuropsychological Performance in Survivors of Breast Cancer More Than 20 Years After Adjuvant Chemotherapy
Authors: Vincent Koppelmans, Monique M.B. Breteler, Willem Boogerd, Caroline Seynaeve, Chad Gundy, Sanne B. Schagen
Journal: Journal of Clinical Oncology (2012)

Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment.This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis.The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance.Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting.