tbuckley/cabot-search huggingface dataset:
Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype
Authors: Thomas G. Gabuzda, Marc A. Schuman, Ruth K. Silver, Hugh B. Lewis
Journal: Journal of Clinical Investigation (1968)

This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with (59)Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days. Infusions of plasma with high erythropoietin titre induced the formation of relatively large quantities of Hb C in erythroid cells of nonanemic sheep, demonstrating the central importance of a humoral mechanism in the change of expression of the hemoglobin genes. THE FOLLOWING CONCLUSIONS WERE DRAWN: hemoglobin phenotype is determined at a stem cell level. Erythroid stem cells appear to undergo gradual renewal. The identity of the plasma factor which induces Hb C formation is not yet known; it is not present in plasma from nonanemic sheep, and its production is not dependent upon hemoglobin genotype. If the plasma factor turns out to be erythropoietin, then this hormone must have an important influence on the pool of erythroid stem cells.
Oxygen-induced contraction in the guinea pig neonatal ductus arteriosus.
Authors: M J Roulet, R F Coburn
Journal: Circulation Research (1981)

We investigated the mechanism of oxygen-induced contractions in ductus arteriosus isolated from neonatal guinea pig. A preparation equilibrated at low Po2 (less than 40 mm Hg) displayed a steady membrane potential of -54.8 mV. Application of oxygen (Po2 (less than approximately or equal to 300 mm Hg) resulted in: (1) stepwise development of tension coupled to action potentials and (2) sustained membrane depolarization to -32.9 mV associated with tonic contraction. Mechanical sensitivity to oxygen persisted at any[K]o up to 126 mM, and tension was always larger at a given [K]o or a given membrane potential with high Po2 than with low Po2. The change in membrane potential per decade change in [K]o was 35 mV at low Po2 and 16 mV at high Po2. Oxygen contractions occurred when the ductal strips were bathed in K-free media or exposed to ouabain. We conclude that oxygen caused a conductance change in the sarcolemma resulting in depolarization, which is coupled to contraction. There is also evidence of a membrane potential-independent contraction mechanism.
Cloning of the esterase-5 locus from Drosophila pseudoobscura and comparison with its homologue in D. melanogaster.
Authors: J P Brady, R C Richmond, J G Oakeshott
Journal: Molecular Biology and Evolution (1990)

A clone of the esterase-5 (Est-5) gene from Drosophila pseudoobscura has been isolated by hybridization to the cloned Est-6 gene of D. melanogaster. Southern analysis and sequencing of the cloned DNA revealed three regions of similarity to Est-6 that have been tentatively identified as genes, Est-5A, Est-5B, and Est-5C. Introduction of each of the three genes separately into D. melanogaster by P-element transformation has demonstrated that Est-5B encodes an enzyme with the same physical properties as EST 5 in D. pseudoobscura. Sequence analysis indicates that Est-5B encodes a 545-amino-acid protein and is composed of two exons separated by a 55-bp intron in the same position as the 51-bp intron in Est-6. Comparison of the Est-5B coding region with that of Est-6 reveals an overall similarity (73% at both the nucleotide and amino acid levels) that is substantially lower than that for other genes sequenced in both of these species. Total nucleotide and nonsynonymous site differences between Est-6 and Est-5B are more abundant in the second exon than in the first, suggesting differential effects of selection or mutation on these two exons. Comparisons of the 5'-flanking DNA of Est-5B and Est-6 reveal four short conserved sequence elements, but the remaining upstream sequences show no significant similarity. Conservation in the 3'-flanking DNA is limited to the presence of two polyadenylation sites that may correlate with the existence of two transcripts from both Est-5B and Est-6. The patterns of nucleotide substitutions and amino acid replacements between Est-5B and Est-6 are consistent with the hypothesis that mutation and genetic drift are responsible for the differences between these two genes.
Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus
Authors: Libin Rong, Harel Dahari, Ruy M. Ribeiro, Alan S. Perelson
Journal: Science Translational Medicine (2010)

Computational modeling suggests that the rapid emergence of resistance to drugs against hepatitis C virus is a result of preexisting resistant virus and potent suppression of wild-type virus.
DNA Mismatch Repair Status and Colon Cancer Recurrence and Survival in Clinical Trials of 5-Fluorouracil-Based Adjuvant Therapy
Authors: F. A. Sinicrope, N. R. Foster, S. N. Thibodeau, S. Marsoni, G. Monges, R. Labianca, G. Yothers, C. Allegra, M. J. Moore, S. Gallinger, D. J. Sargent
Journal: JNCI Journal of the National Cancer Institute (2011)

Approximately 15% of colorectal cancers develop because of defective function of the DNA mismatch repair (MMR) system. We determined the association of MMR status with colon cancer recurrence and examined the impact of 5-fluorouracil (FU)-based adjuvant therapy on recurrence variables. We included stage II and III colon carcinoma patients (n = 2141) who were treated in randomized trials of 5-FU-based adjuvant therapy. Tumors were analyzed for microsatellite instability by polymerase chain reaction and/or for MMR protein expression by immunohistochemistry to determine deficient MMR (dMMR) or proficient MMR (pMMR) status. Associations of MMR status and/or 5-FU-based treatment with clinicopathologic and recurrence covariates were determined using χ 2 or Fisher Exact or Wilcoxon rank-sum tests. Time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were analyzed using univariate and multivariable Cox models, with the latter adjusted for covariates. Tumors showing dMMR were categorized by presumed germline vs sporadic origin and were assessed for their prognostic and predictive impact. All statistical tests were two-sided. In this study population, dMMR was detected in 344 of 2141 (16.1%) tumors. Compared with pMMR tumors, dMMR was associated with reduced 5-year recurrence rates (33% vs 22%; P < .001), delayed TTR ( P < .001), and fewer distant recurrences (22% vs 12%; P < .001). In multivariable models, dMMR was independently associated with delayed TTR (hazard ratio = 0.72, 95% confidence interval = 0.56 to 0.91, P = .005) and improved DFS ( P = .035) and OS ( P = .031). In stage III cancers, 5-FU-based treatment vs surgery alone or no 5-FU was associated with reduced distant recurrence for dMMR tumors (11% vs 29%; P = .011) and reduced recurrence to all sites for pMMR tumors ( P < .001). The dMMR tumors with suspected germline mutations were associated with improved DFS after 5-FU-based treatment compared with sporadic tumors where no benefit was observed ( P = .006). Patients with dMMR colon cancers have reduced rates of tumor recurrence, delayed TTR, and improved survival rates, compared with pMMR colon cancers. Distant recurrences were reduced by 5-FU-based adjuvant treatment in dMMR stage III tumors, and a subset analysis suggested that any treatment benefit was restricted to suspected germline vs sporadic tumors.
<i>Clostridium difficile</i> and Methicillin-Resistant <i>Staphylococcus aureus:</i> Emerging Concepts in Vaccine Development
Authors: David C. Kaslow, John W. Shiver
Journal: Annual Review of Medicine (2010)

Both Clostridium difficile and Staphylococcus aureus asymptomatically colonize a significant percentage of humans, particularly during the first year of life. The epidemiology of both has been and continues to be quite dynamic; presently, we are in the midst of epidemics of infections by C. difficile and S. aureus. These ancient microbes are now armed with more potent virulence factors, which have extended their reach from the hospital into community settings, and from the elderly and debilitated hosts into the younger and otherwise healthy population. This review presents some emerging concepts that will likely shape efforts to develop active and passive immunization interventions in response to the reemergence of these bacterial pathogens.
PPARγ in the endothelium regulates metabolic responses to high-fat diet in mice
Authors: Takeshi Kanda, Jonathan D. Brown, Gabriela Orasanu, Silke Vogel, Frank J. Gonzalez, Juliano Sartoretto, Thomas Michel, Jorge Plutzky
Journal: Journal of Clinical Investigation (2008)

Although endothelial dysfunction, defined as abnormal vasoreactivity, is a common early finding in individuals with type 2 diabetes, the endothelium has not been known to regulate metabolism. As PPARγ, a transcriptional regulator of energy balance, is expressed in endothelial cells, we set out to investigate the role of endothelial cell PPARγ in metabolism using mice that lack PPARγ in the endothelium and BM (γEC/BM-KO). When γEC/BM-KO mice were fed a high-fat diet, they had decreased adiposity and increased insulin sensitivity compared with control mice, despite increased serum FFA and triglyceride (TG) levels. After fasting or olive oil gavage, γEC/BM-KO mice exhibited significant dyslipidemia and failed to respond to the FFA and TG lowering effects of the PPARγ agonist rosiglitazone. BM transplantation studies, which reconstituted hematopoietic PPARγ, established that these metabolic phenotypes were due to endothelial PPARγ deficiency. We further found that the impairment in TG-rich lipoprotein metabolism in γEC/BM-KO mice was associated with fatty acid–mediated lipoprotein lipase inhibition and changes in a PPARγ-regulated endothelial cell transcriptional program. Despite their metabolic improvements, high-fat diet–fed γEC/BM-KO mice had impaired vasoreactivity. Taken together, these data suggest that PPARγ in the endothelium integrates metabolic and vascular responses and may contribute to the effects of PPARγ agonists, thus expanding what endothelial function and dysfunction may entail.
(21) Can pemphigus be cured?
Authors: J.S. Pasricha
Journal: British Journal of Dermatology (1987)

In 1981, we started using an arbitrarily designed regime for pemphigus, consisting of 100 mg dexamethasone dissolved in 5% glucose given by an intravenous drip over 1 h, daily on three consecutive days (pulse) and repeated every month. This was later modified with the addition of 500 mg cyclophosphamide along with the dexamethasone on the first day and 50 mg cyclophosphamide daily orally in between the pulses. Treatment can be divided into four phases. During phase I, the patient continues to develop relapses of pemphigus within a variable number of days after the pulse but the lesions heal quickly. The relapses become progressively milder and stop after a few months, but the dexamethasone-cyclophosphamide pulses are continued once a month; this is called phase II, and lasts from 6 to 9 months. In phase III, the monthly pulses are stopped but the patient continues to take 50 mg cyclophosphamide orally per day. After a year or so, all treatment is withdrawn and the patient is observed for any relapses (phase IV). Fifty-seven patients have been enrolled in the last 4 years. Four are now without any treatment (phase IV), 12 are only on 50 mg cyclophosphamide a day (phase III), another 12 are in remission but still taking dexamethasone-cyclophosphamide (phase II), and 24 patients still have active disease (phase I). Four patients have been lost to follow-up and one has died. Side-effects of corticosteroids have not been observed. Our results indicate that it is possible to induce long remissions, and maybe cure, pemphigus with this regime.
Class II transactivator regulates the expression of multiple genes involved in antigen presentation.
Authors: C H Chang, R A Flavell
Journal: The Journal of Experimental Medicine (1995)

CIITA (a major histocompatibility complex [MHC] class II transactivator) has been shown to be required for the expression of MHC class II genes in both B cells and interferon gamma-inducible cells. Here we demonstrate that CIITA not only activates MHC class II genes but also genes required for antigen presentation. Mutant HeLa cells, defective in the expression of classic MHC class II genes, invariant chain, and the newly described human histocompatibility leukocyte antigen-DM genes, were used to study the role of CIITA in the regulation of these genes. Upon transfection with CIITA cDNA, the mutant cells expressed all three genes, suggesting that CIITA is a global regulator for the expression of genes involved in antigen presentation.
Update in Mechanical Ventilation 2010
Authors: Jean-Christophe M. Richard, Jean-Claude Lefebvre, Didier Tassaux, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

This article reviews selected contributions published in 2010 regarding epidemiology, clinical use, and consequences of invasive and noninvasive mechanical ventilation (MV). This includes the use of protective ventilation and of different modes, some specific risks of MV, such as ventilator-induced diaphragm dysfunction, and the importance of spontaneous breathing activity under MV, with or without sedation.
Methodologic Diligence Is Needed to Define and Validate Tumor-Size Response Metrics to Predict Overall Survival in First-Line Metastatic Colorectal Cancer
Authors: Ulrich R. Mansmann, Rüdiger P. Laubender
Journal: Journal of Clinical Oncology (2013)

(TTG)asatumor-sizeresponsemetrictopredictoverallsurvival(OS) in patients with first-line metastatic colorectal cancer treated with irinotecan,fluorouracil,andleucovorinboluswithorwithoutbevacizumab.Longitudinaltumor-sizedatafromatotalof991patientswith a median number of five measurements per patient is presented. A tumor growth inhibition model 2 is fit to individual tumor growth curvesovertimefromwhichdifferenttumor-sizeresponsemetricsare
Effect of Raloxifene on Serum Triglycerides in Women With a History of Hypertriglyceridemia While on Oral Estrogen Therapy
Authors: Molly C. Carr, Robert H. Knopp, John D. Brunzell, Barbara S. Wheeler, Xiaodong Zhu, Mark Lakshmanan, Amy S. Rosen, Pamela W. Anderson
Journal: Diabetes Care (2005)

OBJECTIVE—Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH DESIGN AND METHODS—This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49–73 years, with a documented history of oral estrogen–induced hypertriglyceridemia (serum triglycerides ≥3.39 mmol/l [≥300 mg/dl]). RESULTS—At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (≥11.3 mmol/l [≥1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL2 levels (P = 0.013 and 0.03, respectively). CONCLUSIONS—Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.
New treatment options in ankylosing spondylitis: a role for anti-TNFα therapy
Authors: J Sieper, J Braun
Journal: Annals of the Rheumatic Diseases (2001)

Anti-TNFalpha treatment seems to be highly effective in AS. The results available indicate that this treatment is at least as effective as in RA. Furthermore, because no other treatments are available for AS--in contrast with RA or psoriatic arthritis--infliximab may even become a first line immunosuppressive treatment in patients with severe active AS. A dose of 5 mg/kg body weight seems to be required and intervals between 6 and 12 weeks seem to be necessary depending on the disease activity. It remains to be seen what the long term effects will be, whether the patients benefit from long term treatment, and whether radiological progression and ankylosis can be stopped. Allergy, lupus-like diseases, and tuberculosis are rare side effects which need to be considered. At first glance, the possible benefits of anti-TNFalpha treatment seem to outweigh these shortcomings, including the high cost.
Treatment of Recurrent Erythema Nodosum Leprosum with Infliximab
Authors: William R. Faber, Annigje J. Jensema, Wouter F.M. Goldschmidt
Journal: New England Journal of Medicine (2006)

To the Editor: A 52-year-old woman with multibacillary (borderline lepromatous) leprosy, who had been treated intermittently with dapsone since 1965, presented to our department in 1996 with active...
Gene Expression Signatures Differentiate Ovarian/Peritoneal Serous Carcinoma from Diffuse Malignant Peritoneal Mesothelioma
Authors: Ben Davidson, Zhen Zhang, Lilach Kleinberg, Mei Li, Vivi Ann Flørenes, Tian-Li Wang, Ie-Ming Shih
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Ovarian/primary peritoneal serous carcinoma (OC/PPC) and diffuse peritoneal malignant mesothelioma (DMPM) are highly aggressive tumors that are closely related morphologically and histogenetically. It remains unclear whether both tumors are molecularly distinct neoplasms. The current study compared global gene expression patterns in OC/PPC and DMPM. Experimental Design: Ten OC/PPC and five DMPM effusions were analyzed for gene expression profiles using the Affymetrix U133 Plus 2 arrays and the dCHIP analysis program. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Results: Unsupervised hierarchical clustering using all 54,675 genes in the array classified the samples into two groups: DMPM specimens versus OC/PPC specimens. A total of 189 genes that were differentially expressed in these two groups were selected based on statistical significance. Genes overexpressed in DMPM (n = 68) included calretinin, vitronectin, claudin 15, α4 laminin, hyaluronan synthase 1, cadherin 11, RAB7, v-maf, and the epidermal growth factor–containing fibulin-like extracellular matrix protein 1. Genes overexpressed in OC/PPC (n = 121) included insulin-like growth factor II (IGF-II); IGF-II binding protein 3; cyclin E1; folate receptors 1 and 3; RAB25; MUC4; endothelin-1; CD24; kallikreins 6, 7, and 8; claudins 3, 4, and 6; Notch3; and MMP-7. Quantitative real-time PCR validated the differential expression of 13 genes, and immunohistochemistry confirmed the differences for four gene products. Conclusions: Expression profiling separates OC/PPC from DMPM and identifies a number of genes that are differentially expressed in these tumors. The molecular signatures unique to OC/PPC and DMPM should provide a molecular basis to study both tumors and new potential markers for facilitating their differential diagnosis.
THE VACUOLATING VIRUS OF MONKEYS
Authors: W. H. Gaylord, G.-D. Hsiung
Journal: The Journal of Experimental Medicine (1961)

Cells infected with the vacuolating virus, SV(40), respond by swelling to several times their normal volume. Within enlarged nuclei, virus-containing inclusions appear which are acidophilic and Feulgen-positive. The formation of nuclear inclusions is followed by the appearance of cytoplasmic vacuoles and then shrinkage of the cell. Inclusions were found to exhibit unique double staining when a light-green counterstain was used in the Feulgen reaction. The virus is of low electron density, round, and 300 A in diameter. It occurs in large numbers, singly and in short chains, and it appears to multiply at the expense of chromatin.
Herpes-Type Virus Particles in Tissue Culture of Kaposi's Sarcoma From Different Geographic Regions2
Authors: G. Giraldo, E. Beth, F. Haguenau
Journal: JNCI Journal of the National Cancer Institute (1972)

Typical herpes-type virus particles were observed in 5 of 8 selected tissue culture lines derived from different cases of Kaposi's sarcoma from 2 equatorial African regions, Congo and Uganda. Common and different traits of cellular morphology related to viral involvement were found. In one line, morphologic aspects and preliminary immunologic characterization suggested a virus resembling cytomegalovirus. The other 4 cases presented one important trait in common: The appearance of viruses (at an early stage in lines 13, 16, 19) in undifferentiated cells that resembled fibroblastoid or macrophage elements.
Testing Founder Effect Speciation: Divergence Population Genetics of the Spoonbills Platalea regia and Pl. minor (Threskiornithidae, Aves)
Authors: C. K. L. Yeung, P.-W. Tsai, R. T. Chesser, R.-C. Lin, C.-T. Yao, X.-H. Tian, S.-H. Li
Journal: Molecular Biology and Evolution (2010)

Although founder effect speciation has been a popular theoretical model for the speciation of geographically isolated taxa, its empirical importance has remained difficult to evaluate due to the intractability of past demography, which in a founder effect speciation scenario would involve a speciational bottleneck in the emergent species and the complete cessation of gene flow following divergence. Using regression-weighted approximate Bayesian computation, we tested the validity of these two fundamental conditions of founder effect speciation in a pair of sister species with disjunct distributions: the royal spoonbill Platalea regia in Australasia and the black-faced spoonbill Pl. minor in eastern Asia. When compared with genetic polymorphism observed at 20 nuclear loci in the two species, simulations showed that the founder effect speciation model had an extremely low posterior probability (1.55 × 10(-8)) of producing the extant genetic pattern. In contrast, speciation models that allowed for postdivergence gene flow were much more probable (posterior probabilities were 0.37 and 0.50 for the bottleneck with gene flow and the gene flow models, respectively) and postdivergence gene flow persisted for a considerable period of time (more than 80% of the divergence history in both models) following initial divergence (median = 197,000 generations, 95% credible interval [CI]: 50,000-478,000, for the bottleneck with gene flow model; and 186,000 generations, 95% CI: 45,000-477,000, for the gene flow model). Furthermore, the estimated population size reduction in Pl. regia to 7,000 individuals (median, 95% CI: 487-12,000, according to the bottleneck with gene flow model) was unlikely to have been severe enough to be considered a bottleneck. Therefore, these results do not support founder effect speciation in Pl. regia but indicate instead that the divergence between Pl. regia and Pl. minor was probably driven by selection despite continuous gene flow. In this light, we discuss the potential importance of evolutionarily labile traits with significant fitness consequences, such as migratory behavior and habitat preference, in facilitating divergence of the spoonbills.