tbuckley/cabot-search huggingface dataset:
Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes
Authors: E Maneiro
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the effect of nitric oxide (NO) on mitochondrial activity and its relation with the apoptosis of human articular chondrocytes.Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities, and mitochondrial membrane potential (Delta psi m). The activities of the mitochondrial respiratory chain (MRC) complexes (complex I: NADH CoQ(1) reductase, complex II: succinate dehydrogenase, complex III: ubiquinol cytochrome c reductase, complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from normal cartilage. The Delta psi m was measured by 5,5',6,6'-tetracholoro-1,1',3,3'-tetraethylbenzimidazole carbocyanide iodide (JC-1) using flow cytometry. Apoptosis was analysed by flow cytometry. The mRNA expression of caspases was analysed by ribonuclease protection analysis and the detection of protein synthesis by western blotting. Sodium nitroprusside (SNP) was used as an NO compound donor.SNP at concentrations higher than 0.5 mmol/l for 24 hours induced cellular changes characteristic of apoptosis. SNP elicited mRNA expression of caspase-3 and caspase-7 and down regulated bcl-2 synthesis in a dose and time dependent manner. Furthermore, 0.5 mM SNP induced depolarisation of the mitochondrial membrane at 5, 12, and 24 hours. Analysis of the MRC showed that at 5 hours, 0.5 mM SNP reduced the activity of complex IV by 33%. The individual inhibition of mitochondrial complex IV with azide modified the Delta psi m and induced apoptosis.This study suggests that the effect of NO on chondrocyte survival is mediated by its effect on complex IV of the MRC.
T-T interactions in the induction of suppressor and helper T cells: analysis of membrane phenotype of precursor and amplifier cells.
Authors: M Feldmann, P C Beverley, J Woody, I F McKenzie
Journal: The Journal of Experimental Medicine (1977)

The Ly and Ia phenotypes of T lymphocytes involved in the in vitro generation of helper and suppressor cells were identified. The precursors of both cells are found in adult thymectomized spleen. Helper precursors are Ly-1+2-3-Ia-, while suppressor precursors are Ly-1-2+3+Ia-, although the suppressor effector is Ia+. In both cases a second 'amplifier' cell is required for differentiation of precursors to occur. This cell is found in anti-lymphocyte serum-treated spleen and has the phenotype Ly-1+2+3+Ia-.
Blockade of rabbit atrial sodium channels by lidocaine. Characterization of continuous and frequency-dependent blocking.
Authors: F R Gilliam, C F Starmer, A O Grant
Journal: Circulation Research (1989)

Lidocaine block of the cardiac sodium channel is believed to be primarily a function of channel state. For subthreshold potentials, block is limited to the inactivated state, whereas above threshold, block results from the combination of open- and inactivated-state block. Since, in the absence of drug, inactivation develops with time constants that vary from several hundred milliseconds to a few milliseconds as potential is varied from subthreshold to strongly depolarized levels, we would predict a similar voltage dependence of at least a fraction of block. Prior theoretical analyses from our laboratory suggest that there should be a direct parallel between blockade determined with a single pulse and trains of pulses. We tested these predictions by measuring the blockade of sodium current in cultured atrial myocytes during exposure to 80 microM lidocaine. We selected two test potentials for most of our studies, -80 mV, which was clearly in the subthreshold range of potentials, and -20 mV, which was close to the peak of the current-voltage curve. With single pulses of increasing duration, block developed with a single exponential time course and with time constants that decreased from 694 +/- 117 msec at -80 mV to 373 +/- 54 msec at -20 mV. In the absence of drug, inactivation developed with a time constant 176 +/- 17 at -80 mV and 2.9 +/- .5 msec at -20 mV. Despite the much slower onset of inactivation at -80 mV, no second-order delay in block development was observed. This suggests that at -80 mV block is occurring to a channel conformation that is accessed without delay rather than the classical inactivated state. We compared the kinetics of block during a single continuous pulse with trains of pulses at -20 mV. The rate of block onset was faster during the pulse trains, suggesting an element of "activated state" block. We computed shifts in apparent inactivation from observed steady-state blockade. The computed shifts agree well with those observed, indicating that shifts in apparent inactivation result largely from voltage-sensitive equilibrium blockade. The classical states described in the Hodgkin-Huxley formalism may be too restrictive to fully describe the voltage- and time-dependent block of cardiac sodium channels.
Organelle Genome Complexity Scales Positively with Organism Size in Volvocine Green Algae
Authors: David Roy Smith, Takashi Hamaji, Bradley J.S.C. Olson, Pierre M. Durand, Patrick Ferris, Richard E. Michod, Jonathan Featherston, Hisayoshi Nozaki, Patrick J. Keeling
Journal: Molecular Biology and Evolution (2013)

It has been argued that for certain lineages, noncoding DNA expansion is a consequence of the increased random genetic drift associated with long-term escalations in organism size. But a lack of data has prevented the investigation of this hypothesis in most plastid-bearing protists. Here, using newly sequenced mitochondrial and plastid genomes, we explore the relationship between organelle DNA noncoding content and organism size within volvocine green algae. By looking at unicellular, colonial, and differentiated multicellular algae, we show that organelle DNA complexity scales positively with species size and cell number across the volvocine lineage. Moreover, silent-site genetic diversity data suggest that the volvocine species with the largest cell numbers and most bloated organelle genomes have the smallest effective population sizes. Together, these findings support the view that nonadaptive processes, like random genetic drift, promote the expansion of noncoding regions in organelle genomes.
Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics
Authors: Jian Gang Zhang, Junichi Eguchi, Carol A. Kruse, German G. Gomez, Habib Fakhrai, Stephanie Schroter, Wenxue Ma, Neil Hoa, Boris Minev, Christina Delgado, H. Terry Wepsic, Hideho Okada, Martin R. Jadus
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Allogeneic glioma cell lines that are partially matched to the patient at class I human leukocyte antigen (HLA) loci and that display tumor-associated antigens (TAA) or antigenic precursors [tumor antigen precursor proteins (TAPP)] could be used for generating whole tumor cell vaccines or, alternatively, for extraction of TAA peptides to make autologous dendritic cell vaccines. Experimental Design: Twenty human glioma cell lines were characterized by molecular phenotyping and by flow cytometry for HLA class I antigen expression. Twelve of the 20 cell lines, as well as analyses of freshly resected glioma tissues, were further characterized for protein and/or mRNA expression of 16 tumor antigen precursor proteins or TAA. Results: These 20 human glioma cell lines potentially cover 77%, 85%, and 78% of the U.S. Caucasian population at HLA-A, HLA-B, and HLA-C alleles, respectively. All cells exhibited multiple TAA expressions. Most glioma cells expressed antigen isolated from immunoselected melanoma-2 (Aim-2), B-cyclin, EphA2, GP100, β1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13Rα2, Her2/neu, hTert, Mage, Mart-1, Sart-1, and survivin. Real-time PCR technology showed that glioblastoma specimens expressed most of the TAA as well. Tumor-infiltrating lymphocytes and CD8+ CTL killed T2 cells when loaded with specific HLA-A2+ restricted TAA, or gliomas that were both HLA-A2+ and also positive for specific TAA (Mart-1, GP100, Her2/neu, and tyrosinase) but not those cells negative for HLA-A2 and/or lacking the specific epitope. Conclusions: These data provide proof-in-principle for the use of allogeneic, partially HLA patient–matched glioma cells for vaccine generation or for peptide pulsing with allogeneic glioma cell extracts of autologous patient dendritic cells to induce endogenous CTL in brain tumor patients.
Recombination Rates and Genomic Shuffling in Human and Chimpanzee—A New Twist in the Chromosomal Speciation Theory
Authors: Marta Farré, Diego Micheletti, Aurora Ruiz-Herrera
Journal: Molecular Biology and Evolution (2012)

A long-standing question in evolutionary biology concerns the effect of recombination in shaping the genomic architecture of organisms and, in particular, how this impacts the speciation process. Despite efforts employed in the last decade, the role of chromosomal reorganizations in the human–chimpanzee speciation process remains unresolved. Through whole-genome comparisons, we have analyzed the genome-wide impact of genomic shuffling in the distribution of human recombination rates during the human–chimpanzee speciation process. We have constructed a highly refined map of the reorganizations and evolutionary breakpoint regions in the human and chimpanzee genomes based on orthologous genes and genome sequence alignments. The analysis of the most recent human and chimpanzee recombination maps inferred from genome-wide single-nucleotide polymorphism data revealed that the standardized recombination rate was significantly lower in rearranged than in collinear chromosomes. In fact, rearranged chromosomes presented significantly lower recombination rates than chromosomes that have been maintained since the ancestor of great apes, and this was related with the lineage in which they become fixed. Importantly, inverted regions had lower recombination rates than collinear and noninverted regions, independently of the effect of centromeres. Our observations have implications for the chromosomal speciation theory, providing new evidences for the contribution of inversions in suppressing recombination in mammals.
Periodic breathing during sleep in patients affected by fibromyalgia syndrome
Authors: M Sergi, M Rizzi, A. Braghiroli, P. Sarzi Puttini, M. Greco, M. Cazzola, A Andreoli
Journal: European Respiratory Journal (1999)

Seventeen patients affected by fibromyalgia syndrome (FMS) (16 females and one male) and 17 matched healthy subjects underwent formal polysomnography, a sleep questionnaire and lung function tests. FMS patients slept significantly less efficiently than the healthy controls (p&lt;0.01), had a higher proportion of stage 1 sleep (mean+/-SD, 21+/-6% versus 11+/-4%; p&lt;0.001), less slow wave sleep (p&lt;0.01) and twice as many arousals per hour of sleep (p&lt;0.001). The respiratory pattern of FMS patients showed a high occurrence of periodic breathing (PB) (15+/-8% of total sleep time) in 15/17 patients, versus 2/17 control subjects. The short length of apnoeas and hypopnoeas did not affect the apnoea/hypopnoea index (5.1+/-3.5 versus 3.2+/-1.6; NS), but FMS patients had a greater number of desaturations per hour of sleep (8+/-5 versus 3+/-3; p&lt;0.01). Pulmonary volumes did not differ between the two groups, but FMS patients had a lower transfer factor of the lung for carbon monoxide (TL,CO (5.8+1 versus 7.7+1 mmol x min(-1) x kPa(-1); p=0.001). PB occurrence correlated with TL,CO (r=-0.62; p=0.01), number of desaturations (r=0.76, p=0.001) and carbon dioxide tension in arterial blood (Pa,CO2) (r=-0.50; p=0.05). Stepwise multiple linear regression analysis showed desaturation frequency (p=0.0001) and TL,CO (p=0.029) to be the best predictors of PB percentage (R2 0.73; p=0.0001). Patients complaining of daytime hypersomnolence had a higher number of tender points, about twice as many arousals per hour and a lower sleep efficiency than patients who did not report this symptom. TL,CO was more impaired and the occurrence of PB was higher. The occurrence of periodic breathing in fibromyalgia syndrome patients, which was previously unreported, and is shown to be linked to a reduction of transfer factor of the lung for carbon monoxide could play a major role in the symptoms of poor sleep of these patients.
Limitations of a Home Characteristics Questionnaire as a Predictor of Indoor Allergen Levels
Authors: GINGER L. CHEW, HARRIET A. BURGE, DOUGLAS W. DOCKERY, MICHAEL L. MUILENBERG, SCOTT T. WEISS, DIANE R. GOLD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We examined associations between reported home characteristics and levels of indoor allergens in 499 homes of a birth cohort of children of allergic / asthmatic families from the Boston area. The risk of having dust mite allergen (Der f 1 or Der p 1) ⩾ 2 μ g/g on the bedroom floor was highest in houses, but 16% of apartments had levels this high. Compared with that from smooth floors, dust from carpeted bedroom floors had 2.1 times the risk of dust mite allergen ⩾ 10 μ g/g, but levels exceeded 2 μ g/g in 32% of uncarpeted floors. The risk of dust mite allergen ⩾ 10 μ g/g of dust from plastic-encased mattresses was 0.5 times that for cloth mattresses, but levels in 21% of plastic- encased mattresses were ⩾ 2 μ g/g. In 93% of homes with and 3% of homes without cats, Fel d 1 was ⩾ 8 μ g/g, but 34% of homes without cats had Fed d 1 ⩾ 1 μ g/g. Cockroach allergen (Bla g 1 or Bla g 2) was ⩾ 2 U/g of kitchen dust in 26% of apartments and only 6% of houses, and it was detected in 48% of homes with no reported signs of cockroaches in the previous 12 mo. Home characteristics reporting is a relatively weak predictor of the absence of allergen, and exposure can occur even when no cats are present, beds are encased in plastic, no carpets are present, and no signs of cockroaches have been reported.
T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor.
Authors: M J Berendt, R J North
Journal: The Journal of Experimental Medicine (1980)

The results of this paper are consistent with the hypothesis that progressive growth of the Meth A fibrosarcoma evokes the generation of a T-cell-mediated mechanism of immunosuppression that prevents this highly immunogenic tumor from being rejected by its immunocompetent host. It was shown that it is possible to cause the regression of large, established Meth A tumors by intravenous infusion of tumor-sensitized T cells from immune donors, but only if the tumors are growing in T-cell-deficient recipients. It was also shown that the adoptive T-cell-mediated regression of tumors in such recipients can be prevented by prior infusion of splenic T cells from T-cell-intact, tumor-bearing donors. The results leave little doubt that the presence of suppressor T cells in T-cell-intact, tumor-bearing mice is responsible for the loss of an earlier generated state of concomitant immunity, and for the inability of intravenously infused, sensitized T cells to cause tumor regression. Because the presence of suppressor T cells generated in response to the Meth A did not suppress the capacity of Meth A-bearing mice to generate and express immunity against a tumor allograft, it is obvious that they were not in a state of generalized immunosuppression.
Convulsive seizures and viloxazine.
Authors: J G Edwards
Journal: BMJ (1977)

metabolism in the liver is unknown. 9The pharmacokinetics of disulfiram have not been elucidated because there are no sensitive and specific methods of determining disulfiram and its metabolites.Acute toxicity studies with disulfiram in rats have shown no signs of liver necrosis but disulfiram decreases the drug metabolising capacity of the liver.'°11This mechanism probably accounts for disulfiram's inhibition of diphenylhydantoin and warfarin metabolism.'2 13 Our findings indicate that long-term toxicity studies in animals should be performed to detect possible hepatic damage after pro- prolonged administration of disulfiram.We thank Dr K Winkler for allowing us to report observations in case 1.
Solomon Leonard Barron
Authors: D. B. J. Davison
Journal: BMJ (2014)

Through ecological analyses and case-control studies, the possible relation of gastric cancer and leukaemia to dibromochloropropane (DBCP) contamination of drinking water in Fresno County, California, has been examined. The ecological analyses examined the correlation between gastric cancer and leukaemia (including the lymphatic varieties), mortality rates, and DBCP concentrations in drinking water by census tract in Fresno County, 1960-83. No correlation was found between gastric cancer or leukaemia and DBCP. The gastric cancer case-control study consisted of 263 deaths from gastric cancer in the county, 1975 to mid-1984, and 1044 controls, using information on residential history and occupation of both cases and controls. Analyses were based on residence at death, as well as one and ten years before death. The case-control study did not find any relation between gastric cancer and DBCP in drinking water. Hispanics in the county were found to experience a relative risk of gastric cancer of 2.77, compared with non-Hispanics. A similar case-control study consisting of 259 cases of leukaemia and 1161 controls found no relation between all leukaemia or lymphatic leukaemia and DBCP in drinking water. Farm workers, however, do appear to have an increased risk of leukaemia.
Overexpression of the ETS-Related Gene, <i>ERG</i>, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study
Authors: Guido Marcucci, Claudia D. Baldus, Amy S. Ruppert, Michael D. Radmacher, Krzysztof Mrózek, Susan P. Whitman, Jonathan E. Kolitz, Colin G. Edwards, James W. Vardiman, Bayard L. Powell, Maria R. Baer, Joseph O. Moore, Danilo Perrotti, Michael A. Caligiuri, Andrew J. Carroll, Richard A. Larson, Albert de la Chapelle, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2005)

To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.
THE ANTIBODY RESPONSE TO SWINE INFLUENZA
Authors: Carlos T. Rosenbusch, Richard E. Shope
Journal: The Journal of Experimental Medicine (1939)

Antibodies that neutralize swine influenza virus became detectible in the serum of swine on the 6th or 7th day after infection with swine influenza. Their appearance corresponded rather closely with clinical recovery. In swine with the milder filtrate disease, neutralizing antibodies did not appear until sometime between the 7th and 10th days. The maximum antibody titers ranged from 1:60 to 1:160 and were attained on from the 14th to the 27th days after infection.
Platinum-Complexed Antitumor Immunoglobulins That Specifically Inhibit DNA Synthesis of Mouse Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Esther Hurwitz, Rina Kashi, Meir Wilchek
Journal: JNCI Journal of the National Cancer Institute (1982)

Platinum salts were complexed with antitumor reactive immunoglobulins (Ig). The Pt-complexed antitumor Ig retained their specific antibody binding activity. The inhibition of DNA synthesis by Pt salts (K2 PtCl4 and cis-diamminedichloroplatinum II) and Pt-Ig complexes was studied in 2 tumor cell lines of mice. The Pt-Ig complexes were much more effective inhibitors of DNA synthesis when complexed with Ig, which had binding affinity toward the test tumor cells.
On the Metrics and Euler-Lagrange Equations of Computational Anatomy
Authors: Michael I. Miller, Alain Trouvé, Laurent Younes
Journal: Annual Review of Biomedical Engineering (2002)

This paper reviews literature, current concepts and approaches in computational anatomy (CA). The model of CA is a Grenander deformable template, an orbit generated from a template under groups of diffeomorphisms. The metric space of all anatomical images is constructed from the geodesic connecting one anatomical structure to another in the orbit. The variational problems specifying these metrics are reviewed along with their associated Euler-Lagrange equations. The Euler equations of motion derived by Arnold for the geodesics in the group of divergence-free volume-preserving diffeomorphisms of incompressible fluids are generalized for the larger group of diffeomorphisms used in CA with nonconstant Jacobians. Metrics that accommodate photometric variation are described extending the anatomical model to incorporate the construction of neoplasm. Metrics on landmarked shapes are reviewed as well as Joshi's diffeomorphism metrics, Bookstein's thin-plate spline approximate-metrics, and Kendall's affine invariant metrics. We conclude by showing recent experimental results from the Toga & Thompson group in growth, the Van Essen group in macaque and human cortex mapping, and the Csernansky group in hippocampus mapping for neuropsychiatric studies in aging and schizophrenia.