tbuckley/cabot-search huggingface dataset:
Feline glucose-6-phosphate dehydrogenase cellular mosaicism. Application to the study of retrovirus-induced pure red cell aplasia.
Authors: J L Abkowitz, R L Ott, J M Nakamura, L Steinmann, P J Fialkow, J W Adamson
Journal: Journal of Clinical Investigation (1985)

Neoplasms result from the uncontrolled proliferation of abnormal or transformed cells. The early stages of this process are difficult to study because of the lack of sensitive and specific markers of clonal evolution in an experimental system. We have developed a cat model using cellular mosaicism for glucose-6-phosphate dehydrogenase (G-6-PD). Our findings confirm that the structural locus for feline G-6-PD is on the X-chromosome and demonstrate that it is randomly inactivated in somatic cells. Heterozygous cats have balanced ratios of G-6-PD enzyme types in peripheral blood cells and hematopoietic progenitors that remain stable over time. In our initial studies, we used the model to analyze the events surrounding marrow failure experimentally induced by selected strains of feline leukemia virus (FeLV). Two G-6-PD heterozygous cats, one F1 male hybrid and one domestic cat were infected with FeLV (C or KT) and developed pure red cell aplasia (PRCA). Colonies arising from the more mature erythroid colony-forming cell were not detected in marrow culture of anemic animals although erythroid bursts persisted, suggesting that the differentiation of early erythroid progenitors (BFU-E) was inhibited in vivo. The ratio of G-6-PD types in hematopoietic progenitors and peripheral blood cells from the heterozygous cats did not change when the animals developed PRCA. Thus, the anemia did not result from the clonal expansion of a transformed myeloid stem cell. With this experimental approach, one may prospectively assess clonal evolution and cellular interactions in other FeLV-induced diseases.
Targeting Vascular Endothelial Growth Factor for Relapsed and Refractory Adult Acute Myelogenous Leukemias
Authors: Judith E. Karp, Ivana Gojo, Roberto Pili, Christopher D. Gocke, Jacqueline Greer, Chuanfa Guo, David Qian, Lawrence Morris, Michael Tidwell, Helen Chen, James Zwiebel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Vascular endothelial growth factor (VEGF) promotes acute myelogenous leukemia (AML) cell growth and survival and may contribute to drug resistance. bevacizumab, an anti-VEGF monoclonal antibody, exhibits clinical activity against diverse malignancies when administered with cytotoxic chemotherapy. We conducted a Phase II clinical trial of bevacizumab administered after chemotherapy to adults with refractory or relapsed AML, using a timed sequential therapy (TST) approach. Experimental Design: bevacizumab 10 mg/kg was administered on day 8 after 1-β-d-arabinofuranosylcytosine 2 g/m2/72 h beginning day 1 and mitoxantrone 40 mg/m2 beginning day 4. In vivo laboratory correlates included AML cell VEGF receptor-1 (FLT-1) expression, marrow microvessel density, and free serum VEGF before and during TST with bevacizumab. Results: Forty-eight adults received induction therapy. Myelosuppression occurred in all of the patients similar to other TST regimens. Toxicities were decreased ejection fraction (6%), cerebrovascular bleed (4%), and mortality of 15%. Overall response was 23 of 48 (48%), with complete response (CR) in 16 (33%). Eighteen (14 CR and 4 partial response) underwent one consolidation cycle and 5 (3 CR and 2 partial response) underwent allogeneic transplant. Median overall and disease-free survivals for CR patients were 16.2 months (64%, 1 year) and 7 months (35%, 1 year). Marrow blasts demonstrated FLT-1 staining before bevacizumab and marked decrease in microvessel density after bevacizumab. VEGF was detected in pretreatment serum in 67% of patients tested, increased by day 8 in 52%, and decreased in 93% (67% undetectable) 2 h after bevacizumab. Conclusions: In this single arm study, cytotoxic chemotherapy followed by bevacizumab yields a favorable CR rate and duration in adults with AML that is resistant to traditional treatment approaches. The clearance of marrow blasts in some patients after bevacizumab suggests that VEGF neutralization might result directly in leukemic cell death. The potential biological and clinical activity of bevacizumab in AML warrants additional clinical and laboratory study.
Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells
Authors: Mercedes Rincón, Juan Anguita, Tetsuo Nakamura, Erol Fikrig, Richard A. Flavell
Journal: The Journal of Experimental Medicine (1997)

Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon γ trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.
A De Novo Mutation in α-Tropomyosin That Causes Hypertrophic Cardiomyopathy
Authors: Hugh Watkins, Ryuichiro Anan, Domenico A. Coviello, Paolo Spirito, J.G. Seidman, Christine E. Seidman
Journal: Circulation (1995)

Two missense mutations in the gene for alpha-tropomyosin have been described that segregate with hypertrophic cardiomyopathy in single families. To confirm that these mutations are the cause of the disease, we have investigated the origins of one of these mutations, Asp175Asn, in a third and unrelated family.The presence or absence of an alpha-tropomyosin mutation and the haplotypes of the flanking chromosomal regions were determined for members of a family with hypertrophic cardiomyopathy. Haplotypes were constructed by use of an intragenic polymorphism and 10 flanking polymorphisms spanning a region of 35 centimorgans. The Asp175Asn missense mutation was present in the proband and his two affected offspring but not in any of the proband's three siblings. Although both parents were deceased, the haplotypes of the four parental chromosomes could be reconstructed. One parental chromosome was transmitted to two offspring: one bearing the Asp175Asn mutation (the affected proband) and one clinically unaffected sibling who lacked the alpha-tropomyosin mutation. Thus, the Asp175Asn mutation must have arisen de novo.De novo mutations in the alpha-tropomyosin gene can result in hypertrophic cardiomyopathy that may appear to be sporadic but in subsequent generations gives rise to familial disease. Individuals with sporadic hypertrophic cardiomyopathy should be advised of the risk of transmission to offspring. In addition, these findings provide the strongest genetic evidence that mutations in the alpha-tropomyosin gene are directly responsible for hypertrophic cardiomyopathy.
Energy demands during a judo match and recovery
Authors: F Degoutte, P Jouanel, E Filaire
Journal: British Journal of Sports Medicine (2003)

To assess energy demand during a judo match and the kinetics of recovery by measuring the metabolites of the oxypurine cascade, lipolytic activity, and glycolytic pathway.Venous blood samples were taken from 16 national judoists (mean (SEM) age 18.4 (1.6) years), before (T(1)) and three minutes (T(2)), one hour (T(3)), and 24 hours (T(4)) after a match. A seven day diet record was used to evaluate nutrient intake.Nutrient analysis indicated that these athletes followed a low carbohydrate diet. Plasma lactate concentration had increased to 12.3 (1.8) mmol/l at the end of the match. An increase in the levels of extracellular markers of muscle adenine nucleotide catabolism, urea, and creatinine was observed at T(2), while uric acid levels remained unchanged. High concentrations of urea persisted for 24 hours during the recovery period. Ammonia, hypoxanthine, xanthine, and creatinine returned to control levels within the 24 hour recovery period. Uric acid concentrations rose from T(3) and had not returned to baseline 24 hours after the match. The levels of triglycerides, glycerol, and free fatty acids had increased significantly (p<0.05) after the match (T(2)) but returned to baseline values within 24 hours. Concentrations of high density lipoprotein cholesterol and total cholesterol were significantly increased after the match.These results show that a judo match induces both protein and lipid metabolism. Carbohydrate availability, training adaptation, and metabolic stress may explain the requirement for these types of metabolism.
Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid
Authors: Y. Sakuma-Oyama, A.M. Powell, N. Oyama, S. Albert, B.S. Bhogal, M.M. Black
Journal: British Journal of Dermatology (2004)

Background Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a-specific enzyme-linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti-BP180 autoantibodies in BP sera. However, it remains unclear whether the diagnostic potential of the ELISA is equivalent to that of the 'gold-standard' diagnostic technique of immunofluorescence (IF). Objectives To examine the usefulness of a commercially available BP180-NC16a ELISA in the initial serodiagnosis of BP. Methods Sera from a large cohort of patients with BP (n = 102) and control subjects (age- and sex-matched normal volunteers, n = 60; pemphigus foliaceus, n = 18; pemphigus vulgaris, n = 16) were assayed by BP180-NC16a ELISA. All BP sera were obtained at presentation before initiation of systemic immunosuppressive therapy. The values of IgG antibody levels measured by ELISA were compared with those measured by indirect IF on salt-split skin. Results Receiver operating characteristic analysis was used to calculate the cut-off value for the ELISA in the diagnosis of BP which maximizes both sensitivity and specificity, and to estimate the diagnostic accuracy of the ELISA as represented by the area under the curve (AUC = 0·965). A cut-off value of 9 was associated with a sensitivity of 89% (91 of 102 BP sera showed a positive result) and a specificity of 98%. Fifty-eight of 60 normal controls and all the pemphigus sera showed a negative result. There was a correlation between the mean ELISA values and indirect IF titres (Spearman rank correlation 0·286; P = 0·004). Conclusions Our results suggest that the BP180-NC16a ELISA is a useful tool for the detection of pathogenic anti-BP180 IgG autoantibodies at the initial disease stage of BP. Because it is not only highly sensitive and specific, but is also easy to perform, is objective, and semiquantitative, the ELISA may provide valuable information for the accurate and reliable serodiagnosis of BP.
Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells
Authors: Jie Tang, Phyllis Flomenberg, Larry Harshyne, Lawrence Kenyon, David W. Andrews
Journal: Clinical Cancer Research (2005)

Abstract Purpose: There is growing interest in developing cellular immune therapies for glioblastoma multiforme, but little is known about tumor-specific T-cell responses. A glioblastoma multiforme–specific T-cell assay was developed using monocyte-derived dendritic cells to present tumor antigens from the established glioblastoma multiforme cell line U118. Experimental Design: Peripheral blood mononuclear cells (PBMC) and tumor cells were obtained from nine patients with newly diagnosed brain tumors: five glioblastoma multiforme, two oligodendroglioma, one ependymoma, and one astrocytoma. PBMCs were incubated overnight with autologous tumor cells or autologous dendritic cells loaded with a U118 cell lysate, and responses were detected by IFN-γ ELISPOT and cytokine flow cytometry assays. Results: PBMCs from all glioblastoma multiforme patients exhibited IFN-γ responses to autologous tumor but not to HLA-mismatched U118 cells. Glioblastoma multiforme–specific IFN-γ responses were primarily mediated by CD8+ T cells and represented ∼2% of total CD8+ T cells. Additionally, all glioblastoma multiforme patients responded to autologous dendritic cells loaded with U118 lysate but not with low-grade astrocytoma cell lysates. PBMCs from four patients with other brain tumor types and one normal donor failed to respond to U118 lysate–loaded autologous dendritic cells. These data indicate that the IFN-γ responses to U118 lysate–loaded autologous dendritic cells are glioblastoma multiforme specific. Moreover, PBMCs stimulated 1 to 2 weeks with U118 lysate–loaded dendritic cells exhibited MHC class I–restricted cytotoxicity against autologous tumor cells. Conclusions: Glioblastoma multiforme patients exhibit circulating tumor-specific CD8+ T cells that recognize shared tumor antigens from the glioblastoma multiforme cell line U118. These data show that glioblastoma multiformes are immunogenic and support the development of immunotherapy trials.
Nephrogenic systemic fibrosis: a gadolinium-associated fibrosing disorder in patients with renal dysfunction
Authors: J Kay
Journal: Annals of the Rheumatic Diseases (2008)

Nephrogenic systemic fibrosis (NSF) is a debilitating fibrosing disorder that develops in patients with underlying kidney disease following exposure to gadolinium-containing contrast agents. NSF presents with cutaneous hyperpigmentation and induration and joint contractures, but fibrosis may also develop in other organs. NSF has been observed in up to 18% of patients receiving chronic haemodialysis and also may occur in individuals with stages 3 and 4 chronic kidney disease and, occasionally, in individuals who had experienced acute renal failure. Mortality is increased significantly among individuals with NSF. Although no medical treatment has been proved to be universally effective in patients with NSF, imatinib mesylate shows potential as a therapeutic agent and is currently being studied in these patients.
Nuclear Targeting of Akt Enhances Kinase Activity and Survival of Cardiomyocytes
Authors: Isao Shiraishi, Jaime Melendez, Youngkeun Ahn, Maryanne Skavdahl, Elizabeth Murphy, Sara Welch, Erik Schaefer, Kenneth Walsh, Anthony Rosenzweig, Daniele Torella, Daria Nurzynska, Jan Kajstura, Annarosa Leri, Piero Anversa, Mark A. Sussman
Journal: Circulation Research (2004)

Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent studies by our group have found accumulation of activated Akt in the nucleus, suggesting that biologically relevant target(s) of Akt activity may be located there. To test this hypothesis, a targeted Akt construct was created to determine the antiapoptotic action of nuclear Akt accumulation. Nuclear localization of the adenovirally encoded Akt construct was confirmed by confocal microscopy. Cardiomyocytes expressing nuclear-targeted Akt showed no evidence of morphological remodeling such as altered myofibril density or hypertrophy. Nuclear-targeted Akt significantly elevated levels of phospho-Akt and kinase activity and inhibited apoptosis as effectively as myristolated-Akt in hypoxia-induced cell death. Transgenic overexpression of nuclear-targeted Akt did not result in hypertrophic remodeling, altered cardiomyocyte DNA content or nucleation, or enhanced phosphorylation of typical cytoplasmic Akt substrates, yet transgenic hearts were protected from ischemia-reperfusion injury. Gene array analyses demonstrated changes in the transcriptional profile of Akt/nuc hearts compared with nontransgenic controls distinct from prior characterizations of Akt expression in transgenic hearts. Collectively, these experiments show that targeting of Akt to the nucleus mediates inhibition of apoptosis without hypertrophic remodeling, opening new possibilities for therapeutic applications of nuclear-targeted Akt to inhibit cell death associated with heart disease.
Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile.
Authors: R P Bolton, M A Culshaw
Journal: Gut (1986)

Faecal metronidazole and hydroxymetronidazole concentrations measured by high pressure liquid chromatography are reported during 10 episodes of Clostridium difficile colitis in nine patients. Bactericidal faecal concentrations were present in all patients with acute disease receiving oral or intravenous metronidazole, and all responded to therapy. Metronidazole and hydroxymetronidazole concentrations fell as the diarrhoea improved and neither substance was detectable in the faeces of five patients after recovery. This demonstration of intracolonic therapeutic concentrations of metronidazole supports the clinical experience of oral metronidazole being effective in the treatment of antibiotic associated diarrhoea caused by C difficile and also suggests a potential role for intravenous metronidazole in this disease.
Sahaja yoga in asthma
Authors: R Manocha
Journal: Thorax (2003)

<h3>PURPOSE</h3> To compare MR with thallium-201 scintigraphy in the follow-up of patients who have undergone thyroidectomy and modified radical neck dissection for differentiated thyroid cancer. <h3>METHODS</h3> Both MR imaging and 201Tl scintigraphy were performed in 39 patients after surgery for differentiated thyroid cancer. Ten patients did not have recurrence; 29 patients had 51 recurrent tumors in the neck and mediastinum. <h3>RESULTS</h3> Among 51 tumor sites, 39 sites of recurrence were detected by MR and 24 were detected by 201Tl scintigraphy. The true-positive rate, false-negative rate, true-negative rate, and false-positive rate in detecting recurrent thyroid cancer were 76.5, 23.5, 100, and 0%, respectively, for MR and 47.1, 52.9, 100, and 0%, respectively, for 201Tl scintigraphy. MR was more sensitive than 201Tl scintigraphy in detecting recurrent tumors (especially small metastatic nodes). On T2-weighted MR images, recurrent tumor was characterized by high signal intensity. Scarring in the postoperative thyroid bed was characterized by low signal intensity on both T1- and T2-weighted images. Abnormal accumulation of 201Tl in the postoperative thyroid bed was not observed. <h3>CONCLUSIONS</h3> Although both MR images and 201Tl scintigraphy were effective in distinguishing recurrent tumor from postoperative fibrous tissue, MR images were more sensitive than 201Tl scintigraphy in detecting recurrent tumors. These results suggest that MR imaging is more useful than 201Tl scintigraphy in the follow-up evaluation of patients after neck surgery for differentiated thyroid cancer.
Primary Lymphoma of the Heart
Authors: Jeffrey Kuvin, Nisha Parikh, Robert Salomon, Arthur Tischler, Philip Daoust, Yevgeniy Arshanskiy, Karl Coyner, Philip Carpino, Natesa G. Pandian, Carey Kimmelstiel, Caroline Foote, John Erban, Hassan Rastegar
Journal: Circulation (2005)
Contemporary results of mitral valve repair for infective endocarditis
Authors: Bernard Iung, Juliette Rousseau-Paziaud, Bertrand Cormier, Eric Garbarz, Olivier Fondard, Eric Brochet, Christophe Acar, Jean-Paul Couëtil, Ulrik Hvass, Alec Vahanian
Journal: Journal of the American College of Cardiology (2004)
Modulatory Effects of Arachidonic Acid on the Delayed Rectifier K <sup>+</sup> Current in Rat Pulmonary Arterial Myocytes
Authors: Sergey V. Smirnov, Philip I. Aaronson
Journal: Circulation Research (1996)

The effect of arachidonic acid (AA) on the delayed rectifier K + current (I K ) was evaluated in rat pulmonary myocytes by using the whole-cell patch-clamp technique. Externally applied AA (50 μmol/L) caused a membrane depolarization, averaging 16 mV in six cells. AA (1 to 50 μmol/L) caused a dual effect on I K . First, AA accelerated the rate of I K activation, increasing current amplitude at the beginning of voltage step. Second, AA caused a marked acceleration of current decay, thereby reducing I K amplitude measured toward the end of the depolarizing steps. These effects were not prevented by indomethacin or nordihydroguaiaretic acid, blockers of cyclooxygenase and lipoxygenase, respectively. AA did not affect the voltage dependence of current activation or inactivation. The magnitude of the inhibitory effect on I K was correlated with the number of double bonds but was independent of tail length in fatty acids containing between 14 and 22 carbons. Linoleic acid (18:2, cis -9,12) inhibited I K much more than did its trans -stereoisomer, linolelaidic acid. Arachidonyl alcohol, which is uncharged, and arachidonyl coenzyme A, which does not ‘flip’ across the cell membrane, were less effective than AA in inhibiting I K ; this effect of fatty acids may therefore require passage across the cell membrane. The enhancement of early I K was mimicked by the protein kinase C (PKC) stimulator 1-oleoyl-2-acetyl- sn -glycerol (10 μmol/L), was suppressed by ATP removal from the pipette solution, and was blocked by PKC inhibitors chelerythrine (10 μmol/L) and staurosporine (100 nmol/L). This effect may therefore require PKC-dependent phosphorylation.
Respiratory function of the rib cage muscles
Authors: JN Han, G Gayan-Ramirez, R Dekhuijzen, M Decramer
Journal: European Respiratory Journal (1993)

Elevation of the ribs and expansion of the rib cage result from the co-ordinated action of the rib cage muscles. We wished to review the action and interaction of the rib cage muscles during ventilation. The parasternal intercostal muscles appear to play a predominant role during quiet breathing, both in humans and in anaesthetized dogs. In humans, the parasternal intercostals act in concert with the scalene muscles to expand the upper rib cage, and/or to prevent it from being drawn inward by the action of the diaphragm. The external intercostal muscles are considered to be active mainly during inspiration, and the internal intercostal muscles during expiration. The respiratory activity of the external intercostals is minimal during quiet breathing both in man and in dogs, but increases with increasing ventilation. Inspiratory activity in the external intercostals can be enhanced in anaesthetized animals and humans by inspiratory mechanical loading and by CO2 stimulation, suggesting that the external intercostals may constitute a reserve system, that may be recruited when the desired expansion of the rib cage is increased. The triangularis sterni is an important expiratory muscle during quiet breathing in animals, but it is not active during quiet breathing in man. However, during expiration below functional residual capacity (FRC), and during speech, laughing and coughing, the triangularis sterni is recruited and plays an increasingly important role.
Plastid Sequences Contribute to Some Plant Mitochondrial Genes
Authors: D. Wang, M. Rousseau-Gueutin, J. N. Timmis
Journal: Molecular Biology and Evolution (2012)

DNA of plastid (chloroplast) origin comprises between 1% and 10% of the mitochondrial genomes of higher plants, but functions are currently considered to be limited to rare instances where plastid tRNA genes have replaced their mitochondrial counterparts, where short patches of mitochondrial genes evolved using their homologous plastidic copies by gene conversion or where a new promoter region is created. Here, we show that, in some angiosperms, plastid-derived DNA in mitochondrial genomes (also called mtpt for mitochondrial plastid DNA) contributes codons to unrelated mitochondrial protein-coding sequences and may also have a role in posttranscriptional RNA processing. We determined that these transfers of plastid DNA occurred a few to 150 Ma and that mtpts can sometimes remain dormant many millions of years before contributing to the mitochondrial proteome.