tbuckley/cabot-search huggingface dataset:
Crosstalk of β-Adrenergic Receptor Subtypes Through G <sub>i</sub> Blunts β-Adrenergic Stimulation of L-Type Ca <sup>2+</sup> Channels in Canine Heart Failure
Authors: Jia-Qiang He, Ravi C. Balijepalli, Robert A. Haworth, Timothy J. Kamp
Journal: Circulation Research (2005)

The mechanisms underlying the blunted contractile response to beta-adrenergic receptor (beta-AR) stimulation in heart failure (HF) are incompletely understood, especially with regard to beta-AR subtype-specific regulation of L-type Ca2+ channels. We evaluated the impact of HF induced by pacing tachycardia on beta-AR regulation of L-type Ca2+ channels in a canine model. To evaluate changes in the relative subcellular distribution of beta-AR subtypes, left ventricular membranes enriched in surface sarcolemma and T-tubular sarcolemma were prepared. Radioligand binding using [(125)I]cyanopindolol revealed that HF resulted in a comparable decrease in the density of beta1-ARs in both surface and T-tubule sarcolemma (55+/-4%, n=7, P<0.001; and 45+/-10%, n=7, P<0.01, respectively), but no significant change in beta2-AR density was observed. Whole-cell patch clamp studies demonstrated a markedly blunted increase in I(Ca,L) in response to saturating concentrations of the nonselective beta-AR agonist isoproterenol (0.1 micromol/L) in failing myocytes compared with control (129+/-20%, n=11, versus 332+/-35%, n=7; P<0.001). Experiments testing beta1-AR- and beta2-AR-selective stimulation showed that the major component of the blunted response to nonselective beta-AR stimulation in HF was caused by beta2-AR activation, resulting in a pertussis toxin-sensitive, Gi-mediated inhibition of the beta1-AR-induced increase in I(Ca,L). In conclusion, canine HF results in the following: (1) a uniform reduction in beta1-AR density in surface and T-tubule membrane fractions without a change in beta2-AR density; and (2) the emergence of distinct Gi-coupling to beta2-ARs resulting in accentuated antagonism of beta1-AR-mediated stimulation of I(Ca,L). These results have implications for optimizing the use of beta-AR drugs in HF.
Characteristics of hexokinase, pyruvate kinase, and glucose‐6‐phosphate dehydrogenase during adult and neonatal reticulocyte maturation
Authors: G. Jansen, L. Koenderman, G. Rijksen, B. P. Cats, G. E. J. Staal
Journal: American Journal of Hematology (1985)

Erythrocytes from adults and newborn infants (at term and premature) were separated by Percoll density gradient centrifugation into four fractions of increasing density. Glycolytic enzymes, especially the age-dependent ones, hexokinase (EC 2.7.1.1, HK), pyruvate kinase (EC 2.7.1.40, PK), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PD) were studied during reticulocyte maturation and further red cell senescence. Analysis of the fraction with lowest density showed an almost linear and steep decline of HK, PK, and G6PD activity with a decreasing number of reticulocytes. In the next three fractions of increasing density, the activity decline was far less. These data are therefore illustrative for a biphasic activity decay pattern of HK, PK, and G6PD during both adult and neonatal red cell aging. The strong decline in HK activity could not be ascribed to the disappearance of a particulate (mitochondrial) bound fraction of the enzyme during reticulocyte maturation. All hexokinase activity in human reticulocytes was found to be cytosolic in contrast with rabbit reticulocytes in which 70% of HK activity was particulate.
Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity
Authors: Jennifer E Fenner, Robyn Starr, Ann L Cornish, Jian-Guo Zhang, Donald Metcalf, Robert D Schreiber, Kathleen Sheehan, Douglas J Hilton, Warren S Alexander, Paul J Hertzog
Journal: Nature Immunology (2005)
A hominoid-specific nuclear insertion of the mitochondrial D-loop: implications for reconstructing ancestral mitochondrial sequences
Authors: H. Zischler, H. Geisert, J. Castresana
Journal: Molecular Biology and Evolution (1998)

A nuclear integration of a mitochondrial control region sequence on human chromosome 9 has been isolated. PCR analyses with primers specific for the respective insertion-flanking nuclear regions showed that the insertion took place on the lineage leading to Hominoidea (gibbon, orangutan, gorilla, chimpanzee, and human) after the Old World monkey-Hominoidea split. The sequences of the control region integrations were determined for humans, chimpanzees, gorillas, orangutans, and siamangs. These sequences were then used to construct phylogenetic trees with different methods, relating them with several hominoid, Old Work monkey, and New World monkey mitochondrial control region sequences. Applying maximum-likelihood, neighbor-joining, and parsimony algorithms, the insertion clade was attached to the branch leading to the hominoid mitochondrial sequences as expected from the PCR-determined presence/absence of this integration. An unexpected long branch leading to the internal node that connects all insertion sequences was observed for the different phylogeny reconstruction procedures. This finding is not totally compatible with the lower evolutionary rate in the nucleus than in the mitochondrial compartment. We determined the unambiguous substitutions on the branch leading to the most recent common ancestor (MRCA) of the mitochondrial inserts according to the parsimony criterium. We propose that they are unlikely to have been caused by damage of the transposing nucleic acid and that they are probably due to a change in the evolutionary mode after the transposition.
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study
Authors: Manabu Funayama, Kenji Ohe, Taku Amo, Norihiko Furuya, Junji Yamaguchi, Shinji Saiki, Yuanzhe Li, Kotaro Ogaki, Maya Ando, Hiroyo Yoshino, Hiroyuki Tomiyama, Kenya Nishioka, Kazuko Hasegawa, Hidemoto Saiki, Wataru Satake, Kaoru Mogushi, Ryogen Sasaki, Yasumasa Kokubo, Shigeki Kuzuhara, Tatsushi Toda, Yoshikuni Mizuno, Yasuo Uchiyama, Kinji Ohno, Nobutaka Hattori
Journal: The Lancet Neurology (2015)
Benefits of pulmonary rehabilitation on exercise desaturation in COPD patients
Authors: Daniela Gologanu, Diana Ionita, Ioana Daha, Mirela Barbu, Alina Croitoru, Miron Bogdan
Journal: European Respiratory Journal (2014)

Background: Oxygen desaturation during exercise can have important consequences for the prognosis of patients with COPD.

Aim: To study the effects of pulmonary rehabilitation on exercise desaturation.

Method: We studied 16 COPD patients who performed pulmonary function tests, 6MWT and cardiopulmonary exercise testing (CPET) at the beginning and at the end of a seven weeks outpatient rehabilitation program. Oxygen desaturation after exercise was defined by a decrease (exercise minus resting) ≥ 4% in pulse oximetric saturation (SpO2) or by an postexercise SpO2 < 90%.

Results: Among the 16 patients, 8 were desaturators after both 6MWT and CPET, 1 after 6MWT only and 1 after CPET only. Desaturators had lower baseline gas transfer: mean % predicted DLCO 54,5% in the 6MWT desaturators versus 77,1% in nondesaturators, p<0,001; mean % predicted DLCO 53,8% in the CPET desaturators versus 78% in nondesaturators, p=0.013. Two thirds of the patients who desaturated after 6MWT and only 12% of those who desaturated after CPET did not desaturate any longer after completing rehabilitation. Mean postexercise saturation (assessed both after 6MWT and after CPET) was significantly higher after rehabilitation (mean postexercise SpO2 after 6MWT was 89,38% before and 92.06% after rehabilitation, p=0,014; mean postexercise SpO2 after CPET was 88,86% before and 90,71% after rehabilitation, p=0,015).

Conclusions: Pulmonary rehabilitation improves exercise desaturation in COPD patients. This improvement is evident in desaturations after 6MWT which is similar with the activities of daily living. Thus, pulmonary rehabilitation can delay desaturation consequences and improve quality of life and disease progression in COPD patients.
Development of left ventricular hypertrophy in young spontaneously hypertensive rats after peripheral sympathectomy.
Authors: A F Cutilletta, L Erinoff, A Heller, J Low, S Oparil
Journal: Circulation Research (1977)

The effects of peripheral sympathectomy with nerve growth factor antiserum (NGFAS) on blood pressure, systemic hemodynamics, myocardial function, myocardial hypertrophy, and renin were studied in male spontaneously hypertensive (SH) rats of the Okamoto strain and normotensive control Kyoto-Wistar (WKY) rats. NGFAS prevented the developing of hypertension in the SH rats but did not alter blood pressure in the WKY rats. The NGFAS-treated SH rats developed the same hemodynamic abnormalities as the sham-treated rats, including increased peripheral vascular resistance and depressed cardiac output; Indices of left ventricular performance, including peak flow velocity, stroke power, stroke work, dP/dtmax, and flow acceleration (dF/dt), were diminished in the SH rats compared to the WKY rats. NGFAS treatment further depressed ventricular function in the SH rats, but had little effect on the WKY rats; Plasma renin activity in both the SH and WKY rats was unaffected by NGFAS treatment. Although NGFAS treatment effectively prevented the development of hypertension in the SH rats, it did not influence the development of left ventricular hypertrophy as reflected by increases in left ventricular mass, RNA, DNA, and hydroxyproline content. The data suggest that the development of myocardial hypertrophy and myocardial dysfunction in the SH rat is in part independent of hypertension and plasma renin activity.
THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE
Authors: W. J. M. Scott
Journal: The Journal of Experimental Medicine (1924)

1. The resistance of rats to bacterial intoxication is greatly decreased after double adrenalectomy. 2. This decreased resistance is dependent upon a functional insufficiency of the adrenal cortex. 3. A dose of killed streptococci or staphylococci can be obtained that is invariably fatal to adrenalectomized rats, before hypertrophy of cortical accessories, but never kills control rats.
Podoplanin in cancer cells is experimentally able to attenuate prolymphangiogenic and lymphogenous metastatic potentials of lung squamoid cancer cells
Authors: Hanako Suzuki, Mitsuho Onimaru, Yoshikazu Yonemitsu, Yoshihiko Maehara, Seiji Nakamura, Katsuo Sueishi
Journal: Molecular Cancer (2010)

Abstract Background Podoplanin, a mucin-like transmembrane glycoprotein, is reportedly expressed in a variety of malignant cells and is generally regarded as a factor for promoting tumor progression in conventional studies. By contrast, a clinicopathologically conflicting role for podoplanin, namely as a favorable prognostic factor for patients with lung/cervical squamous cell carcinoma (SCC), has recently been reported. Here, we investigated the role of podoplanin expressed in lung squamoid cancer cells (LSCCs) in experimental tumor progression. Results Using EBC-1 cells, a lung SCC cell line without podoplanin expression and with lymphogenous metastatic potential, stable transformants with or without an exogenous human podoplanin gene were established and applied to a mouse tumor implantation model. In vivo examinations revealed that exogenous podoplanin had no influence on tumor growth, whereas it significantly restrained axillary lymph node metastasis associated with the suppression of lymphangiogenesis but not angiogenesis and with the downregulation of EBC-1-derived VEGF-C but not other lymphangiogenesis-related factor mRNAs in implanted tumor tissue. In vitro examinations to clarify the mechanisms underlying the in vivo phenomena revealed that exogenous podoplanin significantly suppressed the expression of VEGF-C mRNA and of the protein, and also increased the level of phosphorylated c-jun N terminal kinase (JNK) in EBC-1 cells. The former effect of exogenous podoplanin was impaired by treatment with either JNK inhibitor sp600125 or podoplanin-siRNA, and the latter effect was impaired by treatment with podoplanin-siRNA, suggesting that podoplanin was able to activate JNK, thereby downregulating VEGF-C gene expression in LSCCs (podoplanin-JNK-VEGF-C axis). Furthermore, supporting evidence in regard to the axis present in LSCCs was obtained from similar experiments using H157 cells, another lung SCC cell line expressing endogenous podoplanin. Conclusions Our findings suggested that LSCC-associated podoplanin was functional and could attenuate the potential for lymph node metastasis, possibly based on the suppression of tumor lymphangiogenesis; thus, podoplanin in cancer cells may become a useful biomarker to measure the malignancy of lung SCC.
Recurrent Hepatocellular Carcinoma: It's the Virus!
Authors: W. Ray Kim, Gregory J. Gores
Journal: Journal of Clinical Oncology (2013)

influence the incidence of HCC recurrence, antiviral treatment and preoperative serum HBV DNA were found to have a significant impact on postoperative recurrence and subsequent death. While these results, particularly those of the randomized trial, are exciting and significant, the study has limitations. Inexplicably, the randomization failed to balance important aspects of the two study arms. Patients who were assigned to no antiviral treatment had a significantly higher proportion of incomplete or no tumor encapsulation (73% v 53%), poor differentiation (81 v 62%) and increased serum alpha fetoprotein ( 20 ng/mL, 72% v 57%). On the other hand, patients who were assigned to receive antiviral therapy were enriched with uninodular tumors (88% v 72%), small ( 3 cm) lesions (14% v 6%), and low Barcelona Clinic Liver Cancer stage tumors (0 or A, 88% v 73%), although these differences did not reach statistical significance. These characteristics place patients in the antiviral group at a lower risk of tumor recurrence with a potential for clinical benefits associated with antiviral therapy. A subsequent post hoc multivariable analysis may not necessarily correct the inherent differences between the two arms. As one considers the validity of the conclusion of the study and questions how antiviral therapy may reduce the incidence of HCC, it is
Platelet-Activating Factor Induces Up-regulation of Antiapoptotic Factors in a Melanoma Cell Line through Nuclear Factor-κB Activation
Authors: Kook Heon Seo, Hyun-Mi Ko, Han-A Kim, Jung-Hwa Choi, Sung Jun Park, Kyoung-Jin Kim, Hern-Ku Lee, Suhn-Young Im
Journal: Cancer Research (2006)

In this study, we investigated the influence of platelet-activating factor (PAF) on the induction of apoptosis-regulating factors in B16F10 melanoma cells. PAF increased the expression of mRNA and the protein synthesis of antiapoptotic factors, such as Bcl-2 and Bcl-xL, but did not increase the expression of the proapoptotic factor, Bax. A selective nuclear factor-kappaB (NF-kappaB) inhibitor, parthenolide, inhibited the effects of PAF. Furthermore, PAF inhibited etoposide-induced increases in caspase-3, caspase-8, and caspase-9 activities, as well as cell death. p50/p65 heterodimer increased the mRNA expression of Bcl-2 and Bcl-xL and decreased etoposide-induced caspase activities and cell death. In an in vivo model in which Matrigel was injected s.c., PAF augmented the growth of B16F10 cells and attenuated etoposide-induced inhibition of B16F10 cells growth. These data indicate that PAF induces up-regulation of antiapoptotic factors in a NF-kappaB-dependent manner in a melanoma cell line, therefore suggesting that PAF may diminish the cytotoxic effect of chemotherapeutic agents.
Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries
Authors: E Cardis, M Vrijheid, M Blettner, E Gilbert, M Hakama, C Hill, G Howe, J Kaldor, C R Muirhead, M Schubauer-Berigan, T Yoshimura, F Bermann, G Cowper, J Fix, C Hacker, B Heinmiller, M Marshall, I Thierry-Chef, D Utterback, Y-O Ahn, E Amoros, P Ashmore, A Auvinen, J-M Bae, J Bernar Solano, A Biau, E Combalot, P Deboodt, A Diez Sacristan, M Eklof, H Engels, G Engholm, G Gulis, R Habib, K Holan, H Hyvonen, A Kerekes, J Kurtinaitis, H Malker, M Martuzzi, A Mastauskas, A Monnet, M Moser, M S Pearce, D B Richardson, F Rodriguez-Artalejo, A Rogel, H Tardy, M Telle-Lamberton, I Turai, M Usel, K Veress
Journal: BMJ (2005)

<h3>OBJECTIVE</h3> To determine provincial trends in provision of intrapartum care by general practitioners and family physicians (GP/FPs) for the 11 years from 1984 to 1995. <h3>DESIGN</h3> Analyses of provincial Medical Care Fee-for-Service Utilization data for births from 1984-1985 to 1994-1995. <h3>SETTING</h3> 10 provinces of Canada. <h3>MAIN OUTCOME MEASURES</h3> Proportion of vaginal births billed by GP/FPs (expressed as total number of vaginal births billed by GP/FPs divided by total number of vaginal births). <h3>RESULTS</h3> In 1994-1995, the proportion of vaginal births billed by GP/FPs ranged from 77.2% in British Columbia and 70.8% in Nova Scotia to 28.9% in Ontario and 23.6% in Prince Edward Island. These proportions have remained relatively high and stable during the period studied in some provinces, such as British Columbia and Nova Scotia, and have declined steadily and notably in others. <h3>CONCLUSIONS</h3> Data show that GP/FPs9 involvement in vaginal births in most Canadian provinces is decreasing. This trend demonstrates a shift in GP/FPs9 practice patterns and could indicate a coming shortage of obstetrical care providers.
P16.32 * TOWARDS COMPUTER AIDED NEURORADIOLOGICAL DIAGNOSTICS OF BRAIN TUMORS
Authors: J. Slotboom, A. Pica, R. Wiest, S. Bauer, M. Zbinden, A. Raabe, N. Porz, P. Schucht, B. Sick
Journal: Neuro-Oncology (2014)

INTRODUCTION: MRI and MRS are the modalities of choice for the initial diagnosis of brain tumors. Despite the overwhelming amount of performed studies on the available MRI/MRS parameters, the differential diagnosis for individual patients remains difficult: statistical significant differences between patient groups suffering from different types of brain tumors could be shown, but many of these differences are not relevant for individual diagnostics. It is hypothesized that the full potential of MRI/MRS is currently not used in routine diagnostics. To illustrate this claim, this paper will introduce a novel computer aided diagnostic method. It is shown that apparent diffusion coefficients (ADCs) only are sufficient for reliable individual diagnostics of high grade (HGG) versus low grade glioma (LGG) without contrast agents; a task that could not be performed by visual ADC-map inspection alone. METHODS: The key characteristics of the method are: (a.) the determination of so-called histogram- and co-occurrence matrix-based texture parameters (TPMs) from regions of interest drawn by a neuroradiologist encircling the complete tumor-affected volume (high cellular density compartments, edema, and necrosis); (b.) the mean and higher order statistical moments of these texture parameters are used; (c.) these texture features are the input parameters to a random forest classification algorithm (RFC) which is trained to perform the classification, i.e. the diagnosis. A random forest is a classification method consisting of a combined ensemble of decision trees. It is a highly flexible statistical model allowing capturing multiple interactions and non-linearities without over-fitting the data, yielding high accuracy predictions. Moreover, the RFC can be utilized for feature selection identifying a subset of important feature within up to thousands of features. The performance of the RFC is evaluated by its prediction power on new cases by comparison with the experts' diagnoses. RESULTS: The TPMs of a total of 184 ADC-maps were extracted from 18 grade-II and 21 grade-IV glioma patients and were contoured as described above and were classified with the RFC-algorithm. Using the-leave-one out method for validation (on patient level), resulted in 91 out of 104 correctly classified grade-IV, and 61 out of 80 resulted correctly classified grade-II ADC-maps, meaning a classification error of just 17.4% for discriminating the two diseases. CONCLUSION: Using RFC applied on texture parameters of ADC-maps, HGG can automatically be discriminated from LGG with a high level of accuracy, without the need of any MR-contrast agents. Since the method is very simple to apply, and non time consuming its application in a clinical setting is easily feasible. Currently new classifiers on other image modalities than ADC-maps are constructed to discriminate malignant glioma from other malignant brain tumor types.
Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats
Authors: Vez Repunte-Canonigo, Celine Lefebvre, Olivier George, Tomoya Kawamura, Marisela Morales, George F Koob, Andrea Califano, Eliezer Masliah, Pietro Paolo Sanna
Journal: Molecular Neurodegeneration (2014)

A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS. We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington's disease, Parkinson's disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function. Altogether, differentially regulated genes and pathway analysis identify specific pathways that can be targeted therapeutically to increase trophic support, e.g. IGF, ErbB and netrin signaling, and reduce neuroinflammation, e.g. PGD2 synthesis, which may be beneficial in the treatment of chronic forms of HIV-associated neurocognitive disorders in the setting of viral suppression.