tbuckley/cabot-search huggingface dataset:
Endothelial, not hemodynamic, differences are responsible for preferential leukocyte rolling in rat mesenteric venules.
Authors: K Ley, P Gaehtgens
Journal: Circulation Research (1991)

At the onset of the inflammatory process, leukocytes roll along venular but not arteriolar walls before they firmly attach and emigrate. To test whether differences in hydrodynamic flow conditions are responsible for the preferential occurrence of leukocyte rolling in venules, we varied wall shear rate, gamma w, between 30 and 2,000 sec-1 by selective micro-occlusion of side branches in venules and arterioles (diameter, 20-37 microns) of the exposed mesentery of anesthetized rats. In venules, 39% (range, 6-77%) of all passing leukocytes were found interacting with the endothelium (rolling), whereas this fraction was only 0.6% in arterioles. The fraction of rolling leukocytes in venules decreased from 49 +/- 13% at gamma w less than 100 sec-1 (N = 12) to 24 +/- 13% at gamma w greater than 400 sec-1 (N = 12). Mean leukocyte rolling velocity in venules increased with gamma w, but the most frequent rolling velocity class was 20-40 microns/sec at all shear rates. In arterioles, even prolonged (up to 90 minutes) conditions of reduced flow (gamma w less than 150 sec-1) did not induce leukocyte rolling. Radial distribution of freely flowing leukocytes not different in arterioles and venules. The data indicate that hemodynamic factors are not responsible for the difference of leukocyte adhesion between arterioles and venules. The venular endothelium appears to be specialized to support leukocyte adhesion during inflammation. This finding correlates with reports on preferential expression of various endothelial-leukocyte adhesion molecules on venular endothelial cells.
Flies, Genes, and Learning
Authors: Scott Waddell, William G Quinn
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Flies can learn. For the past 25 years, researchers have isolated mutants, engineered mutants with transgenes, and tested likely suspect mutants from other screens for learning ability. There have been notable surprises—conventional second messenger systems co-opted for intricate associative learning tasks, two entirely separate forms of long-term memory, a cell-adhesion molecule that is necessary for short-term memory. The most recent surprise is the mechanistic kinship revealed between learning and addictive drug response behaviors in flies. The flow of new insight is likely to quicken with the completion of the fly genome and the arrival of more selective methods of gene expression.
Use of collagen sponge incorporating transforming growth factor-β1 to promote bone repair in skull defects in rabbits
Authors: Hiroki Ueda, Liu Hong, Masaya Yamamoto, Keiji Shigeno, Masatoshi Inoue, Toshinari Toba, Makoto Yoshitani, Tatsuo Nakamura, Yasuhiko Tabata, Yasuhiko Shimizu
Journal: Biomaterials (2002)
Regional variations in antigenic properties of skin. A possible cause for disease-specific distribution of skin lesions.
Authors: L Sison-Fonacier, J C Bystryn
Journal: The Journal of Experimental Medicine (1986)

The possibility that the distribution of skin lesions in some cutaneous diseases is due to variations in the antigenic properties of skin was investigated by mapping the expression of the skin-specific pemphigus vulgaris and bullous pemphigoid antigens in different regions of the body. The expression of both antigens was relatively stable within the same region, but varied between regions in a pattern that was distinct for each antigen. For each antigen there was a correlation between regions of high expression and location of skin lesions in autoimmune diseases involving the antigen. The results indicate that there are marked regional differences in the antigenic properties of skin and suggest this may influence the distribution of cutaneous lesions in some skin diseases.
CYP6B1 and CYP6B3 of the Black Swallowtail (Papilio polyxenes): Adaptive Evolution through Subfunctionalization
Authors: Zhimou Wen, Sanjeewa Rupasinghe, Guodong Niu, May R. Berenbaum, Mary A. Schuler
Journal: Molecular Biology and Evolution (2006)

Gene duplication provides essential material for functional divergence of proteins and hence allows organisms to adapt to changing environments. Following duplication events, redundant paralogs may undergo different evolutionary paths via processes known as nonfunctionalization, neofunctionalization, or subfunctionalization. Studies of adaptive evolution at the molecular level have progressed rapidly by computationally analyzing nucleotide substitution patterns but such studies are limited by the absence of information relating to alterations of function of the encoded enzymes. In this respect, evolution of the Papilio polyxenes cytochrome P450 monooxygenases (P450s) responsible for the adaptation of this insect to furanocoumarin-containing host plants provides an excellent model for elucidating the evolutionary fate of duplicated genes. Evidence from sequence and functional analysis in combination with molecular modeling indicates that the paralogous CYP6B1 and CYP6B3 genes in P. polyxenes have probably evolved via subfunctionalization after the duplication event by which they arose. Both enzymes have been under independent purifying selection as evidenced by the low dN/dS ratio in both the coding region and substrate recognition sites. Both enzymes have maintained their ability to metabolize linear and angular furanocoumarins albeit at different efficiencies. Comparisons of molecular models developed for the CYP6B3 and CYP6B1 proteins highlight differences in their binding modes that account for their different activities toward linear and angular furanocoumarins. That P. polyxenes maintains these 2 furanocoumarin-metabolizing loci with somewhat different activities and expression patterns provides this species with the potential to acquire P450s with novel functions while maintaining those most critical to its exclusive feeding on its current range of host plants.
Effect of histamine on the energy metabolism of K+-depolarized hog carotid artery.
Authors: J W Peterson
Journal: Circulation Research (1982)

In a previous study (Peterson and Glück, 1982), activation of hog carotid artery with high-K+ medium caused no increase in aerobic glycolysis (lactic acid production). In contrast, histamine alone is found to stimulate aerobic glycolysis in a tension-dependent fashion (GLück and Paul, 1977). In this study, the addition of histamine to the already K+-depolarized hog carotid artery induced additional contraction, elevated tissue cyclic adenosine 3',5'-monophosphate [cAMP] levels, coupled the rate of aerobic glycolysis to external [Ca++] and isometric tension, and caused suprabasal energy utilization to exceed that required to support the contraction alone by approximately 25%. Increased cytoplasmic free-[Ca++] per se does not stimulate aerobic glycolysis. In the presence of histamine, however, aerobic glycolysis is Ca++-sensitive. Whereas a cycle of Ca++ depletion and restoration has only a small effect on basal metabolic rates in arteries activated with high-K+ alone, the same procedure with arteries stimulated by high-K+ with added histamine causes a dramatic shift in basal metabolic rates toward higher levels of glycolysis.
Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection
Authors: Irene Cacciola, Teresa Pollicino, Giovanni Squadrito, Giovanni Cerenzia, Daniela Villari, Roberto de Franchis, Teresa Santantonio, Santa Brancatelli, Giuseppe Colucci, Giovanni Raimondo
Journal: Hepatology (2000)

No data are available about the amount of hepatitis B virus (HBV) genomes in liver of patients with chronic HBV infection. The aim of this study was to quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)-positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche "Amplicor HBV Monitor" kit for quantifying liver HBV DNA and analyzed hepatic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-negative individuals. Eight of the HBsAg carriers had active HBV replication, and for 3 of them we analyzed samples obtained before and at the end of 1 year of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected patients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HBsAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA milliliter of serum was 34,500 to 2,620,000 in patients with active viral replication, 20,000 to 3,900, 000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDV-infected individuals, and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that cases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observed after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA.
Hypoxic ventilatory response and acute mountain sickness
Authors: JS Milledge, PS Thomas, JM Beeley, JS English
Journal: European Respiratory Journal (1988)

The acute ventilatory response to hypoxia (HVR) and to hypercapnia (CO2VR) was measured in 32 members of two mountaineering expeditions prior to their departure. Both teams made rapid ascents to their base camps at 5200 m and 4300 m and remained there for at least four days. Symptom scores for acute mountain sickness (AMS) were collected daily for these four days. There was a range of AMS from the unaffected to severe sickness requiring evacuation, but there was no correlation between AMS scores and HVR or CO2VR. When ascent to altitude takes a day or more, HVR (measured at sea level) is probably not the major determinant of ventilation and from our studies does not predict susceptibility to AMS. The rate of respiratory acclimatization is probably more important.
Dietary factors and pulmonary function: a cross sectional study in middle aged men from three European countries
Authors: C. Tabak, H. A Smit, L. Rasanen, F. Fidanza, A. Menotti, A. Nissinen, E. J M Feskens, D. Heederik, D. Kromhout
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Results of epidemiological studies relating individual dietary factors to chronic obstructive pulmonary disease (COPD) are inconsistent. To evaluate the cross sectional association of dietary factors with pulmonary function, data were collected from middle aged men in three European countries. <h3>METHODS</h3> The data were collected in the 1960s in Finland (n = 1248), Italy (n = 1386), and the Netherlands (n = 691). Dietary intake was estimated using the cross-check dietary history method. Forced expiratory volume (FEV<sub>0.75</sub> or FEV<sub>1</sub>, here called FEV) was measured by spirometry. Associations were adjusted for age, height, smoking, body mass index (BMI), alcohol consumption, and energy intake. <h3>RESULTS</h3> FEV was positively associated with intake of vitamin E in Finland, with intake of fruit in Italy, and with intake of β-carotene in the Netherlands. In all three countries men with intakes of both fruit and vegetables above the median had a higher FEV than those with a low intake of both foods. The difference in FEV ranged from 110 to 169 ml before and from 53 to 118 ml after energy adjustment. Differences in FEV for intake of three antioxidants (vitamins C and E and β-carotene) above versus below the median ranged from 61 to 181 ml before and from –35 to 58 ml after energy adjustment. Intake of fish was not associated with FEV. <h3>CONCLUSIONS</h3> In three European countries a high intake of fruit and vegetables was positively associated with pulmonary function. A high intake of all three antioxidants tended to be positively associated with pulmonary function before, but not after, adjustment for energy intake. Associations of individual antioxidants with pulmonary function were not consistent across countries.
Importance of leucine zipper domain of mitranscription factor (MITF) for differentiation of mast cells demonstrated using mice/mice mutant mice of which MITF lacks the zipper domain
Authors: Eiichi Morii, Hideki Ogihara, Dae-Ki Kim, Akihiko Ito, Keisuke Oboki, Young-Mi Lee, Tomoko Jippo, Shintaro Nomura, Kazutaka Maeyama, M. Lynn Lamoreux, Yukihiko Kitamura
Journal: Blood (2001)
1009 IS SKIN TOXICITY A PREDICTOR OF BETTER SURVIVAL OF PATIENTS WITH HCC TREATED WITH SORAFENIB?
Authors: A. De Santis, C. Iegri, S. Trapani, M. Lupo, F. Giubilo, C. Bassanelli, F. Attili, G. Gallusi, A.F. Attili
Journal: Journal of Hepatology (2012)
Relation of Variations in Activation Order to Intraventricular Pressures during Premature Beats
Authors: KAY MILLAR, ROBERT H. EICH, J. A. ABILDSKOV
Journal: Circulation Research (1966)

A comprehensive study on open chest anesthetized dogs was done to investigate the influence of intraventricular activation order on cardiac performance and to evaluate the degree to which entry into the conduction system might contribute to the synchrony of contraction in the ventricle opposite the stimulus site. Intraventricular pressures were measured during premature beats from several ventricular sites and over the entire range of the cardiac cycle. For each site, intraventricular pressures during the premature beats were plotted vs. time of delivery of the stimulus and also vs. time of onset of pressure rise in the ventricle being considered. The prior observation that higher ventricular pressures occur during premature beats initiated in the opposite ventricle was confirmed. Evidence is presented that the major factor responsible is the increased filling and recovery interval permitted by the conduction time of the activation front arriving from the opposite ventricle. After correction for filling and recovery time, there were still differences due to site of origin of the premature beat, with those delivered to the apex resulting in the highest left ventricular pressures. The hypothesis that a more synchronous contraction results from stimulation of sites on the contralateral, rather than the ipsilateral ventricle, was not substantiated.
Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age
Authors: Todd A. Jusko, Renata Sisto, Ana-Maria Iosif, Arturo Moleti, Sonˇa Wimmerová, Kinga Lancz, Juraj Tihányi, Eva Šovčiková, Beata Drobná, L’ubica Palkovičová, Dana Jurečková, Kelly Thevenet-Morrison, Marc-André Verner, Dean Sonneborn, Irva Hertz-Picciotto, Tomáš Trnovec
Journal: Environmental Health Perspectives (2014)

Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively.Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs.A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders.Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003).In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.
Effect of ischaemia and role of eicosanoids in release of atrial natriuretic factor from rat heart
Authors: B. N. Chen, T. E Rayner, M. F Menadue, P. L McLennan, J. R Oliver
Journal: Cardiovascular Research (1993)

The aim was to investigate (1) the relationship between atrial natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the potential role of eicosanoids in ANF release during global ischaemia, particularly the cyclo-oxygenase derivatives (prostaglandins) and the lipoxygenase derivatives (leukotrienes).Using an isolated perfused, spontaneously beating rat heart, global ischaemia was achieved by the reduction of perfusion flow rate relative to basal flow rate. ANF was measured by radioimmunoassay.A decrease in perfusion flow rate by 75-80% to a final value of 2-2.5 ml.min-1.g-1 heart (n = 6) caused a gradual but sustained increase of ANF release which reached a plateau after 12 min, attaining a peak value of 89.9 (SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60% (n = 5) also resulted in an increased ANF secretion, with a peak of 125.6(23.2)% over baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value of 5-6.75 ml.min-1.g-1 heart (n = 4) showed no change in ANF release. The mean basal value of ANF release was 8.23(2.39) ng.min-1.g-1 heart (n = 26). In a separate series of experiments using a reduction of 55-60% in perfusion flow rate but with the addition to the perfusion medium of the specific cyclo-oxygenase inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred during the period of global ischaemia. Neither inhibitor affected ANF release during basal perfusion rates (7-9 ml.min-1.g-1 heart).ANF released in response to global ischaemia is likely to be mediated by prostanoids generated via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase pathway. Both pathways may provide important paracrine/autacoid regulatory roles for the protection of the heart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately leading to a reduction in load on the heart.
Effect of Antiangiogenic Therapy on Slowly Growing, Poorly Vascularized Tumors in Mice
Authors: W.-D. C. Beecken, A. Fernandez, A. M. Joussen, E.-G. Achilles, E. Flynn, K.-M. Lo, S. D. Gillies, K. Javaherian, J. Folkman, Y. Shing
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Angiogenesis is essential for tumor growth and progression. Therefore, inhibition of angiogenesis is being studied as a new anticancer therapy. Because cytotoxic chemotherapy is more effective on rapidly growing tumors than on slowly growing tumors, it has been assumed that antiangiogenic therapy will also be effective only on rapidly growing, highly vascularized tumors. We compared the effects of two angiogenesis inhibitors, TNP-470 and angiostatin, on slowly growing, poorly vascularized and rapidly growing, highly vascularized human tumors in mice. Methods: Slowly growing (RT-4) and rapidly growing (MGH-U1) human bladder carcinoma cell lines were grown in severe combined immunodeficiency mice. Established tumors were treated with one of the two angiogenesis inhibitors. Tumor volumes, vascularity, and proliferation indices were determined. The in vitro effects of TNP-470 and of angiostatin on the proliferation of RT-4 and MGH-U1 cells were also investigated. All statistical tests were two-sided. Results: RT-4 and MGH-U1 tumor growth was statistically significantly inhibited by both angiogenesis inhibitors (P<.001). Both inhibitors decreased the blood vessel density in both tumor types but did not alter the in vivo proliferation indices of the tumors. TNP-470, but not angiostatin, marginally decreased the in vitro proliferation of MGH-U1 cells. Conclusion: Slowly growing, poorly vascularized tumors in animal models respond as well as rapidly growing, highly vascularized tumors to therapy with the angiogenesis inhibitors TNP-470 and angiostatin.
Correlation of early murine leukemia virus titer and H-2 type with spontaneous leukemia in mice of the BALB/c times AKR cross: a genetic analysis.
Authors: F Lilly, M L Duran-Reynals, W P Rowe
Journal: The Journal of Experimental Medicine (1975)

Tissue extracts from 6-wk old mice of the AKR strain (H-K) show high levels of infectious murine leukemia virus, and these mice show a near 100% incidence of spontaneous leukemia. In F1 mice of the cross, BALB/c times AKR (H-2K/H-2K), both the occurrence of virus and the incidence of spontaneous leukemia are suppressed to very low values, due largely to the presence of the FV-1b allele inherited from the BALB/c parent. Mice of the (BALB/c times AKR) F-1 times AKR backcross generation were observed for possible correlations between virus expressions at 6 wk of age, H-2 type and leukemia incidence. H-2 type showed at most a weak influence on the occurrence of infectious virus, but there was a very strong correlation between the level of virus expression and the occurrence of leukemia and a strong correlation between H-2 type and leukemia. In addition, there was a highly significant nonrandom distribution of virus-negative mice among the backcross litters, suggesting a maternal effect on virus expression.
The haematopoietic GTPase RhoH modulates IL3 signalling through regulation of STAT activity and IL3 receptor expression
Authors: Mehtap S Gündogdu, He Liu, Daniela Metzdorf, Dagmar Hildebrand, Michael Aigner, Klaus Aktories, Klaus Heeg, Katharina F Kubatzky
Journal: Molecular Cancer (2010)

Abstract Background RhoH is a constitutively active member of the family of Rho GTPases. Its expression is restricted to the haematopoietic lineage, where it serves as a positive regulator for T cell selection and mast cell function and as a negative regulator for growth-related functions in other lineages. Here, we examined the activation of signal transducer and activator of transcription (STAT) proteins in response to stimulation with interleukin 3 (IL3). Results Using the murine IL3-dependent cell line BaF3 we investigated the influence of RhoH protein expression levels on IL3-mediated cellular responses. RhoH overexpressing cells showed lower sensitivity to IL3 and decreased STAT5 activation. SiRNA-mediated repression of RhoH gene expression led to an increase in proliferation and STAT5 activity which correlated with an increased number of IL3 receptor α chain molecules, also known as CD123, expressed at the cell surface. Interestingly, these findings could be reproduced using human THP-1 cells as a model system for acute myeloid leukaemia, where low RhoH levels are known to be an unfavourable prognostic marker. Overexpression of RhoH on the other hand caused an induction of STAT1 activity and western blot analysis revealed that activated STAT1 is phosphorylated on Tyr701. STAT1 is known to induce apoptosis or cell cycle arrest and we detected an upregulation of cyclin-dependent kinase inhibitors (CDKI) p21 Cip1 and p27 Kip1 in RhoH overexpressing BaF3 cells. Conclusions We propose that RhoH functions as a negative regulator for IL3-induced signals through modulation of the JAK-STAT pathway. High levels of RhoH allow the IL3-dependent activation of STAT1 causing decreased proliferation through upregulation of p21 Cip1 and p27 Kip1 . Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients.