tbuckley/cabot-search huggingface dataset:
Activation of Apoptosis Signal-Regulating Kinase 1 in Injured Artery and Its Critical Role in Neointimal Hyperplasia
Authors: Yasukatsu Izumi, Shokei Kim, Minoru Yoshiyama, Yasuhiro Izumiya, Kaoru Yoshida, Atsushi Matsuzawa, Hidenori Koyama, Yoshiki Nishizawa, Hidenori Ichijo, Junichi Yoshikawa, Hiroshi Iwao
Journal: Circulation (2003)

Apoptosis signal-regulating kinase 1 (ASK1), recently identified as one of the mitogen-activated protein kinase kinase kinases, is activated by various extracellular stimuli and involved in a variety of cellular function. Therefore, we first examined the role of ASK1 in vascular remodeling.We used rat balloon injury model and cultured vascular smooth muscle cells (VSMCs). Arterial ASK1 activity was rapidly and dramatically increased after balloon injury. To specifically inhibit endogenous ASK1 activation, dominant-negative mutant of ASK1 (DN-ASK1) was transfected into rat carotid artery before balloon injury. Gene transfer of DN-ASK1 significantly prevented neointimal formation at 14 days after injury. Bromodeoxyuridine labeling index at 7 days after injury showed that DN-ASK1 remarkably suppressed VSMC proliferation in both the intima and the media. We also examined the role of ASK1 in cultured rat VSMCs. Infection with DN-ASK1 significantly attenuated serum-induced VSMC proliferation and migration. We also compared neointimal formation after cuff placement around the femoral artery between mice deficient in ASK1 (ASK1-/- mice) and wild-type (WT) mice. Neointimal formation at 28 days after cuff injury in ASK1-/- mice was significantly attenuated compared with WT mice. Furthermore, we compared the proliferation and migration of VSMCs isolated from ASK1-/- mice with WT mice. Both proliferation and migration of VSMCs from ASK1-/- mice were significantly attenuated compared with VSMCs from WT mice.ASK1 activation plays the key role in vascular intimal hyperplasia. ASK1 may provide the basis for the development of new therapeutic strategy for vascular diseases.
Mammary-specific deletion of parathyroid hormone–related protein preserves bone mass during lactation
Authors: Joshua N. VanHouten, Pamela Dann, Andrew F. Stewart, Christine J. Watson, Michael Pollak, Andrew C. Karaplis, John J. Wysolmerski
Journal: Journal of Clinical Investigation (2003)

Large amounts of calcium are transferred to offspring by milk. This demand results in negative calcium balance in lactating mothers and is associated with rapid bone loss. The mechanisms of bone loss during lactation are only partly understood. Several studies have suggested that parathyroid hormone–related protein (PTHrP) might be secreted into the circulation by the lactating mammary gland and regulate bone turnover during lactation. Because mammary development fails in the absence of PTHrP, conventional PTHrP knockout mice cannot be used to address this possibility. To examine this hypothesis, we therefore used mice carrying a β-lactoglobulin promoter-driven Cre transgene, one null PTHrP allele, and one floxed PTHrP allele. Expression of Cre specifically in mammary epithelial cells during late pregnancy and lactation resulted in efficient deletion of the PTHrP gene; mammary gland PTHrP mRNA and milk PTHrP protein were almost completely absent. Removal of PTHrP from the lactating mammary glands resulted in reductions in levels of circulating PTHrP and 1,25-dihydroxy vitamin D and urinary cAMP. In addition, bone turnover was reduced and bone loss during lactation was attenuated. We conclude that during lactation mammary epithelial cells are a source of circulating PTHrP that promotes bone loss by increasing rates of bone resorption.
Recent advances in the discovery of flavonoids and analogs with high‐affinity binding to P‐glycoprotein responsible for cancer cell multidrug resistance
Authors: Ahcène Boumendjel, Attilio Di Pietro, Charles Dumontet, Denis Barron
Journal: Medicinal Research Reviews (2002)

Abstract P‐glycoprotein (P‐gp) is a plasma membrane glycoprotein that confers multidrug resistance on cells by virtue of its ability to exclude cytotoxic drugs in an ATP‐dependent manner. The most commonly considered hypothesis is that P‐gp acts as an ATP‐driven drug‐export pump, the mechanism of which is not understood in detail. Therefore, a tremendous effort is being made to find out modulator molecules to inhibit P‐gp. We have been developing flavonoid derivatives as a new class of promising modulators using a new in vitro rational‐screening assay based on measurements of the binding‐affinity toward the C‐terminal nucleotide‐binding domain (NBD2) of P‐gp. This review is focused on our results obtained with a variety of flavonoids. Structure–activity relationships of flavonoids as potential MDR modulators are reported. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 512–529, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10015
Selective reovirus infection of murine hepatocarcinoma cells during cell division. A model of viral liver infection.
Authors: J Taterka, M Sutcliffe, D H Rubin
Journal: Journal of Clinical Investigation (1994)

Reovirus type 1, strain Lang (1/L), can infect hepatocytes in vivo only after hepatocellular damage is induced by hepatotoxins, surgical trauma, resection, or profound immunosuppression. To examine the role of cell cycle and cellular differentiation on liver cell susceptibility to reovirus infection, a murine hepatocarcinoma cell line, Hepa 1/A1, was infected with reovirus and assayed for the presence of infectious virus or reovirus antigen in cells. Despite a > 95% binding of reovirus to hepatocarcinoma cells as indicated by cytometric analysis; only 10% of hepatoma cells contained infectious virus by infectious center assay. In comparison, 100% of L cells were infected. Analysis of intracellular reovirus antigen revealed its presence in dividing but not in quiescent hepatocytes. This correlation of cellular division and cell capacity to support viral replication suggests that induction of hepatocyte proliferation may be a mechanism for liver susceptibility to reovirus infection.
Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate
Authors: Pedro Cuevas, Luis Antonio Outeiriño, Carlos Azanza, Javier Angulo, Guillermo Giménez-Gallego
Journal: Military Medical Research (2015)

Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.
Ethnic differences in respiratory impairment
Authors: Carlos A Vaz Fragoso, Gail McAvay, Thomas M Gill, John Concato, Philip H Quanjer, Peter H Van Ness
Journal: Thorax (2013)

<h3>Objective</h3> Spirometric Z scores by lambda-mu-sigma (LMS) rigorously account for age-related changes in lung function. Recently, the Global Lung Function Initiative (GLI) expanded LMS spirometric Z scores to multiple ethnicities. Hence, in aging populations, the GLI provides an opportunity to rigorously evaluate ethnic differences in respiratory impairment, including airflow limitation and restrictive pattern. <h3>Methods</h3> Using data from the Third National Health and Nutrition Examination Survey, including participants aged 40–80, we evaluated ethnic differences in GLI-defined respiratory impairment, including prevalence and associations with mortality and respiratory symptoms. <h3>Results</h3> Among 3506 white Americans, 1860 African Americans and 1749 Mexican Americans, the prevalence of airflow limitation was 15.1% (13.9% to 16.4%), 12.4% (10.7% to 14.0%) and 8.2% (6.7% to 9.8%), and restrictive pattern was 5.6% (4.6% to 6.5%), 8.0% (6.9% to 9.0%) and 5.7% (4.5% to 6.9%), respectively. Airflow limitation was associated with mortality in white Americans, African Americans and Mexican Americans—adjusted HR (aHR) 1.66 (1.23 to 2.25), 1.60 (1.09 to 2.36) and 1.80 (1.17 to 2.76), respectively, but associated with respiratory symptoms only in white Americans—adjusted OR (aOR) 2.15 (1.70 to 2.73). Restrictive pattern was associated with mortality but only in white Americans and African Americans—aHR 2.56 (1.84 to 3.55) and 3.23 (2.06 to 5.05), and associated with respiratory symptoms but only in white Americans and Mexican Americans—aOR 2.16 (1.51 to 3.07) and 2.12 (1.45 to 3.08), respectively. <h3>Conclusions</h3> In an aging population, we found ethnic differences in GLI-defined respiratory impairment. In particular, African Americans had high rates of respiratory impairment that were associated with mortality but not respiratory symptoms.
NON-PARALYTIC POLIOMYELITIS IN THE CHIMPANZEE
Authors: David Bodian, Howard A. Howe
Journal: The Journal of Experimental Medicine (1945)

1. Thirteen cases of non-paralytic poliomyelitis infection in chimpanzees are described. Nine of these animals were excreting virus in. their stools at periods of from 3 days to 8 weeks following inoculation. 2. All animals killed during the acute stage showed lesions in the brain distributed in centers usually involved in, and compatible with the presence of, poliomyelitic infection. In 2 chimpanzees typical cord lesions were also present. No lesions were found in the brains of 4 control chimpanzees which had had no virus contact as far as known. The occurrence of a purely systemic or peripheral form of poliomyelitis, without lesions in the central nervous system, has thus not been established. 3. Four instances of arrest of the pathological process near the portal of entry into the brain, indicating partial resistance, are included in this series. One was a chimpanzee inoculated intranasally (A1-75) who had severe tuberculosis at the time of inoculation. The second was an animal convalescent after intracerebral inoculation (A1-74), who sustained a second infection limited to the olfactory bulbs when inoculated intranasally 2 months later with homologous virus. The third (A5-01) was inoculated orally with human stool, but contammation of the olfactory area resulted with infection of the olfactory bulbs and of the forebrain; virus was present in the stools of this animal. The fourth chimpanzee (A48) had suffered an initial non-paralytic attack after stomach tube inoculation, followed by a second attack about 9 months later after oral inoculation with part of the same virus-containing pool (human stools). The second attack consisted of a facial paralysis, with arrest of the pathological process near the facial nucleus. 4. Although cerebral lesions were light in some of the non-paralytic and inapparent infections, their presence in all indicates the action of virus on the central nervous system with the possibihty of production of at least partial local resistance. It is not unreasonable to assume that this may occur in inapparent human cases, although the point is, of course, not susceptible to critical proof in man. 5. The degree of severity of pathological involvement in non-paralytic cases varies from a fully developed distribution of lesions in brain and spinal cord in some chimpanzees, to mild and scattered lesions in the brains of others. This suggests that if the extent of pathological reaction is an indicator of subsequent local resistance to reinfection, the degree of protection afforded by a non-paralytic attack of poliomyelitis to even homologous virus must be variable.
Tumors of the Immunocompromised Patient
Authors: Israel Penn
Journal: Annual Review of Medicine (1988)

Immunocompromised patients are prone to develop certain malignancies, particularly involving cells of the immune system itself (1-3). In this chapter we describe the various neoplasms, note the differences between these and similar cancers in the general population, emphasize similar tumor patterns in different types of immunodeficiency, and discuss possible etiologic factors.
Lung structure-function correlation in patients with primary ciliary dyskinesia
Authors: M. Boon, F. L. Vermeulen, W. Gysemans, M. Proesmans, M. Jorissen, K. De Boeck
Journal: Thorax (2015)

<h3>Background</h3> Primary ciliary dyskinesia (PCD) is a rare disease, characterised by chronic airway infection. In cystic fibrosis, FEV<sub>1</sub> is insensitive to detect patients with structural damage, and Lung Clearance Index (LCI) was proposed as a better marker of early lung damage. In PCD, the relationship between functional and structural abnormalities has been less studied. We aimed to re-examine this in a cohort of children and adults with mild to moderate PCD. <h3>Methods</h3> Thirty-eight patients with PCD (5.2–25.0 years) and 70 healthy controls (4.4–25.8 years) were recruited to compare LCI, measured by N<sub>2</sub> multiple breath washout and FEV<sub>1</sub> in a prospective observational trial. In a subset of 30 patients who underwent chest imaging, structural abnormalities were evaluated with cystic fibrosis computed tomography (CFCT) scores. <h3>Results</h3> LCI was abnormal in 28 of 38 patients and a moderate correlation was observed between LCI and FEV<sub>1</sub> (r=−0.519, p=0.001). Moreover, LCI correlated well with CFCT total score (r=0.800, p&lt;0.001) and also with subscores for airway wall thickening (r=0.809, p&lt;0.001), mucus plugging (r=0.720, p&lt;0.001) and bronchiectasis (r=0.494, p&lt;0.001). Concordance was seen between LCI and CFCT in 25 of 30 (83%) patients, but between FEV<sub>1</sub> and CFCT in only 16 of 30 (53%) patients. LCI was more sensitive (90.9%, 95% CI 70.8 to 98.6) to detect patients with structural abnormalities than FEV<sub>1</sub> (36.4%, 95% CI 17.2 to 59.3). <h3>Conclusions</h3> We demonstrated that measuring LCI in patients with PCD is of clinical relevance; it was more frequently abnormal than FEV<sub>1</sub>, correlated well with CFCT and was more sensitive than FEV<sub>1</sub> to detect patients with structural abnormalities.
Sequence of morphological events during topical application of retinoic acid on the rhino mouse skin
Authors: FRANCOISE BERNERD, M. DEMARCHEZ, J.-P. ORTONNE, J. CZERNIELEWSKI
Journal: British Journal of Dermatology (1991)

Journal Article Sequence of morphological events during topical application of retinoic acid on the rhino mouse skin Get access FRANÇOISE BERNERD, FRANÇOISE BERNERD Centre International de Recherches Dermatologues Galderma, Valbonne, France Dr F. Bernerd, Centre International de Recherches Dermatologiques Galderma, Sophia Antipolis. 06565 Valbonne, France Search for other works by this author on: Oxford Academic Google Scholar M. DÉMARCHEZ, M. DÉMARCHEZ Centre International de Recherches Dermatologues Galderma, Valbonne, France Search for other works by this author on: Oxford Academic Google Scholar J.‐P. ORTONNE, J.‐P. ORTONNE Departement de Dermatologle, Hopital Fastear, Nice, France Search for other works by this author on: Oxford Academic Google Scholar J. CZERNIELEWSKI J. CZERNIELEWSKI Centre International de Recherches Dermatologues Galderma, Valbonne, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 5, 1 November 1991, Pages 419–425, https://doi.org/10.1111/j.1365-2133.1991.tb14766.x Published: 01 November 1991
In Search of a Real “Targeted” Therapy for Thyroid Cancer
Authors: Marcia S. Brose
Journal: Clinical Cancer Research (2012)

Over the past 5 years, patients with progressive radioactive iodine-refractory thyroid cancer have responded to "targeted" multikinase inhibitors, which inhibit angiogenesis and not the tumor cell. Here, selumetinib targets the mitogen-activated protein kinase pathway in papillary thyroid carcinoma and shows limited single-agent activity in the patients with tumors that harbor the (V600E)BRAF mutation.
Single-Molecule Mechanics of R403Q Cardiac Myosin Isolated From the Mouse Model of Familial Hypertrophic Cardiomyopathy
Authors: M. J. Tyska, E. Hayes, M. Giewat, C. E. Seidman, J. G. Seidman, D. M. Warshaw
Journal: Circulation Research (2000)

Abstract —Familial hypertrophic cardiomyopathy (FHC) is an inherited cardiac disease that can result in sudden death in the absence of any overt symptoms. Many of the cases documented to date have been linked with missense mutations in the β-myosin heavy chain gene. Here we present data detailing the functional impact of one of the most deadly mutations, R403Q, on myosin motor function. Experiments were performed on whole cardiac myosin purified from a mouse model of FHC to eliminate potential uncertainties associated with protein expression systems. The R403Q mutant myosin demonstrated 2.3-fold higher actin-activated ATPase activity, 2.2-fold greater average force generation, and 1.6-fold faster actin filament sliding in the motility assay. The force- and displacement-generating capacities of both the normal and mutant myosin were also characterized at the single molecule level in the laser trap assay. Both control and mutant generated similar unitary forces (≈1 pN) and displacements (≈7 nm) without any differences in event durations. On the basis of the distribution of mean unitary displacements, this mutation may possibly perturb the mechanical coordination between the 2 heads of cardiac myosin. Any of these observations could, alone or possibly in combination, result in abnormal power output and potentially a stimulus for the hypertrophic response.
Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival
Authors: Johanna Tommiska, Hannaleena Eerola, Mira Heinonen, Laura Salonen, Milja Kaare, Jonna Tallila, Ari Ristimäki, Karl von Smitten, Kristiina Aittomäki, Päivi Heikkilä, Carl Blomqvist, Heli Nevanlinna
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The p53 R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival. Experimental Design: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancer patients and 736 healthy population controls. The clinical and biological variables were tested for association by univariate analysis and the effects of several variables on survival by Cox's proportional hazards regression model. Results: The distribution of the genotypes was similar in all groups studied, suggesting no association with breast cancer risk. Unselected breast cancer patients with 72P homozygous genotype presented significantly more often with lobular carcinoma, whereas R72 allele carriers had a significantly higher frequency of ductal carcinomas (P = 0.004). No significant association with other histopathologic variables, like tumor grade, hormone receptor status (estrogen and progesterone receptors), or tumor-node-metastasis stage, was observed. Survival analysis showed that unselected breast cancer patients with 72P homozygous genotype had significantly poorer survival than patients with other genotypes (P = 0.003). This effect on survival was independent of p53 expression in the tumors and multivariate analysis showed that 72P homozygous genotype was overall an independent prognostic factor (risk ratio of death, 2.1; 95% confidence interval, 1.4-3.3; P = 0.001). Conclusions: These results suggest no effect of either R72P allele on breast cancer risk but a significantly reduced survival for 72P homozygous breast cancer patients. The finding of codon 72 genotype as an independent prognostic marker for breast cancer warrants further studies.
Complete sequences of the rRNA genes of Drosophila melanogaster.
Authors: D Tautz, J M Hancock, D A Webb, C Tautz, G A Dover
Journal: Molecular Biology and Evolution (1988)

In this, the first of three papers, we present the sequence of the ribosomal RNA (rRNA) genes of Drosophila melanogaster. The gene regions of D. melanogaster rDNA encode four individual rRNAs: 18S (1,995 nt), 5.8S (123 nt), 2S (30 nt), and 28S (3,945 nt). The ribosomal DNA (rDNA) repeat of D. melanogaster is AT rich (65.9% overall), with the spacers being particularly AT rich. Analysis of DNA simplicity reveals that, in contrast to the intergenic spacer (IGS) and the external transcribed spacer (ETS), most of the rRNA gene regions have been refractory to the action of slippage-like events, with the exception of the 28S rRNA gene expansion segments. It would seem that the 28S rRNA can accommodate the products of slippage-like events without loss of activity. In the following two papers we analyze the effects of sequence divergence on the evolution of (1) the 28S gene "expansion segments" and (2) the 28S and 18S rRNA secondary structures among eukaryotic species, respectively. Our detailed analyses reveal, in addition to unequal crossing-over, (1) the involvement of slippage and biased mutation in the evolution of the rDNA multigene family and (2) the molecular coevolution of both expansion segments and the nucleotides involved with compensatory changes required to maintain secondary structures of RNA.
Wt1 ablation and Igf2 upregulation in mice result in Wilms tumors with elevated ERK1/2 phosphorylation
Authors: Qianghua Hu, Fei Gao, Weihua Tian, E. Cristy Ruteshouser, Yaqing Wang, Alexander Lazar, John Stewart, Louise C. Strong, Richard R. Behringer, Vicki Huff
Journal: Journal of Clinical Investigation (2010)

Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic alterations have been identified in WT patients, including inactivating mutations in WT1 and loss of heterozygosity or loss of imprinting at 11p15, which results in biallelic expression of IGF2. However, the mechanisms by which one or a combination of genetic alterations results in tumorigenesis has remained challenging to determine, given the lack of a mouse model of WT. Here, we engineered mice to sustain mosaic, somatic ablation of Wt1 and constitutional Igf2 upregulation, mimicking a subset of human tumors. Mice with this combination of genetic alterations developed tumors at an early age. Mechanistically, Wt1 ablation blocked mesenchyme differentiation, and increased Igf2 expression upregulated ERK1/2 phosphorylation. Importantly, a subset of human tumors similarly displayed upregulation of ERK1/2 phosphorylation, which suggests ERK signaling might contribute to WT development. Thus, we have generated a biologically relevant mouse model of WT and defined one combination of driver alterations for WT. This mouse model will provide a powerful tool to study the biology of WT initiation and progression and to investigate therapeutic strategies for cancers with IGF pathway dysregulation.
Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility
Authors: Julius Gudmundsson, Patrick Sulem, Daniel F Gudbjartsson, Thorarinn Blondal, Arnaldur Gylfason, Bjarni A Agnarsson, Kristrun R Benediktsdottir, Droplaug N Magnusdottir, Gudbjorg Orlygsdottir, Margret Jakobsdottir, Simon N Stacey, Asgeir Sigurdsson, Tiina Wahlfors, Teuvo Tammela, Joan P Breyer, Kate M McReynolds, Kevin M Bradley, Berta Saez, Javier Godino, Sebastian Navarrete, Fernando Fuertes, Laura Murillo, Eduardo Polo, Katja K Aben, Inge M van Oort, Brian K Suarez, Brian T Helfand, Donghui Kan, Carlo Zanon, Michael L Frigge, Kristleifur Kristjansson, Jeffrey R Gulcher, Gudmundur V Einarsson, Eirikur Jonsson, William J Catalona, Jose I Mayordomo, Lambertus A Kiemeney, Jeffrey R Smith, Johanna Schleutker, Rosa B Barkardottir, Augustine Kong, Unnur Thorsteinsdottir, Thorunn Rafnar, Kari Stefansson
Journal: Nature Genetics (2009)
Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells
Authors: Julie Renaud, Géraldine Kerjan, Itsuko Sumita, Yvrick Zagar, Virginie Georget, Doyeun Kim, Coralie Fouquet, Kazunori Suda, Makoto Sanbo, Fumikazu Suto, Susan L Ackerman, Kevin J Mitchell, Hajime Fujisawa, Alain Chédotal
Journal: Nature Neuroscience (2008)