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S F Lax, L-C Horn, T Löning
In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type...
October 21, 2016: Der Pathologe
Jiao Li, Yi Lu, Huiting Liang, Chunyan Tang, Lei Zhu, Jie Zhang, Renshi Xu
In order to searching the possible pathogenesis of amyotrophic lateral sclerosis (ALS), we examined the expression and distribution of FUS/TLS protein in the different anatomic regions, segments and neural cells of adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic mice using the fluorescent immunohistochemistry. Result revealed that, in the SOD1 wild-type mice, the FUS/TLS expression almost wasn't detected. However, in the SOD1 G93A mice, the FUS/TLS expression in the white matter was significantly more than that in the gray matter...
2016: International Journal of Biological Sciences
Xiao-Qian Li, Zai-Li Zhang, Wen-Fei Tan, Xi-Jia Sun, Hong Ma
Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion...
2016: PloS One
Sebastian Hutchinson, Lucy Glover, David Horn
BACKGROUND: African trypanosomes cause lethal diseases in humans and animals and escape host immune attack by switching the expression of Variant Surface Glycoprotein (VSG) genes. The expressed VSGs are located at the ends of telomeric, polycistronic transcription units known as VSG expression sites (VSG-ESs). Each cell has many VSG-ESs but only one is transcribed in bloodstream-form parasites and all of them are inactive upon transmission to the insect vector mid-gut; a subset of monocistronic metacyclic VSG-ESs are then activated in the insect salivary gland...
October 18, 2016: BMC Genomics
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
Logan Horne, Frank R Avilucea, Huifeng Jin, Jared J Barrott, Kyllie Smith-Fry, Yanliang Wang, Bang H Hoang, Kevin B Jones
Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5) in osteosarcoma (OS) tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5), which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained...
October 2016: Translational Oncology
Chunyan Shao, Heng Wang, Xiaodu Wang, Sheng Jiang, Jing Sun, Houhui Song, Jianji Li
Endometritis is a common puerperal disease in livestock. Thus, a practical clinical test for the establishment of diagnosis is needed. We developed a goat model for subclinical endometritis diagnosis by examining cytological, ultrastructural features and molecular expression in cervical discharge collected by cervical cytobrush method. A suspension of E. coli was infused into the uterine horn of goats, and cervical discharge, peripheral blood and endomertrial biopsy samples were collected before inoculation and at 3, 6, 12, 24, 72, 120 and 168 hr post-inoculation (pi)...
October 16, 2016: Journal of Veterinary Medical Science
L-C Horn, C E Brambs, R Handzel, G Mehlhorn, D Schmidt, K Schierle
The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations...
October 13, 2016: Der Pathologe
Nicolas Gaboriaud-Kolar, Vasillios Myrianthopoulos, Konstantina Vougogiannopoulou, Panagiotis Gerolymatos, David A Horne, Richard Jove, Emmanuel Mikros, Sangkil Nam, Alexios-Leandros Skaltsounis
Drug resistance in chronic myelogenous leukemia (CML) requires the development of new CML chemotherapeutic drugs. Indirubin, a well-known mutikinase inhibitor, is the major active component of "Danggui Longhui Wan", a Chinese traditional medicine used for the treatment of CML symptoms. An in-house collection of indirubin derivatives was screened at 1 μM on wild-type and imatinib-resistant T315I mutant CML cells. Herein are reported that only 15 analogues of the natural 6-bromoindirubin displayed potent cytotoxicity in the submicromolar range...
October 11, 2016: Journal of Natural Products
Carolina Roza, Irene Mazo, Iván Rivera-Arconada, Elsa Cisneros, Ismel Alayón, José A López-García
The superficial dorsal horn contains large numbers of interneurons which process afferent and descending information to generate the spinal nociceptive message. Here, we set out to evaluate whether adjustments in patterns and/or temporal correlation of spontaneous discharges of these neurons are involved in the generation of central sensitization caused by peripheral nerve damage. Multielectrode arrays were used to record from discrete groups of such neurons in slices from control or nerve damaged mice. Whole-cell recordings of individual neurons were also obtained...
October 10, 2016: Pflügers Archiv: European Journal of Physiology
Rafael Salas, Karla Ramirez, Horacio Vanegas, Enrique Vazquez
Considerable evidence supports the notion that on- and off-cells of the rostral ventromedial medulla (RVM) facilitate and depress, respectively, spinal nociceptive transmission. This notion stems from a covariation of on- or off-cell activities and spinal nocifensive reflexes. Such covariation could theoretically be due to their independently responding to a common source, or to an RVM-derived modulation of ventral horn neurons. Here, we tested whether on- and off-cells indeed modulate spinal nociceptive neurons...
October 5, 2016: Brain Research
Vassiliki Giannouli, Nikolaos Lougiakis, Ioannis K Kostakis, Nicole Pouli, Panagiotis Marakos, Alexios-Leandros Skaltsounis, Sangkil Nam, Richard Jove, David Horne, Roxane Tenta, Harris Pratsinis, Dimitris Kletsas
A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC50 values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G0/G1 phase and induce apoptosis, as determined by the appearance of apoptotic nuclei...
September 24, 2016: Bioorganic & Medicinal Chemistry Letters
Samuel S Duffy, Chamini J Perera, Preet G S Makker, Justin G Lees, Pascal Carrive, Gila Moalem-Taylor
Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease...
2016: Frontiers in Immunology
Huizhen Huang, Marissa S Kuzirian, Xiaoyun Cai, Lindsey M Snyder, Jonathan Cohen, Daniel H Kaplan, Sarah E Ross
The Neurokinin 1 Receptor (NK1R), which binds Substance P, is expressed in discrete populations of neurons throughout the nervous system, where it has numerous roles including the modulation of pain and affective behaviors. Here, we report the generation of a NK1R-CreER knockin allele, in which CreER(T2) replaces the coding sequence of the TACR1 gene (encoding NK1R) in order to gain genetic access to these cells. We find that the NK1R-CreER allele mediates recombination in many regions of the nervous system that are important in pain and anxiety including the amygdala, hypothalamus, frontal cortex, raphe nucleus, and dorsal horn of the spinal cord...
October 6, 2016: Genesis: the Journal of Genetics and Development
Lihua Ma, Thu Trinh, Yanfang Ren, Robert T Dirksen, Xiuxin Liu
ATP induces pain via activation of purinergic receptors in nociceptive sensory nerves. ATP signaling is terminated by ATP hydrolysis mediated by cell surface-localized ecto-nucleotidases. Using enzymatic histochemical staining, we show that ecto-ATPase activity is present in mouse trigeminal nerves. Using immunofluorescence staining, we found that ecto-NTPDase3 is expressed in trigeminal nociceptive neurons and their projections to the brainstem. In addition, ecto-ATPase activity and ecto-NTPDase3 are also detected in the nociceptive outermost layer of the trigeminal subnucleus caudalis...
2016: PloS One
Junko Nio-Kobayashi, Hazirah B Z Abidin, Jeremy K Brown, Toshihiko Iwanaga, Andrew W Horne, W Colin Duncan
Sialylation creates a negative charge on the cell surface that can interfere with blastocyst implantation. For example, α2,6-sialylation on terminal galactose, catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a β-galactoside-binding lectin. We recently reported the potential involvement of galectin-1 and -3 in the pathogenesis of tubal ectopic pregnancy; however, the precise role of galectins and their ligand glycoconjugates remain unclear. Here, we investigated the expression of the genes encoding α2,3- and α2,6-galactoside sialyltransferases (ST3GAL1 - 6 and ST6GAL1 - 2) and the localization of sialic acids in the Fallopian tube of women with or without ectopic implantation...
October 5, 2016: Molecular Reproduction and Development
Naoki Sasaki, Yui Imamura, Akio Sekiya, Megumi Itoh, Hidefumi Furuoka
In this study, fasciculation of the limbs and tongue was observed in four horses kept by a riding club. Neurogenic muscle atrophy was also observed in biopsy of pathological tissues. In addition, in two cases that subjected to autopsy, Bunina-like bodies of inclusion in the cell bodies of neurons in the spinal cord ventral horn were confirmed, leading to a diagnosis of equine motor neuron disease (EMND). Serum vitamin E concentrations varied between 0.3 and 0.4µg/ml, which is significantly lower than the levels in normal horses...
2016: Journal of Equine Science
Simon Dewar, Natasha Sienkiewicz, Han B Ong, Richard J Wall, David Horn, Alan H Fairlamb
The aim of this study was to identify and characterise mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. RNAi knockdown, in conjunction with drug susceptibly and folate transport studies, were used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterised in whole cells...
October 4, 2016: Journal of Biological Chemistry
Alberto A Chiappori, Gregory A Otterson, Afshin Dowlati, Anne M Traynor, Leora Horn, Taofeek K Owonikoko, Helen J Ross, Christine L Hann, Taher Abu Hejleh, Jorge Nieva, Xiuhua Zhao, Michael Schell, Daniel M Sullivan
LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients...
October 2016: Oncologist
Hany Zaher, Ayman Abdel-Aziz Swelum, Abdel-Salam Eidaroos, Faten Labib
The present study aimed mainly to study the level of nitric oxide (NO) and combined thickness of the uterus and placenta (CTUP) in buffaloes affected by pregnancy pathology. Females (n = 104) were classified into three main groups: nonpregnant (n = 10), healthy pregnant (n = 54), and pathologically pregnant (n = 40). The healthy pregnant animals were subgrouped according to the stage of pregnancy to early stage (n = 15), mid stage (n = 15), late stage (n = 19), and full term (n = 5). The animals in which pregnancy was associated with placental pathology were subgrouped to uterine torsion (n = 27), hydroallantois (n = 5), and abortion (n = 8)...
September 7, 2016: Theriogenology
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