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https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#1
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#2
Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Helen Toledano, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Michael Weintraub, Mony Benifla
Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study...
November 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29142352/localized-pontine-uptake-in-fluorine-18-fuorodeoxyglucose-positron-emission-tomography-computed-tomography-in-a-case-of-hyponatremia-a-case-report-and-review-of-literature
#3
Thangalakshmi Sivathapandi, Shelley Simon, Indirani Elangovan
A rare acquired demyelinating lesion of the pons central pontine myelinolysis (CPM) typically occurs after rapid correction of hyponatremia. There is disruption of blood-brain barrier due to osmotic stress allowing access for inflammatory mediators in extravascular brain tissue, which most likely attracts glial cells of the brain, attracts macrophages, and activates astrocytes. We present a case of female with a known history of inflammatory bowel disease who presented with altered sensorium and hyponatremia...
October 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/29142293/neural-pathways-for-colorectal-control-relevance-to-spinal-cord-injury-and-treatment-a-narrative-review
#4
REVIEW
Brid Callaghan, John B Furness, Ruslan V Pustovit
STUDY DESIGN: Narrative review. OBJECTIVES: The purpose is to review the organisation of the nerve pathways that control defecation and to relate this knowledge to the deficits in colorectal function after SCI. METHODS: A literature review was conducted to identify salient features of defecation control pathways and the functional consequences of damage to these pathways in SCI. RESULTS: The control pathways for defecation have separate pontine centres under cortical control that influence defecation...
November 16, 2017: Spinal Cord
https://www.readbyqxmd.com/read/29137593/central-pontine-myelinolysis-after-living-donor-liver-transplant-a-report-of-2-cases
#5
Ya-Lan Hsu, Chia-En Hsieh, Kuo-Hua Lin, Chen-Te Chou, Ping-Yi Lin, Su-Han Wang, Yao-Li Chen
Here, we present 2 patients who developed central pontine myelinolysis after living-donor liver transplant. Both patients had abnormal sodium level before living-donor liver transplant. Patient 1 presented with severe hyponatremia on admission. After administration of 3% saline, her sodium level during the first 24 hours was kept at 100 mEq/L and then increased to 116 mEq/L during the next 24 hours. The level increased 5.8 mEq/L during the 4- to 5-hour transplant procedure. Patient 2 was admitted to the hospital with an unprovoked seizure...
November 15, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29137445/altered-resting-state-functional-activity-in-isolated-pontine-infarction-patients-with-pathological-laughing-and-crying
#6
Tao Liu, Jianjun Li, Shixiong Huang, Changqinq Li, Zhongyan Zhao, Guoqiang Wen, Feng Chen
We used resting-state functional magnetic resonance imaging to investigate the global spontaneous neural activity involved in pathological laughing and crying after stroke. Twelve pathological laughing and crying patients with isolated pontine infarction were included, along with 12 age- and gender-matched acute isolated pontine infarction patients without pathological laughing and crying, and 12 age- and gender-matched healthy controls. We examined both the amplitude of low-frequency fluctuation and the regional homogeneity in order to comprehensively evaluate the intrinsic activity in patients with post-stroke pathological laughing and crying...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136526/upbeat-nystagmus-is-a-useful-sign-in-the-regional-diagnosis-of-trigeminal-nerve-disorder-with-multiple-sclerosis
#7
Kiyotaka Nakamagoe, Naoki Tozaka, Seitaro Nohara, Rio Kawakami, Shiori Yamada, Tadachika Koganezawa, Akira Tamaoka
Trigeminal nerve disorder is an important neurological sign that is often seen with multiple sclerosis (MS). We investigated eye movements in three MS patients with trigeminal disorder due to pontine lesions near the trigeminal root entry zone (REZ). Upbeat nystagmus was observed in all MS patients with trigeminal REZ lesions. We conjecture that trigeminal nerve disorder and upbeat nystagmus appeared due to simultaneous damage to both the trigeminal nerve and the vestibulo-ocular reflex pathway. If upbeat nystagmus appears in MS patients exhibiting a trigeminal nerve disorder, such as trigeminal neuralgia, and paralysis, pontine lesions near the trigeminal REZ should be considered...
November 9, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29136501/pontine-infantile-glioma-simplified
#8
Vijay Ramaswamy, Michael D Taylor
In this issue of Cancer Cell, Pathania et al. report sporadic childhood histone K27M mutant malignant glioma mouse models that faithfully recapitulate the human tumor phenotypes. Beyond emphasizing the importance of correct timing in mouse modeling of cancer, these models will facilitate research to effectively treat this lethal childhood cancer.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29127718/-frontal-eye-field-in-prosimian-galagos-intracortical-microstimulation-and-tracing-studies
#9
Iwona Stepniewska, Pierre Pouget, Jon H Kaas
The frontal eye field (FEF) in prosimian primates was identified as a small cortical region, above and anterior to the anterior frontal sulcus, from which saccadic eye movements were evoked with electrical stimulation. Tracer injections revealed FEF connections with cortical and subcortical structures participating in higher order visual processing. Ipsilateral cortical connections were the densest with adjoining parts of the dorsal premotor and prefrontal cortex (PFC). Label in a region corresponding to supplementary eye field (SEF) of other primates, suggests the existence of SEF in galagos...
November 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29124503/urological-dysfunction-in-synucleinopathies-epidemiology-pathophysiology-and-management
#10
REVIEW
Ryuji Sakakibara, Fuyuki Tateno, Tatsuya Yamamoto, Tomoyuki Uchiyama, Tomonori Yamanishi
OBJECTIVE: Parkinson's disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA. METHOD: A systematic review. RESULTS: The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention...
November 9, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/29118968/combination-of-ezh2-inhibitor-and-bet-inhibitor-for-treatment-of-diffuse-intrinsic-pontine-glioma
#11
Yaqin Zhang, Weijie Dong, Junying Zhu, Lizhu Wang, Xinjian Wu, Hong Shan
Background: Diffuse intrinsic pontine glioma is an infiltrative, often high-grade glioma of the brainstem that is not amenable to surgical resection. The current treatment of DIPG by radiation therapy showed dramatically improvement of patient's condition, however, the tumor recurs rapidly. More and more studies are focused on the genetic and epigenetic drivers of DIPGs, which may provide more and more novel therapy target for DIPG. EZH2 has been proved to be a potential therapeutic target for H3K27M-mutant pediatric gliomas recently...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29113992/axonemal-dynein-assembly-requires-the-r2tp-complex-component-pontin
#12
Yuanyuan Li, Lu Zhao, Shiaulou Yuan, Jiefang Zhang, Zhaoxia Sun
Pontin (Ruvbl1) and Reptin (Ruvbl2) are closely related AAA ATPases. They are components of the Ruvbl1-Rvubl2-Tah1-Pih1 (R2TP) complexes that function as co-chaperones for the assembly of multiple macromolecular protein complexes. Here, we show that Pontin is essential for cilia motility in both zebrafish and mouse and that Pontin and Reptin function cooperatively in this process. pontin zebrafish mutants display phenotypes tightly associated with cilia defects and cilia motility is lost in a number of ciliated tissues along with a reduction in the number of both outer and inner dynein arms (ODAs and IDAs)...
November 7, 2017: Development
https://www.readbyqxmd.com/read/29101501/severe-hypernatraemic-dehydration-and-unconsciousness-in-a-care-dependent-inpatient-treated-with-empagliflozin
#13
Georg Gelbenegger, Nina Buchtele, Christian Schoergenhofer, Martin Roeggla, Michael Schwameis
A 66-year-old Caucasian male became unconscious 2 weeks after initiation of add-on therapy with empagliflozin for poorly controlled type 2 diabetes mellitus. The inpatient had recently suffered focal pontine stroke, rendering him bedridden and requiring increased nursing care, including assistance with drinking. The patient had received empagliflozin 10 mg once daily for glycaemic control. Investigations revealed hypernatraemia (164 mmol/l), a urine glucose level of 3935 mg/dl, and a creatinine level of 2...
November 3, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29100338/patient-derived-dipg-cells-preserve-stem-like-characteristics-and-generate-orthotopic-tumors
#14
Cheng Xu, Xiaoqing Liu, Yibo Geng, Qingran Bai, Changcun Pan, Yu Sun, Xin Chen, Hai Yu, Yuliang Wu, Peng Zhang, Wenhao Wu, Yu Wang, Zhen Wu, Junting Zhang, Zhaohui Wang, Rui Yang, Jenna Lewis, Darell Bigner, Fangping Zhao, Yiping He, Hai Yan, Qin Shen, Liwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor, with a median survival of less than one year. Due to enormous difficulties in the acquisition of DIPG specimens and the sophisticated technique required to perform brainstem orthotopic injection, only a handful of DIPG pre-clinical models are available. In this study, we successfully established eight patient-derived DIPG cell lines, mostly derived from treatment-naïve surgery or biopsy specimens. These patient-derived cell lines can be stably passaged in serum-free neural stem cell media and displayed distinct morphologies, growth rates and chromosome abnormalities...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099407/ocular-motor-dysfunction-due-to-brainstem-disorders
#15
Seung-Han Lee, Hyo-Jung Kim, Ji-Soo Kim
BACKGROUND: The brainstem contains numerous structures including afferent and efferent fibers that are involved in generation and control of eye movements. EVIDENCE ACQUISITION: These structures give rise to distinct patterns of abnormal eye movements when damaged. Defining these ocular motor abnormalities allows a topographic diagnosis of a lesion within the brainstem. RESULTS: Although diverse patterns of impaired eye movements may be observed in lesions of the brainstem, medullary lesions primarily cause various patterns of nystagmus and impaired vestibular eye movements without obvious ophthalmoplegia...
November 2, 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29097440/desensitization-and-tolerance-of-mu-opioid-receptors-on-pontine-kolliker-fuse-neurons
#16
Erica S Levitt, John T Williams
Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium (GIRK) current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices...
November 2, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29096218/feasibility-of-deep-brain-stimulation-for-controlling-the-lower-urinary-tract-functions-an-animal-study
#17
Shih-Ching Chen, Pei-Yi Chu, Tsung-Hsun Hsieh, Yu-Ting Li, Chih-Wei Peng
OBJECTIVE: To evaluate the feasibility of deep brain stimulation (DBS) and compare the potential of four DBS targets in rats for regulating bladder activity: the periaqueductal gray (PAG), locus coeruleus (LC), rostral pontine reticular nucleus (PnO), and pedunculopontine tegmental nucleus (PPTg). METHODS: A bipolar stimulating electrode was implanted. The effects of DBS on the inhibition and activation of micturition reflexes were investigated by using isovolumetric intravesical pressure recordings...
September 30, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29096034/cns-erdheim-chester-disease-a-challenge-to-diagnose
#18
Zenggang Pan, Bette K Kleinschmidt-DeMasters
Erdheim-Chester disease (ECD) is a rare nonLangerhans cell histiocytosis. Although approximately 50% of cases eventually involve the central nervous system (CNS), the CNS has seldom been reported as the initial biopsy site. The diagnosis of CNS ECD can be challenging due to morphologic overlap with reactive histiocytic proliferation, Langerhans cell histiocytosis (LCH), and extranodal Rosai-Dorfman disease (RDD). We present 3 cases from our files that illustrate the protean manifestations of ECD. Case 1 was a 47-year-old man with ataxia, dysarthria, and intermittent ophthalmoplegia whose cerebellar biopsy had shown only profuse, nonspecific Rosenthal fiber-rich piloid gliosis; ECD was diagnosed only at autopsy...
December 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29095576/is-central-pontine-myelinolysis-reversible
#19
David Lee Rebedew
Central pontine myelinolysis (CPM) is a rare phenomenon that causes significant morbidity and mortality. Active therapeutic interventions for CPM can have a positive impact on recovery and overall prognosis. This case represents a 34-year-old white man with a chronic history of alcohol abuse who had Parkinsonian symptoms 13 days after rapid correction of his serum sodium in the hospital. Similarly to prior CPM case reports, this patient significantly improved following reinduction of hyponatremia, methylprednisolone, and/or plasmapharesis...
December 2016: WMJ: Official Publication of the State Medical Society of Wisconsin
https://www.readbyqxmd.com/read/29090526/a-pediatric-brain-tumor-consortium-phase-ii-trial-of-capecitabine-rapidly-disintegrating-tablets-with-concomitant-radiation-therapy-in-children-with-newly-diagnosed-diffuse-intrinsic-pontine-gliomas
#20
Lindsay B Kilburn, Mehmet Kocak, Patricia Baxter, Tina Young Poussaint, Arnold C Paulino, Christine McIntyre, Annabelle Lemenuel-Diot, Christine Lopez-Diaz, Larry Kun, Murali Chintagumpala, Jack M Su, Alberto Broniscer, Justin N Baker, Eugene I Hwang, Maryam Fouladi, James M Boyett, Susan M Blaney
BACKGROUND: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). PATIENTS AND METHODS: Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m(2) /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT...
November 1, 2017: Pediatric Blood & Cancer
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