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Budd-Chiari syndrome:A single-center experience

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World Journal of Gastroenterology 2014年第43期20卷 16236-16244页

作者： Tanya M Pavri Alan Herbst Rajender Reddy kimberly A Forde Division of Gastroenterology and Hepatology Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104United States Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104United States

AIM: To investigate challenges, risk factors, prognostic indicators, and treatment outcomes associated with Budd-Chiari syndrome (BCS) at a tertiary care center.

关键词： Budd-Chiari syndrome Transjugular intrahepatic portosystemic shunt Liver transplantation Anticoagulation Hepatic vein thrombosis

Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington＇s Disease

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Frontiers in Biology 2016年第6期11卷 439-458页

作者： kimberly D. Girling Yu Tian Wang Djavad Mowafahian Centre for Brain Health & Department of Medicine University of British Columbia V6T 1Z3 Canada

BACKGROUND： Huntington＇s Disease （HD） is an autosomal dominant neurodegenerative disease causing severe neurodegeneration of the striatum as well as marked cognitive and motor disabilities. Excitotoxicity, caused by overstimulation of NMDA receptors （NMDARs） has been shown to have a key role in the neuropathogenesis of liD, suggesting that targeting NMDAR-dependent signaling may be an effective clinical approach for HD. However, broad NMDAR antagonists are generally poor therapeutics in clinical practice. It has been suggested that GluN2A-containing, synaptically located NMDARs activate cell survival signaling pathways, while GluN2B-containing, primarily extrasynaptic NMDARs trigger cell death signaling. A better approach to development of effective therapeutics for HD may be to target, specifically, the cell-death specific pathways associated with extrasynaptic GluN2B NMDAR activation, while maintaining or potentiating the cell- survival activity of GluN2A-NMDARs. OBJECTIVE： This review outlines the role of NMDAR-mediated excitotoxicity in HD and overviews current efforts to develop better therapeutics for HD where NMDAR excitotoxicity is the target. METHODS： A systematic review process was conducted using the PubMed search engine focusing on research conducted in the past 5-10 years. 235 articles were consulted for the review, with key search terms including ＂Huntington＇s Disease,＂＂excitotoxicity,＂＂NMDAR＂ and ＂therapeutics.＂ RESULTS： A wide range of NMDAR excitotoxicity-based targets for HD were identified and reviewed, including targeting NMDARs directly by blocking GluN2B, extrasynaptic NMDARs and/or potentiating GluN2A, synaptic NMDARs, targeting glutamate release or uptake, or targeting specific downstream cell-death signaling of NMDARs. CONCLUSION： The current review identifies NMDAR-mediated excitotoxicity as a key player in HD pathogenesis and points to various excitotoxicity-focused targets as potential future preventative therapeutics for HD.

关键词： Huntington's Disease NMDA receptor excitotoxicity cell death therapeutics

The Psb32 Protein Aids in Repairing Photodamaged Photosystem II in the Cyanobacterium Synechocystis 6803

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Molecular Plant 2011年第6期4卷 1052-1061页

作者： kimberly M. Wegener Stefan Bennewitz Ralf Oelmuller Himadri B. Pakrasi Department of Biology Washington University St Louis MO 63130 USA Present address： Division of Biological Sciences University of Missouri Columbia MO 65211 USA Institute of Plant Physiology Friedrich-Schiller-University Jena Dornburger Str. 159 D-07743 Jena Germany

Photosystem II （PSII）, a membrane protein complex, catalyzes the photochemical oxidation of water to molecular oxygen. This enzyme complex consists of approximately 20 stoichiometric protein components. However, due to the highly energetic reactions it catalyzes as part of its normal activity, PSII is continuously damaged and repaired. With advances in protein detection technologies, an increasing number of sub-stoichiometric PSII proteins have been identified, many of which aid in the biogenesis and assembly of this protein complex. Psb32 （SII1390） has previously been identified as a protein associated with highly active purified PSII preparations from the cyanobacterium Synechocystis sp. PCC 6803. To investigate its function, the subcellular localization of Psb32 and the impact of deletion of the psb32 gene on PSII were analyzed. Here, we show that Psb32 is an integral membrane protein, primarily located in the thylakoid membranes. Al- though not required for cell viability, Psb32 protects cells from oxidative stress and additionally confers a selective fitness advantage in mixed culture experiments. Specifically, Psb32 protects PSII from photodamage and accelerates its repair. Thus, the data suggest that Psb32 plays an important role in minimizing the effect of photoinhibition on PSII.

关键词： Photosynthesis reactive oxygen species photoinhibition photodamage.

Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease

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World Journal of Gastroenterology 2017年第42期23卷 7644-7652页

作者： Huyen-Tran Nguyen Phillip Minar kimberly Jackson Patricia C Fulkerson Division of Allergy and Immunology Department of Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati College of Medicine Division of Gastroenterology Hepatology and Nutrition Department of Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati College of Medicine

AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this *** The electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed antitumor necrosis factor alpha(anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words "inflammatory bowel disease", "immunization", "vaccination", "pneumococcal", "varicella", and "hepatitis B". Non-human and non-English language studies were excluded. Search results were reviewed by authors toselect articles that addressed safety and efficacy of immunizations in inflammatory bowel *** A total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients(17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies. CONCLUSION Immunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy.

关键词： Vaccination Immunosuppression Earlyonset inflammatory bowel disease Very early-onset inflammatory bowel disease

Dynamics and mechanisms of permethrin resistance in a field population of the horn fly, Haematobia irritans irritans

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Insect Science 2009年第2期16卷 175-184页

作者： Andrew Y. Li kimberly H. Lohmeyer J. Allen Miller USDA ARS Knipling-Bushland US Livestock Insects Research Laboratory 2700 Fredericksburg Road Kerrville TX 78028 USA

A study was conducted at the Pressler ranch, near Kerrville, Texas, USA between 2002 and 2006 to determine the dynamics and mechanisms of resistance to permethrin in a field population of the horn fly, Haematobia irritans irritans （L.）. Changes of resistance to pyrethroid insecticide associated with use of a pour-on formulation of cyfluthrin in 2002 and use of diazinon ear tags in subsequent years were studied using a filter paper bioassay technique and a polymerase chain reaction assay that detects two sodium channel mutations, kdr and super-kdr resistance alleles. A maximum of 294-fold resistance to permethrin was observed in the summer of 2002. A significant decrease in the resistance level was observed in spring 2003, and resistance continued to decline after animals were treated with diazinon ear tags. In response to pyrethroid treatments, the allelic kdr and super-kdr frequency increased from 56.3% to 93.8% and from 7.5% to 43.8%, respectively in 2002, and decreased significantly in 2003 when the pyrethroid insecticide was no longer used to treat animals. Females were found to have a higher allelic super-kdr frequency than males in 2002, while no difference was detected between males and females in the allelic kdr frequency. There was a significant positive correlation between frequencies of the sodium channel mutations and levels ofpermethrin resistance, suggesting that the sodium channel mutations, kdr and super-kdr, are the major mechanisms of resistance to pyrethroids in this horn fly population. Results of synergist bioassays also indicated possible contributions of two metabolic detoxification mechanisms, the mixed function oxidases （MFO） and glutathione S-trans- ferases （GST）. Compared to a horn fly infestation of an untreated herd, treatments with the pyrethroid pour-on formulation failed to control horn flies at the Pressler ranch in 2002. Sustained control of horn flies was achieved with the use of diazinon ear tags in 2003 and subsequent years.

关键词： efficacy horn fly insecticide resistance PCR permethrin pyrethroids

Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases

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Neural Regeneration Research 2022年第10期17卷 2149-2152页

作者： Andrea N.Nortey kimberly N.Garces Abigail S.Hackam Bascom Palmer Eye Institute University of Miami Miller School of MedicineMiamiFLUSA

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and *** studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired *** availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative ***-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous *** is also accumulating that interleukin-27 has neuroprotective activities in the retina and ***-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic ***,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain *** this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and *** also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.

关键词： central nervous system cytokine inflammatory interleukin-27 neuroprotection retina

Acquired segmental colonic hypoganglionosis in an adult Caucasian male:A case report

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World Journal of Gastrointestinal Surgery 2019年第2期11卷 101-111页

作者： Allan MF Kwok Andrew B Still kimberly Hart Department of Surgery Wollongong Hospital Department of Anatomical Pathology Wollongong Hospital

BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely *** SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of *** investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring *** Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.

关键词： Acquired hypoganglionosis Hirschprung’s disease Adult Ganglion cells Acetylcholinesterase Calretinin Case report

Application of reprogrammed patient cells to investigate the etiology of neurological and psychiatric disorders

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Frontiers in Biology 2012年第3期7卷 179-188页

作者： kimberly M. CHRISTIAN Hongjun SONG Guo-li MING Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA Department of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USA The Solomon Snyder Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA

Cellular reprogramming allows for the de novo generation of human neurons and glial cells from patients with neurological and psychiatric disorders. Crucially, this technology preserves the genome of the donor individual and thus provides a unique opportunity for systematic investigation of genetic influences on neuronal pathophysiology. Although direct reprogramming of adult somatic cells to neurons is now possible, the majority of recent studies have used induced pluripotent stem cells （iPSCs） derived from patient fibroblasts to generate neural progenitors that can be differentiated to specific neural cell types. Investigations of monogenic diseases have established proof-of-principle for many aspects of cellular disease modeling, including targeted differentiation of neuronal populations and rescue of phenotypes in patient iPSC lines. Refinement of protocols to allow for efficient generation of iPSC lines from large patient cohorts may reveal common functional pathology and genetic interactions in diseases with a polygenic basis. We review several recent studies that illustrate the utility of iPSC-based cellular models of neurodevelopmental and neurodegenerative disorders to identify novel phenotypes and therapeutic approaches.

关键词： reprogramming iPSCs neurodevelopment neurodegeneration

Meeting the Health-care Needs of the Rural Elderly:The Unique Role of Village Doctors

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China & World Economy 2013年第3期21卷 44-60页

作者： kimberly Singer Babiarz Hongmei Yi Renfu Luo Center for Primary Care and Outcomes Research Stanford University Center for Chinese Agricultural Policy Institute of Geographical Sciences and Natural Resources ResearchChinese Academy of Sciences

Despite their recent deterioration, village clinics have historically been an important source of health care for the poor and elderly in rural China. In this paper, we examine the current role of village clinics, the patients who use them and some of the services they provide. We focus specifically on the role of village clinics in meeting the health-care needs of the rural poor and elderly. We find that although clinics are continuing to decline financially, they remain a source of care for the rural elderly and poor. We estimate that the elderly are 10-15 percent more likely than young individuals to seek care at a clinic. We show that clinics provide many unique services to support the rural elderly （and the elderly poor）, such as in-home patient care, the option for patients to pay on credit, and free and discounted services.

关键词： elderly health care village doctor