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BDnF rescues prefrontal dysfunction elicited by pyramidal neuron-specific DTnBP1 deletion in vivo

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Journal of Molecular Cell Biology 2017年第2期9卷 117-131页

作者： Wen Zhang Kathryn M. Daly Bo Liang Lifeng Zhang Xuan Li Yun Li Da-Ting Lin Intramural Research Program National Institute on Drug Abuse National Institutes of Health 333 CasseU Drive Baltimore MD 21224 USA The Jackson Laboratory 600 Main Street Bar Harbor ME 04609 USA The Solomon H. Snyder Department of neuroscience Johns Hopkins University School of Medicine 725 N. Wolfe Street Baltimore MD 21205 USA

Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTnBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutant mice exhibit abnormalities in beha- viors and impairments in neuronal activities. However, how diminished DTnBP1 expression contributes to clinical relevant fea- tures of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTnBP1 in pyramidal neurons of the medial prefrontal cortex （mPFC）. We demonstrated that DTnBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pu[se inhibition （PPI） behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTnBP1 in pyramidal neurons diminished activity- dependent secretion of brain-derived neurotrophic factor （BDnF）. Finally, we showed that chronic BDnF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTnBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTnBP1 in the pathogenesis of schizophrenia, and under- score BDnF restoration as a potential therapeutic strategy for schizophrenia.

关键词： schizophrenia GABAergic disinhibition PFC BDnF Dtnbp1

BRITTOn CHAnCE In MEMORIAM

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 221-222页

作者： ALBERT S.MILDVAn The Johns Hopkins University School of Medicine 725 N.Wolfe Street Room 511 HunterianBaltimoreMD 21205USA

Britton Chance was a truly inspiring scientist,among the *** long and vigorous career in biochemistry,biophysics,and biological instrumentation began with his now-classic kinetic and spectroscopic studies of the mecha... 详细信息

关键词： Enzyme-substrate intermediates electron transport oxidative phosphorylation proton gradient electron tunneling near-infrared imaging glyoxalase I methemoproteins

Time for a reset and recalibration: Healthcare in the post COVID era

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International Journal of nursing Sciences 2021年第2期8卷 143-144页

作者： Patricia M.Davidson Michelle Patch Johns Hopkins School of nursing 525 N.Wolfe StreetBaltimoreMD21205USA

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2),the virus that causes coronavirus disease 2019(C0VID-19),has changed the world forever,accelerating a myriad of ***-19 has sent shock waves around the world and there is almost no dimension of our lives that has not been touched by the pandemic's *** society has been ravaged by pandemics over centuries,it is the 1918 influenza pandemic that provides us with recent learning and guideposts for what the future will look like[1].

关键词： Acute COV calibration

Role of transcatheter arterial embolization for massive bleeding from gastroduodenal ulcers

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World Journal of Gastroenterology 2009年第47期15卷 5889-5897页

作者： Romaric Loffroy Boris Guiu The Russell H Morgan Department of Radiology and Radiological Science Division of Cardiovascular and Interventional Radiology The Johns Hopkins Hospital 600 North Wolfe Street Blalock 545 BaltimoreMD 21287 United States Division of Vascular and Interventional Radiology University of Dijon School of Medicine Bocage Teaching Hospital 2 bd du Maréchal de Lattre de Tassigny BP 77908 21079 Dijon Cedex France

Intractable bleeding from gastric and duodenal ulcers is associated with significant morbidity and mortality. Aggressive treatment with early endoscopic hemostasis is essential for a favourable outcome. In as many as 12%-17% of patients,endoscopy is either not available or unsuccessful. Endovascular therapy with selective catheterization of the culprit vessel and injection of embolic material has emerged as an alternative to emergent operative intervention in high-risk patients. There has not been a systematic literature review to assess the role for embolotherapy in the treatment of acute upper gastrointestinal bleeding from gastroduo-denal ulcers after failed endoscopic hemostasis. Here,we present an overview of indications,techniques,and clinical outcomes after endovascular embolization of acute peptic-ulcer bleeding. Topics of particular relevance to technical and clinical success are also discussed. Our review shows that transcatheter arterial embolization is a safe alternative to surgery for massive gastroduodenal bleeding that is refractory to endoscopic treatment,can be performed with high technical and clinical success rates,and should be considered the salvage treatment of choice in patients at high surgical risk.

关键词： Peptic ulcer Massive bleeding Endoscopy Angiography Embolization

Comment on“Treatment of chronic prostatitis in Chinese men”by Liang CZ et *** Asian Journal of Andrology

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Asian Journal of Andrology 2009年第2期11卷 149-149页

作者： Robert H.Getzenberg Johns Hopkins Medicine The Donald S.Coffey Professor of UrologyBrady Urological Institute DirectorUrology Research Laboratories600 N.Wolfe StreetBaltimoreMD 21287-2101USA

The manuscript by Liang et al.[1]entitled Treatment of chronic prostatitis in Chinese men appears to be an important and comprehensive analysis of the issue of chronic prostatitis(CP)as well as treatment avenues that are pursued within a Chinese *** analyses of more than 12000 men confirm other studies[2]which demonstrate that CP represents a large problem in adult male *** the numbers that are seen in urology clinics may under represent the true magnitude of these symptom profiles that are *** study also confirms the fact that antibiotics,as commonly used,do not seem to have much efficacy within this group.

关键词： al. prostatitis fir

晶状体乳化联合可拆除缝线小梁切除术的安全性和有效性

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世界核心医学期刊文摘（眼科学分册） 2006年第5期2卷 17-18页

作者： Stark W.J. Goyal R.K. Awad O. 王静波 600 n wolfe street Baltimore MD 21287 United States Dr.

Aim: To evaluate the combined phacoemulsification with acrylic intraocular lens implantation and trabeculectomy with releasable sutures, without the use of antimetabolites, performed by one surgeon. Methods: A retrospective analysis was performed on 251 eyes of 198 patients after a combined phaco/trabeculectomy procedure, followed up for an average of 16 months for vision, intraocular pressure (IOP), and number of glaucoma medications. Cox proportional hazard regression analysis provided measures of relative risk (RR) or hazards ratios and 95%confidence intervals (CIs) associated with the occurrence of several conditions or complications of surgery. Results: Mean preoperative variables were best corrected vision, 0.6 (SD 0.4) logMAR(20/80 Snellen); IOP, 18.7 (4.9)mmHg; and number of glaucoma medications, 1.7 (0.8). Mean postoperative results were best corrected vision, 0.2 (0.4) logMAR (20/32 Snellen); IOP, 15.1 (3.2) mm Hg; and number of glaucoma medications, 0.3 (0.6). Postoperatively, the mean decreases from baseline were 19.2%for IOP and 84.1%for number of glaucoma medications; 85%of eyes required fewer glaucoma medications and 78%of eyes were medication free, with IOP control. There were no significant operative or postoperative complications. Conclusion: Combined phacoemulsification and trabeculectomy with releasable sutures, in the absence of antimetabolites, is a safe, effective, and stable alternative for patients with cataracts and glaucoma.

关键词：小梁切除术后晶状体乳化可拆除缝线安全性联合人工晶状体植入青光眼药物矫正视力抗代谢药物回顾性分析

Clinical utility of cerebrovascular reactivity mapping in patients with low grade gliomas

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World Journal of Clinical Oncology 2011年第12期2卷 397-403页

作者： Jay J Pillai Domenico Zacá neuroradiology Division Russell H Morgan Department of Radiology and Radiological ScienceThe Johns Hopkins UniversitySchool of Medicine and The Johns Hopkins Hospital600 N.Wolfe StreetPhipps B-100BaltimoreMD 21287United States

AIM:To evaluate neurovascular uncoupling(nVU)associated with low grade gliomas(LGG)using blood oxygen level dependent(BOLD)cerebrovascular reactivity ***:Seven patients with low grade gliomas referred by neurosurgeons for presurgical mapping were included in this pilot *** reactivity(CVR)mapping was performed by acquiring BOLD images while patients performed a block-design breath-hold(BH)hypercapnia *** mapping was expressed as BOLD percentage signal change(PSC)from baseline associated with performance of the BH hypercapnia *** T2*Dynamic Susceptibility Contrast perfusion imaging was performed and relative cerebral blood volume(rCBV)and relative cerebral blood flow(rCBF)maps were *** T1 weighted MR images were also acquired.A correlation analysis between intratumoral normalized(via ratio with contralateral homologous regions)BOLD BH PSC[referred to as(nCVR)]and intratumoral normalized resting state rCBV(rCBF)values(i.e.,nCBV and nCBF,respectively)was ***:no significant correlation was seen between the normalized BOLD BH PSC(i.e.,nCBV)and nCBV or ***,the average nCVR(median=0.50,z=-2.28,P=0.01)was significantly less than 1.0,indicating abnormally reduced vascular responses in the tumor regions relative to normal contralesional homologous regions,whereas the average nCBV(median=0.94,z=-0.92,P=0.375)and nCBF(median=0.93,z=-1.16,P=0.25)were not significantly higher or lower than 1.0,indicating iso-perfusion in the tumor regions relative to normal contralesional homologous *** findings suggest that in LGG,hyperperfusion that is seen in high grade gliomas is not present,but,nevertheless,abnormally decreased regional CVR is present within and adjacent to *** the patients all demonstrated at least some residual function attributable to the cortical regions of impaired CVR,but were incapable of producing a BOLD response in these regions regardless of the tasks performed,such

关键词： Blood oxygen level dependent Brain tumor Cerebrovascular reactivity Functional MRI neurovascular uncoupling Presurgical mapping

Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer’s disease mouse model

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Translational neurodegeneration 2023年第1期12卷 70-89页

作者： Carolyn Tallon Benjamin J.Bell Medhinee M.Malvankar Pragney Deme Carlos nogueras-Ortiz Erden Eren Ajit G.Thomas Kristen R.Hollinger Arindom Pal Maja Mustapic Meixiang Huang Kaleem Coleman Tawnjerae R.Joe Rana Rais norman J.Haughey Dimitrios Kapogiannis Barbara S.Slusher Johns Hopkins Drug Discovery Johns Hopkins University School of MedicineBaltimoreMD 21205USA neurology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Cell Biology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Oncology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Medicine Johns Hopkins University School of MedicineBaltimoreMD 21205USA Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD 21205USA Psychiatry and Behavioral Science Johns Hopkins University School of Medicine855 N.Wolfe StreetRangos 278BaltimoreMD 21205USA Intramural Research Program Laboratory of Clinical InvestigationNational Institute on AgingNational Institutes of Health251 Bayview BlvdSte 8C228BaltimoreMD 21224USA Johns Hopkins University School of Medicine 600 N.Wolfe StreetPathology 517BaltimoreMD 21287USA

Background Cognitive decline in Alzheimer’s disease(AD)is associated with hyperphosphorylated tau(pTau)propagation between neurons along synaptically connected networks,in part via extracellular vesicles(EVs).EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of *** report,for the first time,that human tau expression elevates brain ceramides and nSMase2 *** To determine the therapeutic benefit of inhibiting this elevation,we evaluated PDDC,the first potent,selective,orally bioavailable,and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse ***,we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus(AAV)encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the *** contralateral transfer of the double mutant human tau to the dentate gyrus was *** examined ceramide levels,histopathological changes,and pTau content within EVs isolated from the mouse *** Similar to human AD,the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity;both were completely normalized by PDDC *** PS19 mice also exhibited elevated tau immunostaining,thinning of hippocampal neuronal cell layers,increased mossy fiber synaptophysin immunostaining,and glial activation,all of which were pathologic features of human *** treatment reduced these *** plasma of PDDC-treated PS19 mice had reduced levels of neuronal-and microglial-derived EVs,the former carrying lower pTau levels,compared to untreated *** the tau propagation model,PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral *** PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity,leading to the slo

关键词： Alzheimer’s disease Extracellular vesicles neutral sphingomyelinase 2 Tau Ceramide

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衣索比亚农村需行手术的倒睫患者的特征

世界核心医学期刊文摘（眼科学分册） 2005年第12期1卷 36-37页

作者： Melese M West E.S Alemayehu W 韩静 116 Wilmer Building 600 N Wolfe Street Baltimore MD 21287 United States.Dr

Aims: To determine the characteristics of trichiasis patients presenting for surgery in Wolayta Zone of Ethiopia. Methods: Patients referred for trichiasis surgery by community health agents were evaluated by trained integrated eye care workers (IECWs) for the presence of trichiasis, locations of inturned lashes, severity of trichiasis, corneal opacity, and visual acuity. Results: 1635 individuals with trichiasis presented for surgery. 82% had bilateral trichiasis; 91% of patients reported trichiasis duration of > 2 years. Epilation was practised by over three fourths of the study subjects. A high proportion of patients tested positive for ocular Chlamydia trachomatis at presentation. 17% had monocular blindness and 8% were binocularly blind. Corneal opacity was highly associated with the trichiasis duration and severity and visual loss was associated with corneal opacity. Conclusion: Severe trichiasis reflects the magnitude of the trachoma problem in Ethiopia. Visual impairment due to trichiasis is highly associated with disease severity and duration. Early intervention to correct trichiasis before it become severe is recommended to prevent visual impairment.

关键词：比亚视力损害角膜混浊沙眼衣原体眼保健单眼盲社区保健持续时间