Herpes Simplex Encephalitis - University of Oklahoma ：单纯疱疹病毒性脑炎-俄克拉何马大学
DWI在脑部的应用
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Infection Trauma Hemorrhage DWI Vasculitis and vasculopathies Leukodystrophies
Neoplastic lesions
Encephalopathies
Epilepsy
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Introduction
Cytotoxic edema – characterized by abnormal cellular uptake of water and myelin edema – characterized by intramyelinic accumulation of vacuolated or free water – have high signal intensity on the diffusion trace, with decreased ADC as a result of isotropically restricted water diffusion. On the other hand,vasogenic edema, caused by increased permeability of the blood–brain barrier, and interstitial edema, caused by subependymal water diffusion in acute hydrocephalus have intermediate signal on the DW image with increased ADC DWI区分水肿的性质： 细胞毒性水肿和和髓鞘性水肿——由于同向性弥散受限，弥散相呈 高信号，ADC值下降； 血管源性水肿和间质性水肿——弥散不受限，弥散相呈中等信号， ADC值升高。
病毒性脑炎
炎罕见脑脊液糖降低，如果出现脑脊液中糖降低，则提示
由其他感染引起。
尽管HSE可见脑脊液黄变，但这对诊断并无特异性。 CSF PCR检查对病毒性脑炎的诊断很有帮助。在有经验的 实验室，在HSE病程第一周大约95%的患者HSE-DNA检测 为阳性，假阴性结果最可能发生于起病的24-48小时和病后 10-14天。HSE PCR检测的特异性超过95%。PCR检查可用
⑵中毒性脑病：许多因素如缺血、缺氧、中毒、营养 缺乏、肿瘤等可以引起临床表现与病毒性脑炎相似的临
床表现，其鉴别要点见表2：
表2：中毒性脑病与HSE鉴别
中毒性脑病 一、临床表现 发热 头痛 精神抑制状态 局灶性神经病学体征 癫痫类型 不常见 不常见 稳步恶化 不常见 全身性发作 常见 常见 可有波动 常见 全身或部分性发作 单纯疱疹性病毒性脑炎
人和健康带毒者是主要传染源，主要通过密切接触
与性接触传播，亦可通过飞沫传播。HSV首先在 口腔和呼吸道或生殖器引起原发感染，机体迅速产 生特异性免疫力而康复，但不能彻底消除病毒，病 毒以潜伏状态长期存在宿主体内，而不引起临床症
状。神经节中的神经细胞是病毒潜伏的场所，
HSV-1主要潜伏在三叉神经节，HSV-2潜伏在骶神 经节。
可发生局灶性神经功能缺陷如偏瘫和失语，甚至可进
展为昏迷。
在一个对46例单纯疱疹病毒性脑炎的回顾性分析中， 入院时症状包括前驱的流感样症状（48%），突然发作 的头痛、混乱和意识水平改变（52%），失语或缄默
（46%），深昏迷（35%），颅内压增高（33%），局
灶性神经体征（89%）和在疾病过程中约61%的病人发 生癫痫。
3、诊断程序：对于疑是脑炎的病例，如果影像学检查 排除了腰穿的禁忌症（占位性损害或严重的脑水肿和脑移 位），应作腰穿检查。如果已存在严重的脑水肿，建议先 用类固醇或/和甘露醇降低颅内压，然后再作腰穿。尽管有
CJD病5例、慢性
至7月中旬能简单言语，但别人基本无法听懂，仍不能自
行坐立，于7月23日出院，出院后病情基本同出院时状态， 4年后死于肺炎。
98年3月6日EEG示高度异常，节律未见；复合性θ 、δ
波弥漫分布；
5月19日EEG高度异常,见1.1C/S周期波；6月23日EEG高度
脱失，并可见神经元核内包涵体及噬神经元现象，脑
实质部分区域空泡形成，胶质细胞增生并见少量中性
粒细胞浸润。
脑组织匀浆单疱I型病毒PCR检测阳性，血该项检测阴
性。血麻疹抗体IgM、IgG检测阴性。改诊为慢性单纯 疱疹病毒性脑炎。
5月20日开始予阿昔洛韦针治疗3周。 5月中旬肌阵挛达高峰，此后肌阵挛好转，至6月中旬肌
慢性单纯疱疹性脑炎国内迄今未见报告。 Love等报道2例因难治性癫痫行手术治疗的儿童病例，
其脑组织病检见慢性炎症， HSV-1 型 DNA 检测阳性 [6] 。
Urushitani等报告一例以持续性肌阵挛起病的慢性单疱
脑炎，阿昔洛韦治疗后病情好转[7]。
Yamada对1例病程长达5年，表现为进行性偏瘫、认知
功能下降的老年病例进行死检，发现神经元核内包涵
体，电镜下见单疱病毒[8]。
本文该病例起先诊断为很可能CJD，予行脑活检光镜下
虽见到胶质细胞增生及空泡形成,但这两种改变的程度 不如前述5例CJD明显。
另该病例光镜下见神经元核内包涵体及炎症改变，而
CJD不可以有此两点改变。
核内包涵体见于神经变性疾病及亚急性硬化性全脑炎
3、辅助检查：
颅脑MRI检查4例，2例豆状核、尾状核对称性T2高信号病灶、
DWI呈高信号、ADC呈低信号、T1加权无改变，不伴脑萎缩，
脑炎PPT课件
） • 最常累及颞叶皮质、眶额皮质与边缘结构
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单纯疱疹病毒（herpes simplex virus,HSV)属ＤＮＡ病毒
Ⅰ型
• 多引起非生殖器部位 感染
• 免疫抑制剂治疗有效 • 病毒学和相关抗体检测阴性
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脑肿瘤
• 脑肿瘤病程相对较长，CSF蛋白明显增 高，头部CT增强扫描有强化效应。
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温可高达38-40℃，可持续1周左右，退热药效果差。 • 1/4出现口唇、面颊疱疹（oral herpes）
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口 唇 疱 疹
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Clinical manifestations
●精神症状较突出，出现率为69-85%，表 现为人格改变，注意力涣散、反应迟钝、 语言减少、记忆力及定向力障碍、行为 异常、幻觉、甚至木僵和缄默
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Clinical manifestations
有67%的患者出现不同形式的痫性发作， 甚至出现癫痫持续状态。
形式多样 可为首发症状 典型部分性发作-颞叶受损
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Clinical manifestations
• 部分患者可出现中枢神经系统局灶性损 害症状
• 如偏瘫、失语、视野缺损、展神经麻痹 及其他脑神经损害征象
• EEG：常见颞区和额区为主弥漫性高波幅慢波， 颞区的周期性高波幅尖波—是本病特征．脑电 图有时比ＣＴ更早发现异常．
• ＣＴ：一侧或双侧颞叶和额叶低密度病灶
herpesviruses(水痘-带状疱疹病毒)
Epidemiology (1)
HSV is spread by contact, as the virus is shed in saliva, tears, genital and other secretions. By far the most common form of infection results from a kiss given to a child or adult from a person shedding the virus. Primary infection is usually trivial or subclinical in most individuals. It is a disease mainly of very young children ie. those below 5 years.
Primary HSV keratitis – dendritic ulcers Recurrent HSV keratitis
HSV conjunctivitis
Iridocyclitis, chorioretinitis and cataract
Genital Herpes
Genital lesions may be primary, recurrent or initial. Many sites can be involved which includes the penis, vagina, cervix, anus, vulva, bladder, the sacral nerve routes, the spinal and the meninges. The lesions of genital herpes are particularly prone to secondary bacterial infection eg. S.aureus, Streptococcus, Trichomonas and Candida Albicans. Dysuria is a common complaint, in severe cases, there may be urinary retention. Local sensory nerves may be involved leading to the development of a radiculitis. A mild meningitis may be present. 60% of patients with genital herpes will experience recurrences. Recurrent lesions in the perianal area tend to be more numerous and persists longer than their oral HSV-1 counterparts.
CT在儿科疾病诊断中的应用
当前33页，共73页，星期一。
TORCH—临床及CT表现
生时或几周后出现症状。小头、智低、脑 瘫、癫痫、双目失明
CT表现为：小头畸形，基底节，皮质脑室 周围广泛分布的钙化，脑积水，脑实质片 状低密度区，常见积水性脑畸形，孔洞脑 畸形
常染色体显性遗传 CT 1. 视神经胶质瘤 2. 巨颅
3. 胶质错构瘤
4. 血管发育不良
当前51页，共73页，星期一。
结节硬化症
病理：脑内、室管膜下错构瘤结节、胶质 增生、脱髓鞘，巨细胞性星形细胞瘤
临床三联征：智低、癫痫、皮脂腺瘤 CT表现：错构瘤结节和钙化斑
皮质区钙化 脑实质内低密度区 脑室扩大 脑内肿瘤
因VK及凝血因子Ⅶ、Ⅱ、Ⅸ、Ⅹ缺乏造成 的。这些凝血因子又称VitK依赖因子。在 肝脏合成时必须有足够的VitK参与
VitK缺乏时，这些凝血因子合成减少，导 致出血
由于母乳内 VitK含量少。造成本病大多数 为纯母乳喂养的足月儿。
当前30页，共73页，星期一。
晚发VK缺乏症临床表现
2周至3个月发病，多数发生在1-2月内 易激惹，尖叫，呕吐，意识障碍，抽搐 心率、呼吸加速，嗜睡 前囟隆起和体温不稳定等 凝血及凝血酶元时间延长，有出血倾向 少数新生儿颅内出血，无临床症状
新生儿颅骨解剖特点
经产道挤压，顶枕骨重叠变形，数天内可 恢复。
顶骨常可骨化不全，甚至完全未骨化。 颅缝和颅底软骨连合新生儿期较著明，宽
约35mm，12岁不超过12mm。
当前3页，共73页，星期一。
颅骨发育
后囟及前外侧囟生后3个月内闭合，前囟及后外侧囟 约在1.52岁闭合。
Time-Dependent Transformation of the Herpesvirus Tegument
J OURNAL OF V IROLOGY,Aug.2009,p.8082–8089Vol.83,No.16 0022-538X/09/$08.00ϩ0doi:10.1128/JVI.00777-09Copyright©2009,American Society for Microbiology.All Rights Reserved.Time-Dependent Transformation of the Herpesvirus TegumentᰔWilliam W.Newcomb and Jay C.Brown*Department of Microbiology and Cancer Center,University of Virginia Health System,Charlottesville,Virginia22908Received16April2009/Accepted28May2009All herpesviruses have a layer of protein called the tegument that lies between the virion membrane and thecapsid.The tegument consists of multiple,virus-encoded protein species that together can account for nearlyhalf the total virus protein.To clarify the structure of the tegument and its attachment to the capsid,we usedelectron microscopy and protein analysis to examine the tegument of herpes simplex virus type1(HSV-1).Electron microscopic examination of intact virions revealed that whereas the tegument was asymmetricallydistributed around the capsid in extracellular virions,it was symmetrically arranged in cell-associated virus.Examination of virions after treatment with nonionic detergent demonstrated that:(i)in extracellular virus thetegument was resistant to removal with Triton X-100(TX-100),whereas it was lost nearly completely whencell-associated virus was treated in the same way;(ii)the tegument in TX-100-treated extracellular virions wasasymmetrically distributed around the capsid as it is in unextracted virus;and(iii)in some images,tegumentwas seen to be linked to the capsid by short,regularly spaced connectors.Further analysis was carried out withextracellular virus harvested from cells at different times after infection.It was observed that while the amountof tegument present in virions was not affected by time of harvest,the amount remaining after TX-100treatment increased markedly as the time of harvest was increased from24h to64h postinfection.The resultssupport the view that HSV-1virions undergo a time-dependent change in which the tegument is transformedfrom a state in which it is symmetrically organized around the capsid and extractable with TX-100to a statewhere it is asymmetrically arranged and resistant to extraction.All herpesviruses have a tegument,a layer of protein located between the virus membrane and the capsid.Depending on the virus species,the tegument can be20to40nm in thickness,and it may be uniformly or asymmetrically distributed about the capsid(7,17,24,33).The tegument is composed predomi-nantly of virus-encoded proteins that together can account for up to half or more of the total virion protein mass.Tegument proteins are thought to be those involved in the early stages of infection before progeny virus proteins are synthesized.The tegument has been most thoroughly studied in herpes simplex virus type1(HSV-1).Examination of virions by elec-tron microscopy has demonstrated that the tegument is not highly structured.Its morphology is described as predomi-nantly granular withfibrous elements also present(7,19). Analysis by cryo-electron microscopy,followed by icosahedral reconstruction has shown that the tegument is not icosahe-drally ordered,although a small amount of tegument density is observed close to the capsid surface at the pentons(3,47). The HSV-1tegument is composed of approximately20dis-tinct,virus-encoded protein species whose amounts vary con-siderably.The predominant components are UL47,UL48,and UL49,each of which occurs in more than800copies per virion (8,46).In contrast,others,such as RL2(ICP0),RS1(ICP4), UL36,and UL37,occur inϳ100copies or less.Trace amounts of host cell-encoded proteins are also present(15).Many of the tegument proteins are required for virus replication(34), and functions have been defined for most(9,12,31,40).Biochemical studies have demonstrated that the tegument makes noncovalent contacts with both the virus capsid and the membrane.Studies of capsid-tegument contacts have empha-sized binding of UL36,a tegument protein,to UL25,a capsid protein located near the vertices and involved in DNA encap-sidation(5,20,29).Other tegument proteins such as UL48 (VP16),UL37,and UL49(VP22)are found to associate with UL36and may be bound to the capsid indirectly by way of UL36(13,44).UL16binds reversibly to the capsid while UL46 (VP11/12)has been shown to bind to both the membrane and the capsid(21,22,26).Binding of tegument proteins to the membrane has been shown to occur by way of attachment to UL11(45)and also to the internal domains of membrane glycoproteins,including glycoprotein D(gD),gH,and gE(4, 6,11).We describe here the results of a study in which electron microscopy and protein analysis were used to clarify the struc-ture of the HSV-1tegument and its attachment to the capsid. The study was designed to extend the observation that most of the HSV-1tegument remains attached to the capsid when the membrane is removed from the virus by treatment with non-ionic detergent(19).Cell-associated and extracellular virions were compared after treatment with Triton X-100(TX-100).MATERIALS AND METHODSCell and virus growth.All experiments were carried out with the KOS strain of HSV-1which was grown on monolayer cultures of Vero cells as described previously(35).Cells were grown and infected in150-cm2tissue cultureflasks or 800-cm2roller bottles.Virus and capsid purification.Extracellular virus was prepared from the infected cell supernatant which was harvested in15-ml aliquots and centrifuged for5min at1,000ϫg to remove cells.The time of harvest varied in individual experiments and is given in the text.Virus was pelleted from the supernatant by centrifugation at23,000rpm for45min in a Beckman SW41rotor operated at 4°C.Pellets were resuspended in300l of TNE(0.01M Tris-HCl,0.5M NaCl,*Corresponding author.Mailing address:Department of Microbi-ology Box800734,University of Virginia Health System,1300Jeffer-son Park Ave.,Charlottesville,VA22908.Phone:(434)924-1814.Fax: (434)982-1071.E-mail:jcb2g@.ᰔPublished ahead of print on3June2009.80821mM EDTA[pH7.5]),and virus was further purified by centrifugation(23,000 rpm,40min;SW50.1rotor;4°C)on a gradient of20%-50%sucrose in TNE.The virus band was identified by scattered light and harvested from the gradient with a Pasteur pipette.Preparations yieldedϳ300l virus at a concentration ofϳ0.3 mg of protein/ml from15ml of culture supernatant.Capsids were isolated from extracellular virus by TX-100treatment of virions purified as described above.Aliquots of100l of virus in TNE were adjusted to 0.5%TX-100and incubated for5min at4°C.Capsids were isolated by centrif-ugation(23,000rpm for40min in an SW50.1rotor at4°C)on a600-l gradient of20to50%sucrose prepared in TNE containing0.5%TX-100.After centrif-ugation,gradients were photographed and fractionated to recover capsids(ϳ100l;0.25mg of protein/ml).Capsids from cell-associated virus were isolated beginning with infected cells (ϳ5ϫ108cells)harvested18to24h postinfection in batches of three800-cm2 roller bottles.Cells were harvested by scraping,suspended in30ml of water,and frozen atϪ80°C.After thawing,cells were lysed by adjusting them to0.5% TX-100containing1mM EDTA,followed by incubation for5min at4°C.Nuclei were then removed from the lysate by centrifugation for5min at800ϫg,and capsids were pelleted from the postnuclear supernatant by centrifugation(SW28 rotor;23,000rpm for45min at4°C)through a5-ml cushion containing35% sucrose,0.5%TX-100,and1mM EDTA.Capsids were then resuspended in1ml of TNE containing2mM dithiothreitol and purified by two steps of sucrose density gradient ultracentrifugation as described previously(29).Preparations yieldedϳ200l of capsids at a concentration of0.25to0.5mg of protein/ml. Trypsin treatment of tegument-containing capsids.Studies on the trypsin treatment of tegument-containing capsids were carried out beginning with ex-tracellular HSV-1harvested30to40h postinfection and purified as described above.100-l aliquots were adjusted to0.5%TX-100and trypsin at a concen-tration of0.1or0.5g/ml.Mixtures were incubated for30min at37°C and the capsids were then isolated by ultracentrifugation on a600-l gradient of20to 50%sucrose in TNE containing0.5%TX-100and protease inhibitors as de-scribed previously(27).Centrifugation was for40min at23,000rpm in a Beck-man SW55Ti rotor operated at4°C.After centrifugation,gradients were photo-graphed and fractionated with capsid-containing fractions used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE).Comparable experiments were not carried out with cell-associated virus since TX-100was expected to remove the tegument from these virions.Electron microscopy.Infected cells,purified virus and capsids to be examined by thin-section electron microscopy were centrifuged into a small(ϳ0.3ml) pellet andfixed overnight with2%glutaraldehyde.Further steps offixation, embedding and sectioning were carried out as previously described(16).Sections were stained with1%uranyl acetate(5min at room temperature),followed by 0.25%lead citrate(2min at room temperature).Capsids to be examined by negative staining were adsorbed to carbon-Formvar-coated copper electron mi-croscope grids,stained for1min with1%uranyl acetate,and air dried as described previously(28).All electron microscopy was carried out on a Philips EM400T transmission electron microscope operated at80keV.Images were recorded onfilm and converted to digital form by scanning in aflatbed scanner. Measurement of images was performed with ImageJ and Photoshop CS3.The spacing of the connectors linking capsid and tegument was measured directly from images and also after densitometric scanning of the region between capsid and tegument with ImageJ.The results obtained with the two methods did not differ significantly.Other methods.Sucrose gradients were photographed with top illumination from a high intensity lamp so virus and capsid bands could be observed by scattered light.Images were recorded with a digital camera.DNA-containing capsids were identified by spotting2l of capsid suspension onto a polyvinyli-dene difluoride membrane,staining for2min with GelRed(1:10,000dilution), washing with phosphate-buffered saline,and visualization with UV illumination. Previously described procedures were used for SDS-PAGE,followed by Coo-massie blue staining(30).Stained gels were recorded by scanning in aflatbed scanner and the bands were measured quantitatively with UN-SCAN-IT(version 5.2;Silk Scientific).RESULTSIntact virus.Tegument analyses were carried out beginning with two distinct virus populations:cell-associated HSV-1and virions harvested from the extracellular medium.Examination by electron microscopy showed that most cell-associated virus was located near the outer surface of the cell attached to the surface or to projections from it(Fig.1a and b).As expected, extracellular virions were found to be free of cell-derived ma-terial(Fig.1d to f).Micrographs showed that the structure of the tegument was quite different in the two virus populations. Whereas it was uniformly distributed around the capsid in cell-associated virus,it was markedly asymmetric in extracel-lular virions as described previously(7,17)(compare Fig.1a-to c with Fig.1d to f).Counts showed40of40(100%)and88 of488(18%)virions with a symmetric tegument morphology in cell associated and extracellular virions,respectively.Cell-as-sociated virions were interpreted to be progeny virions as pa-rental virus,derived from an infected cell supernatant,is ex-pected to have an asymmetric tegument.TX-100extraction.To examine the tegument in capsids from the two virus populations,virions were treated with0.5%TX-100as described in Materials and Methods,and the capsids FIG.1.Electron micrographs showing cell-associated(a to c)and extracellular HSV-1(d to f).Note that the tegument is symmetrically arranged around the capsid in cell-associated virus and asymmetric in extracellular virions.Arrows indicate representative virions with sym-metric teguments in panels a and b,while in panels d and e arrows indicate virions where the tegument is asymmetric.V OL.83,2009HSV-1TEGUMENT TRANSFORMATION8083were purified by sucrose density gradient centrifugation.Ex-amination of the gradients showed that a band of DNA-con-taining capsids sedimented coincidently with nuclear C capsidsin both TX-100-treated cell-associated and extracellular viruspopulations(Fig.2a).Further analysis was done with capsidsfrom the two bands(starred in Fig.2a)and also with nuclear Ccapsids(marked as asterisks in thefigure)as a control.The twovirus-derived capsid populations are identified as TX-100-treated cell-associated viruses(TCAV)and TX-100-treatedextracellular viruses(TEV),respectively.In addition to theDNA-containing capsids,each virus population was found toyield small amounts of capsids sedimenting coincidently withnuclear A and B capsids(Fig.2a).Electron microscopic examination showed that whereasTEV capsids were coated with abundant tegument as expected,little or none was observed with TCAV(Fig.2b;compare lanes1and2).Although the TEV capsid was largely obscured bycomponents of the tegument,in TCAV the capsid was visiblewith a diameter comparable to that of nuclear C capsids(Fig.2b;compare lanes1and3).Capsomers were apparent in mostTCAV images.Measurement of the particle diameters ofTCAV,TEV,and nuclear C capsids yielded values of111.5Ϯ4.2nm(nϭ58),164.7Ϯ9.6nm(nϭ33),and112.2Ϯ1.9nm(nϭ31),respectively(Fig.3).SDS-polyacrylamide gel analysis supported the view thatTCAV contain little tegument.While TEV were found to becomposed of capsid proteins UL19,UL38,and UL18plusadditional protein species presumptively identified as tegu-ment proteins UL36,UL46,UL47,UL48,and UL49,TCAVshowed capsid proteins with only trace amounts of protein thatcould correspond to tegument components(compare Fig.2c,lanes1and2).The TCAV protein composition was quitesimilar to that of nuclear C capsids(Fig.2c;compare lanes1and3).Since it was unexpected to observe that the tegument wasremoved by TX-100treatment of cell-associated HSV-1,weconsidered three alternative possibilities:(i)TCAV were ac-tually C capsids derived from the infected cell nucleus;(ii)TCAV were produced from tegument-containing capsids bythe action of host cell enzymes or other factors that would notbe present to affect capsids derived from extracellular virus;and(iii)TCAV were produced only at the low salt concentra-tion routinely used for extraction of cell-associated virus.In response to thefirst possibility,we note that the distribu-tion of capsid types produced by TX-100treatment of cell-associated virus(mostly C-like capsids with only a trace of Aand B capsids)was quite different from the capsids isolatedfrom infected cell nuclei(predominantly B capsids;Fig.2a[compare lanes1and3]).Further,the nuclei produced byTX-100treatment of infected cells were not damaged in a waythat would allow capsids to escape.In fact,upon deliberatedisruption,these nuclei yielded normal amounts of capsids,including C capsids(data not shown).The second possibility was addressed by adding extracellular FIG.2.Analysis of HSV-1capsids by sucrose density gradient cen-trifugation(a),electron microscopy(b),and SDS-PAGE(c).Analysiswas performed with capsids isolated by TX-100treatment of cell-associated virus(lane1),TX-100extraction of extracellular virus(lane 2),and capsids isolated from the nuclei of HSV-1-infected cells(lane 3).Bands marked by asterisks in panel a were the ones used for analysis in panels b and c.Note that tegument remains attached to capsids derived from extracellular,but not cell-associated virus.8084NEWCOMB AND BROWN J.V IROL.virions to infected cells prior to TX-100treatment.Such mix-tures yielded both TEV and TCAV in the proportion present in the original preparation (data not shown),indicating that host cell factors are not capable of removing the tegument from TEV during the TX-100extraction process.We conclude that TCAV are most likely to be derived from cell-associated virus as suggested above.The effect of NaCl concentration was tested by exchanging the salt concentrations used for TX-100extraction;cell-asso-ciated virus was extracted in TNE (0.5M NaCl),while low-salt buffer was used for extracellular virus.No effect was observed in either case (data not shown).At both salt concentrations tegument was removed from cell-associated virus and was re-sistant to extraction in virus harvested from the extracellular medium.Tegument structure.The structure of the tegument in TEV was further examined by electron microscopy of thin-sectioned material.Images showed DNA-containing capsids surrounded to a variable extent by tegument (Fig.4).In most images thetegument was seen to be asymmetrically distributed about the capsid as it is in the extracellular virions from which the TEV were prepared.Three images of this type are arrowed in Fig.4,but others can be identified.In some images the tegument was found to have gaps or irregularities,suggesting that some teg-ument may have been lost or not incorporated as the virus was formed (Fig.4).DNA was seen to project from the capsid in some cases,an effect we suggest may be due to capsid or tegument damage during preparation (see boxed image in Fig.4).In some images the tegument could be seen to be attached to the capsid by short connectors (Fig.5a and b).These were variable in diameter,and most were 6.0to 10.0nm in length.Visual examination indicated a degree of regularity to the connector spacing.Measurement of the spacing in 13capsids yielded a mean value of 16.8Ϯ4.8nm (n ϭ54;Fig.5c).Linkage between the capsid and tegument was also probed by trypsin treatment of TEV.It was expected that the degree of trypsin sensitivity in the linkage would be revealing about its overall strength.Experiments were performed by treating ex-tracellular HSV-1simultaneously with 0.5%TX-100and tryp-sin.After incubation,the resulting capsids were examined by sucrose density gradient centrifugation and SDS-PAGE to de-termine whether the tegument had been removed (Fig.6).Sucrose gradient analysis of control reactions incubated without trypsin yielded two bands of DNA containing capsids (Fig.6a,lane 1).Of these,the predominant band (starred in Fig.6a)corresponded in migration to TEV,and this identifi-cation was confirmed by SDS-polyacrylamide gel analysis,which revealed the presence of tegument proteins,as expected of TEV (Fig.6b,lane 1).The minor band migrated coinciden-tally with C capsids (Fig.6a,lane 1).FIG.3.Capsid diameter as determined in TX-100-extracted cell-associated virus (top),TX-100-extracted extracellular virus (middle),and C capsids isolated from the nuclei of HSV-1-infected cells (bot-tom).Measurements were made from electron micrographs of speci-mens after negative staining as described in Materials and Methods.Note the larger diameter of tegument-containing capsids (middle)compared to those lacking tegument (top andbottom).FIG.4.Electron micrograph showing extracellular HSV-1virions after treatment with 0.5%TX-100.Note that the tegument is asym-metrically distributed around the capsid as it is in intact virions (ar-rows).DNA can be seen to be in the process of being extruded from some capsids;one such capsid is boxed.Gaps or irregularities can be observed in the tegument of many TEV,indicating that it was eroded or was never firmly attached to the capsid.V OL .83,2009HSV-1TEGUMENT TRANSFORMATION 8085When reactions were performed in the presence of trypsin,the results of sucrose gradient analyses were found to depend on the trypsin concentration.At a low concentration (0.1g/ml),gradients revealed two bands of capsids:a predominant,DNA-containing band migrating coincidentally with C capsids and a minor band of capsids lacking DNA and migrating with A capsids (Fig.6a,lane 2).No band of TEV was observed.Only A-like capsids were seen when the trypsin concentration was high (0.5g/ml;Fig.6a,lane 3).SDS-polyacrylamide gelFIG.5.Electron microscopic analysis of TEV exhibiting connec-tions between the capsid and the tegument.A representative image of a TEV with connectors is shown at low (a;boxed image)and high (b)magnifications.Connectors are indicated by arrows in panel b.The spacing between connectors was measured in 13TEV images,and the results are shown in panel c.FIG.6.Sucrose density gradient (a)and SDS-PAGE (b)analysis of TEV before (lane 1)and after (lanes 2and 3)treatment with trypsin.SDS-PAGE analyses were performed with TEV or capsids recovered from gradient bands marked by asterisks in panel a.Note that the effect of trypsin depended on the dose used.At 0.1g/ml,trypsin caused removal of the tegument,but DNA was retained in the capsid.In contrast,a concentration of 0.5g of trypsin/ml caused the loss of both tegument and DNA.8086NEWCOMB AND BROWN J.V IROL .analysis of the C-like and A-like capsids revealed capsid pro-teins with only negligible amounts of tegument present(Fig. 6b,lanes2and3).The results of these experiments are interpreted to indicate that tegument proteins were removed from TEV by both low and high trypsin doses.This interpretation is supported by SDS-polyacrylamide gel analyses showing an absence of tegu-ment proteins in the capsids recovered from trypsin-containing incubations(Fig.6b,lanes2and3).The high trypsin dose additionally caused release of the capsid DNA,as described previously(27).DNA release resulted in the creation of A capsids,as observed by sucrose gradient analysis(Fig.6a,lane3). Effects of extracellular incubation.Experiments with extra-cellular virus were carried out to determine when the tegument first becomes resistant to extraction with TX-100.Extracellular virus was harvested at progressively longer times after infection and divided into two aliquots.One was treated with TX-100, while the other was held as a control,and SDS-polyacrylamide gel analysis was used to determine the protein composition of each.The results demonstrated that the tegument content of viri-ons was not greatly affected by the time of harvest over the range of24to64h postinfection(Fig.7a).The three major tegument protein species(UL47,UL48,and UL49)were all found to be present,and the amount did not vary systemati-cally during the harvest period examined.Similarly,the con-tent of a control capsid protein(UL38)did not vary,indicating that analysis was performed with approximately the same amount of virus at each time point(Fig.7b).In contrast,a substantial increase in tegument was observed after TX-100treatment in64-h compared to24-h TEV.As in the case of virus,UL47,UL48,and UL49were the predomi-nant tegument protein components of TEV,but the amount of each relative to a control protein(UL38)increased substan-tially with time after infection(Fig.7a,lanes1to3,and Fig.7b, top panel).Control experiments demonstrated that the pres-ence of living cells was not required for the observed time-dependent increase in the amount of TX-100-resistant tegu-ment.The same increase was observed when extracellular virus was removed from cells prior to incubation(data not shown). Since the amount of tegument present in virions was not af-fected by time after infection,it is concluded that the tegument becomes progressively more resistant to TX-100extraction at increasing times postinfection.DISCUSSIONTegument function.Herpesvirus tegument proteins are thought to be those whose function is required promptly after initiation of infection,before expression of virus genes can take place.The HSV-1alpha-gene transactivating factor(UL48)isan example of this.UL48is a tegument protein essential for HSV-1replication(1,2,32).It is released from the tegument as the parental capsid enters the host cell cytoplasm.UL48 then binds to a cellular protein,Oct-1(18),and in a complex with Oct-1it activates transcription of immediate-early(alpha) genes such as ICP0,ICP4,and ICP22(2,32).Other HSV-1 tegument proteins thought to function soon after virus entry include UL36,UL41,ICP34.5,and ICP22(12,34,39,40).In order for a tegument protein to function prior to virus gene expression it must be assembled into the virion tegument as a progeny virion is formed and then released from the capsid when a new host cell is infected.In HSV-1,most tegument proteins become associated with the capsid during secondary envelopment in the cytoplasm.A progeny capsid buds into a vesicle containing a region of tegument on its outer surface, creating a doubly enveloped,tegument-containing capsid.The outer of the two membranes then fuses with the host cell cytoplasmic membrane,exposing a virion to the extracellular FIG.7.(a)SDS-PAGE analysis of TEV and extracellular HSV-1. Extracellular virus was harvested at different times after infection(24, 48,and64h)and divided into two equal aliquots.TEV was prepared from one,while the other served as a control.Gel analysis is shown for TEV(lanes1to3)and for virus(lanes4to6).HSV-1B capsids were examined as a control(lane7).(b)Quantitative determination of selected gel bands.Note that while the amount of tegument protein present in TEV increased with time of virus harvest,the amount in virions was not affected.V OL.83,2009HSV-1TEGUMENT TRANSFORMATION8087environment(23).The tegument is shed completely or nearly so when parental capsids enter the peripheral cytoplasm in the subsequent cycle of infection(23).Symmetric and asymmetric tegument.Although individual HSV-1virions have been observed with either a symmetric or an asymmetric tegument(7,17,24,33),it was novel in the present study to note the correlation of symmetric tegument with cell-associated virus(Fig.1).It was similarly novel and unexpected to observe that the tegument of cell-associated virus was removed by TX-100treatment(Fig.2and3).Previ-ous studies with extracellular virus emphasized the resistance of the tegument to TX-100extraction(19).Since cell-associ-ated virus is a precursor of extracellular virions,the different morphology and TX-100extractability suggests that the release of progeny virus is accompanied by a global structural trans-formation or maturation in the tegument.The tegument be-comes more tightly associated with the capsid,and much of it is changed in location.Tegument transformation.Studies of the time course have demonstrated a time-dependent progression linking virions with extractable and unextractable teguments.Thefirst virions able to be recovered from the extracellular medium(ϳ24h postinfection)were found to resemble cell-associated virus in that much of the tegument was removed after treatment with 0.5%TX-100(Fig.7).At later times postinfection,an increas-ing proportion of the tegument became unextractable.This observation indicates that resistance to TX-100does not occur immediately as progeny virions detach from the host cell but rather it develops gradually over a period of40h or more. Resistance to TX-100extraction appeared to involve all or most of the predominant tegument proteins(Fig.7).The most apparent difference between cell-associated and extracellular virus has to do with the host cell in the subsequent cycle of infection.Cell-associated virus is well suited to infect adjacent cells,while extracellular virus has the potential to infect more remote ones.We suggest that the progressively stronger tegument-capsid association observed in extracellular virus may be an adaptation to maintain virus infectivity as it transits through the external environment.Removal of the tegument once a suitable host cell is infected may be caused by host cell factors such as protease activity(10)or possibly by reversibility in the tegument-capsid interaction,as suggested by studies of tegument components UL16and UL46(21,22, 26).Both cell-associated and extracellular virions were found to be infectious(data not shown).Alternatively,the important feature of extracellular virus may be the asymmetric arrangement of the tegument.An asymmetric tegument may expose the site of DNA exit from the capsid,making uncoating more facile as recently suggested by Maurer et al.(17).It is also possible that resistance of the tegument to TX-100extraction is simply a manifestation of virion decay.Protein oxidation or denaturation may account for tegument aggregation to one side of the virion and to a strengthened association with the capsid.Either could eventu-ally attenuate the infectivity of extracellular virus. Tegument-capsid attachment.Investigations into the nature of capsid-tegument association have focused on UL36,a large tegument protein(3139amino acids in length)present inϳ120 copies/virion(8).UL36is attached to the capsid by way of a noncovalent interaction with UL25,a capsid protein located near the vertices and involved in DNA encapsidation(5,20,29, 41,43).Yeast two-hybrid and immunological analyses have demonstrated that UL36binds directly to other tegument pro-teins including UL37,UL41,and UL48,suggesting the tegu-ment may be organized around UL36;other tegument proteins would be bound directly or indirectly to UL36(13,44).It is consistent with this idea that UL48binds to tegument proteins UL41,UL46,UL47,and UL49(14,25,36,44).Two tegument proteins,UL46and UL16,have been found to attach reversibly to the capsid,indicating that these may also be involved in linking the tegument to the capsid(21,22,26).Electron microscopic examination of TEV as reported here demonstrated the presence of short connections between cap-sid and tegument with a spacing of16.8Ϯ4.8nm(Fig.5).For comparison,the spacing between adjacent capsomers,adjacent triplexes and adjacent pentons is15.6,9.4,and65.6nm,re-spectively(48).The observed connector spacing,therefore, correlates best with attachment involving capsomers.The ob-served spacing is too small to support the view that connections are exclusively at pentons,as suggested by structural analyses and by attachment of UL36to UL25sites near the pentons(3, 5,42,47).The sensitivity of the tegument to trypsin digestion in TEV was determined as an overall measure of the strength of the capsid-tegument contact(Fig.6).In the past,measurement of trypsin sensitivity has been most useful in demonstrating that whereas the major capsid protein is quite resistant to digestion with a high trypsin concentration(1mg/ml[37]),much lower concentrations were sufficient to detach pentons or to promote DNA release from C capsids(27,38).The results described here indicate that the capsid-tegument connection is quite sensitive to trypsin treatment.All or nearly all of the tegument was removed from TEV after a30-min digestion with0.1g of trypsin/ml at37°C,a treatment that was too mild to cause DNA release from the same capsids(Fig.6).We suggest that protease digestion may be a part of the way the tegument is removed from capsids in infected cells shortly after capsids enter the peripheral cytoplasm.Such digestion could account for the protease activity shown to be required for migration of capsids to the nucleus and DNA uncoating(10). In the future it will be of interest to continue to probe the interaction between the capsid and tegument with the goal of accounting for how the tegument acquires its resistance to TX-100extraction.Although many possibilities suggest them-selves,it is clear that association must be noncovalent in na-ture.In the present study it was noted that all capsid-tegument contacts were broken when specimens were prepared for SDS-PAGE,even when analysis was performed with the most TX-100resistant virions.ACKNOWLEDGMENTSWe thank Anna Maria Copeland and Fred Homa for thoughtful comments about the manuscript.We also thank Rebecca Mingo and Jennifer Thompson for suggestions regarding experimental design and interpretation.This study was supported by NIH award AI041644.REFERENCES1.Batterson,W.,and B.Roizman.1983.Characterization of the herpes simplexvirion-associated factor responsible for the induction of alpha genes.J.Virol.46:371–377.8088NEWCOMB AND BROWN J.V IROL.。
医学微生物学第八第三十一章疱疹病毒
EBV的增殖性感染
病毒增殖，感染细胞溶解死亡 增殖性感染相关抗原
EBV早期抗原（EA）非结构蛋白，具DNA多聚酶活性 EBV衣壳抗原（VCA）与病毒DNA组成EBV的核衣壳 EBV膜抗原（MA） EBV的中和抗原（gp320）
EBV非增殖性感染
包括： 潜伏感染 病毒基因组处于潜伏状态 ,感染的B细胞的“转化”
ELISA检测lgM抗体和lgG抗体，适用于早期感染和流 行病学调查
治疗与预防
丙氧鸟苷（ganciclovir DHPG）有防止CMV扩散作用 耐丙氧鸟苷的CMV感染可选用磷甲酸钠，但效果比前
者差 CMV病毒活疫苗致癌潜能的问题有待解决 CMV包膜糖蛋白的亚单位疫苗是研究的方向
gp320膜蛋白疫苗，正在英国大学生患者中作 小规模接种，以期观察该疫苗是否能降低传染 性单核细胞增多症的发病率
African or Burkitt’s Lymphoma
Although BL is a very rapidly growing tumour it responds well to treatment.
鼻咽癌
我国南方（广东、广西）及东南亚是鼻咽癌高发 区
多发生于40岁以上中老年人 EBV与鼻咽癌
在所有病例的癌组织中有EBV基因组存在和表达病 人血清中有高效价EBV抗原（主要VCA和EA）的lgG 和 lgA 抗体病情好转后，这些抗体的滴度也随之 下降
微生物学检查
EBV分离培养困难
经紫外线灭活的CMV可转化啮齿类动物胚胎成纤维细胞 某些肿瘤如宫颈癌、结肠癌等中CMV DNA检出率高
微生物学检查
尿等标本离心沉淀，姬姆萨染色镜检，检查巨大细胞 及核内和浆内嗜酸性包涵体
第16章 脑膜刺激征
第十六章脑膜刺激征meningeal irritatation sign软脑脊膜受到炎症、出血或理化内环境的改变刺激时可出现一系列提示脑膜受损的病征，称脑膜刺激征。
【病因和机理】头痛、呕吐的发生是由于脑膜上的三叉神经与迷走神经感觉性终末器受炎症性及机械性刺激所致。
颈强直是由于支配颈肌群的颈丛神经受炎症，理化改变等刺激后引起颈部肌肉痉挛并伴有疼痛所致。
而阳性的克氏征、布氏征、则是由于相应支配的神经根受刺激所引起。
病因可分为感染性因素、非感染性因素两种。
前者主要是细菌、病毒、螺旋体真菌、寄生虫等病原体引起的脑炎和脑膜炎。
后者主要是蛛网膜下腔出血、脑肿瘤、风湿病、白血病及某些病外疾病对脑膜的影响。
【临床表现】1.头痛、呕吐:头痛常剧烈，是最常见的症状，病程早期即可出现。
一般为弥漫性，有时有枕部和额部特别显著。
呕吐则多为喷射性。
2.颈肌强直:颈部肌肉强硬对被动运动有抵抗，如被动屈颈则有肌痉挛及疼痛。
3.克氏征:下肢髋、膝关节屈曲成直角，然后使小腿伸直，正常可伸直达135°以上，如遇抵抗，小于135°并觉疼时为阳性。
4.布氏征:患者抑卧，被动向前屈颈时，两下肢自动屈曲为阳性，为小脑脑膜刺激征。
另外还有皮肤感觉过敏，对听觉和视觉刺激过敏等。
【鉴别诊断】一、细菌感染（一）脑膜炎双球菌性脑膜炎（meningococcal meningitis）冬春季节流行，起病急，病情险恶，脑膜刺激征表现显著:剧烈头痛、呕吐（呈喷射状）颈强并伴颈枕部、脊柱疼痛，克氏征、布氏征均强阳性，视听感觉过敏。
但在流行期间可有“钝挫型”，脑膜刺激征不明显，略有低热，乏力、腰痛等。
脑脊液大多呈脓样混浊，细胞数可极高（在1.0×109/L以上）,分类以中性分叶核占优,蛋白增加,糖及氯化物明显减少。
皮肤出血点和脑脊液可查到脑膜炎双球菌。
（二）结核性脑膜炎（tuberoublor meningitis）多见于儿童，发病多渐起，亦可相当急聚，临床症状除发热、畏寒、头痛等一般中毒症状，各项体征以颈肌强硬出现最早，有早期诊断意义。
探索宇宙奥秘英文作文
探索宇宙奥秘英文作文The universe is a vast and mysterious place, full of wonders that we have yet to fully understand. From the swirling galaxies to the enigmatic black holes, there is so much out there that we have only just begun to explore.It's mind-boggling to think about the sheer size of the universe. Just trying to comprehend the distances between stars and galaxies can make your head spin. And yet, despite the enormity of it all, we are just a tiny speck in the grand scheme of things.One of the most intriguing aspects of the universe is the possibility of other forms of life beyond our planet. The idea that we may not be alone in the cosmos is both thrilling and humbling. Who knows what kind of beings or civilizations could be out there, waiting to be discovered?The study of the universe has led to some incredible technological advancements. From the Hubble Space Telescopeto the Mars rovers, we have been able to catch glimpses of distant worlds and gather data that has expanded our understanding of the cosmos.Of course, there are still so many unanswered questions about the universe. What is dark matter, and how does it shape the cosmos? Are there other dimensions beyond the ones we can perceive? These mysteries continue to fuel our curiosity and drive us to keep exploring.。
【疾病名】单纯疱疹性脑炎【英文名】herpessimplexencephalitis【缩写..
【疾病名】单纯疱疹性脑炎【英文名】herpes simplex encephalitis【缩写】【别名】单纯疱疹病毒脑炎；单纯疱疹脑炎；单纯性疱疹脑炎；疱疹病毒性脑炎；疱疹性脑炎；herpes simplex virus encephalitis【ICD号】B00.4【概述】单纯疱疹脑炎又称疱疹病毒性脑炎；既可见于初发性单纯疱疹病毒感染，也可见于复发性患者。
本病呈散发性，在非流行性病毒脑炎中系最常见的一种，据统计约占病毒性脑炎的10%～20%，病情严重、预后较差。
【流行病学】1.传染源 急性期患者及慢性带毒者均为传染源。
一般人群中，5%成年人为无症状携带者；单纯疱疹病毒存在于感染者的疱疹液、病损部位分泌物以及唾液及粪便中；也可从外生殖器并无明显病损的患者精液中检出。
2.传播途径 单纯疱疹病毒对外界抵抗力弱，主要通过患者病损部位直接接触健康人黏膜或皮肤微小破损处而传播；通过空气飞沫传播则是HSV-I型感染的另一重要途径。
性交、接吻是传播本病的重要方式之一，导致生殖器疱疹的发病。
因此，生殖器疱疹被列入性传播疾病范畴。
患病孕妇也可导致胎儿宫内感染。
此外，单纯疱疹病毒感染还可经消化道途径传播。
3.易感人群 人群普遍易感，成年人群中有很高的HSV抗体检出率，Tischendorf报道，80%～90%欧洲居民曾遭受HSV-1亚型的感染。
据估计，全球人口中约1/3罹患过单纯疱疹，大多获自隐性感染；但HSV抗体的存在尚不能完全保护机体免受疱疹病毒的重复感染，患者也可先后遭受两个亚型的单纯疱疹病毒感染；不过，曾遭受HSV-1亚型感染者，倘再罹患HSV-2亚型感染时，病情可相对较轻。
本病的发生多为散发或原有潜伏病毒感染的反复发作。
研究表明，单纯疱疹病毒感染率在经济水平低下、居住条件拥挤地区的人群较高；儿童营养不良或其他原因所致的免疫功能低下者，较易于罹患单纯疱疹病毒感染；有时可在儿童集中的区域内，如幼托机构出现暴发流行。
Mysteries of the Universe
The mysteries of the universe are vast and awe-inspiring, encompassing everything from the nature of dark matter and dark energy to the origins of the cosmos and the possibility of extraterrestrial life. Some of the most intriguing mysteries include:1.Dark Matter and Dark Energy: These are two of the most enigmaticcomponents of the universe, comprising the majority of its mass and energy. Yet, their true nature and properties remain largely elusive, challenging our understanding of the fundamental forces at play in the universe.2.The Big Bang: The origin of the universe itself is a profoundmystery, with the Big Bang theory providing a framework forunderstanding the rapid expansion of space and the subsequentevolution of galaxies, stars, and planets. However, manyquestions remain about what preceded the Big Bang and what lies beyond the observable universe.3.Black Holes: These enigmatic cosmic phenomena have captivatedscientists and the public alike, as their extreme gravitational pull and mysterious interiors defy our current understanding of physics. The nature of the singularity at the heart of a black hole and the potential links to other cosmic mysteries aresubjects of ongoing research.4.Exoplanets and the Search for Life: The discovery of thousandsof exoplanets beyond our solar system has fueled speculationabout the potential for life elsewhere in the universe.Understanding the conditions necessary for life to exist and the likelihood of finding extraterrestrial civilizations are among the most tantalizing mysteries in astronomy.5.Quantum Mechanics and Gravity: The quest to reconcile theprinciples of quantum mechanics with the force of gravityrepresents a major frontier in theoretical physics, withprofound implications for understanding the behavior of matter at the smallest and largest scales.These mysteries, among many others, continue to inspire scientists and philosophers to push the boundaries of human knowledge and imagination, offering a glimpse into the profound complexities of the cosmos.。
中枢神经系统感染的临床诊断与治疗.
病因及发病机制：90%为HSV-Ⅰ感染，HSV-Ⅱ感 染只占6%-15%；HSV的核心为双链线状DNA，其 包膜为典型类脂双层膜，膜的糖蛋白具有独特抗原性， 决定病毒株的特异性。
14
HSV侵犯CNS的机制（1）
临床表现（2）
可能出现的症状： 精神症状：达70％～85％，表现为人格改变、缄默、
懒散、不主动进食、烦躁、记忆力减退、行为异常、 幻觉、妄想
意识障碍：定向力障碍、严重者昏迷 抽搐：多种形式 偏瘫 高颅压，甚至脑疝 锥体外系症状 脑膜刺激征、脑干炎
19
【辅助检查】
血常规：WBC↑、中性粒细胞↑，ESR ↑ CSF：压力↑；2/3患者细胞数↑，一般为50～150
3
CNS感染的侵入途径Fra bibliotek血液源性侵入
邻近器官直接扩散
神经干逆行感染
4
中枢神经感染的分类
目前尚无统一分类标准，多采用ICD-10分 类方法
按受累部位：脑和/或脊膜炎；脑炎；脑膜脑炎；脑脊髓炎 按病原体：病毒性；细菌性；真菌性；寄生虫性等(ICD-10) 按病理特点：包涵体性；出血性；坏死性和脱髓鞘性等
21
5、细小病毒感染
细小病毒家族包括：猫瘟病毒、犬细小病毒、阿留申 群岛水貂病病毒、猪细小病毒、腺病毒以及细小病毒 B19等。病毒属于带衣壳的DNA病毒。寄生在RBC中 造成急慢性感染症状。
细小病毒B19感染引起的常见疾病是第十五病（Fifth disease），表现为双颊部掌掴样皮疹、关节炎、一 过性肝炎以及中枢神经系统累及。
传播媒体 蚊 蚊 蚊
蚊 蚊 蚊 蚊 蜱 蜱 蜱
第二章 中枢神经系统感染
第二章中枢神经系统感染中枢神经系统感染（infections of the central nervous system），是由病毒（virus）、细菌（bacteria）、螺旋体（fungus）、寄生虫（parasite）、立克次体等多种感染源引起的中枢神经系统的常见、多发性疾病。
常见的感染途径有：○1血行感染（经呼吸道或皮肤黏膜进入血液，由血液系统进入颅内。
）○2直接感染（穿透性外伤或邻近结构感染后蔓延入颅）○3神经干逆行感染（如单纯疱疹病毒，狂犬病毒等嗜神经病毒感染皮肤、呼吸道或肠道黏膜，经过神经末梢进入神经干）侵犯中枢神经系统实质、被膜及血管等。
中枢神经系统感染性疾病种类较多。
按照病变部位可分为脑炎、脊髓炎或脑脊髓炎；脑膜炎、脊膜炎或脑脊膜炎；临床有时常难以截然分开，当两者均明显时，则常以脑膜脑炎命名。
按照发病情况及病程可分为急性、亚急性、慢性感染。
按照致病因子不同可分为病毒性脑炎、细菌性脑炎、真菌性脑炎、寄生虫性脑病等。
按照病理特点分为包涵体性、出血性、坏死性、脱髓鞘性等。
根据流行情况可分为流行性及散发性等。
本节重点介绍常见的病毒性脑炎中的单纯疱疹病毒性脑炎（占已知病毒性脑炎的20%-68%）。
其他内容见相关章节。
单纯疱疹性脑炎（herpes simplex encephalitis，HSE）是世界各地散发性脑炎中最常见者，又称急性坏死性脑炎或急性包涵体脑炎。
发病率为0.2/10万-0.5/10万人。
我国尚无确切发病统计，近年来本病发病日趋增多。
任何年龄均可发病，无性别差异，病情险恶，死亡率高。
本病属于中医“温病”、“头痛”、“痉症”、“神昏”、“痿证”、“癫狂”的范畴。
病因病机（1）邪犯卫气温热毒邪侵袭卫表，经腧不利，见发热、恶寒，颈项强直；邪热上扰清窍，则神倦嗜睡，头痛；邪热犯及肺胃或湿热之邪留恋三焦则见口渴，恶心，呕吐。
（2）气营两燔邪热入于气营，里热炽盛，见高热，头痛，项强，热炽中焦则口渴，恶心，呕吐，热扰心神则烦燥，嗜睡或昏迷。
单纯疱疹病毒性脑炎治疗前后血清NSE含量及脑电图分析
单纯疱疹病毒性脑炎治疗前后血清NSE含量及脑电图分析汪芳;丁莉;邵良;盛美红;朱易华;王慧俐;李新铃;黄怀宇【期刊名称】《中国实用神经疾病杂志》【年(卷),期】2009(012)012【摘要】单纯疱疹病毒性脑炎（herpes simplex encephalitis，HSE），又称急性坏死性脑炎，系单纯疱疹Ⅰ型（HSV—Ⅰ型）病毒感染侵入脑内引起的中枢神经系统急性炎症性疾病。
若未经早期诊断治疗，病死率超过70％。
本文旨在观察42例HSE患者治疗前后血清神经元特异性烯醇化酶（neuron specific enocase，NSE）浓度及脑电图的变化，并探讨其与HSE的关系。
【总页数】2页(P29-30)【作者】汪芳;丁莉;邵良;盛美红;朱易华;王慧俐;李新铃;黄怀宇【作者单位】江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001;江苏南通大学第二附属医院,南通,226001【正文语种】中文【中图分类】R512.3【相关文献】1.早期康复治疗对脑出血患者神经功能转归及血清NSE含量的影响 [J], 陈立英;高媛;康增军;崔蕾2.高压氧治疗对病毒性脑炎患者的疗效观察及其对血清NSE含量的影响 [J], 司晓宁;李东娟;罗织云3.依达拉奉治疗急性缺血性小卒中患者血清NSE含量变化的临床观察 [J], 解学军;赵艳茹4.黄芪桂枝五物汤结合有氧康复运动治疗小儿痉挛型脑瘫的疗效及对血清BDNF、NSE含量和运动功能的影响 [J], 张燕; 向守娟; 王梅5.益肾通脉方治疗对急性脑梗死患者临床疗效及血清NSE含量、Barthel评分的影响 [J], 李国胜;李纯妤;王民因版权原因，仅展示原文概要，查看原文内容请购买。
单纯疱疹病毒Ⅰ型最新研究进展——病原学、防控及应用
单纯疱疹病毒Ⅰ型(herpes simplex virus 1,HSV-1)的感染普遍存在,婴儿的脑部感染多为原发性感染,而成年人感染多由潜伏感染的病毒再激活引起[1~2]。
原发性的病毒感染和潜伏感染后的再激活都有可能引起程度不同的慢性炎症过程。
目前没有特异性的抗HSV-1的治疗药物,也没有用于预防其感染的疫苗。
临床常用的治疗药物是以口服阿昔洛韦(acyclovir,ACV)为代表的核苷类似物[3]。
HSV-1感染的治疗价格十分高昂,仅在美国,每年就有约1770万美元用于治疗5.9万例新发和2.9万例复发的疱疹性眼病,其中ACV 用于治疗疱疹病毒性眼病的费用高达8532美元[4]！此外,耐药毒株病例的不断出现,也为抗病毒治疗提出了更高的要求[1~2]。
研究表明,HSV-1能通过改变有丝分裂后细胞中病毒生长所涉及的非必需基因而具有溶瘤活单纯疱疹病毒玉型最新研究进展———病原学、防控及应用收稿日期:2020-02-07;修回日期:2020-05-18基金项目:国家自然科学基金资助项目(31772739,31572515);科技部“十三五”国家重点研发计划“烈性外来动物疫病防控技术研发”项目(2017YFD0502306);科技部“十三五”国家重点研发计划“畜禽群发普通病防控技术研究”项目(2017YFD0502205)作者简介:田文骏(1994—),男,甘肃永靖人,硕士研究生,主要从事兽医生物医学研究,E-mail:****************;*通信作者:王晓佳(1976—),女,黑龙江佳木斯人,中国农业大学副教授,博士生导师,主要从事病毒与宿主细胞相互作用及抗病毒药物筛选方面的研究。
田文骏,郑成,王晓佳*(中国农业大学动物医学院农业部动物流行病学与人畜共患病重点实验室,中国北京100193)摘要:单纯疱疹病毒Ⅰ型(herpes simplex virus 1,HSV-1)感染可引起广泛的临床症状,包括口腔感染造成的组织损伤,以及严重的中枢神经系统感染造成的脑炎。
宇宙生命之谜相似的文章
宇宙生命之谜相似的文章1. "The Fermi Paradox: Where are all the extraterrestrial civilizations?" - This article explores the question of why, despite the high probability of extraterrestrial life in the universe, we have not yet made contact with any advanced civilizations. It delves into various theories and possible explanations for this paradox.2. "The Search for Exoplanets: Are we alone in the universe?" - This article discusses the recent advancements in exoplanet discoveries and how they contribute to our understanding of the potential for life beyond Earth. It explores the conditions necessary for habitability and the ongoing efforts to identify other potentially habitable planets.3. "The Origins of Life: How did life begin on Earth?" - This article looks into the mystery of how life originated on our own planet and considers the possibility of similar conditions existing elsewhere in the cosmos. It delves into various hypotheses and studies that aim to uncover the chemical and environmental processes that led to the emergence of life.4. "The Drake Equation: Estimating the number of extraterrestrial civilizations" - This article explores the famous Drake Equation, a mathematical formula that attempts to estimate the number of technologically advanced civilizations in our galaxy. It discusses the variables involved and the implications of different values, sparking further debate on the existence of intelligent life in the universe.5. "Astrobiology: The study of life beyond Earth" - This articleprovides an overview of the interdisciplinary field of astrobiology, which combines principles from biology, astronomy, chemistry, and more to investigate the potential for life elsewhere in the universe. It discusses the methods and tools used in astrobiology research and presents the latest discoveries and insights.。
Therapy for herpes virus symptoms nervous system t
专利名称：Therapy for herpes virus symptoms nervous system that utilizes a 1,4-dihydropyridinecalcium channel blocker发明人：ジク、ハワード申请号：JP2002544071申请日：20001121公开号：JP2004513965A公开日：20040513专利内容由知识产权出版社提供摘要： Therapy for Bell's palsy in mammals, have been proposed based on both the herpes virus and endothelin, the causal hypothesis related to the herpes simplex virus for Bell's palsy in particular. In short, the same treatment can be applied to Ramsay Hunt, but zoster virus may be included in the causal hypothesis in this case. It is also presented herpesvirus-related symptoms in other affected such as herpes simplex encephalitis. This therapy, calcium channel blocker of a therapeutically effective dose of 1,4-dihydropyridine derivative class (which is, for example, but felodipine, nifedipine, nimodipine, and Arenojipin Nisojipin including further) I use. This therapy has been proposed to be continued until the 10th day of progress, it is to start as soon as possible. Herpes also other antagonists such as famciclovir or acyclovir can be administered in a therapeutically effective dose.申请人：ジク、ハワード代理人：曾我 道照,曾我 道治,古川 秀利,鈴木 憲七,梶並 順,醍醐 美知子更多信息请下载全文后查看。
一种自身免疫性脑炎的治疗方法
一种自身免疫性脑炎的治疗方法摘要：自身免疫性脑炎是一种由于自身免疫功能缺陷所引起的中枢神经性疾病，严重危害着患者的生命健康。
目前在医疗机构中治疗自身免疫性脑炎的治疗方法有很多种，本文将综述一种用糖皮质激素作为治疗药物的治疗手段。
脑炎是一种中枢神经性疾病，根据发病的原因是否由生物因素引起可以分为两种，第一种是病原性感染性脑炎，这种脑炎指的是由于病原微生物的侵入而使得脑膜等中枢神经结构遭到感染所引起的脑炎，常伴有头痛、发热等症状；另一种脑炎为非感染性脑炎，主要是由自身免疫机制所引起的，常伴有精神行为异常、认知障碍等。
糖皮质激素是目前临床治疗手段的一线免疫治疗[1]。
目前这种方法在临床应用十分广泛，本文将就这一治疗手段进行比较详细的叙述。
1.自身免疫性脑炎1.自身免疫性脑炎简介自身免疫性脑炎是一种中枢神经性疾病，这种脑炎并不是由于病原体侵犯而引起的感染，而是因为免疫系统的自我攻击引起中枢神经系统炎症。
在我国，每年都有许多患者因为自身免疫性脑炎而来医院医治，这种疾病严重威胁着患者的生命健康。
所以对于自身免疫性脑炎治疗的研究十分有意义。
1.自身免疫性脑炎的发病机制对于自身免疫性脑炎而言，其并不是完全脱离了外界因素而存在的。
自身免疫性脑炎虽然属于非感染性脑炎，但是也有可能是由于病原体的侵入而引起的。
只不过病原体侵入的部位并不一定是脑部。
一项研究结果显示，许多单状疱疹病毒感染引起的脑炎的患者在治疗结束后，还会产生继发性自身免疫性脑炎[2]。
众所周知，在治疗病原体的过程中，需要药物来治疗，而这种药物治疗的过程中，是通过药物来诱导出抗体，起到杀灭病原体的作用。
但是，在杀灭病原体以后，抗体并没有完全消失，一些抗体依然存在大脑，识别可以结合的靶点。
而且，在大脑中，有一些靶点是很容易与这些抗体结合，所以这些抗体并与这些靶点结合并进行攻击这些靶点，导致自身免疫性脑炎。
另外，肿瘤的发生也会引起自身免疫性脑炎，在某一项研究中，年轻女性抗NMDAR脑炎患者患卵巢畸胎瘤的比例高达58%[3]。
皮亚齐发现的小行星的永久编号
皮亚齐发现的小行星的永久编号皮亚齐博士（Francesco Piazzi）是意大利小行星学与天体测定的先驱，也是现代天文史上最重要的人物之一。
他在1801年发现的第一颗小行星是1-Ceres，编号为3594。
尽管这是第一次以皮亚齐博士的名字提到，他的贡献在现代小行星学方面显示出巨大的重要性。
他把“小行星”一词用来描述他发现的小天体，这是一个更具可操作性的词语，而以前关于这一发现的术语都比较模糊。
小行星3594（Ceres）是轨道位于火星和木星之间其他小行星的主要成员，这些小行星被称为“冥王星系”。
1847年，查尔斯冈登（Charles P. Gongennen）发现的另一颗小行星编号为6895（Pallas）。
他实际上是从皮亚齐本人的望远镜上发现的，他从皮亚齐的好友处得到了台大老师的设备和实践。
此后，皮亚齐的望远镜被称为“神奇的望远镜”，用于发现更多的小行星。
1848年科马悬（K.P. Kruger）从皮亚齐望远镜上发现了第三颗，编号为4575（Juno）。
随着小行星研究的发展，对小行星永久划分编号的需求日益增长。
1852年，煜昌红协会（Monsieur Hrof）首次提出了一套全球小行星的编号划分系统，根据发现时间的先后划分小行星的编号，这一系统推行至今，所有发现的小行星都按照煜昌红系统编号，即3594-Ceres、6895-Pallas和4575-Juno。
根据煜昌红协会设定的编号系统，任何发现的小行星都可以通过一个独特的永久编号来描述，以记录这颗天体在天文史上的作用。
该编号系统不仅为未来发现的小行星提供了一个可以管理的系统，也为学术界提供了一个可以便捷参考的编号源，以减少表述的混乱，让研究发展做到贤可物。
皮亚齐博士发现的第一颗小行星编号为3594，被称为“冥王星”，这个小行星以皮亚齐博士的名字永垂不朽，这代表着他在天文学方面给后代带来的巨大影响。
他的发现给小行星学与天体测定领域做出了不可磨灭的贡献，而煜昌红协会提出的小行星编号划分系。
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Acute Bacterial Infections
Bacterial Infections
Acute meningitis Cerebritis
Granulomatous meningitis and granuloma Ventriculitis and ependymitis Brain abscess
Bacterial Infection: Pyogenic Abscess
Ellison D et al., 1998
Syphilis
• Treponema pallidum • Primary syphilis – localized disease • Secondary syphilis – systemic disease • Tertiary syphilis
septic focus in the paranasal sinuses, middle ear, or dental infection. • About 25% of the cases are secondary to hematogenous spread from an infectious source outside the head. Example: congenital heart disease with right-to-left shunt. • The rest are due to trauma and miscellaneous etiology such as compromised immunity such as transplantation. • Bacterial profile is related to the route of spread and include Streptococcus milleri, anaerobic bacteria, Actinomyces israelii and others.
– Chronic granulomas – Aortitis – Neurosyphilis, tabes dorsalis
• dementia, confusion, irritability, headache, tremors, incontinence • Abnormal gait, sensory ataxia (degeneration of dorsal columl., 1997
Brain Abscess
Definition: A localized suppurative infection within the brain parenchyma.
Pathogenesis: • About 50% of the cases are due to localized spread of a
Cerebritis Ventriculitis and ependymitis
Brain abscess
Infectious Agents of the CNS
Bacteria: Pneumococcal meningitis, tuberculoma, neurosyphilis, etc.
Fungus: Aspergillus abscess, cryptococcal meningitis, etc.
Route of entry: Blood, local infection, penetrating, contaminated surgical procedures (eg. VP-shunt), etc.
Miscellaneous: Age, local factors, environmental factors, underlying compromised immune system, cardiac abnormalies, race and ethnic group, etc.
General: They can occur as fungal meningitis or space occupying lesions such as abscess or solid inflammatory mass.
Shape of the fungus: The pathology is often related to the shape of the fungus. Fungi that exist only as yeast form in human body often cause meningitis, those with filamentous form often cause infarction and abscess, those that can exist as both forms can cause both.
• Cerebritis. • Arterial and venous infarction of the brain. • Mycotic aneurysm. • Hydrocephalus, due to scarring of the
arachnoid granulations.
Complications of Bacterial Infections
Subdural empyema and epidural abscess Changes associated with spirochetal infections
Acute bacterial Meningitis
Definition: An acute inflammatory process that is limited to the meninges and subarachnoid space.
• Recognize the complications of bacterial meningitis.
• Identify the characteristics of tertiary syphilis. • Name the common causes of fugal meningitis. • Recognize the histopathologic features of herpes
Virus: Herpes simplex encephalitis, poliomyelitis, etc. Protozoa: Primary amoebic meningoencephalitis,
toxoplasmosis, malarial encephalitis, etc. Metazoa: Cysticercosis, schistosomiasis, etc. Prion: Creutzfeldt-Jakob disease, Kuru, Fatal familial
encephalitis.
Parameters of CNS Infection
Infectious agents: Bacteria, fungus, virus, protozoa, metazoa, prion.
Mechanism: Acute, chronic, mixed, suppurative, abscess, granulomatous.
and dorsal roots)
– Argyll Robertson pupil – pupils accommodate but don’t react to light
• Dx: VDRL, FTA-ABS • Rx: penicillin G
Fungal Infection
Fungal Infections of the CNS
Epidemiology: Some species are more common than the other and the incidence is geographically related.
Predisposing factors: Unlike bacterial infections that predisposing factors play a relatively minor role, predisposing factors and underlying systemic disorders play a major role. Particularly, patients are not always immunocompromised.
Thrombosed vessel
Hemorrhagic Ventriculitis
Infarct
Grahams and Lantos, 2002
Petechial hemorrhage Ellison D et al., 1998 in meningococcemia
Ellison D et al., 1998
Epidemiology: • About 25,000 cases/year in the U.S. • Over 70% occur in children under 5 years-old. • Mortality without antibiotics: 90-100% • Mortality with antibiotic treatment: 5-15%. • Morbidity: 43%.
Basic Pathologic Patterns in CNS Infection
Meningitis Meningoencephalitis Encephalitis, Myelitis, Encephalomyelitis
Choroid plexitis Subdural empyema and epidural abscess
Pathology of Acute Bacterial Meningitis
Macroscopic: • Cerebral edema and congested leptomeninges. • Thrombosis, hemorrhagic infarctions. • Purulent exudate in the subarachnoid space.