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Muscle-selective synaptic disassembly and reorganization in MuSK antibody positive MG miceAnna Rostedt Punga ⁎,1,Shuo Lin,Filippo Oliveri,Sarina Meinen,Markus A.RüeggDepartment of Neurobiology/Pharmacology,Biozentrum,University of Basel,Basel,Switzerlanda b s t r a c ta r t i c l e i n f o Article history:Received 23February 2011Revised 15April 2011Accepted 21April 2011Available online 30April 2011Keywords:Myasthenia Gravis MG MuSKNeuromuscular junction MasseterMuscle atrophy DenervationMuSK antibody seropositive (MuSK+)Myasthenia Gravis (MG)patients present a distinct selective fatigue,and sometimes atrophy,of bulbar,facial and neck muscles.Here,we study the mechanism underlying the focal muscle involvement in mice with MuSK+experimental autoimmune MG (EAMG).8week-old female wildtype C57BL6mice and transgenic mice,which express yellow ﬂuorescence protein (YFP)in their motor neurons,were immunized with the extracellular domain of rat MuSK and compared with control mice.The soleus,EDL,sternomastoid,omohyoid,thoracic paraspinal and masseter muscles were examined for pre-and postsynaptic changes with whole mount immunostaining and confocal microscopy.Neuromuscular junction derangement was quanti ﬁed and compared between muscles and correlated with transcript levels of MuSK and other postsynaptic genes.Correlating with the EAMG disease grade,the postsynaptic acetylcholine receptor (AChR)clusters were severely fragmented with a subsequent reduction also of the presynaptic nerve terminal area.Among the muscles analyzed,the thoracic paraspinal,sternomastoid and masseter muscles were more affected than the leg muscles.The masseter muscle was the most affected,leading to denervation and atrophy and this severity correlated with the lowest levels of MuSK mRNA.On the contrary,the soleus with high MuSK mRNA levels had less postsynaptic perturbation and more terminal nerve sprouting.We propose that low muscle-intrinsic MuSK levels render some muscles,such as the masseter,more vulnerable to the postsynaptic perturbation of MuSK antibodies with subsequent denervation and atrophy.These ﬁndings augment our understanding of the sometimes severe,facio-bulbar phenotype of MuSK+MG.©2011Elsevier Inc.All rights reserved.IntroductionAbout 40–70%of acetylcholine receptor (AChR)-antibody seronegative Myasthenia Gravis (MG)patients have antibodies against the muscle tyrosine kinase (MuSK)(Hoch et al.,2001;Sanders et al.,2003).In MuSK-antibody seropositive (MuSK+)MG patients,there is often selective involvement of bulbar-,neck-and facial muscles,as well as muscles that are usually asymptomatic in AChR-antibody seropositive (AChR+)MG,such as the paraspinal muscles (Sanders and Juel,2008).Contrary to conventional AChR+MG patients,the majority of MuSK+patients does not experience symptomatic relief from acetylcholine esterase inhibitors (AChEI)(Evoli et al.,2003)but instead may respond with pronounced nicotinic adverse effects,such as muscle fasciculations and cramps (Punga et al.,2006).Pronounced atrophy of facial muscles has also been described in MuSK+patients,although the concomitant treatment of corticosteroids in most cases has made it dif ﬁcult tojudge whether the MuSK antibodies or the cortisone treatment is the cause of the atrophy (Farrugia et al.,2006).Muscle biopsy studies of the intercostal muscle and biceps brachii muscle from MuSK+patients have shown little AChR loss (Selcen et al.,2004;Shiraishi et al.,2005),however,the neuromuscular junction (NMJ)pathophysiology in the most affected facial or bulbar muscles has not been studied.Nevertheless,MuSK antibodies have been shown to be pathogenic in animals,both after immunization with the extracellular domain of the MuSK protein itself (Jha et al.,2006;Shigemoto et al.,2008;2006;Xu et al.,2006)and after passive transfer of sera from MuSK+MG patients (Cole et al.,2008;ter Beek et al.,2009).MuSK is essential to the process of NMJ formation,maintenance (Wang et al.,2006)and integrity,as perturbations in MuSK protein expression cause pronounced disassembly of the entire NMJ (Hesser et al.,2006;Kong et al.,2004).Other NMJ proteins that are essential for synaptogenesis include Dok-7,a downstream adaptor protein to MuSK (Okada et al.,2006),Lrp4,the co-receptor for neural agrin (Kim et al.,2008;Zhang et al.,2008),rapsyn and the AChR subunits.The effects of MuSK antibodies in-vivo on the gene expression of those synaptic proteins in the facial or bulbar muscles have not yet been established.Here,we hypothesized that low expression levels of MuSK may render some muscles more vulnerable to the effect of MuSK antibodies in the EAMG mouse model.We show that MuSK antibodiesExperimental Neurology 230(2011)207–217⁎Corresponding author at:Institute of Neuroscience,Department of Clinical Neuro-physiology,Uppsala University Hospital,Uppsala,Sweden.Fax:+4618556106.E-mail address:annarostedtpunga@ (A.R.Punga).1Present address:Department of Clinical Neurophysiology,Uppsala University Hospital,Uppsala,Sweden.0014-4886/$–see front matter ©2011Elsevier Inc.All rights reserved.doi:10.1016/j.expneurol.2011.04.018Contents lists available at ScienceDirectExperimental Neurologyj o u r n a l h o me p a g e :w w w.e l s e v i e r.c om /l o c a t e /y e x n rinduce severe fragmentation of the postsynaptic AChR clusters in particular in the masseter and thoracic paraspinal muscles,with less fragmentation in the limb muscles.The severe postsynaptic pertur-bation results in subsequent denervation of muscleﬁbers,not previously described in EAMG or MG.We propose that one underlying mechanism for the severe involvement of the facial masseter muscle, with severely impaired NMJ architecture,atrophy and denervation,is its low intrinsic levels of MuSK.Moreover,muscles respond to the partial denervation caused by MuSK antibodies in two different ways: (1)terminal nerve sprouting in muscles with high intrinsic levels of MuSK(i.e.soleus,sternomastoid)and(2)no nerve sprouting in muscles with low intrinsic MuSK levels(i.e.masseter,omohyoid).MethodsProduction of recombinant rat MuSKpCEP-PU vector containing the His-tagged extracellular domain of recombinant rat MuSK(aa21-491;(Jones et al.,1999))was transfected(Lipofectamine2000;Invitrogen)into HEK293EBNA cells.The overexpressed protein was puriﬁed from the cell superna-tant over a Ni-NTA superﬂow column(Qiagen)and was subsequently dialyzed against PBS.Protein concentration was determined at OD 280nm and purity was ensured by SDS-PAGE.Experimental animalsC57BL6mice and mice expressing yellowﬂuorescence protein (YFP)in their motor neurons under Thy-1promoter(Feng et al., 2000)were originally supplied from Jackson Laboratories(Bar Harbor, Maine,US).For immunization,8week-old female mice were used.All mice were housed in the Animal Facility of Biozentrum,University of Basel,where they had free access to food and water in a room with controlled temperature and a12hour alternating light–dark cycle.All animal procedures complied with Swiss animal experimental regu-lations(ethical application approval no.2352)and EC Directive 86/609/EEC.ImmunizationThe immunization procedure has been described previously(Jha et al.,2006).Brieﬂy,eleven C57BL6and seven Thy1-YFP female mice aged8weeks were anesthetized(Ketamine:111mg/kg and Xylazine: 22mg/kg)and immunized with10μg of MuSK emulsiﬁed in complete Freund's adjuvant(CFA,Difco laboratories,Detroit,Michigan,US) subcutaneously in the hind foot pads,at the base of the tail and dorsolateral on the back.At day28post-injection,immunization was repeated.A3rd immunization was given to mice that did not show any myasthenic weakness after56days.Control mice(8female mice) were immunized with PBS/CFA.Clinical and neurophysiological examinationMuscle weakness was graded every week,as described(Nakayashiki et al.,2000).Brieﬂy,mice were exercised by20consecutive paw grips on a grid and were then placed on an upside-down grid.The time they could hold on to the grid reﬂected the grade of fatigue and muscle weakness.EAMG grades were as follows:grade0,no weakness;grade1, mild muscle fatigue after exercise;grade2,moderate muscle fatigue; and grade3,severe generalized weakness.Evaluation of the response to AChEIs was performed by i.p.injection of a mix of neostigmine bromide (0.0375mg/kg)and atropine sulfate(0.015mg/kg)in mice with EAMG grades2and3(Berman and Patrick,1980).Repetitive stimulation of the sciatic nerve and recording from the gastrocnemius muscle with monopolar needle electrodes was performed under anesthesia,in mice with EAMG grades2(n=2)and3(n=2),using a Saphire1L EMG machine(Medelec).Decrement was calculated as percent amplitude change between the1st and4th compound motor action potentials evoked by a train of10impulses where10%was considered as pathological.ELISASera were obtained from tail vein blood on day0(preimmune sera)and day35post-immunization.ELISA plates(Nunc MaxiSorp, Fisher Thermo Scientiﬁc,Rockford,IL,US)were coated with250ng/ ml of His-labeled rat MuSK(50μl/well),blocked with3%BSA/PBS and then incubated with a sera dilution row(1:3000–1:2,000,000).Pre-immune sera constituted negative and rabbit-anti-MuSK antibody (Scotton et al.,2006)positive controls.After washing,plates were incubated with secondary HRPO-conjugated goat-anti-mouse (1:2000)and goat anti-rabbit antibodies(1:2000;both from Jackson Immuno Research Laboratories,Westgrove,PA,US).HRPO activation by a TMB substrate was terminated with1N HCl after5min. Absorbance was read at450nm.Non-speciﬁc binding,determined by incubation of plates with pre-immune serum,was subtracted.The data were displayed as“half maximum MuSK immunoreactivity”,which represents the immunore-activity at a dilution of1:27,000,where the majority of sera obtained50% of maximum absorbance(in the linear range of the absorption at450nm).Western blotWestern blot of masseter muscles was conducted as described (Bentzinger et al.,2008).10μg of protein was resolved on a4–12%Nu-PAGE Bis–Tris gel(Invitrogen,Eugene,OR,US),transferred to nitrocellulose membrane,probed with rat monoclonal anti-NCAM (CD56;1:100;GeneTex)and rabbit polyclonal anti-pan-actin(1:1000; cell signaling)and then recognized with HRPO-conjugated antibodies (1:5000;Jackson Immuno Research Laboratories,Westgrove,PA,US). Quantitative RT-PCR analysisMouse muscle RNA was extracted and puriﬁed as previously described(Punga et al.,2011).RT-PCR reactions(triplicates)were carried out with Power SYBR Green PCR Master Mix reagent(Applied Biosystems,Warrington,UK).β-actin was used as endogenous control (Punga et al.,2011;Murphy et al.,2003;Yuzbasioglu et al.,2010).The following primer sets were used:MuSK:5′-GCCTTCAGCGGGACTGAG-3′and5′-GAGGCGTGGTGA-CAGG-3′Lrp4:5′-GGATGGCTGTACGCTGCCTA-3′and5′-TTGCCGTTGTCA-CAGTGGA-3′Dok-7:5′-CTCGGCAGTTACAGGAGGTTG-3′and5′-GCAATGC-CACTGTCAGAGGA-3′A C h Rα1:5′-G C C A T T A A C C C G G A A AG T G A C-3′a n d5′-CCCCGCTCTCCATGAAGTT-3′AChRε:5′-CTGTGAACTTTGCTGAG-3′and5′-GGAGATCAG-GAACTTGGTTG-3′AChRγsubunit:5′-AACGAGACTCGGATGTGGTC-3′and5′-GTCGCACCACTGCATCTCTA-3′Rapsyn:5′-AGGTTGGCAATAAGCTGAGCC-3′and5′-TGCTCTCACT-CAGGCAATGC-3′MuRF-1:5′-ACC TGC TGG TGG AAA ACA-3′and5′-AGG AGC AAG TAG GCA CCT CA-3′β-actin:5′-CAGCTTCTTTGCAGCTCCTT-3′and5′-GCAGCGA-TATCGTCATCCA-3′A C h E:5′-G G G C T C C T A C T T T C T G G T T T A C G-3′a n d5′-GGGCCCGGCTGATGAG-3′208 A.R.Punga et al./Experimental Neurology230(2011)207–217NMJ whole mount analysisAlexa Fluor555-conjugatedα-bungarotoxin(1μg/ml;Invitrogen) was injected into soleus,EDL,sternomastoid,omohyoid,masseter and the thoracic paraspinal muscles as described(Bezakova and Lomo, 2001).At least12images of each muscle per mouse(6MuSK-immunized YFP-transgenic mice and4CFA-immunized control mice) were collected with a confocal laser-scanning microscope(Leica TCS SPE).Laser gain and intensity were equal for all images.Quantiﬁcation of pre-and postsynaptic area was performed in ImageJ(http://imagej. /ij/index.html).NMJs containing terminal nerve sprouts(processes with YFP expression)were counted in muscles fromﬁve MuSK+EAMG mice with disease grades1–3.At least275NMJs per muscle were analyzed. The number of postsynapse fragments per NMJ was counted using a ﬂuorescence microscope(Leica DM5000B)in at least50NMJs per muscle deriving fromﬁve MuSK+EAMG grades1–2and from four control mice(Supplemental Fig.1).Fragmentation was classiﬁed as follows:1)normal pretzel-like NMJ;2)slight to moderate fragmen-tation;and3)severe fragmentation or absent postsynapse.The degree of postsynaptic perturbation per muscle was judged based on the percentage of NMJs belonging to each postsynaptic class and was further subdivided into number of postsynapse fragments per NMJ:1–3,4–6,7–9,10–12and more than12.Each NMJ was given the median score for that subgroup.The fragmentation score was obtained by taking the ratio of the score between the EAMG mice and control mice.Statistical analysisIndependent,2-sample t-test was performed for parametric data. For ordinal data(ELISA),the non-parametric test Spearman Rank Correlation was applied.A p-value b0.05was considered signiﬁcant.Fig.1.(A)Development of EAMG after immunization with recombinant rat MuSK.Progress of clinical EAMG grade at the time points week4,5,7and10.*The mice with EAMG grade 3were sacriﬁced after week7(hence no new grade3mice week10)and the remaining mice were sacriﬁced andﬁnally evaluated at week10.(B)One mouse,representative of the most severely affected MuSK+EAMG mice,withﬂaccid paralysis and pronounced kyphosis.(C)Repetitive nerve stimulation performed in the same mouse.Stimulation of the sciatic nerve and recording of the gastrocnemius muscle demonstrated a35%decrement between the1st and4th compound motor action potentials at low frequency3Hz stimulation.(D)Correlation of clinical EAMG grade with MuSK antibody titer.Half of maximum MuSK immunoreactivity(1:27,000dilution)in sera from MuSK immunized mice was assessed by Elisa at450nm.R=0.483(Spearman's Rank Correlation);p b0.05.209A.R.Punga et al./Experimental Neurology230(2011)207–217ResultsMuSK+EAMG presents with prominent kyphosis,paralysis and weight lossOut of the18mice immunized with MuSK,theﬁnal EAMG grade 0was seen in3mice(17%),grade1in8mice(44%),grade2in4mice (22%)and grade3in3mice(17%)(Fig.1A).No difference in disease incidence was found between the groups of C57BL6mice and the YFP-transgenic mice.Based on this,the data were pooled in the current study.The most severe phenotype of EAMG(grade3)includedﬂaccid paralysis,pronounced kyphosis and weight loss(Fig.1B).In-vivo nerve stimulation at3Hz with recording from the gastrocnemius muscle revealed a decrement of10–40%in the MuSK+EAMG mice (Fig.1C),whereas the control mice had normal neuromuscular transmission(data not shown).MuSK immunoreactivity in sera(day 35)correlated with clinical severity(Fig.1D;Spearman Rank Correlation;R=0.483;p b0.05),although some mice developed measurable MuSK antibodies without showing obvious muscle weakness or fatigue.Bulbar symptoms underlying weight loss in MuSK+EAMG The MuSK immunized mice steadily decreased signiﬁcantly in body weight after the2nd immunization(Fig.2A),in contrast to the control mice,and theﬁnal body weight of the MuSK+mice was signiﬁcantly smaller(p b0.001;Fig.2B).This severe weight loss was slowed but not stopped after introduction of wet food(data not shown).Since the timeline of the weight drop also correlated with development of muscle fatigue,the weight loss was assumed to be indicative of chewing and swallowing difﬁculties,some of the cardinal symptoms of MuSK+MG.To determine whether loss of muscle weight signiﬁcantly contributed to the overall lower body weight in the MuSK+EAMG mice,the weight ofﬁve different muscles was assessed.The masseter was the only muscle with a signiﬁcant weight reduction(p b0.01;Fig.2C),implying that this muscle is atrophic and further indicating chewing difﬁculties.Adverse effects of AChEIs in MuSK+EAMGTo elucidate whether AChEIs have any beneﬁcial effect on fatigue or weakness in MuSK+EAMG,a neostigmine test was performed in the mice with EAMG grade3(n=3).No apparent improvement in weakness at rest or exercise-induced fatigue was seen;instead the mice experienced shivering and constant twitching of the tail,trunk and limbs starting after approximately13min(Supplemental Video1).This effect wore off after40min and was interpreted as nicotinic side effects and neuromuscular hyperactivity,usually seen after an overdose of AChEIs.Thus,this intolerance towards AChEIs in MuSK+EAMG indicates an abnormal sensitivity to acetylcholine.Impairment of NMJs in different musclesBecause muscle groups in the bulbar/facial/back region are selectively involved in the MuSK+EAMG model,we next examined the morphological changes of NMJs in the thoracic paraspinal muscles, masseter,omohyoid and sternomastoid and compared them with those in two limb muscles(EDL and soleus).Typical features of postsynaptic impairment were a fainting of AChRﬂuorescence,areas lacking AChRs(holes)and disassembly of AChR clusters.To quantify these impairments,we classiﬁed NMJs into three classes as illustrated in Fig.3A.All muscles from MuSK+EAMG mice displayeddifferentFig.2.Weight loss in MuSK+EAMG.(A)The course of weight loss in two MuSK+mice with EAMG grade3compared to control(Ctrl CFA)mice(n=8).Initial body weight was comparable and weight loss started after the2nd immunization and weight kept dropping even though wet food was provided ad libitum.(B)Mean body weight was dramatically reduced in the MuSK immunized mice(MuSK+;n=18),compared to the control mice.Results shown as mean±SEM(gram);***p b0.001.(C)Muscles were weighed and compared between control mice(n=8)and MuSK+EAMG mice(n=18).Results displayed as mean muscle weight±SEM(mg).The only muscle which was signiﬁcantly lighter in the MuSK+mice was the masseter.**p b0.01.210 A.R.Punga et al./Experimental Neurology230(2011)207–217degrees of NMJ impairment (Fig.3B).Moreover,we also observed that the postsynapses were often fragmented into two to three non-continuous fragments (see illustration in Fig.3A),which is in strong contrast to non-interrupted,pretzel-like shape of AChRs in non-immunized mice.This fragmentation was also quanti ﬁed (Supplemental Fig.1)and expressed as “fragmentation score ”.Because fragmentation differs between muscles,this “fragmentation score ”was normalized to the control.As shown in Fig.3C,the fragmentation score varied between a minimum of 2.0in the soleus muscle and a maximum of 3.3in the masseter muscle.The postsynaptic labeling was markedly reduced in the MuSK+EAMG mice compared to control mice (Fig.4A).In the mild to moderately affected mice,AChR cluster area was reduced signi ﬁcantly by 40–50%in all muscles (p b 0.01),except for the soleus,which had a remaining area of 85%(p b 0.05;Fig.4B).In the most severely affected mice,the postsynaptic area was also lost in the soleus muscle and less than 10%of the α-bungarotoxin staining remained in the masseter,sternomastoid and thoracic paraspinal muscles (p b 0.001).In the soleus,the nerve terminal area was unchanged in the severely affected mice,although in the other muscles the presynaptic area was reduced to about 80%in the mild to moderate cases and to 50%in the most severely affected mice (p b 0.01)(Fig.4C).Thus,both the pre-and postsynaptic data suggest that the masseter is the most affected muscle by MuSK antibodies whereas the soleus is the least affected.mRNA transcript expression of NMJ proteins in different muscles in MuSK+EAMGThe mRNA levels of MuSK differ signi ﬁcantly between muscles,with the highest levels in the soleus muscle and lowest levels in the omohyoid muscle (Punga et al.,2011).Consequently,we additionally analyzed MuSK transcript levels in the masseter and these were even lower,with less than 20%of the mRNA levels detected in the soleus muscle (Supplemental Fig.2;p b 0.01).In the MuSK+EAMG mice,MuSK mRNA levels were signi ﬁcantly reduced to 45%of control in the EDL (p b 0.05)and to 25%in the omohyoid muscle (p b 0.001;Fig.5A).Conversely,MuSK mRNA expression was signi ﬁcantly increased in the masseter muscle (p b 0.01)and remained unchanged in the soleus and sternomastoid muscles.The expression of the AChR αsubunit was unchanged (Fig.5B),whereas the AChR εsubunit transcript was downregulated in the soleus and sternomastoid muscles and conversely a trend towards upregulation was seen in the masseter muscle (Fig.5C).The fetal AChR γsubunit mRNA was upregulated up to 1000-fold in the masseter (p b 0.001)and 5-fold in the soleus (p b 0.05;Fig.5D).The transcript levels of rapsyn,Lrp4and Dok-7were not signi ﬁcantly altered (Fig.5E to G).Finally,the transcript levels of acetylcholine esterase (AChE)were signi ﬁcantly down-regulated only in the sternomastoid and omohyoid muscles (p b 0.05;Fig.5H).Fig.3.Postsynaptic fragmentation of NMJs.(A)Examples from each postsynaptic classi ﬁcation.AChRs stained for alfa-bungarotoxin.(B)At least 275neuromuscular junctions (NMJs)per muscle were assessed in a total of 5MuSK+EAMG mice with moderate to severe disease.The appearance of NMJ postsynapses were divided into 3classes as indicated.Sol:soleus;EDL:extensor digitorum longus;STM:sternomastoid muscle;omo:omohyoid;mass:masseter.(C)Postsynapses were analyzed in at least 50NMJs per muscle in a total of 5MuSK+EAMG mice with slight to moderate disease grade and in 4control mice.Each NMJ in a certain subclass (for details see Supplemental Fig.1)was given the median score for that subclass.The fragmentation score for each muscle is the ratio in score between the EAMG mice and control mice.211A.R.Punga et al./Experimental Neurology 230(2011)207–217In summary,particularly the massive upregulation of MuSK transcripts and AChR γin conjunction with the overall trend for upregulation of mRNA for the other postsynaptic genes in the masseter muscle most likely re ﬂects the severely disturbed neuro-muscular transmission in this muscle as a result of the MuSK antibodyattack.Fig.4.Pronounced reduction of postsynaptic and presynaptic area in different muscles in MuSK+EAMG.(A)Whole mount staining of single ﬁber layer bundles from the paraspinal muscle (ps),sternomastoid (STM),masseter (mass),omohyoid (omo),extensor digitorum longus (EDL)and soleus (sol)muscles from one control mouse immunized with CFA/PBS and one mouse with severe MuSK+EAMG.AChRs are visualized by alexa-555-bungarotoxin (red)and the motor nerve terminals by YFP expression (green).The AChRs are almost completely gone from the paraspinal muscles,STM and masseter.Confocal images of 100×magni ﬁcation,scale bar is 10μm.Quanti ﬁcation of (B)postsynapse (AChR clusters)and (C)presynaptic area in the different muscles;soleus (sol),extensor digitorum longus (EDL),omohyoid (omo),masseter (mass),sternomastoid (STM)and paraspinal muscles (ps).Results are given as %of ctrl area±SEM and at least 12NMJs in each muscle/mouse was measured in mice with EAMG grades 1–2(N =4),in mice with severe grade 3(N =2)and in control mice (N =4).**p b 0.01;#p b 0.001.212 A.R.Punga et al./Experimental Neurology 230(2011)207–217Denervation induced muscle atrophy in MuSK+EAMGThe masseter muscle lost weight and consequently we examined the mRNA levels of the atrophy marker muscle-speci ﬁc RING ﬁnger protein 1(MuRF-1)and assessed signs of denervation.For this analysis we included the same muscles as previously examined,with the addition of thoracic paraspinal muscles due to the pronounced kyphosis of the MuSK+EAMG mice.MuRF-1mRNA levels were signi ﬁcantly upregulated in the masseter muscle (p b 0.05;Fig.6A)and on the contrary MuRF-1transcript levels were strongly reduced in the soleus muscle (p b 0.01)in the MuSK+EAMG mice.Further,the protein levels of neural cell adhesion molecule (NCAM),a marker for denervation,were increased in the masseter muscle as detected by Western blot analysis.This is thus additional evidence of denervation in this particular muscle (Fig.6B).Absence of nerve sprouting may contribute to the severe denervation phenotypePresynaptic nerve terminals were visualized by transgenic YFP expression,allowing observation also of NMJs with absent post-synapses.In the masseter,the nerve terminals were still present although many postsynaptic AChRs were partially or completely lost.Intriguingly,no or little nerve sprouting was observed in these cases (Fig.7).This ﬁnding raised the possibility that postsynaptic perturbation in this muscle did not elicit any nerve sprouting response.To test this hypothesis,we examined ≥450NMJs in each of the muscles for such sprouting response.The quantitative examination of 4MuSK+EAMG mice revealed terminal nerve sprouting in approximately 20%of NMJs in the soleus and in 15%of endplates in the sternomastoid (Fig.7).On the contrary,theFig.5.mRNA levels of postsynaptic proteins in MuSK+EAMG.C:control mice immunized with CFA/PBS.MG:EAMG mice immunized with MuSK.mRNA levels in the control mice are set to 100%and levels in the EAMG mice are relative to the control levels.n=6control mice;n=6MuSK+EAMG mice.Genes of interest are relative to the house keeping gene β-actin.*p b 0.05;***p b 0.001.213A.R.Punga et al./Experimental Neurology 230(2011)207–217omohyoid,EDL,thoracic paraspinal muscles and masseter,showed terminal sprouting at only a few NMJs.In most samples no sprouting was observed,which differed signi ﬁcantly from the soleus (p b 0.001)and the sternomastoid muscle (p b 0.05).Interestingly,the degree of nerve sprouting in each muscle correlates with their endogenous levels of MuSK,suggesting that MuSK levels regulate the nerve sprouting response and consequently reorganization of NMJs (Punga et al.,2011).DiscussionMuSK+MG patients often present with focal weakness of facial,bulbar,neck and respiratory muscles and sometimes also of paraspinal and upper esophageal muscles (Sanders and Juel,2008).The pathopysiological role of MuSK antibodies has been questioned based on the normal levels of MuSK and AChRs at the NMJ in cross-sections of the intercostal muscle and biceps brachii muscle of MuSK+MG patients (Selcen et al.,2004;Shiraishi et al.,2005).Further studies in mice have now shown that MuSK antibodies deplete MuSK from the NMJ,which results in disassembly of the postsynaptic apparatus and a reduced packing of AChRs (Jha et al.,2006;Shigemoto et al.,2006;Cole et al.,2010).Nevertheless,the exact mechanism of how MuSK antibodies affect muscles has so far not been revealed.Here we report that MuSK antibodies cause a severe pre-and postsynaptic disassembly in the facial,bulbar and paraspinal muscles but only a slight disruption in the limb muscles (i.e.soleus and EDL).The most affected muscle was the masseter and intriguingly this muscle expressed less than 20%of MuSK transcripts than the least affected soleus muscle.Considering that fast-twitch muscle ﬁbers require larger depolarization to initiate contraction compared to slow-twitch ﬁbers,we propose that the superfast twitch pattern of the masseter in combination with its critically low MuSK levels makes this muscle extra vulnerable to the synaptic perturbation following the MuSK antibody attack (Laszewski and Ruff,1985).Hence,over-expression of MuSK in vulnerable muscles could potentially alleviate the effects of the antibody-mediated attack against MuSK.Earlier studies of AChR+EAMG rats have been shown to respond to rapsyn-overexpression in the tibialis anterior muscle with no loss of AChRs and almost normal postsynaptic folds,whereas the NMJs of untreated muscles showed typical AChR loss and morphological damage (Losen et al.,2005).Nevertheless,we did not ﬁnd any changes in rapsyn mRNA levels across the examined muscles.Additionally,our ﬁndings underline the importance of examining the clinically affected muscles in MuSK+MG in order to draw the right conclusions regarding NMJ morphology.In the MuSK+EAMG model,the mice exhibited obvious bulbar and thoracospinal muscle weakness,similar to the mouse model of congenital myasthenic syndrome with MuSK mutation (Chevessier et al.,2008).This implies a common clinical phenotype in mice with impaired MuSK function and corresponds well with the phenotype of human MuSK+MG.In contrast,we have noticed in parallel rounds with immunization of C57BL6mice with AChR from Torpedo californica that the AChR-antibody seropositive mice did not develop signi ﬁcant weight loss,neck muscle weakness or kyphosis and also that their ﬂaccid paralysis was reversible with AChEI treatment (Punga et al.,unpublished observations).The adverse effect of AChEIs in MuSK+EAMG resembles the neuromuscular hyperactivity reported in MuSK+MG patients (Punga et al.,2006).We hypothesize that the underlying reason for the hypersensitivity in the muscles to the additional amount of available ACh at the NMJ is a consequence of (1)the denervation of the muscle ﬁbers with extensive AChR fragmentation and (2)the downregulation of AChE in some muscles (e.g.omohyoid and sternomastoid),which may result in AChEI overdose-like phenotype.The downregulation of AChE mRNA is most probably a direct consequence to the loss of MuSK,since MuSK binds collagen Q,an interaction that is thought to be largely responsible for the synaptic localization of AChE-collagen Q complex at the NMJ (Cartaud et al.,2004).The fragmentation and spatial dispersion of AChRs most likely inhibits the response to the increased ACh at the NMJ induced by AChEIs in the most clinically affected muscles.This study also investigated the possibility of MuSK antibodies to initiate a cascade that results in denervation-induced atrophy.MRI studies of newly diagnosed MuSK+patients have con ﬁrmed early muscle atrophy in the temporal,masseter and lingual muscles with fatty replacement (Zouvelou et al.,2009;Farrugia et al.,2006).We observed that,particularly in the masseter and paraspinal muscles,some NMJs were completely depleted of AChRs,and the subsequent loss of synaptic transmission most probably resulted in functional denervation.This explanation is further supported by the fact that pharmacological denervation arises after injection of botulinum toxin A (BotA),which also blocks the cholinergic synaptic transmission,and it is sometimes dif ﬁcult to distinguish this from a surgical denervation due to the similarities in pattern,extent and time course (Drachman and Johnston,1975).Previous studies of passively induced AChR+EAMG in rats have shown an upregulation of the AChR ε,but not the γsubunits;thus suggesting that newly expressed AChRs in the case of antibody mediated AChR loss are of the adult type (Asher et al.,1993).However,our observed massive upregulation of AChR γtranscript in the masseter implies that,except for disturbed neuromuscular transmission,denervation is also ongoing since this usually correlates with the predominant expression of embryonic type receptors and re-expression of the fetal type occurs after experimental denervation (Witzemann et al.,1989).Levels of AChR γmRNA are normally extremely low in all muscles except for the extraocular muscles (Kaminski et al.,1996;MacLennan et al.,1997).Concomitantly with the very prominent increase in transcripts encoding AChR γ,MuSKFig.6.Atrophy-and denervation related markers in MuSK+EAMG mice.(A)mRNA levels of MuRF-1expressed as %of control in relation to β-actin.n=6control mice (C)and n=5MuSK+EAMG mice (MG).*p b 0.05.(B)Western blot of NCAM in the masseter muscle of one MuSK+EAMG mice with disease grade 3(MG)and in one CFA-immunized control mouse (Ctrl).NCAM was detected as 3bands at levels 120,140and 180kD and the loading control β-actin (45kD).An equal amount of protein was loaded.**p b 0.01.214 A.R.Punga et al./Experimental Neurology 230(2011)207–217。

医学英语阅读医学英语小短文

医学英语阅读医学英语小短文医学英语阅读医学英语阅读医学英语阅读：致命的军团杆菌Legionnaires“ disease is a serious and sometimes fatal form of pneumonia. Legionnaires“ disease is caused by infection with Legionella bacteria which are found naturally in the environment and thrive in warm water and warm damp places. Man-made water systems sometimes provide environments that let Legionella bacteria increase to large numbers. These man-made systems include showers, spa pools, fountains, and air conditioning cooling towers. People usually get Legionnaires" disease by breathing in mists that come from a water source contaminated with Legionella bacteria. An estimated 8,000 to 18,000 people get Legionnaires" disease in the United States each year. Some people can be infected with Legionella bacteria and have mild symptoms or no illness at all. Patients with Legionnaires" disease usually have fever, chills, and a cough, which may be dry or may produce sputum. Some patients also have muscle aches, headache, tiredness, loss of appetite, and, occasionally, diarrhea. From the time of infection with Legionella bacteria, it takes 2-10 days for symptoms to appear. In most cases, symptoms begin after 5-6 days. Legionnaires" disease is treated with antibiotics, such as erythromycin. The earlier that treatment is begun, the better the outcome. The first known outbreak of Legionnaires" disease was in Philadelphia, USA, in 1976. A total of 221 people contracted the disease and 34 died. Most of those that died were Legionnaires and that"s how the disease got its name. The second largest outbreak was at the Stafford hospital in England in 1985;a total of 101 people contracted the disease and 28 died. 军团病是一种非常严重的、有时可以致命的肺炎。

临床常见疾病医学英语文献阅读

临床常见疾病医学英语文献阅读一、疾病概述在医学领域中，临床常见疾病是指各种在临床实践中经常遇到的疾病，包括但不限于感冒、糖尿病、高血压、心脏病、癌症等。

这些疾病对患者的生活和健康造成严重影响，因此对这些疾病的研究和治疗一直是医学研究的重点。

二、英语文献阅读的重要性1.获取最新研究成果：随着医学研究的不断发展，新的疾病治疗方法和医学技术不断涌现。

通过阅读英语文献，医生和研究人员可以第一时间获取最新的研究成果，及时了解行业动态。

2.学习专业知识：英语文献中包含大量的专业术语和研究方法，医生和研究人员可以通过阅读文献了解最新的医学进展和疾病治疗方法，从而提升自身的专业知识水平。

3.促进国际合作：医学是一个国际性的学科，国际间医学研究人员之间的合作十分重要。

通过阅读英语文献，可以促进国际合作，共同开展对临床常见疾病的研究和治疗。

三、如何正确阅读英语文献1.选择合适的文献：在阅读英语文献时，首先需要选择与自己研究领域相关的文献，避免浪费时间阅读无关的文献。

可以通过PubMed等专业数据库进行检索，筛选出符合自己需求的文献进行阅读。

2.抓住重点：阅读英语文献时，要抓住文献的重点和亮点，了解作者的研究重点和结论，不必深究细节，以节省时间。

3.注重方法和实验设计：在阅读疾病治疗相关的文献时，需要特别关注研究方法和实验设计，了解研究的可靠性和可行性。

同时也要留意研究结果和结论，理性分析研究的价值和意义。

四、如何提高英语文献阅读能力1.积累词汇量：医学英语是一门专业性较强的英语，在阅读英语文献时需要具备一定的医学英语词汇量。

可以通过大量的阅读和记忆来增加词汇量。

2.多练习翻译：阅读英语文献时，经常会遇到一些生词和短语，需要通过翻译来更好地理解文献内容。

3.理性分析：在阅读医学文献时，需要保持理性，不被文献中片面或夸大的观点所影响，要善于辨别真假，提高自己的批判性思维。

五、结语通过正确的阅读英语文献，医生和研究人员可以及时了解最新的医学进展，提高自身的专业知识水平，为临床常见疾病的治疗和研究做出贡献。

anesthesiology 医学英语阅读

anesthesiology 医学英语阅读Anesthesiology is a medical specialty that focuses on providing anesthesia to patients during surgeries or other medical procedures. An anesthesiologist is a medical doctor who specializes in administering anesthesia, monitoring the patient's vital signs during the procedure, and managing pain control.An anesthesiologist's primary role is to ensure the patient's safety and comfort during the surgical or medical procedure. They carefully assess the patient's medical history and physical condition before determining the appropriate anesthesia technique and dosage. They may use general anesthesia, which renders the patient completely unconscious and pain-free, or regional anesthesia, which numbs a specific area of the body while the patient remains awake.During the procedure, an anesthesiologist continuously monitors the patient's heart rate, blood pressure, oxygen levels, and other vital signs. They adjust the anesthesia dosage as needed to maintain the patient's stability and prevent complications. They also manage pain control during and after the procedure, ensuring the patient's comfort and well-being.Anesthesiologists may also be involved in managing patients in critical care units, providing pain relief for chronic conditions, or participating in the management of emergency situations. They work closely with surgeons, nurses, and other healthcare professionals to ensure a smooth and safe patient experience. Anesthesiology is a complex and highly specialized field thatrequires years of education and training. An anesthesiologist must complete medical school, followed by a residency program in anesthesiology. They may also choose to pursue additional fellowship training in a specific area of anesthesiology, such as pediatric anesthesia or pain management.In conclusion, anesthesiology is a medical specialty that focuses on providing anesthesia and pain control to patients during surgeries and other medical procedures. An anesthesiologist plays a crucial role in ensuring the patient's safety, comfort, and well-being throughout the procedure.。

医学英语文献阅读一(1-8词汇)

A reading course IChapter1TextAprematurely 过早地diagnosis 诊断sub health 亚健康immune system 免疫系统respectively 分别地prevalent 普遍地spearhead 为…带头，为…先锋sustained 可持续的intellectual 知识分子transitional 过度的chronic 慢性的infectious传染的massage 按摩，推拿blood circulation 血液循环textBdefect 缺点，缺陷abnormality 畸形，异常cardiac 心脏的，心脏病的cardiac arrest 心搏停止screening test 筛选试验，屏蔽试验coroner 验尸官autopsy 验尸，尸体解剖ventricular 心室的，脑室的fibrillation 纤维性颤动ventricular fibrillation 心室纤维性颤动hypertrophic 肥厚的cardiomyopathy 心肌症hypertrophic cardiomyopathy 肥大型心肌病myocardium 心肌，心肌层coronary 冠状的artery 动脉compress 压缩，压紧syndrome 综合征inherit 继承，遗传chaotic 混乱的，无秩序的erratic 不稳定的，古怪的commotia cordis 心脏震动red flag 危险信号on the outlook 寻找，警惕着syncope 晕厥exertion 努力，用力seizures 癫痫，痉挛screening 筛选asthma 哮喘，气喘implantable 可移植的，可植入的cardioverter 心律转变器，复律器defibrillator 去纤颤器，电震发生器pacemaker 心律调整器，起搏器arrhythmia 心律不齐，心律失常electrocardiogram 心电图V ocabularysub health亚健康massage 按摩，推拿diagnosis 诊断suffernegativeaccelerateinfectioncirculationhealthcaredefectinheritcardiactriggerabnormalitysurgeryscreeningsignaldisordersyndromeprematurechapter2TextAdrug resistance耐药性Aids 艾滋病tuberculosis 肺结核malaria 疟疾scourge 灾祸，苦难的根源penicillin 盘尼西林antibiotic 抗菌素incentive 动机，刺激institution 公共机构，习俗leadership 领导能力，领导surveillance 监督，监视priority 优先，优先权，优先考虑的事hygience 卫生，卫生学lancet 小刀，柳叶刀haemorrhage 大出血tranexamic acid 氨甲环酸malnutrition 营养不良soaring 高耸的，猛增的depletion 消耗，放血stock 库存，血统textBallergy 过敏症，反感allergic 对…过敏/极讨厌的side effect 副作用sulfa 磺胺的，磺胺药剂的immune 免疫的offending 不愉快的medication 药物，药物治疗adverse 不利的，相反的itchy 发痒的，渴望的rash 皮疹hives 荨麻疹，假膜性喉头炎exposure 暴露，揭露anaphylaxis 过敏性，过敏性反应prescription 药方，指示symptom 征兆，症状wheeze 喘息serum 血清，浆液injection 注射，注射剂foreign 外国的，异质的medical facilities 医疗设施latex 乳胶，乳液application 应用，敷用amoxicillin 阿莫西林，氢氨苄青霉素ampicillin 氨苄西林，氨苄青霉素augmentin 安灭菌，奥格门汀carbenicillin 羧苄青霉素dicloxacillin 双氯西林，双氯青霉素cephalosporin 头孢菌素cefaclor 头孢克洛，氯氨苄青霉素cefadroxil 头孢氢氨苄cefepime 头孢吡肟cefprozil 头孢丙烯cephradine 头孢拉啶，先锋霉素cephalexin 头孢氨苄sulfasalazine 柳氮磺胺吡啶Bactrim 复方新诺明sulfate 硫酸盐insulin 胰岛素manifest 证明，表明iodine 碘，碘酒bloodstream 血液，血液的流动vessel 脉管，血管nausea 恶心，晕船，极端的憎恶vomit 呕吐，吐出dizziness 头晕，头昏眼花V ocabularysymptioninsulinsurveillancedizzinessimmuneallergicresistancemalariasulfaantibioticitchyforeignvomitbloodstreaminjectionhygieneprescriptionasthmahealthcareanaphylaxicchapter3textAhospice 临终关怀，临终关怀医院catch on 变得流行terminally 不治地，晚期地allusion 暗示，提及influential 有影响的decent 体面的，像样的prolong 延长，拖延existence 生存，生活intervention 干预，介入hostile 敌对的，怀敌意的dedicate 致力，献身explicit 明确的，清楚的intervene 干涉，插入palliative 缓和剂，暂时姑息outstrip 超过，胜过expectancy 期望，期待predictable 可预言的geriatrics 老年病学，老年病人succumb屈服，被压垮dementia 痴呆decay 衰败，衰退textBswallow 吞下，咽下stressful 紧张的，有压力的appreciate 欣赏，感激pursue 继续，从事alternative 选择，替换物available 可得到的，可利用的caregiver 照料者，护理者mission 使命，任务knowledgeable 知识渊博的，有见识的approach 接近expertise 专门知识，专家意见incredibly难以置信地distress 使悲痛，使贫困anticipate 预期，期望compassionate 慈悲的，富于同情心的participation 参与，分享excel 优于，胜过，擅长V ocabularyimmortalterminaldementiahospicedecentanxiousexpectancycaregiverpositiveapproachguidancepursuemissioninterventionemotionalgrievefuneralphysicaltubechapter4textAface lift 面部拉皮手术deposit 沉积物cosmetic 美容的，化妆用的endoscopic 内窥镜的，用内窥镜检查的incision 切口，切割contour 轮廓，周线bandage 绷带wrinkle 皱纹crease 折痕，皱纹swelling 肿胀，增大restrict 限制，约束minimal 最小限度的，极小的invasive 侵略性的，攻击性的invasive surgery 侵入性外科手术anesthesia 麻醉sedation 镇静的，镇静剂visibe 明显的，看得见的temple 太阳穴textBlaser 激光remedy 补救，治疗hyperpigmentation 色素沉着过度discolor 使变色，使褪色discoloration 变色dermabrasion 磨去皮肤疤痕之手术，磨皮手术acne 痤疮，粉刺ablative 烧蚀的vaporize 汽化，使…蒸发downtime 停工期collagen 胶原，胶原蛋白pulse 脉冲，脉动rejuvenation 返老还童，恢复活动sagging 松垂的，下沉的vascular 血管的，淋巴管的lesion 病变，损伤antiviral 抗病毒物质antibacterial 抗菌剂，抗菌药complication 并发症intravenous 静脉内的penetrate 渗透，穿透ointment 药膏，软膏petroleum jelly 凡士林，矿油temporary 暂时的，短暂的dormant 休眠的，静止的herpes 疱疹V ocabularyendoscopicmedicationcomplicationantiviralwrinkleanesthesiavascularswellingexposurehyperpigmentationscarinvasiveintravenouspeeldermabrasiondormantincisiondepositlesioncollagenchapter5textAgenetic 遗传的，基因的loom 可怕地出现，令人惊恐的隐现invade 侵入，侵略staple 主要的，常用的biotechnologist 生物工艺学家estimate 估计ingredient 材料，原料reveal 显示，透漏domesticated 家养的toxicity 毒性，毒性作用，毒性反应allergenicity 变应原性，过敏反应antibiotic 抗生的，抗菌的extinction 灭绝hazardous 有危险的，冒险的tangle 纠纷，混乱状态anomaly 异常，反常事物jurisdiction 管辖权haphazard 随便的，无计划的contaminate 污染，弄脏legislation 立法negligence 疏忽，忽视biotechnology 生物技术，生物工艺学textBaccess 使用权，接近或享用的机会temporarily 临时地affordable 负担得起的shortage 缺乏utilize 使用，利用household 家庭的，日常的intellectually 智力上，理智地resource 资源effective 有效的fertilizer 化肥productive 能生产的，多生产的deterioration 恶化undertake 承担，从事resistance 抵抗，反抗cultivate 培养，耕作cubic 立方体的，立方irrigation 灌溉salinisation 盐渍化consequently 因此，结果enhance 提高，加强invest 投资cyclone 旋风，气旋，飓风flee 逃走，消失，消失debris 碎片，残骸prioritise 给予…优先权，按优先顺序处理quarantine 检疫tariff 关税表，收费表subsidise 资助给…补助金deprive使丧失，剥夺V ocabularyorganismtanglecondimentfertilizershortagecontaminateanomalydebrisbacteriaregulateaccesstariffingredientprioritiseextinctiondeteriorationhaphazardirrigationpandemicutilizationchapter6textAwillpower 意志力，毅力illicit 违法的，非法的staggering令人惊讶的deleterious 有毒的，有害的disintegration 分解，瓦解chronic 慢性的，长期的relapse 旧病复发，故态复萌counteract 抵消，中和disruptive 破坏的，分裂性的psychiatric 精神病学的，精神病治疗的diabetes 糖尿病，多尿症reinstate 使恢复，使复原textBgay teen 同性恋青少年acute 严重的，急性的lesbian 女同性恋bisexual 双性恋的transgender 跨性别者，变性人heterosexual 异性的，异性恋的subgroup 子群straight teen 异性恋青少年，非同性恋青少年homophobia 对同性恋的恐惧，对同性恋的憎恶victimization 欺骗，侵害disparity 不同，不一致marginalize 排斥，使处于社会边缘nongovernmental 非政府的harassment 骚扰，烦恼marijuana 大麻，大麻毒品cocaine 可卡因methamphetamine 甲基苯丙胺，冰毒assault 攻击，袭击pseudonym 笔名，假名stigmatization 污辱adolescent 青少年prognosis 预后，预知grim 冷酷的，糟糕的homophobic害怕同性恋的imperative 必要的，紧急的confidential 表示信任的V ocabularyabsueaddictionillicitchronicdeleteriousstaggeringrelapsedisruptivedisintegrationhomophobiabisexualacutedisparityprognosispseudonymassaultimperativeasthmavictimizationchapter7textAeligibility 合格，资格dialysis 透析transplant 移植renal 肾的premium保费eligible 合格的，符合条件的coverage 承保范围labor 分娩，生产delivery 分娩textBbone mass 骨质osteoporosis 骨质疏松cardiovascular 心血管的cholesterol 胆固醇lipid 脂类triglyceride 三酸甘油酯colorectal 结肠直肠的fecal 粪便的，排泄物的occult 隐性的sigmoidoscopy 乙状结肠镜检查colonoscopy 结肠镜检查barium 钡enema 灌肠，灌肠剂dyslipidemia 血脂异常obesity 肥胖gestational 妊娠期的glaucoma 青光眼hepatitis肝炎pelvic 骨盆的cervical 子宫颈的vaginal 阴道的referral 转介，转诊pneumococcal 肺炎球菌的prostate 前列腺rectal 直肠的mammogram 乳房X线照片cessation 停止，休止chapter8textAspinal 脊髓的，脊柱的diverse 不同的，多种多样的gratifying 悦人的，令人满足的assume 承担rehabilitation 康复，修复physical rehabilitation 物理疗法，物理治疗accredited 公认的，经过认证的supervised fieldwork 实习pinpoint 精确地找到，查明per diem 每天，按日textBneurological 神经病学的substantiate 证实aphasia 失语症trigger 引发，引起innately 天赋的，与生俱来的attune to 习惯于bradykinesia 云动徐缓，动作迟缓initiate 开始，发起cadence 节奏，韵律organized 安排有秩序的，做事有条理的cofounder共同创始人synchronize 使同步，使合拍gait 步法，步态strike 大步，步幅moto control 运动控制improvisation 即兴创作，即席演奏cymbal 铙xylophone 木琴therapeutic 治疗的，有益于健康的overlap 重叠，重复retrieval 恢复，取回vouch 保证，证明devastating 毁灭性的neurotransmitter 神经传导物质norepinephrine 去甲肾上腺素，降肾上腺素melatonin 褪黑激素stress hormone 应激激素cortisol 皮质醇diazepam 安定advanced stage 晚期amygdala 杏仁核hippocampus 海马degenerative 退化的，变质的cortex 皮质hub 中心。

《临床常见疾病：医学英语文献阅读》读书笔记模板

Section Two: Internal Disease第二部分内科疾病
21. Arrhythmia (Heart Rhythm Disorders)心律失常 22. Coronary Artery Disease (CAD)冠心病 23. Hypertension/High Blood Pressure高血压病 24. Heart Failure心力衰竭 25. Acute Respiratory Distress Syndrome (ARDS)急性呼吸窘迫综合征 26. Asthma哮喘 27. Chronic Obstructive Pulmonary Disease (COPD)慢性阻塞肺疾病 28. Pneumonia肺炎 29. Respiratory Failure呼吸衰竭
Section Five: Cancer第五部分恶性肿瘤
66. Breast Cancer乳腺癌 67. Esophagus Cancer食管癌 68. Liver Cancer肝癌 69. Stomach Cancer胃癌 70. Colorectal Cancer结直肠癌 71. Lung Cancer肺癌 72. Cervical Cancer宫颈癌 73. Ovarian Cancer卵巢癌 74. Bladder Cancer膀胱癌
Section Three: Obstetrical and Gynecological Disease第三部分
59. Dysfunctional Uterine Bleeding功能失调性子宫出血
60. Ectopic Pregnancy异位妊娠
Section Four: Pediatric Disease第四部分儿科疾病
目录分析
前言 Introduction

(完整版)医学英语(阅读一分册)翻译及答案

Chapter 1Passage 1 Human BodyIn this passage you will learn:1. Classification of organ systems2. Structure and function of each organ system3. Associated medical termsTo understand the human body it is necessary to understand how its parts are put together and how they function. The study of the body's structure is called anatomy; the study of the body's function is known as physiology. Other studies of human body include biology, cytology, embryology, histology, endocrinology, hematology, immunology, psychology etc.了解人体各部分的组成及其功能，对于认识人体是必需的。

研究人体结构的科学叫解剖学；研究人体功能的科学叫生理学。

其他研究人体的科学包括生物学、细胞学、胚胎学、组织学、内分泌学、血液学、遗传学、免疫学、心理学等等。

Anatomists find it useful to divide the human body into ten systems, that is, the skeletal system, the muscular system, the circulatory system, the respiratory system, the digestive system, the urinary system, the endocrine system, the nervous system, the reproductive system and the skin. The principal parts of each of these systems are described in this article.解剖学家发现把整个人体分成骨骼、肌肉、循环、呼吸、消化、泌尿、内分泌、神经、生殖系统以及感觉器官的做法是很有帮助的。

临床医学英语阅读

临床医学英语阅读The field of clinical medicine is a vast and complex domain that encompasses the study, diagnosis, and treatment of various health conditions. As healthcare professionals navigate this dynamic landscape, the ability to effectively read and comprehend medical literature in English has become increasingly crucial. Clinical medical English reading is a vital skill that enables healthcare providers to stay informed, make evidence-based decisions, and deliver the highest quality of patient care.One of the primary reasons why clinical medical English reading is so important is the global nature of the healthcare industry. Medical research and advancements are often published in English, the lingua franca of the scientific community. Healthcare professionals from diverse linguistic backgrounds must be able to access and understand this wealth of information to ensure they are providing their patients with the most up-to-date and effective treatments. This is particularly true in an era of rapid technological advancement, where new research and innovations are constantly emerging, and healthcare providers must be able to quickly adapt and incorporatethese findings into their practice.Moreover, the ability to read and comprehend clinical medical literature in English is essential for effective communication and collaboration among healthcare professionals. As medical teams become increasingly interdisciplinary and global, the ability to understand and interpret medical terminology, research methodologies, and clinical case studies in English is crucial for ensuring seamless coordination and the delivery of high-quality patient care. This is especially important in emergency situations or when consulting with specialists from different countries, where clear and concise communication in English can mean the difference between life and death.In addition to the practical benefits of clinical medical English reading, the ability to engage with this literature can also have a profound impact on a healthcare provider's professional development and career advancement. By staying up-to-date with the latest research, trends, and best practices in their field, healthcare professionals can enhance their clinical expertise, improve patient outcomes, and position themselves as leaders in their respective domains. Furthermore, the ability to read and critically analyze medical literature in English can open up opportunities for collaboration, research, and publication, which can further bolster a healthcare provider's reputation and career prospects.To effectively engage in clinical medical English reading, healthcare professionals must develop a strong foundation in medical terminology, research methodologies, and academic writing conventions. This may involve formal training in English for specific purposes (ESP) or medical English, as well as ongoing self-directed learning and practice. Additionally, healthcare providers should cultivate a habit of regularly reading and critically analyzing medical literature, staying attuned to new developments and emerging best practices in their field.One effective strategy for clinical medical English reading is to approach the task with a structured and systematic approach. This may involve breaking down complex research articles or case studies into manageable sections, identifying key information and takeaways, and actively engaging with the text through note-taking, highlighting, and summarization. Healthcare providers should also be mindful of potential linguistic and cultural differences that may impact their understanding of the material, and seek out resourcesor support to address any gaps in their knowledge or comprehension.Furthermore, the ability to effectively communicate the insights and findings from clinical medical English reading is equally important. Healthcare providers must be able to synthesize and articulate thekey points and implications of their reading in a clear, concise, and accessible manner, whether in written reports, presentations, or discussions with colleagues and patients.In conclusion, clinical medical English reading is a critical skill for healthcare professionals in the modern era. By developing proficiency in this area, healthcare providers can stay informed, make evidence-based decisions, and deliver the highest quality of patient care. Moreover, the ability to engage with medical literature in English can have far-reaching implications for professional development, career advancement, and the overall advancement of the healthcare industry. As the global healthcare landscape continues to evolve, the importance of clinical medical English reading will only grow, making it an essential competency for all healthcare professionals.。

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A reading course IChapter1TextAprematurely 过早地diagnosis 诊断sub health 亚健康immune system 免疫系统respectively 分别地prevalent 普遍地spearhead 为…带头，为…先锋sustained 可持续的intellectual 知识分子transitional 过度的chronic 慢性的infectious传染的massage 按摩，推拿blood circulation 血液循环textBdefect 缺点，缺陷abnormality 畸形，异常cardiac 心脏的，心脏病的cardiac arrest 心搏停止screening test 筛选试验，屏蔽试验coroner 验尸官autopsy 验尸，尸体解剖ventricular 心室的，脑室的fibrillation 纤维性颤动ventricular fibrillation 心室纤维性颤动hypertrophic 肥厚的cardiomyopathy 心肌症hypertrophic cardiomyopathy 肥大型心肌病myocardium 心肌，心肌层coronary 冠状的artery 动脉compress 压缩，压紧syndrome 综合征inherit 继承，遗传chaotic 混乱的，无秩序的erratic 不稳定的，古怪的commotia cordis 心脏震动red flag 危险信号on the outlook 寻找，警惕着syncope 晕厥exertion 努力，用力seizures 癫痫，痉挛screening 筛选asthma 哮喘，气喘implantable 可移植的，可植入的cardioverter 心律转变器，复律器defibrillator 去纤颤器，电震发生器pacemaker 心律调整器，起搏器arrhythmia 心律不齐，心律失常electrocardiogram 心电图Vocabularysub health亚健康massage 按摩，推拿diagnosis 诊断suffernegativeaccelerateinfectioncirculationhealthcaredefectinheritcardiactriggerabnormalitysurgeryscreeningsignaldisordersyndromeprematurechapter2TextAdrug resistance耐药性Aids 艾滋病tuberculosis 肺结核malaria 疟疾scourge 灾祸，苦难的根源penicillin 盘尼西林antibiotic 抗菌素incentive 动机，刺激institution 公共机构，习俗leadership 领导能力，领导surveillance 监督，监视priority 优先，优先权，优先考虑的事hygience 卫生，卫生学lancet 小刀，柳叶刀haemorrhage 大出血tranexamic acid 氨甲环酸malnutrition 营养不良soaring 高耸的，猛增的depletion 消耗，放血stock 库存，血统textBallergy 过敏症，反感allergic 对…过敏/极讨厌的side effect 副作用sulfa 磺胺的，磺胺药剂的immune 免疫的offending 不愉快的medication 药物，药物治疗adverse 不利的，相反的itchy 发痒的，渴望的rash 皮疹hives 荨麻疹，假膜性喉头炎exposure 暴露，揭露anaphylaxis 过敏性，过敏性反应prescription 药方，指示symptom 征兆，症状wheeze 喘息serum 血清，浆液injection 注射，注射剂foreign 外国的，异质的medical facilities 医疗设施latex 乳胶，乳液application 应用，敷用amoxicillin 阿莫西林，氢氨苄青霉素ampicillin 氨苄西林，氨苄青霉素augmentin 安灭菌，奥格门汀carbenicillin 羧苄青霉素dicloxacillin 双氯西林，双氯青霉素cephalosporin 头孢菌素cefaclor 头孢克洛，氯氨苄青霉素cefadroxil 头孢氢氨苄cefepime 头孢吡肟cefprozil 头孢丙烯cephradine 头孢拉啶，先锋霉素cephalexin 头孢氨苄sulfasalazine 柳氮磺胺吡啶Bactrim 复方新诺明sulfate 硫酸盐insulin 胰岛素manifest 证明，表明iodine 碘，碘酒bloodstream 血液，血液的流动vessel 脉管，血管nausea 恶心，晕船，极端的憎恶vomit 呕吐，吐出dizziness 头晕，头昏眼花Vocabularysymptioninsulinsurveillancedizzinessimmuneallergicresistancemalariasulfaantibioticitchyforeignvomitbloodstreaminjectionhygieneprescriptionasthmahealthcareanaphylaxicchapter3textAhospice 临终关怀，临终关怀医院catch on 变得流行terminally 不治地，晚期地allusion 暗示，提及influential 有影响的decent 体面的，像样的prolong 延长，拖延existence 生存，生活intervention 干预，介入hostile 敌对的，怀敌意的dedicate 致力，献身explicit 明确的，清楚的intervene 干涉，插入palliative 缓和剂，暂时姑息outstrip 超过，胜过expectancy 期望，期待predictable 可预言的geriatrics 老年病学，老年病人succumb屈服，被压垮dementia 痴呆decay 衰败，衰退textBswallow 吞下，咽下stressful 紧张的，有压力的appreciate 欣赏，感激pursue 继续，从事alternative 选择，替换物available 可得到的，可利用的caregiver 照料者，护理者mission 使命，任务knowledgeable 知识渊博的，有见识的approach 接近expertise 专门知识，专家意见incredibly难以置信地distress 使悲痛，使贫困anticipate 预期，期望compassionate 慈悲的，富于同情心的participation 参与，分享excel 优于，胜过，擅长Vocabularyimmortalterminaldementiahospicedecentanxiousexpectancycaregiverpositiveapproachguidancepursuemissioninterventionemotionalalternativegrievefuneralphysicaltubechapter4textAface lift 面部拉皮手术deposit 沉积物cosmetic 美容的，化妆用的endoscopic 内窥镜的，用内窥镜检查的incision 切口，切割contour 轮廓，周线bandage 绷带wrinkle 皱纹crease 折痕，皱纹swelling 肿胀，增大restrict 限制，约束minimal 最小限度的，极小的invasive 侵略性的，攻击性的invasive surgery 侵入性外科手术anesthesia 麻醉sedation 镇静的，镇静剂visibe 明显的，看得见的temple 太阳穴textBlaser 激光remedy 补救，治疗hyperpigmentation 色素沉着过度discolor 使变色，使褪色discoloration 变色dermabrasion 磨去皮肤疤痕之手术，磨皮手术acne 痤疮，粉刺ablative 烧蚀的vaporize 汽化，使…蒸发downtime 停工期collagen 胶原，胶原蛋白pulse 脉冲，脉动rejuvenation 返老还童，恢复活动sagging 松垂的，下沉的vascular 血管的，淋巴管的lesion 病变，损伤antiviral 抗病毒物质antibacterial 抗菌剂，抗菌药yeast 酵母complication 并发症intravenous 静脉内的penetrate 渗透，穿透ointment 药膏，软膏petroleum jelly 凡士林，矿油temporary 暂时的，短暂的dormant 休眠的，静止的herpes 疱疹Vocabularyendoscopicmedicationcomplicationantiviralwrinkleanesthesiavascularswellingexposurehyperpigmentationscarinvasiveintravenouspeeldermabrasiondormantincisiondepositlesioncollagenchapter5textAgenetic 遗传的，基因的loom 可怕地出现，令人惊恐的隐现invade 侵入，侵略staple 主要的，常用的biotechnologist 生物工艺学家estimate 估计ingredient 材料，原料reveal 显示，透漏domesticated 家养的toxicity 毒性，毒性作用，毒性反应allergenicity 变应原性，过敏反应antibiotic 抗生的，抗菌的extinction 灭绝hazardous 有危险的，冒险的tangle 纠纷，混乱状态anomaly 异常，反常事物jurisdiction 管辖权haphazard 随便的，无计划的contaminate 污染，弄脏legislation 立法negligence 疏忽，忽视biotechnology 生物技术，生物工艺学textBaccess 使用权，接近或享用的机会temporarily 临时地affordable 负担得起的shortage 缺乏utilize 使用，利用household 家庭的，日常的intellectually 智力上，理智地resource 资源effective 有效的fertilizer 化肥productive 能生产的，多生产的deterioration 恶化undertake 承担，从事resistance 抵抗，反抗cultivate 培养，耕作cubic 立方体的，立方irrigation 灌溉salinisation 盐渍化consequently 因此，结果enhance 提高，加强invest 投资cyclone 旋风，气旋，飓风flee 逃走，消失，消失debris 碎片，残骸prioritise 给予…优先权，按优先顺序处理quarantine 检疫tariff 关税表，收费表subsidise 资助给…补助金deprive使丧失，剥夺Vocabularyorganismtanglecondimentfertilizershortagecontaminateanomalydebrisbacteriaregulateaccesstariffingredientprioritiseextinctiondeteriorationhaphazardirrigationpandemicutilizationchapter6textAwillpower 意志力，毅力illicit 违法的，非法的staggering令人惊讶的deleterious 有毒的，有害的disintegration 分解，瓦解chronic 慢性的，长期的relapse 旧病复发，故态复萌counteract 抵消，中和disruptive 破坏的，分裂性的psychiatric 精神病学的，精神病治疗的diabetes 糖尿病，多尿症reinstate 使恢复，使复原textBgay teen 同性恋青少年acute 严重的，急性的lesbian 女同性恋bisexual 双性恋的transgender 跨性别者，变性人heterosexual 异性的，异性恋的subgroup 子群straight teen 异性恋青少年，非同性恋青少年homophobia 对同性恋的恐惧，对同性恋的憎恶victimization 欺骗，侵害disparity 不同，不一致marginalize 排斥，使处于社会边缘nongovernmental 非政府的harassment 骚扰，烦恼marijuana 大麻，大麻毒品cocaine 可卡因methamphetamine 甲基苯丙胺，冰毒assault 攻击，袭击pseudonym 笔名，假名stigmatization 污辱adolescent 青少年prognosis 预后，预知grim 冷酷的，糟糕的homophobic害怕同性恋的imperative 必要的，紧急的confidential 表示信任的Vocabularyabsueaddictionillicitchronicdeleteriousstaggeringrelapsedisruptivedisintegrationhomophobiabisexualacutedisparityprognosispseudonymassaultimperativeasthmavictimizationchapter7textAeligibility 合格，资格dialysis 透析transplant 移植renal 肾的premium保费eligible 合格的，符合条件的coverage 承保范围labor 分娩，生产delivery 分娩textBbone mass 骨质osteoporosis 骨质疏松cardiovascular 心血管的cholesterol 胆固醇lipid 脂类triglyceride 三酸甘油酯colorectal 结肠直肠的fecal 粪便的，排泄物的occult 隐性的sigmoidoscopy 乙状结肠镜检查colonoscopy 结肠镜检查barium 钡enema 灌肠，灌肠剂dyslipidemia 血脂异常obesity 肥胖gestational 妊娠期的glaucoma 青光眼hepatitis肝炎pelvic 骨盆的cervical 子宫颈的vaginal 阴道的referral 转介，转诊pneumococcal 肺炎球菌的prostate 前列腺rectal 直肠的mammogram 乳房X线照片cessation 停止，休止chapter8textAspinal 脊髓的，脊柱的diverse 不同的，多种多样的gratifying 悦人的，令人满足的assume 承担rehabilitation 康复，修复physical rehabilitation 物理疗法，物理治疗accredited 公认的，经过认证的supervised fieldwork 实习pinpoint 精确地找到，查明per diem 每天，按日textBneurological 神经病学的substantiate 证实aphasia 失语症trigger 引发，引起innately 天赋的，与生俱来的attune to 习惯于bradykinesia 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