Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques

The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results is that behavioral decline occurred with high CSF viral loads but not necessarily with high plasma viral loads. Compared to saline controls, all treated animals showed significant decreases in performance on all three behavioral tasks during the morphine-only dependency period. During the post infection period, only the morphine plus SIV group showed a significant further decline and this only occurred for the MS task. Taken together, these data demonstrate a clear effect of morphine to produce behavioral deficits and also suggest that morphine can act synergistically with SIV/HIV to exacerbate behavioral deficits.     

Morphine Potentiates Neuropathogenesis of SIV Infection in Rhesus Macaques

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. Their effect on the pathogenesis of HIV-1 infection however remains controversial. Using the simian immunodeficiency virus/macaque model of HIV pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. Sixteen rhesus macaques were divided into two groups; four were administered saline and 12 others morphine routinely. Both groups of animals were then inoculated with SIVmacR71/17E and followed longitudinally for disease pathogenesis. The morphine group (M+V) exhibited a trend towards higher mortality rates and retardation in weight gain compared to the virus-alone group. Interestingly, a subset of M+V animals succumbed to disease within weeks post-infection. These rapid progressors also exhibited a higher incidence of other end-organ pathologies. Despite the higher numbers of circulating CD4+ and CD8+ T cells in the M+V group, CD4/CD8 ratios between the groups remained unchanged. Plasma and CSF viral load in the M+V group was at least a log higher than the control group. Similarly, there was a trend toward increased virus build-up in the brains of M+V animals compared with controls. A novel finding of this study was the increased influx of infected monocyte/macrophages in the brains of M+V animals.     

M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques

Mycobacterium tuberculosis is the most common communicable infectious disease worldwide and the top killer of human immunodeficiency virus (HIV)-infected people. Because of common dual HIV and M. tuberculosis infections, the emergence of multidrug-resistant M. tuberculosis strains, the lack of effective vaccination, the morbidity, and the mortality of M. tuberculosis infection are increasing sharply. Therefore, there is an urgent need for vaccine and drug development against M. tuberculosis infection. These require appropriate animal models that closely resemble human disease. To this end, we infected Chinese rhesus macaques with the M. tuberculosis H37Rv strain. Bronchoscopy was used to inoculate nine monkeys with different doses of M. tuberculosis H37Rv strain. Regardless of the M. tuberculosis dose, all monkeys were infected successfully. This was shown by clinical, laboratory, and histopathology assessments. Among nine infected monkeys, six developed acute rapid progressive tuberculosis and the remaining animals mirrored early-stage chronic disease. These data, taken together, demonstrate that Chinese rhesus macaques are highly susceptible to M. tuberculosis infection and develop similar manifestations of disease that are seen in humans. This model affords new opportunities for studies of M. tuberculosis disease pathology and therapeutics.     

恶性淋巴瘤累及腹部淋巴结CT表现分析

目的 探讨恶性淋巴瘤累及腹部淋巴结的CT表现特征.方法 回顾分析48例恶性淋巴瘤累及腹部淋巴结的病例,其中Hodgkin病(HD)16例,非Hodgkin淋巴瘤(NHL)32例.手术病理证实7例,淋巴结活检病理证实41例.全部病例均行上中腹部CT平扫及全腹部增强扫描,观察淋巴结的大小、形态、密度、强化方式及增大淋巴结的优势分布.结果 48例恶性淋巴瘤累及腹部淋巴结的病例中,68.75%HD和87.50%NHL淋巴结增大呈普遍均匀强化,31.25%HD和12.50%NHL呈均匀强化合并小坏死灶.HD和NHL均优势地累及腹主动脉周围(72.92%)、肠系膜(47.92%)、胰腺周围(35.42%)、小网膜(20.83%)淋巴结.结论 CT检查能较好地显示腹部恶性淋巴瘤淋巴结的病理改变、病变范围,对恶性淋巴瘤的诊断及其临床的分期及疗效的判定有较高价值.     

Effect of Morphine on the Neuropathogenesis of SIVmac Infection in Indian Rhesus Macaques

Morphine is known to prevent the development of cell-mediated immune (CMI) responses and enhance expression of the CCR5 receptor in monocyte macrophages. We undertook a study to determine the effect of morphine on the neuropathogenesis and immunopathogenesis of simian immunodeficiency virus (SIV) infection in Indian Rhesus Macaques. Hypothetically, the effect of morphine would be to prevent the development of CMI responses to SIV and to enhance the infection in macrophages. Sixteen Rhesus Macaques were divided into three experimental groups: M (morphine only, n = 5), VM (morphine + SIV, n = 6), and V (SIV only, n = 5). Animals in groups M and VM were given 2.5 mg/kg of morphine sulfate, four times daily, for up to 59 weeks. Groups VM and V were inoculated with SIVmacR71/17E 26 weeks after the beginning of morphine administration. Morphine prevented the development of enzyme-linked immunosorbent spot-forming cell CMI responses in contrast to virus control animals, all of which developed CMI. Whereas morphine treatment had no effect on viremia, cerebrospinal fluid viral titers or survival over the time course of the study, the drug was associated with a tendency for greater build-up of virus in the brains of infected animals. Histopathological changes in the brains of animals that developed disease were of a demyelinating type in the VM animals compared to an encephalitic type in the V animals. This difference may have been associated with the immunosuppressive effect of the drug in inhibiting CMI responses.     

肺癌纵隔淋巴结清除的疗效

目的 探讨肺癌纵隔淋巴结清除术的必要性和术后的效果。方法 自1995年5月-2002年7月，对27例肺癌病人进行根治性手术中，同侧肺门及纵隔淋巴结清除，其中病理证实纵隔淋巴结转移21例(78％)。根据肺癌分期进行化疗。结果 27例手术病人，中心型肺癌18例，周围型肺癌9例；鳞状细胞癌14例，腺癌8例，小细胞癌5例。清除淋巴结116组．阳性64组(占56．9％)。结论 根治性肺癌手术对于病人的生存时间具有重要意义，并可指导对病人的进一步治疗。     

卵巢癌腹膜后淋巴结转移的研究

目的研究卵巢癌腹膜后淋巴结转移及影响因素。方法我们研究了89例行卵巢癌根治术并行腹主动脉旁淋巴结(PAN)和盆腔淋巴结(PLN)清除术的卵巢癌患者。结果腹膜后淋巴结转移总例数为23例(25.8%)。按临床分期,Ⅰ期转移3例(5.8%),Ⅱ期转移3例(27.3%),Ⅲ期转移12例(60%),Ⅳ期转移5例(83.3%)。临床分期与腹膜后淋巴结转移率间存在相关(P<0.01)。PAN和PLN转移率分别为Ⅰ期3例(5.8%)和0;Ⅱ期3例(23.1%)和1例(9.1%);Ⅲ期10例(50%)和7例(35%);Ⅳ期4例(66.7%)和3例(50%)。PLN转移与PAN转移存在显著相关(P<0.01)。23例腹膜后淋巴结转移患者中,12例仅有PAN转移,3例仅有PLN转移,8例均有PAN和PLN转移。PAN是发生转移最多的部位:肠系膜下动脉以上15例(16.9%),肠系膜下动脉以下13例(14.6%)。转移至髂总淋巴结为8例(9%)、髂外淋巴结7例(7.9%)、腹股沟浅淋巴结6例(6.7%)、闭孔淋巴结5例(5.6%)。结论卵巢癌腹膜后淋巴结转移率包括PAN与PLN与临床分期有关,PAN是卵巢癌淋巴结转移的一级淋巴结,PLN转移与PAN转移有关。     

大鼠淋巴结利福平浓度的测定

（1. ［摘要］目的研究大鼠口服利福平后淋巴结的药物浓度变化特点，为淋巴结结核治疗方法的改进提供理论依据。方法Wistar大鼠15只，随机分为3组，每组5只，禁食12 h后，喂服利福平10 mg&;#8226;kg-1，分别于给药后2，8，24 h行眼球摘除取血并摘取肠系膜淋巴结，采用高效液相色谱法测定不同时间的腹腔淋巴结药物浓度及血清药物浓度。结果血清利福平与淋巴结利福平浓度呈良好线性关系，日内、日间RSD均＜7%，能满足测定要求。各时间点利福平淋巴结浓度达到其抑菌浓度水平，但均显著低于血药浓度(P＜0.01)。结论该方法准确度高，是一可靠的测定淋巴结利福平浓度的方法；淋巴结内利福平浓度显著低于血药浓度，淋巴结结核的治疗需要提高淋巴结局部药物浓度。     

腹痛患儿行肠系膜淋巴结超声检查的诊断价值

目的:探讨腹痛患儿行肠系膜淋巴结超声检查的诊断价值。方法:择取2016年3月～2018年4月期间在某院因腹痛进行超声检查的小儿共375例为研究对象,开展高频彩色多普勒超声检查,统计超声诊断结果。结果:超声发现腹腔淋巴结肿大259例,腹痛小儿329例,其中淋巴结肿大者225例。肠系膜淋巴结肿大患儿与健康儿童的性别、年龄差异无统计学意义(P0.05);淋巴结横径与纵径均长于健康儿童,差异有统计学意义(P0.05)。结论:腹痛患儿应及时进行临床超声检查,进行肠系膜淋巴结诊断,效果确切,值得推广应用。     

甲状腺癌颈部淋巴结转移规律的超声诊断研究

目的探讨超声对甲状腺癌颈部淋巴结转移规律的诊断价值。方法根据1991年美国头颈外科基金学院颈部淋巴结分组方法及2002年美国癌症联合委员会(AJCC)的Ⅶ区法对颈部可疑淋巴结进行分区,回顾性分析274例甲状腺癌颈部淋巴结转移的超声诊断符合率。结果超声对转移淋巴结的诊断符合率为82.8%,敏感度为57.8%,特异度为93.4%。超声诊断颈部Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵ区的敏感度及特异度分别为62.5%、98.3%;41.2%、96.4%;53.1%、95.1%;50.0%、97.2%和34.1%、89.7%。结论超声对甲状腺癌颈部淋巴结转移的诊断符合率较高,术前进行超声甲状腺癌颈部淋巴结分区对临床手术有一定的指导意义。     

Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes

Despite the absence of conventional lymphatics, there is efficient drainage of both cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the CNS to regional lymph nodes. CSF drains from the subarachnoid space by channels that pass through the cribriform plate of the ethmoid bone to the nasal mucosa and cervical lymph nodes in animals and in humans; antigen presenting cells (APC) migrate along this pathway to lymph nodes. ISF and solutes drain from the brain parenchyma to cervical lymph nodes by a separate route along 100–150 nm wide basement membranes in the walls of cerebral capillaries and arteries. This pathway is too narrow for the migration of APC so it is unlikely that APC traffic directly from brain parenchyma to lymph nodes by this route. We present a model for the pivotal involvement of regional lymph nodes in immunological reactions of the CNS. The role of regional lymph nodes in immune reactions of the CNS in virus infections, the remote influence of the gut microbiota, multiple sclerosis and stroke are discussed. Evidence is presented for the role of cervical lymph nodes in the induction of tolerance and its influence on neuroimmunological reactions. We look to the future by examining how nanoparticle technology will enhance our understanding of CNS-lymph node connections and by reviewing the implications of lymphatic drainage of the brain for diagnosis and therapy of diseases of the CNS ranging from neuroimmunological disorders to dementias. Finally, we review the challenges and opportunities for progress in CNS-lymph node interactions and their involvement in disease processes.     

中晚期非小细胞肺癌患者纵隔淋巴结转移及清扫的临床分析

目的探讨中晚期非小细胞肺癌纵隔淋巴结合理的手术清扫范围和临床意义。方法回顾性分析2009年1月至2010年8月收治的46例中晚期非小细胞肺癌纵隔淋巴结清扫手术。结果本组共发现共清除纵隔淋巴结262组,病理证实有转移的90组,占34.3%。跳跃性N2在鳞癌和腺癌发生率的差别经检验无统计学意义(P>0.05)。结论非小细胞肺癌患者的淋巴结转移具有跳跃性和多发性的特点,只有广泛清扫纵隔淋巴结才有可能达到根治,临床意义重大。     

彩超对腹膜后肿大淋巴结良恶性的鉴别诊断价值

目的探讨超声诊断腹膜后肿大后淋巴结良恶性病变的声像图特征与临床实用价值。方法对48例(95枚)腹膜后淋巴结肿大的患者在行组织活检前应用彩超观察内部回声,血流特点,大小及其形态特征,多普勒测值(收缩期最大血流速度、舒张末期血流速度、阻力指数等改变)结果良性肿大淋巴结多呈椭圆形,内部回声尚均质,但结核性肿大淋巴结内见钙化强回声及液化,并破溃与周围组织粘连成团,界限不清,血流为零星,阻力指数在0.42~0.55,为低阻力型;恶性肿大淋巴结多呈类圆形及圆形,内部回声不均匀、稍低,边界欠规则,血流极其丰富,有者达包膜下,呈树枝状分布,走形迂曲,阻力指数0.59~0.79,为高阻力型。结论通过对淋巴结超声测值即大小及形态特征,结合内部回声,与周围组织关系,血流分布情况,阻力指数等改变,对淋巴结良恶性鉴别具有使用价值,可作为肿大淋巴结病因诊断的首选方法,并为进一步穿刺活检及超声造影提供依据。     

The Disposition of Coal Dusts in the Lungs and Tracheobronchial Lymph Nodes of Dogs

The Disposition of Coal Dusts in the Lungs and TracheobronchialLymph Nodes of Dogs. Morrow, P.E. and Yuile, C.L. (1982). Fundam.Appl. Toxicol. 2:300–305. The pulmonary disposition, histopathologyand lymphatic uptake of anthracite (Tamaqua) and bituminous(Lower Kittaning) coal dusts were measured as part of a pulmonaryretention study which revealed a mean half-time of 1.92 yearsin dogs (Morrow et al. 1981). After brief (1-2.5 hr) exposuresto either natural or neutron-activated coals having an averageairborne mass concentration of {small tilde}90 mg m^–3and a 1.8 µm mass median aerodynamic diameter (g 2.5),dogs (n=12) were serially sacrificed up to 52 weeks after exposure.Coal dusts were found only in the lungs and pulmonary lymphnodes. The coals were considered indistinguishable as to theirpulmonary clearance and disposition and lymphatic uptake. Allcoals in the lung were associated mainly with the peribronchiolarand perivascular lymphatics or connective tissue spaces, andsome were found in alveolar macrophages. The lymphatic uptakeof coal dusts followed the powder function 0.55 t^0.613 wheret is in weeks and uptake is expressed as percent of the initialalveolar burden. In terms of pulmonary dust clearance, only4 percent of the initial alveolar burden appeared to have beentranslocated to the tracheobronchial lymph nodes in the first50 weeks, but this constituted {small tilde}14 percent of thetotal alveolar clearance. Histopathologically, one distinctionwas found: animals exposed to the highest level of neutron-activatedanthracite showed patchy hyaline thickening of some small bloodvessels and alveolar septa. The response was low grade, probablyexposure-related, but otherwise unremarkable.     

CT灌注成像在颈部恶性淋巴结鉴别诊断中的应用

目的探讨CT灌注区分不同病理类型颈部淋巴结的价值。方法对39例颈部恶性淋巴结病变患者行CT灌注,测量并比较不同病理类型淋巴结的血流量(BF)、血容量(BV)、渗透性(P值)灌注参数及TDC曲线。结果原发组、转移组淋巴结BF、BV、P值均大于正常组(P<0.05);继发组淋巴结BF、BV大于原发组(P<0.05)。原发组以"低平"型为主,表现为缓慢上升到一较高的峰值后,在峰值水平呈水平走势;转移组以"快升快降"型为主,主要表现为快速上升到达峰值后会又快速下降形成一波峰。结论颈部恶性淋巴结与正常淋巴结及不同病理类型恶性淋巴结灌注特点不同,利用CT灌注结合CT形态学表现可以提高对颈部淋巴结病变诊断水平。     

探讨原发性颈淋巴结结核的诊断及治疗方法

目的探讨原发性颈淋巴结结核的诊断及治疗方法。方法选取2010年1月至2012年12月期间原发性颈淋巴结结核患者60例,对患者的临床资料及诊疗方法进行回顾分析。结果本次60例患者中15例患者经细针穿刺针吸活检方法对病症进行确诊,45例患者均经手术切除病理检查确诊。本次共53例患者行手术治疗,并于术后行半年抗结核治疗,剩余患者行1年抗结核治疗。对患者治疗后行1年以上随访,未见颈淋巴结复发。结论原发性颈淋巴结结核患者主要诊疗方法是细针穿刺针吸活检及切除病理诊断,同时,对确诊患者及时行抗结核治疗效果显著。     

Targeting Suppressive Oligonucleotide to Lymph Nodes Inhibits Toll-like Receptor-9-Mediated Activation of Adaptive Immunity

Purpose

This paper aims to investigate the immunoinhibitory properties of a lymph nodes-targeting suppressive oligonucleotide (ODN) for the potential treatment of autoimmune diseases or chronic inflammation.

Methods

Synthetic suppressive ODN engineered with an albumin-binding diacyl lipid at the 5′-terminal (lipo-ODN) was synthesized. In vitro and in vivo experiments were designed to compare the immune suppressive properties of lipo-ODN and unmodified ODN. Cellular uptake and distribution, inhibition of Toll-like receptor (TLR) activation, lymph nodes (LN) draining, and the suppression of antigen-specific immune responses in an ovalbumin protein model was investigated.

Results

Compared to unmodified ODN, lipid functionalized suppressive ODN demonstrated enhanced cellular uptake and TLR-9 specific immune suppression in TLR reporter cells. Additionally, injection of a low dose of lipid-modified suppressive ODN, but not the unconjugated ODN, accumulated in the draining LNs and exhibited potent inhibition of antigen-specific CD8⁺ T cell and B cell responses in vivo.

Conclusions

Targeting suppressive ODN to antigen presenting cells (APCs) in the local LNs is an effective approach to amplify the immune modulation mediated by ODN containing repetitive TTAGGG motif. This approach might be broadly applicable to target molecular adjuvants to the key immune cells in the LNs draining from disease site, providing a simple strategy to improve the efficacy of many molecular immune modulators.

     

纳米炭定位前哨淋巴结在cN0甲状腺乳头状癌中的临床研究

目的 应用纳米炭注射的方法标记cN0甲状腺乳头状癌前哨淋巴结,评价纳米炭定位前哨淋巴结的可行性及临床价值.方法 应用纳米炭对48例甲状腺乳头状癌患者行前哨淋巴结定位活检,并常规行患侧功能性颈淋巴结清扫术,将前哨淋巴结及清扫的颈淋巴结分别送检,记录两者的位置及数目并比较两者的病理学状况,分析前哨淋巴结分布区域及甲状腺癌淋巴转移特点.结果 48例甲状腺乳头状癌患者中有45例显示了前哨淋巴结,平均每例2.58枚,21例为阳性,其检出率、准确率、敏感性、假阴性率分别为93.75%、93.33%、87.50%、12.50%,前哨淋巴结检出率在IV区和VI区最多,阳性率在IV区和VI区最高(P＜0.05).结论 纳米炭作为一种新型的淋巴示踪剂,具有淋巴染色特异性高、染色快、持续时间长、不易引起甲状旁腺染色的优势,能准确反应甲状腺乳头状癌淋巴转移情况,是甲状腺前哨淋巴结活检较可靠的示踪剂,对cN0甲状腺乳头状癌的颈淋巴清扫范围及清扫的彻底性 具有重要的临床指导价值.     

超声诊断对颈部淋巴结疾病定性的探讨

目的运用超声诊断仪对颈部淋巴结疾病病灶进行检查,共同探讨超声诊断对颈部淋巴结疾病的定性诊断。方法运用普通高频二维超声成像(B-US)、能量多普勒超声成像(PDI)、超声弹性成像(UE)等技术检查已病理证实的颈部淋巴结病灶,评估不同超声检查方法对不同颈部淋巴结病灶的敏感度及特异度等数据。结果 B-US及PDI的敏感度及准确度较高,而UE检查的特异性则高于B-US及PDI检查。结论通过多种超声检查途径综合分析颈部淋巴结病灶,能准确的对病灶进行定性诊断。