鼠伤寒杆菌核糖体制剂用作血吸虫抗原佐剂的探讨

目的：探讨鼠伤寒杆菌核糖体制剂对血吸虫抗原的佐剂作用。方法：小鼠分别用鼠伤寒杆菌核糖体制剂（ＳＴＲＰ）加日本血吸虫成虫抗原（ＳＷＡ）和日本血吸虫成虫抗原免疫后，其体液免疫水平用ＥＬＩＳＡ检测，保护性免疫力用减虫率表示。结果：用ＳＴＲＰ＋ＳＷＡ免疫的小鼠的抗体水平显著高于单用ＳＷＡ免疫的小鼠。尾蚴攻击感染后，ＳＴＲＰ＋ＳＷＡ免疫组小鼠和ＳＷＡ免疫组小组的减虫率，分别为４７％和１７％，前者高于后者。结论：ＳＴＲＰ可以增强小鼠对血吸虫抗原的体液免疫应答反应，并且可诱导小鼠产生较强的抗尾蚴攻击感染能力。     

Ageing and Toll-like receptor expression by innate immune cells in chronic human schistosomiasis

There has been no systematic study of the immune response of individuals aged over 60 years living in Schistosomiasis mansoni-endemic areas, although senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals aged over 60 years with chronic schistosomiasis is no longer negligible. Moreover, several elderly individuals who have always lived in these endemic areas stay protected from infection. An important question for studies of ageing and disease control in developing countries is which differences in the immunological profile of these negatively tested (non-infected) individuals can account for their resistance to either infection or reinfection. We show, in the present study, that non-infected (negative) elderly individuals develop innate immune mechanisms of protection that replace the age-associated decline in T cell function. Non-infected elderly individuals from endemic areas of schistosome infection present an increase in the frequency of the natural killer (NK) CD56(low) subset of NK cells expressing Toll-like receptors (TLR)-1, -2, -3 and -4 as determined by flow cytometry analysis. In addition, the proportion of dendritic cells expressing TLR-1 is elevated as well as the frequency of monocytes expressing TLR-1 and -4. These results suggest that TLR expression by cells of the innate immune system may be related to the negative status of infection in some elderly individuals who are constantly exposed to S. mansoni. Developing mechanisms of protection from infection may represent a biomarker for healthy ageing in this population.     

Definition and mapping of epitopes recognized by specific monoclonal antibodies to Schistosoma bovis 28 kDa glutathione S-transferase: relation with anti-egg viability immunity

Monoclonal antibodies to the 28kDa glutathione S-transferase of Schistosoma bovis have been constructed in mice and used to characterize the epitope(s) potentially implied in the induction of anti-fecundity and anti-egg viability immune responses. Among the MoAbs produced three were particularly studied: Sb4-50 (IgG2a) and Sb4-56 (IgG1) which inhibited Sb28GST activity and Sb4-10 (IgG1) which did not. The use of overlappting peptides covering the entire amino acid sequence of Sb28GST, allowed us to define the linear epitopes recognized by these anti-Sb28GST MoAbs. Amino acid residues 202-211 were recognized by both MoAbs Sb4-50 and Sb4-56 and MoAb Sb4-10 recognized amino acid residues 58-67. Their capacity to inhibit GST activity suggested binding to the active site or to neighbouring regions, which include the C-terminal domain (a.a. 190-211) of the protein. When passively transfered into BALB/c mice MoAbs induced a significant reduction in egg hatching and an increase in immature eggs. Effects on worm burdens were, however, variable and no clear-cut association between the inhibition of enzyme activity and anti-fecundity or anti-viability activities was recorded. Our data indicate that beside the anti-fecundity and anti-viability immunity related to the impairment of GST activity, immune response to epitopes located in other regions of the molecule also contribute to the reduction of egg viability .     

云南省主要感染季节不同阶段人群血吸虫感染情况观察

目的了解云南省血吸虫病重疫区主要感染季节的不同阶段居民血吸虫感染、再感染情况,为制定更具针对性的防治措施提供依据。方法根据农事活动和季节变化将主要感染季节分为前期、中期和后期3个阶段。选择高原峡谷型血吸虫病流行区洱源县的4个自然村作为观察点,将6~60岁居民随机分为Ⅰ、Ⅱ两组,Ⅰ组人群观察主要感染季节前期和后期血吸虫感染、再感染情况;Ⅱ组人群观察主要感染季节中期血吸虫感染、再感染情况。在各阶段开始前10d用吡喹酮治疗,观察期结束后30d查病。同时选择30名学生作为记录员,记录各自家庭成员每天接触疫水的时间。结果在主要感染季节前期、中期和后期居民血吸虫感染率分别为32.17%、12.42%、7.10%,平均每人每天接触疫水时间分别为(82±26)min、(30±14)min和(14±6)min。结论云南省重疫区主要感染季节的前期(栽插期)血吸虫感染率最高,主要与感染性钉螺密度高和居民接触疫水时间长有关。     

肝纤维化时血浆内皮素含量的动态观察

目的测定肝纤维化时血浆内皮素(ET)含量的动态改变.方法36只家兔随机分为正常组、病理组.于感染血吸虫尾蚴后第70,100,130天,每组随机选6只取血和肝分别作血浆ET含量和肝组织羟脯氨酸(HYP)含量测定.结果正常组各阶段间ET和HYP含量均无显著性差异(P＞0.05),病理组血浆ET含量和肝HYP与肝胶原纤维分布面积百分比均随着病程延长而增加.结论结果提示肝纤维化时血浆ET含量的增加可能参与了肝组织纤维化的进展.     

超声对常见弥漫性肝病原发性肝癌发生率的比较

目的利用超声比较两种弥漫性肝病（乙肝后肝硬化与晚期血吸虫肝病）基础上合并原发性肝癌（HCC）的发生率。方法回顾性分析1999年1月～2009年1月十年间彩色多普勒超声检查的27004例患者的肝脏声像图和部分病人CT、手术及穿刺病理结果原始资料。结果筛选出其中肝炎后肝硬化患者416例,合并HCC患者162例（肝癌发生率为38.94％）;晚期血吸虫肝病患者641例,合并Hnc患者20例（肝癌发生率为3.12%）。结论肝炎后肝硬化患者HCC发生率显著高于晚期血吸虫肝病患者HCC的发生率,揭示两种不同病因肝硬化的预后。     

慢性血吸虫病腹部CT表现探讨(附516例报告)

目的回顾分析慢性血吸虫病的腹部CT表现,以提高对该病的影像学特征的认识及对其诊断的准确性。方法对516例从粪便检查找到虫卵确诊的病例全部行腹部平扫及增强扫描,对合并肝内占位者,行双期增强扫描及延时扫描。结果肝内不同形态的钙化达502例,以地图样钙化最多,达350例;肝内汇管区低密度灶及中心血管影216例;肝硬化410例;门脉系钙化88例;肝实质囊状低密度影30例;肝癌106例;结肠壁增厚89例;结肠钙化149例;结肠癌49例;脾脏增大438例;脾脏钙化64例;脾脏恶性肿瘤3例。结论慢性血吸虫病主要损伤肝及结肠等腹部脏器,脾脏次之;肝内典型地图样钙化有定性意义,肝内汇管区低密度灶及中心血管影也较具特征性;CT腹部扫描是诊断慢性血吸虫病的重要影像学方法。     

An invertebrate smooth muscle with striated muscle myosin filaments

Muscle tissues are classically divided into two major types, depending on the presence or absence of striations. In striated muscles, the actin filaments are anchored at Z-lines and the myosin and actin filaments are in register, whereas in smooth muscles, the actin filaments are attached to dense bodies and the myosin and actin filaments are out of register. The structure of the filaments in smooth muscles is also different from that in striated muscles. Here we have studied the structure of myosin filaments from the smooth muscles of the human parasite Schistosoma mansoni. We find, surprisingly, that they are indistinguishable from those in an arthropod striated muscle. This structural similarity is supported by sequence comparison between the schistosome myosin II heavy chain and known striated muscle myosins. In contrast, the actin filaments of schistosomes are similar to those of smooth muscles, lacking troponin-dependent regulation. We conclude that schistosome muscles are hybrids, containing striated muscle-like myosin filaments and smooth muscle-like actin filaments in a smooth muscle architecture. This surprising finding has broad significance for understanding how muscles are built and how they evolved, and challenges the paradigm that smooth and striated muscles always have distinctly different components.The muscles of animals are of two basic types: striated or smooth. The presence or absence of striations depends on whether or not the thick (myosin) and thin (actin) filaments are in longitudinal register (1). In striated muscles, thin filaments of similar lengths are aligned via their attachment to transversely arranged Z-lines, which form the boundaries of the contractile unit, called the sarcomere. Thick filaments, also of similar lengths and in register, lie midway between the Z-lines (1). The repeating pattern of sarcomeres joined end-to-end gives rise to the striations seen in the light microscope (2). Smooth muscles, in contrast, lack both Z-lines and aligned, uniform-length thick and thin filaments; striations are therefore absent, creating a “smooth” appearance in the light microscope. In these muscles the Z-lines are replaced by narrower dense bodies, which act as attachment sites for thin filaments (3). In most animals, striated muscles are specialized for rapid, precisely controlled movements, whereas smooth muscles are used for slow or sustained contraction (1, 3). Within these broad categories there is considerable diversity in structure and function across species. Thus, striated muscles may be cross-striated (vertebrates and invertebrates) or obliquely/helically striated (invertebrates only) (4, 5), and smooth muscles may have relatively short (vertebrates and many invertebrates) or very long (molluscan) myosin filaments (6).Our knowledge of the molecular structure and function of smooth muscle, and how this contrasts with striated muscle, has come mostly from studies of vertebrates. Several key differences are found: (i) The striated muscle myosin II heavy chain (MHC II) has key sites of sequence conservation in the tail and head, which clearly distinguish it from smooth and nonmuscle myosin II sequences (7, 8). (ii) Striated muscles are regulated via Ca²⁺ binding to troponin on the thin filaments (9), whereas smooth muscles lack troponin and are regulated by Ca²⁺-induced phosphorylation of the myosin regulatory light chains (10). (iii) The thick filaments in striated muscles have a helical, bipolar structure, in which the polarity of myosin molecules reverses midway along the filament length, whereas smooth muscle thick filaments are nonhelical and side-polar, with oppositely oriented myosin molecules on opposite sides of the filament along its entire length (11, 12). Whether comparable differences occur in invertebrate muscle has been little studied, with the exception of molluscan smooth muscles, which have giant thick filaments (containing high levels of paramyosin) that are specialized to function in the long-lived, high-tension “catch” state (13).Here we have studied the molecular structure and function of the muscles of the parasitic flatworm Schistosoma mansoni, which is responsible for the tropical disease schistosomiasis, affecting 200 million people worldwide (14). Our interest in these muscles was catalyzed by reports that the drug used to treat schistosomiasis (praziquantel) may act on the myosin molecule (15), and that muscle proteins like myosin, paramyosin, and certain regions of actin might be useful targets for the development of an antischistosomal vaccine or chemotherapy (16–18). We show that the adult form of S. mansoni has exclusively smooth muscles, and yet its thick filaments have the bipolar, helical structure characteristic of striated muscle filaments from other invertebrates. This similarity in thick filament structure is supported by sequence analysis, which groups the schistosome MHC II with other striated muscle myosin sequences, not with their smooth/nonmuscle counterparts. Whereas the thick filaments of schistosome smooth muscles have striated muscle characteristics, their thin filaments appear to lack troponin and are not regulated by Ca²⁺; they are thus similar to other smooth muscle thin filaments. We conclude that, in contrast to vertebrates, schistosome smooth muscles are hybrids, incorporating proteins and filament structures from both smooth and striated muscles.     

血吸虫循环抗原检测在血吸虫病普查中的应用

目的了解血吸虫循环抗原（ScAg）检测在普查中的应用效果，发挥ScAg检测在血吸虫病传播阻断中的作用。方法在现场单盲试验普查条件下测试血吸虫病血清库质控血清，应用ScAg在不同程度感染的血吸虫病流行区批量检测。对ScAg阳性者作9送9检粪孵追踪观察。结果ScAg检测EPG≤8的血吸虫病患者血清阳性率为95．45％，EPG≥16的血吸虫病患者血清阳性为100．00％，对正常人和华支睾吸虫病患者血清的特异性为100．00％。对高、中、低流行区普查ScAg的阳性率分别为7．27％、3．06％、2．70％。对ScAg阳性的病例粪孵9送9检累计阳性率为34．29％，粪检累计总阳性数中，第1次只检出16．67％，连续第3次的累计阳性率仅为50．00％。连续化疗地区ScAg检测阳性的粪孵阳性率为12．50％，间歇性选择化疗地区ScAg阳性者的粪孵阳性率占75．00％以上。结论9送9检粪孵累计阳性结果显示，检出率随粪检次数增加而升高，粪检漏检多、工作量大、不能正确反映当地疫情。ScAg检测是一种敏感性高，特异性好的简便快速方法，普查结果能反映不同感染度流行地区的实际状况，有利于制定防治策略，了解防治后成效。