Evolution of neurotransmitter receptor systems

The presence of hormones, neurotransmitters, their receptors and biosynthetic and degradative enzymes is clearly not only associated with the present and the recent past but with the past several hundred million years. Evidence is mounting which indicates substantial conservation of protein structure and function of these receptors and enzymes over these tremendous periods of time. These findings indicate that the evolution and development of the nervous system was not dependent upon the formation of new or better transmitter substances, receptor proteins, transducers and effector proteins but involved better utilization of these highly developed elements in creating advanced and refined circuitry. This is not a new concept; it is one that is now substantiated by increasingly sophisticated studies. In a 1953 article discussing chemical aspects of evolution (Danielli, 1953) Danielli quotes Medawar, "... endocrine evolution is not an evolution of hormones but an evolution of the uses to which they are put; an evolution not, to put it crudely, of chemical formulae but of reactivities, reaction patterns and tissue competences." To also quote Danielli, "In terms of comparative biochemistry, one must ask to what extent the evolution of these reactivities, reaction patterns and competences is conditional upon the evolution of methods of synthesis of new proteins, etc., and to what extent the proteins, etc., are always within the synthetic competence of an organism. In the latter case evolution is the history of changing uses of molecules, and not of changing synthetic abilities." (Danielli, 1953). Figure 4 outlines a phylogenetic tree together with an indication of where evidence exists for both the enzymes that determine the biosynthesis and metabolism of the cholinergic and adrenergic transmitters and their specific cholinergic and adrenergic receptors. This figure illustrates a number of important points. For example, the evidence appears to show that the transmitters and their associated enzymes existed for a substantial period before their respective receptor proteins. While the transmitters and enzymes appear to exist in single cellular organisms, there is no solid evidence for the presence of adrenergic or cholinergic receptors until multicellular organisms where the receptors appear to be clearly associated with specific cellular and neuronal communication (Fig. 4). One can only speculate as to the possible role for acetylcholine and the catecholamine in single cell organisms.(ABSTRACT TRUNCATED AT 400 WORDS)     

DNA错配修复基因甲基化在肝细胞癌发生发展中的作用

目的探讨DNA错配修复基因(MMR)hMLH1,hMSH2和hMSH3甲基化在肝细胞癌(HCC)发生发展中的作用。方法采用甲基化特异性聚合酶链反应(MSP)法对38例新鲜HCC组织,相应非肿瘤肝组织,2例正常的捐肝组织及6种肝癌细胞系的hMLH1,hMSH2和hMSH3基因启动子CpG岛甲基化进行检测;培养6种肝癌细胞系,MSP法检测加入5-aza-2‘-deoxycytidine前后hMSH2基因在HCC中的甲基化状态改变;逆转录．聚合酶链反应(RT-PCR)方法检测加入5-aza-2’-deoxycytidine前后hMSH2在肝癌细胞株中的mRNA表达改变。结果HCC标本中13．2％(5／38)发生了hMLH1启动子甲基化,68．4％(26／38)发生了hMSH2启动子甲基化;相应的非肿瘤肝组织中hMLH1,hMSH2启动子甲基化阳性率分别为2．6％(1／38),55．3％(21／38);2例正常肝组织中未发现甲基化;6株肝癌细胞系中有5株发生了hMSH2启动子甲基化,而未发现有MLH1启动子甲基化。所有标本中均未发现有hMSH3启动子甲基化。5-aza-2‘-deoxycytidine处理细胞株后,可部分或完全逆转hMSH2启动子甲基化,各细胞株的mRNA均有不同程度的表达增加。结论hMSH3基因启动子CpG岛甲基化与HCC的发生发展关系不大。hMSH2基因甲基化与mRNA表达密切相关,是基因表达调节的一种重要方式。hMLH1和hMSH2基因启动子CpG岛的高甲基化在HCC中是一个常见的基因改变,DNA错配修复基因尤其是hMSH2基因启动子甲基化在HCC的发生中起了重要作用,是早期事件,其可能为临床诊断HCC提供新的检测指标。     

Immunotactoid glomerulopathy with fingerprint immune deposits

Summary Immunotactoid glomerulopathy is a distinct clinico-pathological entity which has recently been defined. The term immunotactoid refers to highly organized immune depositions appearing as rod-like microtubular structures in ultrastructural examination. We describe a patient with mixed connective tissue disease who demonstrates characteristic features of immunotactoid glomerulopathy. The diagnosis was made after excluding amyloidosis, cryoglobulinaemia and lupus nephritis. In addition to immunotactoid microtubules, ultrastructural examination also demonstrated presence of fingerprint depositions which were intimately mixed with immunotactoid structures. Fingerprint deposits have been described in lupus nephritis and cryoglobulin-related nephropathy, but rarely in other glomerulonephritis. These unique findings in our patient may suggest a previously unsuspected relationship between the syndrome of immunotactoid glomerulopathy and systemic lupus erythematosus.     

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study

Objectives

Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.

A genipin-crosslinked gelatin membrane as wound-dressing material: in vitro and in vivo studies

A naturally occurring crosslinking agent (genipin) was used in this study to crosslink gelatin hydrogel to develop a wound-dressing membrane. The study was to investigate the in vitro characteristics of the genipin-crosslinked gelatin membrane. The glutaraldehyde-crosslinked counterpart, at a similar crosslinking degree, was used as control. Additionally, an in vivo experiment was undertaken to study the wound healings covered with the glutaraldehyde- and genipin-crosslinked dressings in a rat model. The in vitro results obtained suggested that crosslinking of gelatin membranes with glutaraldehyde or genipin may produce distinct crosslinking structures. The differences in crosslinking structure can significantly affect the mechanical property, water-vapor-transmission rate, swelling ratio, degradation against enzyme and cellular compatibility of the crosslinked membranes. In the in vivo study, it was found that the degree of inflammatory reaction for the wound treated with the genipin-crosslinked dressing was significantly less severe than that covered with the glutaraldehyde-crosslinked dressing throughout the entire course of the study. Additionally, the healing rate for the wound treated with the genipin-crosslinked dressing was notably faster than its glutaraldehyde-crosslinked counterpart.     

Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.