多发性骨髓瘤的个体型阳性细胞检查及意义

近年来抗个体型抗体(antiidiotypeantibodies,抗Id抗体)的理论研究及应用有了迅速地发展,已成为免疫学研究中活跃领域之一。个体型是指在同一个体内,不同的抗体形成细胞所产生的免疫球蛋白(Ig)有各自不同的抗原特异性。决定个体型抗原特异性的部位在抗体可变区的超可变区,是针对超可变区某些抗原决定簇的抗体。在     

Characterization of integrin chains in normal and neoplastic human pancreas.

Integrins are a complex family of non-covalently linked heterodimeric glycoproteins which function as cell adhesion molecules, interacting with extracellular matrix molecules such as laminin, fibronectin, vitronectin, and collagen, and also having a role in intercellular adhesion. Each integrin subfamily is characterized by a common beta chain associated with variable alpha chains. We have examined, using immunohistological methods, the expression of the VLA (very late activation) family comprising beta 1 in association with alpha 1-6, and also alpha 6 in association with beta 4, the LFA beta chain beta 2, and the vitronectin receptor, in association with beta 1 or beta 5 and as the complex alpha v beta 3. Cryostat sections of normal pancreas, pancreatic adenocarcinomas, and ampullary tumours were studied together with six pancreatic carcinoma cell lines. Normal pancreas showed expression of beta 1 in all parenchyma. alpha 2 and alpha 6 had a similar distribution whereas alpha 3 expression was confined to ducts, including the very smallest radicles. Staining along the basement membranes of ducts was seen with beta 4 and the anti-vitronectin alpha v chain receptor antibody 13C2. Islet cells failed to stain with any antibody. No staining of epithelial components was seen with antibodies to alpha 1, alpha 4, alpha 5, or to the alpha v beta 3 form of the vitronectin receptor (beta 3 and alpha v beta 3 using the antibody 23C6). Pancreatic adenocarcinomas and ampullary tumours showed expression of alpha 2, alpha 3, alpha 6, beta 1, beta 4, and the vitronectin receptor (alpha v associated with beta 1 or beta 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of parasite proteins in a membrane preparation enriched for the surface membrane of erythrocytes infected with Plasmodium knowlesi

A subcellular fraction enriched in erythrocyte membranes has been isolated from rhesus monkey erythrocytes infected with Plasmodium knowlesi. Infected cells were lysed by centrifugation through a zone of hypotonic buffer and membranes isolated by equilibrium density gradient centrifugation in the same tube. The purified membrane fraction was shown to include the erythrocyte surface membrane by several methods: electron microscopy, identification of Coomassie Blue stained erythrocyte membrane proteins, identification of band 3 with a monoclonal antibody, and identification of radioiodinated cell surface proteins. The resulting ghosts were shown to be specifically reactive with monkey sera against the variant surface antigens of P. knowlesi by indirect immunofluorescence and membrane agglutination. No reactivity was seen with a monoclonal antibody (13C11) against the intracellular schizont surface. A number of metabolically labelled parasite proteins were enriched in this membrane function, including peptides of 277, 208, 173, 153, 134, 109, 80, 60 and 48 kDa and the variant surface antigens of variable molecular mass (180-207 kDa). These proteins were distinct from the major parasite proteins of total infected erythrocytes and isolated merozoites. The major glucosamine labelled glycoprotein of the internal schizont (230 kDa) was not found in this fraction. Moreover, no fragment of this parasite glycoprotein was found in this membrane fraction, indicating that no part of this molecule is transported to the erythrocyte surface. In contrast, the variant antigen of P. knowlesi, known to be on the erythrocyte surface, could be readily identified as peptides unique to specific cloned parasite lines. We propose that the other nine parasite proteins found within this membrane fraction represent a starting point for the identification of other parasite proteins transported to the surface membrane of the infected erythrocyte.     

实验性犬心肌梗塞和溶栓后再闭塞时血浆中GMP—140,TXB2的变化

本文采用放免法测定实验性犬心肌梗塞和溶栓后再闭塞时血浆中ＧＭＰ－１４０、ＴＸＢ２、６－Ｋ－ＰＧＦ１α的含量变化，并探讨其与心肌梗塞溶栓后再闭塞的关系。结果表明，在血栓形成时血浆中ＴＸＡ２稳定代谢产物ＴＸＢ２水平显著升高（ｐ〈０．０５），在溶栓后再闭塞率高（８７．５％）的非治疗组（Ｂ组）。在溶栓后４小时至溶栓后３天期间呈进行性升高（ｐ〈０．０１），而在再 埘经低（１６．７％）的ＡＰＩ０１３４治疗组（     

The hepatic extracellular matrix

The unique nature of the hepatic extracellular matrix (ECM) is predicted by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin (FN), some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in derranged hepatic function.Parts of this editorial have been adapted from: A. Martinez-Hernandez, P.S. Amenta. Morphology, localization and origin of the hepatic extracellular matrix. In: Zern MA, Reid L (eds) Extracellular matrix: chemistry, biology, and pathology with emphasis on the liver. Marcel Dekker, New York, (in press)     

IgE Anti-IgG Antibodies in Patients with Juvenile and Adult Rheumatoid Arthritis Including Felty's Syndrome

Anti-IgG; antihodies (anti-IgG) of the IgE class were studied in sera from patients with juvenile rheumatoid arthritis (JRA). rheumatoid arthritis (RA) and patients with Felty's syndrome (FS) by use of an indirect immunofluorescence technique. Forty-two percent of 26 patients with JRA had IgE anti-IgG in serum all in low titers. Positive reactions prevailed in patients with multiple joint involvement. Sixty-three percent of 30 patients with RA and 80% of 20 patients with FS had IgE anti-IgG, the titers found in FS patients being significantly higher. In JRA and FS patients the IgE anti-IgG titers were correlated to the titers of anti-IgG of the IgG class, and for FS patients also with the IgM and IgA classes of anti-IgG. In six of 10 patients with RA the synovial fluid samples from both knees contained IgE anti-IgG. In four of these patients the titers of IgE anti-IgG were higher than in the corresponding serum sample, pointing to a local production. After G-200 Sephadex chromatography IgE anti-IgG were demonstrated in the void volume indicating the presence of these autoantibodies in immune complexes. IgE anti-IgG may be involved in the pathogenesis of JRA and RA by eliciting Type I and III reactions.     

Genetics of the low density lipoprotein receptor:

Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs.     

Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Normal and homogeneous red blood cell populations over a wide range of hyper-iso-hypotonic media

The volumes of human erythrocytes after rapid and gradual swelling in hypotonic NaCl media were measured using a Coulter Counter Z_B at temperatures of +4°C and +20°C together with potassium leakage, the degree of hemolysis and the ‘returning volume’, i. e., the volume in an isotonic solution to which the cells will return from that in a hypotonic solution. The methodological and systematic errors in the volume measurements were corrected by taking into account the shape dependence of the Coulter Counter and the change in cell population during hemolysis, whereafter the measured cell volume values and the comparison between them become more reliable. The curves for cell volume as an inverse function of osmotic pressure appeared to be non-linear. The slopes were small at first but shoed a rapid increase as the cells approached their maximal volume. The critical hemolytic volume was approx.8% higher at +20°C after both rapid and gradual swelling than at +4°C and approx.4% higher after a gradual swelling as compared with a rapid swelling both at +4°C and +20°C.A decrease in temperature resulted in an increase in the critical osmotic pressure both in rapid and gradual hemolysis, but did not greatly affect the amount of prelytic K⁺ leakage. The critical osmotic pressure was smaller in gradual hemolysis than in rapid hemolysis and the prelytic K⁺ leakage was doubled at both +4°C and +20°C.The shifts in osmotic fragility as a function of temperature may be due to differences in the visco-elastic properties of the cell membrane, but the shifts in osmotic fragility as a function of swelling rate may be connected with differences in potassium leakage and membrane stretch.     

Absence of Epstein-Barr virus (EBV) in intrahepatic cholangiocarcinoma confirmed by lack of EBV-coded nuclear RNA and latent membrane protein-1

AIMS: Studies are disclosing that Epstein-Barr virus (EBV) is involved in the aetiology of various neoplasms including undifferentiated carcinomas of the aerodigestive tract. The aetiology of intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm arising from intrahepatic biliary epithelia, has yet to be fully evaluated. To date, two cases of EBV-related ICC have been reported, and they presented foci of lymphoepitheliomatous undifferentiated carcinoma components. METHODS AND RESULTS: To determine whether EBV is commonly involved in the developments of ICC, we performed in-situ hybridization and immunohistochemistry for EBV in 215 cases of ICC in Japan, using a probe against EBV-coded nuclear RNA (EBER) and a specific antibody against latent membrane protein-1 (LMP-1), respectively. We did not detect EBV-infected carcinoma cells in any of the ICC cases examined. No lymphoepitheliomatous undifferentiated carcinoma components were found either. CONCLUSION: The results suggest that EBV infection is unlikely to be involved in the pathogenesis of ICC.